' at the beginning of each form. Name and contact information of all individuals have been anonymised by replacing the original text with the generic tag 'xxxx' enclosed in angled brackets. Identification information about universities, trial units, associated research ethics committees, or settings where the RCTs were conducted have been anonymised in the same way. Funder information and web links have been retained when they do not reveal the institution. The name of the RCT and its acronym have also not been anonymised. The text for two patient information sheets is not provided here for copyright reasons and has been replaced by a web link to the online ethical documents.> Title of the research: A phase III study of Prophylactic Irradiation of Tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention (PIT Trial) Invitation to participate in the trial You are being invited to take part in a research trial. Before you decide if you want to take part, it is important for you to understand why the research is being done and what it will involve. Please read the following information carefully and if you wish, discuss it with friends, relatives and your General Practitioner. Ask us if there is anything that is not clear or if you would like more information. It is important to take time to understand this information and decide whether or not you wish to take part. Part 1 tells you the purpose of this trial and what will happen to you if you take part Part 2 gives you more detailed information about the conduct of the trial PART 1 What is the purpose of this research trial? Mesothelioma is a rare form of cancer affecting the protective lining that covers many of the body's internal organs. The most commonly affected areas are the lungs and internal chest wall. In the UK over 2300 patients are diagnosed with mesothelioma each year and the numbers are increasing. As part of the diagnosis and treatment of mesothelioma, you will undergo a procedure which involves inserting a thin tube into the chest wall enabling an internal examination and for any biopsies or samples of fluid to be taken. These procedures can result in the development of skin lumps or nodules along the tract created by inserting the tube. To try and reduce the risk of these nodules developing in the tract or at the site of the scar, some radiotherapy treatment can be given to the chest wall at the site of the tract after the procedure has been performed; this type of radiotherapy is known as prophylactic irradiation of tracts or PIT. Although many hospitals already give patients radiotherapy treatment to the chest wall we still do not know if the treatment works. This trial has been designed to answer the question about the effectiveness of PIT. If PIT is found to be effective in preventing or delaying the development of these skin nodules then it can be offered to all patients as part of their treatment. However, if we discover that PIT is not effective this will save patients from undergoing ineffective treatment and having to spend time making unnecessary extra visits to hospital. This radiotherapy treatment will be given in addition to other mesothelioma treatment, for example, chemotherapy. What is the treatment that is being tested? The treatment being tested is radiotherapy. The trial is to compare a course of radiotherapy treatment with no radiotherapy treatment. Radiotherapy treatment will be delivered once a day for 3 days. The radiotherapy treatment will take around 15 minutes each time. Why have I been chosen? You have recently been diagnosed with mesothelioma and had an internal examination of your chest wall and a biopsy taken and/or had fluid removed from the lining around the lung with a chest drain. Following this procedure your doctor feels that you are suitable to take part in this trial. This is a research trial, and other patients similar to you are also being asked if they would be willing to take part. In total approximately 400 patients will take part in the UK and Europe. Do I have to take part? Your participation in this research trial is entirely voluntary and you will be given sufficient time to decide whether or not you wish to participate. You are free to decide at all times without giving a reason that you no longer wish to participate in the trial. Withdrawal from the trial will not affect your subsequent treatment or relationship with your treating doctor or the hospital staff in any way. What will happen to me if I take part? If you agree to take part, you will be asked to sign a consent form and your doctor will perform a number of checks to ensure that you are eligible for this trial. These checks will include a physical examination to look at your chest wall and the skin around the chest area. The doctor will also ask you about your current levels of activity and whether you are experiencing any pain. These tests are normally done as part of the routine checks for patients who are to be treated with radiotherapy. Female patients may also require a pregnancy test. If you are eligible and agree to take part in the trial you will be randomly allocated to receive radiotherapy treatment or no radiotherapy treatment. This is done by a computer; you or your doctor cannot choose the treatment. Regardless of whether you are assigned to receive the PIT radiotherapy treatment or not you will be followed up in clinic after 6 weeks, 3 months, 6 months and 12 months. You will also receive telephone calls from a trial nurse or research radiographer every 4 weeks. During each telephone call you will be asked to answer a question at home in a diary given to you after you have had the radiotherapy. The research nurse or radiographer will explain to you how to answer the questions. The telephone follow up calls will be missed out on the months when you are seen in clinic. Telephone follow ups will continue until a skin nodule develops or for 2-years after you enrolled on the trial. The following examinations will be performed at each follow up visit: a) At the clinic appointment the doctor will perform: - a physical examination including inspecting the chest wall. If you develop a skin nodule, the position of the nodule in relation to the area in which you were treated (if you were allocated to receive the radiotherapy treatment) will be recorded at this appointment. - an assessment of your levels of physical activity or performance status - any reaction of the skin to the radiotherapy treatment will be assessed - your levels of pain and use of painkillers will be recorded - details of any other treatment for mesothelioma will be recorded b) At the telephone follow up the trial nurse or research radiographer will ask you if you have noticed any skin nodules developing. If you are concerned about a possible skin nodule then you will be assessed in an outpatient clinic within 1 week. Taking part in the PIT trial will not stop you from receiving any additional treatment that you may need such as chemotherapy or radiotherapy given to control your symptoms. Where possible any extra tests for the trial will take place during normal clinic visits. The clinical research team can advise you how much time this will add to your visit. What are the alternatives for treatment? If you do not wish to take part in this trial your doctor will tell you what alternatives are available in your particular situation. What are the possible benefits of taking part? If you are allocated to the group receiving PIT radiotherapy, this may help you but this cannot be guaranteed. The information we get from this trial will help us to treat future patients with the same disease better. Considering that the benefit of radiotherapy cannot be guaranteed we would like you to consider the possible side effects of the treatment, which are listed below: What are the side effects of radiotherapy to the chest wall? Many people who have radiotherapy to their chest wall have little or no side effects. Side effects from radiotherapy are dependent on which part of your body is being treated and the number of treatments you have. People who have had similar treatments can often have different side effects. Here are some of the more common side effects: Early side effects These can vary according to the individual. Tiredness - Tiredness is one of the most common side effects of cancer treatment. Although fatigue may be a symptom that you have already due to your cancer. Skin reactions - Approximately 10 days following radiotherapy, you will probably develop redness and soreness of the skin within the treated area like a sunburn. This will gradually fade over a few weeks. We will give you E45/aqueous cream to moisturise the area and hydrocortisone cream to use if it sensitive or sore. Pain - There may be an ache within the treatment area lasting about one or two days and starting just after treatment. This is nothing to worry about. It is temporary and you can take simple painkillers such as paracetamol if necessary. Shortness of breath - It is extremely uncommon for radiotherapy to cause breathlessness with this type of treatment. Late side effects It is possible for some types of reaction to occur months or years after the treatment has finished. These side effects are permanent. Your doctor will discuss any possible late effects with you if they are at all likely to occur. Skin changes - With time, your skin (within the treated area only) may become paler than your normal skin. Tiny ‘thread’ veins may develop on the treated skin. Bone weakness - Rarely, radiotherapy can make some of the ribs more brittle. After a severe cough or mild trauma this can result in chest pain and/or a minor rib fracture. Pregnancy and Birth Control If it is possible you may conceive (i.e. you are of child bearing age), you will be asked to have a pregnancy test before starting treatment. Effective birth control with one of these methods should be used during the course of treatment. 1. Tubal ligation (informally known as getting one’s “tubes tied”) 2. Insertion of an intra uterine device (IUD or coil) 3. Diaphragm with spermicidal foam/gel/film/cream/pessary 4. Condom with spermicidal foam/gel/film/cream/pessary 5. Male partner who has had a vasectomy 6. Hormonal contraceptives If you become pregnant while in this trial, you must tell the trial doctor immediately. Contact Persons and Further information The research nurses and doctors listed in this section are available to answer any questions you have concerning this research trial. Understand that you are free to ask any questions concerning this research trial that you wish at any time. It is important that you contact the research nurses or trial doctor as soon as you experience any side effects which disrupt your daily life whether you think the treatment has caused them or not. In the event of any problem or emergency, the research nurses and doctors listed in this section may be reached during working hours (9am to 5pm): If you have any concerns with your treatment and need to speak to someone outside these hours (after 5pm and before 9 am), please contact CancerHelp UK provides general information for patients about cancer and its treatment on their website, www.cancerhelp.org.uk. Cancer Research UK has cancer information nurses who provide a confidential service, Tel: or email: Mesothelioma UK is a national resource centre dedicated to providing specialist mesothelioma information, support & improved care and treatment. Freephone helpline Monday - Friday 8:30 am - 4:30 pm or visit www.mesothelioma.uk.com Macmillan Cancer Support provides support and counselling to help people living with cancer, ask Macmillan Tel: 0808 808 0000 or visit www.macmillan.org.uk UK Clinical Research Collaboration (UKCRC) publishes a leaflet entitled ‘Understanding Clinical Trials’. This leaflet gives you more information about medical research and looks at some questions you may want to ask. A copy may be viewed online at www.ukcrc.org or may be obtained by writing to UKCRC . This completes Part 1 of the information sheet. If the information in Part 1 has interested you and you are considering participation, please continue to read the additional information in Part 2 before making any decision PART 2 What if relevant new information becomes available? Sometimes during the course of a research project, new information becomes available about the treatment that is being studied. If this happens, your trial doctor will tell you about it and discuss whether you want to or should continue in the trial. If you decide not to carry on, or if your trial doctor considers it to be in your best interests to withdraw you from the trial, your trial doctor will make arrangements for your care to continue. If you decide to continue in the trial you will be asked to sign an updated consent form. If the trial is stopped for any other reason, you will be told why and your continuing care will be arranged. What will l happen If I don’t want to carry on with the trial? You can withdraw your consent at any time. This will not affect the standard of care you receive. Information collected up to your withdrawal may still be used. If during the study you lose the capacity to consent, you will be withdrawn from the study. Any identifiable data already collected with consent would be retained and used in the study. No further data will be collected or any other research procedures carried out on or in relation to you. What if something goes wrong? Any complaint about the way you are dealt with during the trial or any possible harm you might suffer will be addressed. The trial is being performed by your doctor and insurance against injury will be provided by the hospital that is looking after you [insert institution name]. If you are harmed due to someone’s negligence then you will have grounds for legal action but you may have to pay for it. Regardless of this, if you wish to complain about any aspect of the way you have been approached or treated during the course of this trial, the normal NHS complaints mechanisms will be available to you. By signing a consent form you are NOT waiving any of your legal rights. Confidentiality Information obtained from research will be protected and its handling will be compliant with the Data Protection Act of 1998. The doctor in charge of the trial will keep your original signed consent form in a secure location. Your medical records will not hold any individual results from this trial. Your unique registration number will be used to make sure you cannot be identified outside the trial. All information about you will be treated as confidential and nothing that might identify you will be revealed to any other department or organisation. Your name will not appear in any publication or report about this trial. There will be strict control of access to the files containing clinical information. Your personal information will be accessible to the trial doctors and others involved in the trial for the purpose of the trial and your direct clinical care only. Direct access to your records may also be required by members of the independent ethics committee and/or regulatory agencies. Will My General Practitioner Be Involved? With your permission, your GP will be notified of your participation in this trial. By signing the consent form you are agreeing to this. Will I be paid any costs and reimbursements? There will be no payment to you for entering this trial, nor payment for undergoing investigations that are additional to your standard care. Who is organising and funding the research? The PIT trial is being funded by the UK’s National Institute for Health Research as part of their Research for Patient Benefit Programme. This trial is being organised and coordinated by Consultant Clinical Oncologists (radiotherapy specialists) and the Trials Coordination Unit at The NHS Foundation Trust in . Independent international researchers in the field of mesothelioma have been involved in developing the trial and have positively reviewed the trial. None of the researchers will receive any payment for your participation in the trial. What will happen to the results of the research trial? Independent experts will review the progress of the research, and the results will be published in a respected medical journal. The results will help to decide how to treat mesothelioma in the future. Trials like this are often used in cancer research. Who has reviewed the trial? The trial was given a favourable ethical opinion for conduct in the NHS by the Research Ethics Committee. Thank you for taking time to read this information sheet. You will be given a copy of the information sheet and a signed consent form to keep if you decide to take part in the trial. INFORMATION ABOUT THE RESEARCH Study title: A cluster randomised trial of alternative forms of hydration in cancer patients in the last days of life We would like to invite you to take part in a research study. Before you decide we would like you to understand why the research is being done and what it would involve for you. One of our team will go through the information sheet with you and answer any questions you have. We’d suggest this should take about 15 minutes. Talk to others about the study if you wish. (Part 1 tells you the purpose of this study and what will happen to you if you take part. Part 2 gives you more detailed information about the conduct of the study). Ask us if there is anything that is not clear. Part 1 What is the purpose of the study? As people get closer to death, they tend to eat and drink less than beforehand. When this occurs, it is often unclear to doctors and nurses what they should do for the patient. In some hospitals and hospices the standard treatment is to encourage / help the patient to drink, and to give the patient regular “mouth care”. Mouth care usually involves someone applying water or an artificial saliva product to the inside of the mouth (and a lubricant to the lips). However, in other hospitals and hospices the standard treatment is to give fluid by a drip either into a vein or under the skin (as well as to encourage / help the patient to drink, and to give the patient regular mouth care). The reason for this difference in approach is that there is no research to guide doctors and nurses as to what they should do for the majority of patients. However, there are some instances where it is clear that the patient should be given fluid by a drip as the potential benefit appears to outweigh the potential harm. Similarly, there are some instances where it is clear that the patient should not be given fluid by a drip as the potential harm appears to outweigh the potential benefit, e.g. in a patient with fluid retention (swollen legs / arms). The aim of this research study is to provide evidence to allow doctors and nurses to make the right decision in the majority of patients. The research study is being funded by the Research for Patient Benefit Programme (a part of the National Health Service). The study is being conducted in a number of different hospitals and hospices, because the palliative care teams in these units want to ensure that all patients receive the best end of life care available, and that all treatments given at the end of life are effective (i.e. they do work), and are well tolerated (i.e. they don’t cause side effects). Currently, some of these hospitals and hospices usually give fluid by a drip, whilst other hospitals and hospices usually do not give fluid by a drip (but do encourage / help the patient to drink, and to give the patient regular mouth care). For the purpose of the study, all of the hospitals and hospices will adopt a standard treatment for hydration of patients, but the treatment that they use will be decided by chance (randomly): 50% hospitals and hospices will be giving fluid by a drip, and 50% hospitals and hospices will be encouraging / helping the patient to drink, and giving the patient regular mouth care. In this hospital / hospice, the standard treatment is fluids by a drip, and we only use drinking & regular mouth care alone if there is a very good reason to do so. Your palliative care / clinical team have decided that you should receive the standard treatment at the moment, but will continue to monitor your condition may change this decision based on their clinical judgement. The clinical team, and not the research team, will have the final say in this matter. The purpose of the study is to see whether the problems experienced at the end of life are different in the two groups, and how well patients tolerate the different treatments. The care you will receive will be the same as if you were not in the study, and the study will not involve any more questions, observations, or investigations. The doctors and nurses routinely collect information on all patients; this information will be shared with the research team (and analysed by the University of ). The researcher team will collect the information from your observation chart, drug chart, and medical and nursing notes: the research team will have no direct contact with you during the actual study. Why have we been chosen? The reason we have approached you about the study is that you seem to be approaching the end of life, and are drinking less than normal, or are expected to soon be drinking less than normal. Also, there appears to be no reason not to give you the standard treatment that is used in this hospital / hospice (i.e. fluids by a drip). The palliative care team referred you to the research team, as they felt you may be willing to participate in this study. We are intending to enrol 200 similar patients to the study from twelve hospitals and hospices in the United Kingdom. Do I have to take part? It is up to you to decide to join the study. We will describe the study and go through this information sheet. If you agree to take part, we will ask you to sign a consent form. A copy of the consent and this information sheet will be given to you to keep. You are free to withdraw at any time, without giving a reason. This would not affect the standard of care you receive. What will happen to me if I take part? If you decide to take part in the study, then the care you will receive will be the same as if you were not in the study: you will receive fluids by a drip, as this is the standard treatment in this hospital/hospice. The nursing staff will assess you at least every four hours, and record any symptoms or other problems you may experience. If you do develop any symptoms or other problems, then these will be treated in the normal way. The nursing staff will record any drugs or other treatments you may receive, and any problems relating to fluids by a drip. These observations are done routinely, and there will be no more observations than normal. All of the care will be done by your normal doctors and nurse, and you will have no contact with the research team during the actual study. The research team will collect information about your symptoms, other problems, drugs given, other treatments given, and any problems relating to fluids by a drip. This information will be anonymised (so that your identity is protected), and then sent to the University of for analysis. What do I have to do? If you decide to take part in the study, then you will need to sign a consent form to say that you agree to take part in the study, and that you agree for the research team to have access to/use the routine information collected by your clinical team (doctors and nurses). Otherwise, there is nothing for you to do. If you decide not to take part in the study, then your care will be the same as if you take part in the study, but the research team will not have access to / use the routine information collected by your clinical team. What are the alternatives for treatment? The standard treatment in this hospital / hospice is fluids by a drip. Some of the other hospitals and hospices in the study will have a different standard treatment, i.e. drinking & regular mouth care alone. What are the possible disadvantages and risks of taking part? If you decide to take part in the study, then the care you will receive will be the same as if you were not in the study, and so there are no additional risks (or disadvantages). Mouth care is sometimes uncomfortable, and if this is the case then the doctors and nurses may decide to stop the treatment altogether. Inserting the drip can be uncomfortable, and some people may experience bruising / soreness at the site of the drip. Some patients may also experience fluid retention, which may cause swelling of the arms and legs, and sometimes shortness of breath (due to fluid on the lungs). If this is the case then the doctors and nurses may decide to stop this treatment altogether. What are the possible benefits of taking part? We cannot promise the study will help you but the information we get from this study will help to improve the treatment of people with advanced cancer in the future. What if there is a problem? Any complaints about the way you have been dealt with during the study or any possible harm you might suffer will be addressed. The detailed information on this is given in Part 2. Will my taking part in the study be kept confidential? Yes. We will follow ethical and legal practice and all information about you will be handled in confidence. The details are included in Part 2. If the information in Part 1 has interested you and you are considering participation, please read the additional information in Part 2 before making any decision Part 2 What if relevant information becomes available? Sometimes we get new information about the treatment being studied. If this happens, your researcher doctor might consider you should withdraw from the study. He / she will explain the reasons and arrange for your care to continue. What will happen if don’t want to carry on with the study? You are free to withdraw from the study at any stage, and you do not have to give a reason for withdrawing from the study. If you do withdraw from the study, then your care will not be affected. The research team will continue to use the clinical information collected up to the time you withdraw from the study, but the research team will not be allowed to use any clinical information collected after the time you withdraw from the study. What if there is a problem If you have a concern about any aspect of this study, you should ask to speak to the researchers who will do their best to answer your questions. Researcher name: Contact phone number: If you remain unhappy and wish to complain formally, you are free to do this through the hospital Patient Advice and Liaison Service / hospice complaints procedure. Details can be obtained from Name: Patient Advice and Liaison Service Contact phone number: Email: In the event that something does go wrong and you are harmed during the research and this is due to someone’s negligence then you may have grounds for a legal action for compensation against the hospital / hospice but you may have to pay legal costs. The normal National Health Service / hospice complaints mechanisms will still be available to you. Will my taking part in this study be kept confidential? All information which is collected about you during the course of the research study will be kept strictly confidential, and any information about you which leaves the hospital / hospice will have your name and address removed so that you cannot be recognised. If you join the study, some parts of your medical records and data collected for the study will be looked at by authorised persons from the University of (who are organising the research). They may also be looked at by authorised people to check the study is being carried out correctly. All will have a duty of confidentiality to you as a research participant and we will do our best to meet this duty. What will happen to the results of the research study? The results of the study will be fed back to the Research for Patient Benefit Programme (National Health Service), and then presented at medical meetings, and published in medical journals No patient will be identifiable in any reports, presentations, or publications of the study. Who is organising and funding the research? The research study is being funded by the Research for Patient Benefit Programme (National Health Service), and is being organised (“sponsored”) by the . The hospital/hospice/any individual will not be paid for including you in the study. Who has reviewed the study? All research in the NHS is looked at by independent group of people, called a Research Ethics Committee, to protect your interests. This study has been reviewed and given favourable opinion by the Research Ethics Committee. The study has also been reviewed / approved by the Research for Patient Benefit Programme (National Health Service), and by the . Further information and contact details If you would like further information about the study, then please contact the following members of the research team: Name Principal Investigator: – Consultant in Palliative Medicine Contact phone number: Email: Name Research Nurse (if applicable): Contact phone number: Email: Study title: WorkPlan - A guided workbook intervention to support work related goals among cancer survivors We would like to invite you to take part in our research study. Before you decide we would like you to understand why the research is being done and what it would involve for you. The information sheet explains to you all the steps and procedures of the study. The information is to help you to decide whether or not you would like to take part in the research. What is this research study about? Many cancer patients plan to return to work but have said that they would like more support with the process. WorkPlan is a workbook support package for patients who have been diagnosed with cancer and aims to help patients plan their return to work and to tackle some of the key issues that cancer patients have reported when returning to work. In this study we are testing how useful the package is. We would ask participants to be put into one of two groups (by chance): either a group that get the booklet (and their usual care) or a group that receive usual care only. This is so we can see the difference that the WorkPlan package makes in supporting patients. We hope that this research will benefit future cancer patients and help them in their return to the workplace. Why have I been invited to take part? You have been invited to take part because you: - Are between the ages of 18 and 65 years of age - Speak and write English - Were working prior to receiving your diagnosis - Plan to return to work A total of 80 patients will take part in this study: 40 will be assigned to the workbook group and 40 to the usual care group. Can everyone take part in this study? You would not be able to take part if you: - Have already returned to work - Do not plan to return to work When the researcher contacts you, they will ensure that you are able to take part in the project. They will explain the study in more detail and you will be able to ask any questions. Do I have to take part in this study? No. Participation in this research project is voluntary. It is up to you to decide if you would like to take part in this study. If you do decide to take part in this study, we will ask you to sign a consent form. You do not need to make a decision immediately about whether to take part or not. One of our team will contact you in two weeks to go through the information sheet with you and answer any questions you have prior to deciding whether to take part. If you agree to take part in the study, but then change your mind, you can leave the study without giving any reason. You can withdraw yourself from the project at any time without any explanation. Leaving the study will not affect the standard of care you receive. What will happen to me if I decide to take part? If you decide to take part, an initial appointment will be arranged at a time most convenient for you at the hospital to discuss the project, complete the first set of questionnaires and to tell you which group you have been put in. The group that each person is put in is decided through randomisation – this is a process that is similar to choosing a name out of a hat or rolling a dice. This way we do not know which group a person will be assigned to until appointment. DIAGRAM What will I do if I am in the WorkPlan booklet group? If you are in the booklet group then you would be shown the WorkPlan booklet and we will talk you through how to use it and answer any initial questions. It might be helpful to discuss the workbook with your partner, family or friends. Two and four weeks later we would telephone you to find out how you are getting on and answer any questions. WorkPlan is a 4-week programme of activities aimed at helping people plan their return to work and to set goals to achieve this. It was developed following a previous study with over 250 cancer patients looking at what support they needed to return to work. After the four weeks you would be asked to complete a set of questionnaires by post and you would be asked to complete these again 6 and 12 months later. The questions focus on your mood, experience of work and beliefs about working. You will also receive a small number of questions via text at the end of each month asking about your work status, which you can respond to via text or email. After 4 weeks we would ask you to take part in an interview to find out about your experience of using the workbook, and at the end of the 12 months you would be asked to take part in another interview so you can tell us what you thought about the whole study. What will I do if I am in the usual care group? If you are in the usual care group you would not be given the booklet but would receive your usual care. About four weeks after your initial appointment you would be asked to complete a set of questionnaires by post and you would be asked to complete these again 6 and 12 months later. The questions focus on your mood, experience of work and beliefs about working. You will also receive a small number of questions via text at the end of each month asking about your work status, which you can respond to via text or email. At the end of the 12 months you would be asked to take part in an interview so that you can tell us what you thought about the study. At the end of the study you would be offered a copy of the booklet and a chance to work through the programme, if you would like to do this. Will you access my medical records? We would like to access your medical records in order to obtain information on your condition and treatments (as this can be important in people returning to work). We also wish to record your past medical history along with any other health conditions which you may have as this information may help us to understand the findings of our study. We will access your medical records only if you provide additional consent to this. If you are happy for us to access your medical records, you will be asked to indicate this on the consent form. If you do not want us to access your medical records, you do not have to provide additional consent to this (do not initial the box next to this request). If you agree for the researchers to access your medical records, only the following researchers will have access to the identifiable data: Prof and research assistants who are working on the project and have received training in handling research information. In addition, and only with your permission, we would write to your GP to inform them of your participation in this study. What happens next? Once the study has been completed we will send you a summary of the group results if you would like this. Will I be reimbursed? You will receive £15 after your visit to the hospital to cover your time and your travel expenses. What will happen if I don’t want to carry on with the study? You can leave the study at any time without giving a reason. Any information collected which can be used to identify you (such as name, address) will be destroyed. Only information from you which has been made anonymous will be analysed. What if I am already taking part in another study? If you are taking part in another study you can still choose to take part in this project. Taking part in a study requires time and effort and you need to make sure that taking part in multiple studies will not interfere with your work/home life. If you are already taking part in another study and feel you do not have enough time to take part in this study, you do not have to. What if there is a problem? If you have a concern about any part of this study, you should speak to the researchers who will do their best to answer your questions (Tel: ). You can also contact the Patient Advice and Liaison Service (PALS) on the contact details below: Tel: (Mon-Fri, 9am – 5pm) Web: www.uhb.nhs.uk/pals-­-contact.htm Email: PALS is an impartial and confidential service, which aims to advise and support patients and their families. The PALS website offers details of their service as well as the location of other offices that might be more convenient to you (www.nhs.uk/Service-­-Search/Patient-­-advice-­-and-­-liaison-­-services-­-(PALS)/LocationSearch/363). Will my taking part in this study be kept confidential? Any data collected from you will be kept strictly confidential. You will be assigned a unique code. Results from the questionnaires and tasks will be stored next to your code and in a different place to where your contact details (name, address, telephone number) and consent forms are stored. All hard copies of documents will be stored in locked filing cabinets in the office of Prof , which will be locked when the researchers involved in this study are not there. All other information will be stored on password protected computers. Information which is stored on computers will have your name and contact details removed so that the information cannot be traced directly to you. Only researchers from this research team at University will have access to your information. You can ask to see the information stored about you if you wish to do so. If you believe the information stored is incorrect, the researchers will correct it. If you wish to leave the study, information which may be used to identify you will be destroyed. All verbal information you disclose will also be kept confidential. Confidentiality will only be broken if the researcher has serious concerns for your safety or if they have serious concern that you or others may be harmed. Will my doctor (GP) know that I am taking part in this study? With your permission your family doctor will be informed that you are taking part in this study. They will be sent a brief letter saying that you are taking part in this study. What will happen to the results of this study? Results from your participation will be analysed together with results from all of the other participants in this study. We may publish these results in scientific journals. Results that are published will typically be group results. We will not publish individual results with identifying information. This means it will be impossible for anyone to identify who participated in this study from the publications. We will also send you a clear summary of the group results and the publications, if you would like to receive these. Who is organising the research? The research is funded by the National Institute for Health Research. The study is being undertaken by researchers at . The research is sponsored by University. The person with overall responsibility for the study is Prof , who can be contacted on . Who has reviewed this study? All research in the NHS is looked at by an independent group of people called a Research Ethics Committee to protect your interests. This study has been reviewed and given favorable opinion by Research Ethics Committee (Reference: ). Who can I talk to about this study? You may want to talk about the project with: - your child/family - your friends - your doctor - the researchers (contact details listed below) Please feel free to contact Prof if you have any questions. Thank you for taking the time to read the information sheet. If you require any help with this information sheet please call , or email . Surgical and large bore pleural procedures in Malignant pleural Mesothelioma And Radiotherapy Trial (SMART trial) A Randomised Controlled Trial evaluating whether prophylactic radiotherapy reduces the incidence of procedure tract metastases. 1. Study Title This is a research study examining the role of radiation treatment (radiotherapy) after chest wall procedures (such as surgery, thoracoscopy or chest drain insertion), in patients with cancer of the lining of the lung (mesothelioma). It will try to identify the best timing for radiotherapy to be given in order to minimise the risk of the cancer spreading during the procedure. ‘Randomised Controlled Trial’ means that patients who take part will be randomly allocated to either receive radiotherapy immediately after the procedure or radiotherapy later on, if a lump is discovered near the procedure site. 2. Invitation You have been invited to take part in this research study. However before you decide to take part, it is important for you to understand why the research is being done and what it will involve, therefore please take time to read the following information carefully. It is a good idea to discuss taking part in the trial with your family and/or GP before making a decision. If you would like to take time to do this please let us know and a further appointment will be made to see you in due course. Please feel free to ask us if there is anything that is not clear or if you would like more information. 3. What is the purpose of the trial? Radiotherapy is not able to change the course of mesothelioma but may prevent or suppress the spread of the cancer through the chest wall following surgery. It is often given to patients soon after a chest wall procedure to reduce the risk of this happening. The radiotherapy involves attending hospital on 3 consecutive days soon after the diagnosis and may also be associated with mild side effects (as described below). Recent research suggests that cancer spreading through the chest wall in mesothelioma may not be as common as previously thought and some studies suggest that radiotherapy soon after the procedure may not actually reduce the chances of this happening. Hence it is important that we know when it is best to give radiotherapy in this situation. This trial will endeavour to answer this question. 4. Why have I been chosen? You have been chosen to consider taking part in this trial because you have mesothelioma and have recently had a procedure to your chest. We would like to know whether immediate radiotherapy is useful for patients in exactly your situation. This study is taking place across many centres in the United Kingdom and 203 patients will be asked to participate. 5. Do I have to take part? No, it is up to you to decide whether or not to take part. If you do decide to take part you will be asked to sign a consent form and you will be given a copy for your records along with this information sheet. If you decide to take part, you are free to withdraw at any time without giving a reason. A decision to withdraw or a decision not to take part will not affect your future medical care. 6. What will happen to me if I take part? Your doctor will perform an initial assessment, including finding out about your current health and medications and examining the area of your chest where you had the procedure done. You will also be asked to complete questionnaires about your current level of pain and how your illness is affecting your life, which will take about 10 minutes. You will then be randomly allocated to receive either immediate radiotherapy or deferred radiotherapy in the event that you develop a lump near the procedure site. If you are allocated to the immediate radiotherapy group, an appointment will be arranged with an oncologist to plan the treatment you will receive. This will take about 30 minutes. After this you will need to attend the hospital on 3 consecutive days to receive the treatment. Each visit takes about 30 minutes. All patients will be seen in clinic at 1, 3, 6, 9, 12 months after entry into the trial. Again details of your current health and medications will be recorded. Your chest will be examined to look for any lumps near the procedure site and you will be asked to fill in some more questionnaires on quality of life and pain. When you are not seen in clinic, you will receive a phone call once a month from a nurse who will ask if anything has changed around the procedure site on your chest. They will explain what to look out for and if necessary, a clinic appointment will be arranged for you to see the doctor. Each month you will also be asked to complete a score sheet about your current pain levels, which you will then post back to the hospital. Should a lump be felt near the site of the procedure you will be seen by the doctor and if necessary, radiotherapy will be arranged shortly afterwards and given over 3 working days. If you were in the immediate radiotherapy group, you will be able to discuss with the doctor whether further radiotherapy is necessary. Patients who have been involved in the study at and Bristol may also be invited to undertake an additional short interview at the 6 month follow up visit to discuss their experiences of the trial and treatment so far with a trial nurse. This is an extra part of the study which is entirely voluntary and we are hoping to interview about 20 people in total. These interviews will be recorded but any information used from these interviews will not be identifiable to you. 7. If I take part, which aspects of my treatment will be ‘experimental’ or ‘extra’? As immediate radiotherapy is already commonly given in centres across the UK, the treatment itself is not experimental. This study is trying to work out the best time for it to be given to patients to maximise its benefit without causing undue inconvenience. The first trial visit will be extra to your normal clinical care in order to enrol you into the study. The other follow up visits in the trial are what you would receive as part of your normal clinical care, so these visits will not be extra, however the questionnaires and pain scores are an addition for the trial only. As part of the trial, a nurse will contact you once a month to ensure we respond quickly to any changes you notice around the procedure site. 8. About the radiotherapy Regardless of whether you receive radiotherapy at the beginning of the trial or later on should you develop a lump, the radiotherapy you will be given is the same. It will be given every day for 3 days and you will be able to go home after each dose. Prior to the first treatment you will meet a radiotherapy specialist to discuss and plan the treatment. Each radiotherapy appointment takes about 15 minutes and you will be free to go home once you have received the treatment. The procedure itself is not painful. Possible Side effects Most patients do not experience severe side effects from this type of radiotherapy. However some patients notice mild side effects such as: - Feeling more tired than usual - Skin reactions- these may occur in the area treated and may develop a few days or weeks after the radiotherapy. The skin may become pink and might feel sore or itchy. - The skin is more sensitive than normal after radiotherapy. We advise against using perfumed creams and soaps on the treated area and keeping the area covered if you are in the sun. At each clinic visit we will carefully assess and record any side affects you have noticed from the radiotherapy. 9. Will my medical information be kept confidential? If you consent to join the study, your medical records may be looked at by: - Key members of the research team (doctors and nurses who would usually be involved in your care as well as the doctors and nurses who are coordinating the trial) - Representatives of the Sponsor ( NHS Trust) or the Regulatory Authorities to check the study is being carried out correctly. All of these individuals will have a duty of confidentiality to you as a research participant. It is normal practice that if the radiotherapy is provided at a different hospital, personal and clinical information regarding your care will be shared between these sites. Information about you will be collected for analysis by the Sponsor’s trial team and other collaborators involved in the study. This will include information about your health and other details such as your date of birth and gender. This information will be recorded and stored on a secure database, accessible only to the research team. You will be allocated a personal study number to identify you, so identifiable information (such as your name and contact details) will not be stored on the study database. Some identifiable details, such as your name, address and NHS number, may be transferred to the Sponsor’s trial team on paper or electronic records. This will only be done where necessary for the purposes of monitoring and follow up. In these instances, the information that identifies you will be kept completely secure and accessible only to authorised individuals within the Sponsor’s trial team. Information held by the NHS and records maintained by the NHS Information Centre may be used by the Sponsor’s trial team to keep in touch with you and follow up your health status. 10. What are the possible disadvantages and risks of taking part? As radiotherapy of this type is already administered in many centres across the UK, the side effect and safety profile is already well established. The main risk is experiencing a side effect to radiotherapy, but these are generally mild (as described above). You will need to attend hospital on four occasions for the planning and treatment. We do not know if by having deferred radiotherapy, your chances of the cancer spreading at the procedure site are higher or not. This is what we are trying to find out from this study. You will need to complete some questionnaires for the trial purposes, but these only take a few minutes and you will be provided with stamped addressed envelopes to return them in. Radiotherapy is associated with some additional radiation exposure. However, in patients with mesothelioma, this does not result in an additional significant risk given the long time lag it would take for it to cause harm. 11. What are the possible benefits of participating in the trial? Regardless of which treatment group you are allocated to, you will receive radiotherapy should it become necessary. You will have regular contact with the trial team and be followed up regularly. Regardless of the trial results, you will be helping us find out how patients with mesothelioma should be treated in the future. You will be contributing to our understanding of the disease and helping us to develop better ways to treat your illness in the future. 12. What if new information becomes available? The trial team will continue to review all new research data. If new information that influences the trial becomes available, alterations will be made accordingly. If this happens we will discuss whether you want to continue in the study and provide you with all the information you need to make this decision. 13. What if there is a problem? If you have a concern about any aspect of this study you should ask to speak to the study doctor who will do their best to answer your questions. If you remain unhappy and wish to complain formally, you can do this through the NHS complaints procedure. The study doctor or the hospital switchboard can provide you with contact details for the complaints department. If you are harmed as a result of your participation in the study due to someone’s negligence, NHS trust will provide indemnity and/or compensation via the NHS indemnity scheme. If you are harmed as a result of your participation in the study, not due to negligence, NHS trust will sympathetically consider any claim for compensation. 14. Who is organising and funding the research? NHS Trust is sponsoring the research, which means that the trust has overall responsibility for the safe and appropriate conduction of the trial. The trial has been funded by a grant from the National Institute of Health Research ‘Research for Patient Benefit’ scheme. No payment will be made to trial doctors or nurses for including you in the trial. 15. Who has reviewed the trial? This study has been reviewed and approved by a Research Ethics Committee, the Respiratory Trials Unit and the clinical trials team at NHS Trust as well as the doctors and research department at your own hospital. External experts have also reviewed the trial as part of organising funding for the study. 16. What will happen to the results of the trial? When the study has finished and the results have been analysed, they will be published in a medical journal so that other doctors can read them. If you would like us to write to you personally, explaining the study findings, please indicate this on your consent form. 17. What do I need to do? After reading this sheet, you will be invited to ask questions about the trial. If you would like to take part, we will ask you to sign a consent form. Your GP will be informed that you are taking part, with your consent. If you wish to take a few days to consider whether to take part or would like to discuss the trial with your GP, please inform us. If you decide not to participate, your routine care or legal rights will not be affected in any way. You can withdraw from the study at any time without giving a reason. Thank you for taking the time to read this information and considering taking part in the trial. Purpose and Description of Study I have been told by my physician that I have prostate cancer. It is unclear how my cancer can be most effectively treated. I understand that there is no standard treatment for prostate cancer at this stage but radiation therapy alone, hormonal therapy, or a combination of these have been used with similar results. In order to determine the best therapy for this disease the Clinical Trials Group has organized a study and I have been invited to participate. I have been told that this study will compare two different forms of treatment for my disease and that if I participate, my treatment will be selected randomly and I shall receive either hormone therapy alone or combined hormone therapy and radiation therapy. The chances of my receiving either of the treatments described is equal and I will be told which treatment I have been assigned. If I am assigned to receive hormone therapy alone, I shall be followed closely and if the tumour starts to grow in the pelvis but has not spread elsewhere, I may also then receive radiation therapy. I understand that the purpose of this study is to determine which of the treatments is most effective in prolonging life and giving patients with my stage of prostate cancer the best possible quality of life. About 1200 people from the United States, Canada and other countries will take part in this study. Study Treatment All patients will receive hormone therapy. This will be a combination of antiandrogen (Flutamide or Nilutamide or Bicalutamide) (pills) PLUS an antihormone called a LHRH agonist (injections of Goserelin or Leuprolide or Buserelin) OR bilateral orchiectomy (surgery). I understand that I will choose between the two types of hormonal treatment - injections or orchiectomy. Orchiectomy is a surgical procedure to remove the testicles and this is performed under general anesthetic. I understand that if I decide to have the LHRH agonist injection instead of the removal of the testicles I will have to go and have an injection given to me (once a month or once every two months or once every three months) for the rest of my life or until this treatment fails. I will take the Antiandrogen pills every day for as long as my physician directs. I understand that if I am assigned to receive radiation therapy, the radiation treatments will be given five times each week (for 35 treatments) for 7 weeks. The radiation will treat the prostate gland and the lymph nodes around it unless the lymph nodes have been examined at surgery and found to be free of tumour; in which case, only the prostate will be irradiated. Potential Side Effects and Risks All treatments have side effects and my doctors will be monitoring me closely to manage any problems that might develop. Risks and side effects shared by two or more of the LHRH agents in this trial include: Very Likely (21% or more): I have been told that side effects that can very likely occur as a result of the hormonal treatment include the following: - Impotence (unable to have an erection) and reduced sex drive - Hot flashes - Nausea, vomiting - Pain Less Likely (5-20%): I have been told that side effects that can less likely occur as a result of hormonal treatment include the following: - Excessive development of breasts in men, which may include breast tenderness - Insomnia (difficulty sleeping) - Lethargy (feelings of tiredness) - Increase urge to urinate and need to urinate more often - Altered night vision - Sensitivity to alcohol - Decrease size of testicles - Changes in blood pressure (hypo or hypertension), which has rarely been associated with strokes (Buserelin) - Dizziness which may include room spinning (vertigo) - Numbness and tingling in hands and feet - Local pain, redness and/or irritation at injection sites if I am receiving injections of LHRH agonist - Constipation - Scarring in the lungs may occur in patients treated with the drug Nilutamide which causes shortness of breath and coughing. Most cases recover when the drug is stopped but very rarely this may result in death. If I experience any new or worsening shortness of breath, I will report this immediately to my doctor. - Lack or loss of strength - Headache and blurred vision - Muscle pain - Joint pain - Bone pain - Changes in serum lipids and proteins - Irregular heartbeat - Appetite changes Rarely (1-4%): I have been told that other side effects that can rarely occur as a result of hormonal treatment include the following: - Retaining an increased amount of water in my body tissues. - Itchy rash - Diarrhea - Weight loss or weight gain - Liver sensitivity (jaundice) – If it occurs I understand that I should discontinue the antiandrogen pills and contact my doctor immediately - Elevated liver function tests - Cough - Disease flare reaction (increased bone pain, urinary tract obstruction, spinal cord compression) which can cause pain, tingling in the arms and legs, and problems with movement and sensation, rarely including paralysis - Heart disease including failure and heart attack Additional risks and side effects associated with LEUPROLIDE that are considered to be medically important are: Less likely (5 – 20%): - excess sugar in the blood (hyperglycemia) - neuromuscular disorders Rarely (1 – 4%): - visual changes - gastrointestinal tract bleeding (e.g. in the stomach or intestines) - loss of memory - hearing loss or ringing in the ears - allergic reaction, in severe cases can include anaphylactic shock (anaphylaxis) - fever Lung disorders (including inflammation, pneumonia and fluid collection) have been rarely associated with LEUPROLIDE Additional risks and side effects associated with GOSERELIN that are considered to be medically important are: Rarely (1 – 4%): - decreased bone marrow function, may reduce number of infection fighting cells - flu like syndrome - infection - visual changes - fever - benign tumour of the pituitary gland (pituitary adenoma) Additional risks and side effects associated with BUSERELIN that are considered to be medically important are: Less likely (5 – 20%): - depression Rarely (1 – 4%): - visual changes - loss of memory - allergic reaction, in severe cases can include anaphylactic shock (anaphylaxis) - benign tumour of the pituitary gland (pituitary adenoma) - fever Decreased bone density (bone loss) may occur in patients treated with long term LHRH agonists. Thromboemboli (blood clots) have been rarely associated with the androgen suppression agents used on this trial. During Radiation Therapy: Very likely (5-20%): I have been told that very likely side effects that may occur as a result of treatment with radiation therapy include: - Diarrhea and rectal irritation which can present as a pressure or fullness in the rectum, discomfort and pain near the anus, hemorrhoid irritation and less likely bleeding. - Bladder irritation which could cause me to pass urine more frequently (both day and night) and to have to rush to the bathroom when I get the urge to pass urine. - Slight redness and sensitivity of skin over radiated area – I have been told that this is rarely severe. - Fatigue and nausea (rarely vomiting) – I have been told that these are rarely severe. - Impotence (unable to have an erection). Following Radiation Therapy: Rarely (1-4%): I understand that rare severe persistent side effects of radiation therapy occur in patients and may be the following: - Diarrhea and rectal irritation which can present as a pressure or fullness of the rectum, discomfort near the anus, hemorrhoid irritation and less likely bleeding. Very rarely a rectal ulcer may occur causing some pain, bleeding and mucous with bowel movements. - Bladder irritation which could cause me to pass urine more frequently (both day and night) and to have to rush to the bathroom when I get the urge to pass urine. - Impotence (unable to have an erection) - Narrowing of the bladder neck – I understand that this could cause me to have difficulties passing urine and might make it necessary for me to have an operation. In addition, there is always the risk of very uncommon or previously unknown side effects occurring. I understand that many of these side effects are irreversible and have been discussed by my doctor. I understand that not enough is known about these treatments to know if they may affect an unborn child. Therefore adequate birth control measures will be used by me or my sexual partners while participating in this study. My doctor will be watching me closely to see if side effects are occurring. My doctor may prescribe medication (or may delay the treatment) to keep these side effects under control. If new side effects or information concerning my treatment are identified in the course of the study, I will be informed. Potential Benefits I have been told that it is unknown whether or not I will derive any personal benefit from participation in this study. I understand that this study may demonstrate that hormone therapy alone is just as effective a treatment as combined hormone and radiation therapy. After many years of follow up it may be possible to determine whether hormone therapy alone has fewer long term side effects or complications; or whether the combination of hormone therapy and radiation therapy has more side effects or complications. I have been told that should my disease become worse, if side effects become very severe, if new information indicates that this treatment is not in my best interest, or my doctor feels that this treatment is no longer in my best interest, or the sponsor decides to stop the study, the treatment will be stopped. Further treatment would be discussed. Alternatives I have been told that alternatives which could be considered in my case include radiation therapy alone, other hormonal therapy, or a combination of therapies. My doctor has discussed with me the possible benefits and side effects of these other treatments. Tests, Questionnaire I have been told that a number of investigations (blood tests, x-rays) will be performed while I am on the study. These tests are of the same type that would be done if I was not participating in the study, but may be carried out more frequently than usual, particularly during the early stages of the study. The needles used to take blood or inject substances for body scans might be uncomfortable. I might get a bruise, or rarely, an infection at the site of the needle puncture. I understand that at specified intervals while on the study, I will be asked to fill out a Quality of Life questionnaire that will take 15 to 20 minutes that records how well I feel and how well I am tolerating the treatment, and that this is an important part of this study. Confidentiality, Access to Medical Records Qualified representatives of the following organizations may inspect and receive information from my medical/study records for quality assurance and data analysis: - Clinical Trials Group (), the research group coordinating this study - The research ethics committee who oversees the ethical conduct of this study in your hospital/clinic - Oncology Group - - National Cancer Institute of the U.S. - U.S. Food and Drug Administration (because they oversee the use of drugs in the U.S.) - Other regulatory authorities (because they oversee the use of drugs in other countries) The organizations listed above will keep the information they see or receive about me confidential, to the extent permitted by applicable laws. Because the long term results of this study are important, this form gives lifelong consent for access to my future medical information pertaining to my cancer or treatment. No records bearing my name will be provided to anyone other than the investigators involved in this study. I will not be identifiable as an individual in any publication which may result from this study. Costs I will not be paid for taking part in this study. Taking part in this study may result in added costs to me. In the case of research related side effects or injury, medical care will be provided by my doctor or I will be referred for appropriate medical care. Voluntary Participation I have discussed the information above with my doctor and she/he has answered any questions I have had about my treatment. Participation in this study is voluntary and I understand that I can refuse to participate and am free to withdraw from it at any time. If I refuse to participate, or participate and subsequently withdraw, my doctor will continue to treat me with the best means available. I also understand that if I have questions concerning my participation in this study, I may at any time meet with the physician who is principally responsible for the project. I have received a copy of this consent form. For patients participating through institutions: In the event that physical injury or complications occur as a result of this research, facilities for treatment of injury will be available; however, I will not automatically be provided with reimbursement for medical care or other compensation. This section is an introduction only. Parts B, C and D give more information. • Your Doctor has told you that your lung cancer has spread to your brain. The usual treatment in this situation is for you to start taking steroid tablets and other medications to help with the problems that the cancer may be causing. Your doctor may also consider giving you radiotherapy to your brain. • Doctors are currently uncertain whether the advantages of radiotherapy to the brain outweigh the disadvantages it may cause. • In order to find an answer to that question, and to find out how we may provide the best quality of life for patients like you, we are running a research study, called QUARTZ (Quality of Life After Treatment for Brain Metastases - the name is based on some of the letters in the title of the study). • In the QUARTZ trial we will give all patients steroid tablets. We will also give radiotherapy to half the patients, but not to the other half. The two treatment groups will be decided at random, not by the patients or their doctors. This is to remove the possibility of bias in the results. • Radiotherapy to the brain may improve or delay the start of some symptoms. It may also cause other side effects, such as hair loss, dry skin on your head, headaches, tiredness or feeling sick. • If you decide to join the study, a nurse will telephone you once a week, to check how you are getting on. The nurse will check how you are managing, and then ask you some questions about your symptoms and side effects. These phone calls and checks will be in addition to the usual care and attention you would receive as a patient if you were not in the study. • On the following pages you will find out more information about this study: Part B shows you the overall process. Part C gives detailed information about the study, and Part D lists some of the side effects related to treatment. If you are interested in taking part in this study please read the rest of the information and feel free to talk to your doctor or nurse about anything that you are not sure of. Please remember taking part in this study is voluntary, and if you decided not to take part, or if you take part and then choose to withdraw, your doctor and nurse will continue to look after you to their best ability. Thank you DIAGRAM 1. Study title Quality of Life After Treatment for Brain Metastases 2. Invitation paragraph You are being asked to take part in a research study. Before you decide if you want to take part or not, you need to know why the study is being done and what it will involve. Please take some time to read this information carefully and talk about it with others, if you want to, before making your decision. Ask us if there is anything that is not clear or if you would like to know more. Thank you for reading this. 3. What is the purpose of this study? We want to find out which treatment is better for patients once lung cancer has spread to the brain. This is a very important question as the length of time people live can sometimes be limited and the quality of that time can be different for different people. The sorts of side effects they experience and the impact of these on their lives and their families are very important. All patients will get support from members of their health care team, for example nurses, GPs, social workers, occupational therapists and physiotherapists. You may hear this support called Optimal Supportive Care (OSC). There are a number of treatments that can be given as well as this support. Most patients will have treatment with steroid tablets (for example dexamethasone) and for some patients radiotherapy to the brain is often added. But radiotherapy can cause side effects and it is not known if it improves the quality of life or length of survival for patients with your type of cancer. Early information on the first 151 patients in the QUARTZ study suggests there is no evidence of a clear difference between these two approaches. However further information from more patients is still required, to allow doctors to try to answer this question with more certainty. When the QUARTZ study is completed, we may find out whether or not radiotherapy should be added to steroid tablets and optimal supportive care and which patients may benefit. 4. Why have I been chosen? We are asking 534 people with your type of lung cancer whose cancer has spread to the brain, to take part in this study. As doctors, we are not certain if radiotherapy to the brain is the best treatment for patients like you. It may be that using steroid tablets and the best care we can give you would be as good or perhaps better, than giving you this and radiotherapy as well. You can help us answer this question. 5. What is a randomised controlled trial? Sometimes we do not know which way of treating patients is best. To find out, we look at groups of patients that are having different treatments. In a randomised controlled trial people taking part are put into one of the two treatment groups at random by a computer. Neither you nor your doctor will be able to decide which group you are in. There is an equal chance of you getting either treatment. Allocating treatment this way means that the groups of people getting each treatment should be a similar mix of patients of different ages, sexes and health. Therefore, if there are any differences between the groups, it must be because of the treatment. In this trial, if you are in • Treatment Group 1, you will have optimal supportive care and take the steroid tablet, dexamethasone • Treatment Group 2, you will have optimal supportive care, take the steroid tablet, dexamethasone and have radiotherapy to the brain 6. Do I have to take part in this study? No, it is up to you to decide if you want to take part. If you do decide to take part, we will give you this sheet to keep and we will ask you to sign a consent form to say that you understand what the study involves. If you decide to take part you can change your mind at any time without giving a reason. A decision not to take part in the study or to withdraw from the study at any time, will not affect the standard of care you receive. 7. What will happen to me if I take part? All patients involved in this study will have Optimal Supportive Care and be treated with the steroid, dexamethasone. The term optimal supportive care (OSC) is used to describe the support you will receive from members of your healthcare team. For example, specialist and district nurses, GPs, social workers, occupational therapists etc. All patients will also take steroids tablets called dexamethasone. Your nurse will tell you how often and exactly how to take your steroids. Your nurse will see how you are doing on a regular basis and will tell you if you need to change how often or how many tablets you take. Your nurse will also find out if there is anything else we can do to help you. If you are in treatment group 2, you will also have radiotherapy to the brain. We will ask you to come to hospital as an outpatient and receive one session of treatment for five days in a row. You will not need to attend at weekends. When you attend hospital you will be looked after by the radiographers. The radiographers will ensure that you are resting comfortably on your back on the treatment couch. There will be head rests available if needed. A beam of radiotherapy will be aimed at one side of your head for 2-3 minutes and then the machine will move around to the opposite side and treat that side of your head – again for 2-3 minutes. You will not feel anything during the treatment but you will hear the machine click or buzz. Although the radiographers will be outside the room during treatment, they will be able to see and hear you all the time. The radiographers will be happy to answer any questions you may have during treatment and will also ask your nurse or doctor to see you if needed. Assessments Whichever treatment group you are in, your nurse will catch up with you by telephone every week for at least 12 weeks and then at least every 4 weeks after that, to talk about any problems you may have. You will also be asked to attend hospital at least every 4 weeks if possible. This study will find out how patients feel both physically and emotionally during and after the two types of treatments. To collect this information, we will ask you a short list of questions. The nurse will ask how you have been feeling day to day since the last phone call, as well as asking about any side effects you may be having. If you decide to join the study we will give you the list of questions on a laminated sheet, to remind you what we will ask you each time. You will not need to fill any paper work yourself, as the nurse will ring you every week to discuss each question and will write down your answers during the telephone call. We would also like you to talk through the questionnaire with your nurse if you come into hospital at any time. Your answers to each question will be sent to the . They will be kept private and anonymous. The Clinical Trials Unit will look at them together with answers from other patients to help plan future treatments. Carer Involvement In this study we would also like to look at the effect your disease and treatment has on your ‘main carer’, if you have one. This is the person who gives you the most practical and/or emotional support in your everyday life. This might be your wife, husband, partner, relative or a close friend. The person does not have to be living with you. You know best who your ‘main carer’ is, so we will ask you to tell us the name of that person and to give us his or her contact details. If you decide that you do not want your carer to take part in this study, or you do not have a carer, you can still take part yourself. We will collect this information about your carer using a short questionnaire, which will ask how they are feeling from week to week. Your carer will not need to write anything as your nurse will read through the questions over the telephone each week with them and write down their answers. We would also like to ask your carer to answer some of the same questions that we ask you each week about you. This will mean that if you are unable to come to the telephone at any time we will still be able find out how you are feeling. 8. What about my current medication? If you are not already taking dexamethasone, your steroid will be changed to dexamethasone. Your nurse will tell you how often and exactly how to take your steroids. Otherwise it is likely that you will carry on with any medication you are already taking. Your doctor or nurse will talk to you and check these and how you take your steroids regularly. You may continue other activities as best you can, the only extra thing you will be asked to do is to answer questions over the telephone each week, if you are willing and able to do this. 9. What are the side effects of any treatment given in this study? Some possible side effects are listed below, but you may or may not have these. If you have any concerns about any of these side effects please speak to your nurse or doctor. All patients in this study will be taking steroids, a tablet called dexamethasone. There are many benefits in taking these tablets, such as: - Improved appetite - Increased energy levels - Reduction in headaches, nausea and vomiting - Reduction of weakness or numbness in parts of the body where this has been felt - Improvement in general well being However, these tablets may also cause: - Weight gain - Fluid retention - Muscle weakness - Higher levels of blood sugar - Indigestion (heartburn) - Difficulty sleeping - Mood swings - Increased risk of infection There are also some less common side effects, including increased facial hair and increased risk of bruising. For those who have radiotherapy to the brain, it is important to know that long term side effects (such as memory loss) are very rare with the dose of WBRT used in this trial. The potential benefit of radiotherapy to the brain is the reduction of the size of cancer deposits – although whether this then leads to improved quality of time remains uncertain. However the radiotherapy treatment may cause: Hair loss on the scalp Dry, pink or red skin on your head and ears Headaches Nausea (sickness) Weakness or clumsiness Fatigue (tiredness) Difficulty concentrating for a short period following treatment Please refer to part D for further information on possible treatment side effects. 10. What are the possible benefits of taking part? Entering this study may not directly benefit you. If you are in the group receiving radiotherapy, this treatment may mean you are free of symptoms from your brain for a longer period than if you did not have radiotherapy, but you may experience side effects. In the other group, not having radiotherapy means you will not experience the side effects of that treatment, but also you will not experience any of its beneficial effects. Both groups will experience some of the benefits of taking the steroid tablets as listed in section 9. The information we get from this study will help us to give the best treatment to patients like you in the future who have your type of cancer. We also hope that the treatment and support you have in this study will help you and your carer. 11. What other treatments are available? There are a number of treatments that may be suitable for some patients whose lung cancer has spread to the brain, depending on each individual patient’s pattern of disease and general health. These treatments include surgery, chemotherapy and radiotherapy Most patients are offered steroids to help manage their symptoms. Your doctor would be happy to talk about these options with you. 12. What if I change my mind about joining the study? If you change your mind, you can stop taking part in the study at any time. This will not affect your relationship with the doctors and nurses, or your standard of care after this, in any way. However if you do withdraw from the study, we would still like to follow your progress. If you agree we would like to continue to collect some information from your medical notes. This will help us to look at the long term effects of your treatment. 13. What if I have a complaint? Your hospital has a duty to care for you within the hospital, whether or not you are taking part in a study. Every care will be taken in the course of this study. However, in the unlikely event that you are injured by taking part, compensation may be available. If you suspect that the injury is the result of or the hospital’s negligence then you may be able to claim compensation. After discussing with your research doctor, please make the claim in writing to Dr who is the Chief Investigator for the research and is based at the . The Chief Investigator will then pass the claim to office. You may have to bear the costs of the legal action initially, and you should consult a lawyer about this. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated by members of staff or about any side effects (adverse events) you may have experienced due to your participation in the research, the normal National Health Service complaints mechanisms are available to you. Please ask your research doctor if you would like more information on this. Details can also be obtained from the Department of Health website: http://www.dh.gov.uk “ 14. What if new information becomes available? Sometimes during the life of a study, new information becomes available about treatment. If this happens, your doctor will tell you about it and help you decide if you want to stay in the study or not. If you or your doctor decides to withdraw you from study treatment or follow up, your doctor will make sure your care continues. If you then decide later to continue in the study you will be asked to sign another consent form. 15. Will my taking part in this study be kept confidential? If you decide to take part in this study, information about you will be given to the Clinical Trials Unit at who coordinates the study. Staff from the or regulatory authorities may need to visit the hospital to look at your notes. This is to check that the information being given is correct. Your GP and other doctors involved in your care will be kept fully up to date, but otherwise all information about you and your treatment will remain completely confidential. If you were to lose touch with your hospital doctor, we will check your health status with the Office of National Statistics (ONS). The is registered under the Data Protection Act to hold such information on a confidential basis. 16. What will happen to the results of the study? The full results will be printed in a medical journal and then on the MRC website. However, some reports may be discussed at meetings before this. No person taking part in this study as a patient will be identified in any of these reports. You or your family can see copies of these reports. Just ask a member of your hospital team. 17. Who is organising and funding the study? This study is being funded by Cancer Research UK, Sponsored by the Medical Research Council and coordinated by the . The managing organization is the . 18. Who has reviewed the study? The study has been reviewed by Research Ethics Committee and the Clinical Trials Advisory and Awards Committee (CTAAC). The study has also been considered by an independent patient representative, who has also helped write this information leaflet. 19. Contacts for Further Information If there are any other questions we can help you with please do not hesitate to contact: Local Investigator: Dr Tel: Nurse specialist/trial officer: Sister/Ms/Mrs/Mr Tel: You may also find it helpful to contact any of the following organisations • Website: www.roycastle.org/index.aspx • MacMillan Cancer Support Website: www.macmillan.org.uk Free phone: • CancerHelp UK from Cancer Research UK Patient information from CRUK Website: www.cancerhelp.org.uk/ Cancer Information Nurses available via telephone: Direct line: Freephone number: Thank you very much for taking the time to read this leaflet and for thinking about taking part in this study. If you decide to enter the study, you will be given a copy of this information sheet and also a copy of your signed consent form to keep. A second copy of your consent form will be kept in your hospital notes, a third copy within the hospital study folder and a fourth copy will be sent to the . Steroids All patients in this study will be taking a steroid tablet called dexamethasone. There are many benefits in taking these tablets however, these tablets may also cause: 1. An increase in the appetite This may lead to some weight gain particularly around your middle, neck and face. Many people report that the increase in their appetite is helpful in restoring any previous weight loss. Try to eat sensibly if you are worried about too much weight gain. 2. Fluid retention This is more common around the ankles and/or legs. You can partly reduce this by wearing compression stockings and raising your legs when sitting. 3. Muscle weakness in the arms and legs This may make it difficult to get out of chairs or climb stairs. Try and keep as active as possible around the house and by walking and taking stairs where possible. 4. Higher levels of blood sugar If you notice you are thirstier than normal or passing more urine, please inform your nurse/doctor. There is medication available to resolve these problems. 5. Indigestion (heartburn) This is quite a common side effect but is easily reduced by taking your steroid tablets with or after food. Your doctor can also prescribe you a tablet to prevent you experiencing stomach acid or heartburn problems. 6. Difficulty sleeping. Steroids can cause difficulties sleeping at night. Your nurse can advise you on the best time to take the tablets. 7. Mood swings Occasionally people on steroids report they feel more emotional with high and/or low mood swings. If you think the tablets are affecting your mood please inform your doctor or nurse. 8. Increased risk of infection You will be more vulnerable to such conditions as thrush, urinary infections, chicken pox or shingles whilst on steroid therapy. If you have a sore mouth, burning when passing urine or a rash please contact your doctor or nurse. They will be able to give you simple medication to treat any of the above. 9. Less common side effects - Increase in facial hair - Increased likelihood for skin to bruise Radiotherapy to the brain With the dose of radiotherapy delivered to the brain in this trial, there are no long term side effects. However the radiotherapy treatment may cause: 1. Hair loss on the scalp This will be temporary and may take up to three months to fully regrow. You will be offered a free wig by your hospital until your hair regrows. 2. Dry, pink or red skin on your head and ears This can be helped with the use of simple prescribed moisturising creams such as aqueous or hydrocortisone cream. Remember do not use perfumed soaps on the area being treated and cover your head with a scarf or hat if in the sun. 3. Headache Usually an “over the counter” medication, for example paracetamol, is enough to ease your headache. If your headache does not go away, always tell your doctor or nurse. 4. Nausea (sickness) If you feel sick before, during or after the radiotherapy please tell your doctor or nurse. There are many medications that will reduce or stop this problem, so never feel obliged to suffer vomiting or nausea. 5. Weakness or clumsiness This is usually temporary. Please tell your nurse or doctor as your steroid medication may need to be adjusted. 6. Fatigue (tiredness) Radiotherapy can make you feel more physically tired than usual. This side effect may last some weeks and sometimes may return briefly up to 6 weeks after treatment, but will gradually improve. However, whilst it is wise to rest when you feel very tired it will also help to take regular exercise when you can. Please note if your body becomes too used to resting it will be harder to regain your strength later. If you are worried about any of the above side effects please contact your doctor or nurse. The ROAM Trial Radiation versus Observation following surgical resection of Atypical Meningioma: a randomised controlled trial We would like to invite you to take part in our research study. Before you decide, you should understand why the research is being done and what it would involve for you. A member of our research team will go through this information sheet with you and answer any questions you may have. PART 1 Why is this study needed? Meningiomas are brain tumours arising from the linings of the brain. Most of these tumours are benign (meaning non cancerous) and can be treated with surgery alone. Very rarely these tumours are malignant (cancerous) and need treatment with both surgery and radiotherapy. There is a third group, called atypical meningiomas that fall between the benign and malignant group. Every year in the UK, about 150 patients with atypical meningiomas like yourself have surgery. Following surgery, there is still a chance that atypical meningiomas can regrow. We don’t know whether surgery alone or surgery followed by radiotherapy is more effective in treating these tumours The only way to find out whether surgery alone or surgery plus radiotherapy is better at treating atypical meningioma is to compare them in adults with this tumour type. This type of study is called a Randomised Controlled Trial (RCT). The study will help hospitals and doctors decide which is the most effective treatment to use in the future. Why have I been chosen? You have been asked to take part because you have recently had surgery to remove an atypical meningioma. We would like to recruit 172 patients from a number of hospitals across the UK and mainland Europe. Do I have to take part? No. If you do not wish to take part in the study you do not have to give a reason and you will be followed up after your surgery according to the standard policy for your hospital. Saying no will not effect that treatment you would normally receive. If after enrolling in the study, you decide to change your mind, no more information will be collected about you. All information collected up until the time of withdrawal will be included in the study analysis, unless you request that it is removed. What will happen to me if I join the study? The study will recruit patients over a period of approximately 4 years. Follow up information will be collected at 6 and 12 months following your surgery, then annually until 5 years after your surgery. We will also ask your permission to contact you after the study has finished for future research projects. PART 2 Consent: If you are happy to take part, and are happy with the explanations given to you by the research team, you will be asked to sign a consent form. You will get a copy of the signed consent form and information sheet to keep. Study design: In this study it is surgery alone and surgery plus radiotherapy that is being tested, so people taking part will be split into 2 groups by random chance: Group A: One half of patients will receive surgery plus radiotherapy Group B: One half of patients will receive surgery alone If you decide to take part you will be allocated to one of the 2 groups above. This will be done randomly by a computer. Neither you nor your doctor will be able to choose which group you will be in. If you are allocated to Group A you will receive one 6 week cycle of radiotherapy (usually given daily from Monday to Friday) which will start approximately 8-12 weeks after your surgery. You will then be followed up as per current standard practice at 6 month, 12 month and annual intervals until 5 years after your surgery. This follow up will comprise of MRI scans, collecting information on any adverse events, plus a series of questionnaires to assess quality of life, verbal and visual memory, language, mood and related tests. Follow up will be by your treating neurosurgeon or oncologist. If you are allocated to Group B (active monitoring), the follow up schedule will be exactly as described above for group A. Follow up will be by your treating neurosurgeon. As well as studying which treatment is the most effective at preventing tumour regrowth, we will also look at which is the most cost effective. To be able to do this, we need your NHS number, postcode and date of birth to collect information about your hospital admissions during the study. What are the alternatives for treatment? If you have been approached for this study then there is no alternative treatment for you other than radiotherapy or active observation. Are there any risks or benefits to me if I join the study? There are no direct benefits for you being part of the study compared to people who do not participate, although the information we get from the study may improve the treatment of other people with atypical meningioma in the future. We do not know whether surgery alone is sufficient to treat your tumour, or whether surgery and radiotherapy is needed. We know that radiotherapy affects patients and can cause some side effects including hair loss, skin irritation, wound breakdown, fatigue, headache, mental decline, hormone imbalance and a risk of developing other tumours. We also know that when these tumours regrow further surgery, radiotherapy or radiosurgery (focused radiotherapy) may be needed. You may want to discuss this further with your clinical team. What if there is a problem? If you have any concerns about any aspect of this study, you should speak with the ROAM study team who will do their best to answer your questions. If you remain unhappy and wish to complain formally, you can do this through the NHS Complaints Procedure. Details can be obtained from the hospital that you are being treated in. If you are harmed by taking part in this research project, there are no special compensation arrangements. If you are harmed and this is due to someone’s negligence, you may have grounds for legal action for compensation against the NHS Trust where you are being treated. In this instance you may have to pay your own legal costs. Will my taking part in this study be kept confidential? Yes. Only people working on the study or working to ensure the study is run correctly will have access to the data. All information collected about you during this study will be confidential and will be handled, stored and destroyed in accordance with the Data Protection Act 1998. You will be provided with a letter that will also be sent to your GP. PART 3 Will there be any additional samples taken? Collecting blood and tissue samples during a trial provides researchers with key information. The use of human samples is an essential part of this research and it will help to expand knowledge in the areas of how disease works, how disease can be prevented, diagnosed and treated. During this study a dedicated facility ( Research Tissue Biobank) will be used to store tumour and blood (serum) samples taken from patients taking part in the ROAM study. Ethical approval has been obtained to collect and store these tumour tissue and serum samples from patients in participating sites. A small amount of tumour tissue taken from your recent surgery will be sent to the biobank. Approximately 10 mls of blood (2 teaspoons) will be taken at the same time as each follow up MRI scan and sent to the biobank. We will apply for separate funding to carry out some additional research on the following: 1. The effects of radiotherapy on normal brain tissue situated next to the site where the tumour was removed 2. To look at whether inherited or other biological factors can be used to predict tumour recurrence and individual response to radiotherapy 3. To look at chemicals in your blood which may be used to predict tumour recurrence. What if new information becomes available? The results of the study will be looked at from time to time by the study organisers. If any new information becomes available, the ROAM study team will discuss this with you What will happen to the results of the study? We aim to publish the results of this study in medical literature. Your confidentiality will be maintained at all times and you will not be identified in any publication. A short summary of the study will be provided on our website. Who is doing this study? The study is funded by the National Institute for Health Research’s Health Technology Assessment Programme. It is being run in the hospital where you are being treated, and is being organised by the NHS Foundation Trust. This research has been approved by a research ethics committee, who are happy that the study is being conducted in an appropriate manner. Please ask us if there is anything that is not clear or if you would like more information. Please Contact: Research Nurse: Telephone: Or Contact: Principle Investigator: Telephone: THANK YOU FOR READING THIS INFORMATION SHEET. WE HOPE YOU HAVE FOUND THIS SHEET HELPFUL CReST2 ColoRectal Stenting Trial 2 - Uncovered vs covered endoluminal stenting in the acute management of obstructing colorectal cancer in the palliative setting. An invitation to take part in a research study called CReST 2 You are being invited to take part in a research study called CReST2. Before you decide whether you wish to take part in the CReST2 study, we would like to explain why the research is being done and what it will involve for you. This information sheet provides you with a detailed description of the study so that you can think about whether you want to take part. - Part 1 tells you the purpose of this study and what will happen to you if you take part. - Part 2 gives you more detailed information about the conduct of the study. Please take your time to think about whether you want to take part in the CReST2 study, talk to your friends, family and your GP about the study if you wish and ask us if there is anything that is not clear or if you would like more information. Part 1 What is the purpose of the CReST2 study? Stenting for patients with large bowel obstruction has high initial success rates, but is associated with a risk of complications from the stent at a later date. These complications include reblockage of the bowel, migration of the stent and rarely perforation of the bowel. Therefore we are continuing to research ways of improving treatment and in the CReST2 study we are comparing two types of stent design; uncovered and covered stents. Both types of stent are made of wire mesh but the covered stent has a fabric coating over the wire mesh. Why am I being invited to take part in CReST2? Your doctor will have invited you to consider taking part in CReST2 because you have bowel cancer that has caused an obstruction of your bowel that needs to be treated. The tests that have been performed show that the cancer cannot be cured by surgery and/or that you are not fit enough to undergo major surgery. Your doctor is not sure whether the best treatment for you is to insert an uncovered or a covered stent and so thinks that taking part in CReST2 would be a good option to help find out which of these treatments is best. The CReST2 study aims to include at least 350 people like you with large bowel obstructions caused by colon cancer from hospitals throughout the UK and elsewhere. What are the treatments for large bowel obstruction? Until recently, the standard treatment for patients with a blockage of the large bowel caused by cancer has been emergency surgery to relieve this obstruction. In some cases the ends of the bowel can be joined together but it is often the case that after this surgery the patient was left with a stoma (bringing one end of the bowel out onto the abdominal surface to allow passage of faeces into a bag), often permanently. In patients in whom the bowel cancer cannot be cured by surgery or in patients who are unfit to undergo surgery, stents are now recommended as standard treatment for relief of the obstruction. The stents are specifically designed metal mesh tubes, which if passed across the blockage in the bowel, act to open it up and thereby relieve the obstruction allowing faeces and flatus (wind) to pass normally. In the majority of patients this avoids surgery and the need for surgery and the need for a stoma. The diagram shows what this means: DIAGRAM What does the standard treatment involve? The standard treatment involves insertion of an uncovered stent. This is passed across the blockage in the bowel, acts to open it up and thereby relieve the obstruction allowing faeces and flatus (wind) to pass normally. Following the stent insertion you would continue to be followed up to check that the stent is still working properly. What are the benefits of standard treatment (stenting)? Stenting is the recommended treatment for patients such as yourself with a bowel obstruction caused by cancer. There are advantages of stenting compared to surgery. These include safer treatment, a shorter stay in hospital and less chance of a stoma (bag on the side to collect the bowel content). What are the risks of standard treatment (stenting)? There is a small risk of failure to place the stent due to technical difficulties. In this case, surgery will have been delayed and you will still need to undergo urgent surgery. As with all procedures, complications of stenting can occur. Previous experience has shown a small risk of bowel perforation (making a hole in the bowel wall) whilst placing the stent. This would be treated by immediate surgery. There is a risk that the tumour grows into the stent and causes repeat blockage of the bowel. Migration of the stent (when the stent moves from its original site) has also been seen. This occurs following widening of the narrowed segment and the stent is usually passed with a bowel motion without causing any discomfort. Replacement of the stent is only necessary if recurrence of the blockage occurs. The radiation dose received during stenting is similar to other x-ray treatment procedures (such as x-rays of the heart for coronary artery disease). The x-rays you may have as part of your treatment under the trial are the same as if you were not participating in the study. All x-rays carry with them some risk from the radiation dose. However there will be no additional radiation risk from you taking part in the trial and you are not likely to suffer any short or long term harmful effects from the radiation. Do I have to take part? No. Taking part in research is always voluntary. If you decide to take part you will be given this information sheet to keep, and will be asked to sign a consent form, but you are still free to withdraw at any time and without giving a reason. If you decide not to take part, then you don't have to give a reason why and no one will think badly of you for not wishing to take part. Your specialist will be happy to talk through alternative options. What will happen to me if I agree to take part in CReST2? To begin with, all patients will have been investigated with either a contrast CT (this is a scan which takes images of your body using x-rays) or a contrast enema (this is a fluid that is passed into the large bowel via the bottom and will show up on x-ray). This fluid then allows x-ray pictures to be taken to confirm the diagnosis of large bowel obstruction and to determine the exact site of the blockage. Other patients will have been investigated with a telescope examination of the bowel. The surgeon/radiologist will go through the study information again and answer any questions you have. If you are willing to take part in the CReST2 study you will be asked to sign a separate consent form. Your details will then be passed to the CReST2 trial office at the who will provide your randomly assigned allocated treatment. The below table shows how you will progress through the CReST2 trial: 1) Entry into trial (after signing a consent form). 2) Randomly assigned treatment of a covered or an uncovered stent will be performed by a Radiologist/Endoscopist. 3) Completion of Quality of Life Questionnaires at trial entry date, 30 days after you have had your stent, 3 months, 6 months, 12 months, 18 months and 24 months after you entered the trial. If you decide to take part in CReST2 you will have the obstruction treated by either: i) Insertion of an uncovered stent ii) Insertion of a covered stent. Which of these treatments would I receive? So that we can find out which treatment is best, each person is put into a treatment group randomly (like tossing a coin). You have an equal chance of being allocated to the uncovered or covered stent groups. It is important to realise that the treatment you receive will be decided by chance using a computer programme. The reason for having your treatment decided by chance is that it allows a fair comparison of the different treatments used in the study so that at the end of CReST2 we can decide which is best. Neither you nor your doctor are able to influence which treatment you receive. Dividing people into treatment groups in this way is what is called a ‘randomised clinical trial’ and it is the standard and most reliable way of comparing different treatments. Stent Insertion For both allocated treatments, stent placement will be carried out in the X-ray suite or endoscopy unit. When a stent is inserted you will be given some sedation (this makes you relaxed and probably a little sleepy). You will be positioned on your left side and under x-ray guidance a specially designed guidewire will be passed through the blockage in the bowel. This wire acts as a guide so that the stent can be placed in the correct position in the large bowel. In some cases a flexible telescope (sigmoidoscopy) might be needed to locate the narrowed passage through the bowel. When the stent is in the right place it is released and immediately expands to widen the narrowing of the bowel. When the stent expands there is usually a sudden passage of wind and sometimes liquid faeces, this is normal and is nothing to worry about. After stenting you will be returned to the ward and may be discharged home the following day, as long as your bowels are opening normally. If you are not going to have surgery the stent will remain in place and surgery will be avoided altogether. Would taking part in CReST2 involve extra clinic visits or investigations? Whether or not you take part in the CReST2 study, your progress will be followed up regularly. As a participant in the CReST2 study, you will be followed up for a period of two years. You will be reviewed in the outpatient clinic at four weeks after discharge, then every three months for the first year. You will then be seen every six months for a further year. As part of the CReST2 study, we will ask you to complete questionnaires to tell us how healthy you feel and how well your bowels work. However, you would not be required to attend any additional clinics and the questionnaires will be posted to your home if you are not due to attend a follow up appointment. You may on occasion be contacted by letter, telephone or email to remind you to complete the questionnaires or to be asked the questions over the telephone. What are the possible benefits from taking part in CReST2? It is believed that covered stents may be more effective than uncovered stents leading to less risk of complications and a better Quality of Life. Covered stents may reduce the risk of tumour ingrowth into the stent so have less chance of reblockage. If this is the case, there would be less chance of needing further interventions such as repeat stent insertion or surgery). However, we cannot be sure in advance that covered stents will have all or any of these benefits – that is the reason for doing this trial. We believe that participation in CReST2 will provide you with the best available treatment for your cancer. The main benefit from CReST2 will be that the information gained from the study will help doctors in the treatment of patients in a similar condition to yours in the future. What if new information becomes available? Sometimes we get new information about the treatment being studied. If this happens, your research doctor will discuss how this affects your care and your participation in the CReST2 study. Your research doctor might consider that you should continue in the study or withdraw. Either way, he/she will explain the reasons and arrange for your care to continue. If you decide to continue in the study he may ask you to sign an updated consent form. If the study is stopped for any other reason, your doctor would, again, tell you and arrange your continuing care. What will happen if I don’t want to carry on with the study? You can decide not to continue with study treatment at any time but, if you do, we would still like to follow up your progress and your data would remain on file and be included in the final study analysis unless you request that they should not be. What if something goes wrong? If you are harmed by taking part in this research project, there are no special compensation arrangements. If the harm is due to someone’s negligence, then you may have grounds for a legal action but you may have to pay for this. Whether or not you take part in the study, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated during the course of this study, the normal National Health Service complaints mechanisms would be available to you. If you do have any concerns or wish to complain, the first point of contact would be the local Patient Advice and Liaison Services (PALs) office at: Trust/Hospital Name: Location: Tel No: Position: Taking part in the study would not affect your legal rights. Will my taking part be kept confidential? If you decide to take part in CReST2, all information collected about you during the course of the trial will be kept strictly confidential in the same way as all of your other medical records. Information about your disease and progress will be sent by your doctors to the CReST2 Study Office at the Clinical Trials Unit (), on paper and electronically, where it will be securely stored under the provisions of the 1998 Data Protection Act. This will include a signed copy of your consent form. Your GP, and the other doctors involved in your clinical care, will be notified of your participation in the CReST2 trial and kept informed of your progress. We may use national NHS records to track your progress, but otherwise all information about you and your treatment will remain confidential. With your permission, your relevant medical records may be inspected by authorised individuals from the Clinical Trials Unit (). They may also be looked at by the NHS Trust, the trial Sponsor or the regulatory authorities to check that the study is being carried out correctly. What will happen to the results of the study? Once the trial has finished we will publish the results in a medical journal so that others can benefit. We will also publicise the results on the trial’s website . No individual patients will be identified in any publications. A copy of the published results of the trial will be sent to all patients who have participated in CReST2. In line with clinical trial guidelines, at the end of the study, the data will need to be securely archived for a minimum of 15 years. Arrangements for confidential destruction will then be made. Should you withdraw consent for your data to be used, it will be confidentially destroyed. Who is organising and funding the research? The CReST2 study was developed by the National Cancer Research Institute's Colorectal Cancer Clinical Studies Group, and is funded by the Health Technology Assessment Programme, which is part of the National Institute for Health Research. The study is coordinated by the Clinical Trials Unit at the . The research has been reviewed and approved by all of these organisations, and also by an independent NHS Multicentre Research Ethics Committee. There is no involvement of any companies other than providing stents at reduced price. Who has reviewed the study? All research in the NHS is looked at by an independent group of people called a Research Ethics Committee to protect your safety, rights, wellbeing and dignity. This study has been reviewed and given favourable opinion by Research Ethics Committee. Where can I get further information? If you have any further questions about your disease or clinical trials, please discuss them with your doctor: [Local trial team contact details] You may also find it helpful to contact: Macmillan Cancer Support (www.macmillan.org.uk; ) NHS Choices (http://www.nhs.uk/Conditions/Clinical-trials) The CReST2 study coordinating centre is located at the . Web address: email: CReST2 is funded by the National Institute for Health Research’s HTA programme We would like to invite you to take part in a study called PART (Partial prostate Ablation versus Radical prosTatectomy). Before you decide whether you would like to join the study, it is important for you to understand why the research is being done and what it will involve. We will go through this patient information leaflet with you and answer any questions you might have. You can also talk to anyone else (e.g. family or GP) about your decision whether or not to take part. You do not have to decide straight away. WHAT IS THE PURPOSE OF THE PART STUDY? You have been diagnosed with intermediate risk, localised prostate cancer on one side of the prostate gland only. Your doctor has discussed your treatment options with you and it has been agreed that you would normally be a suitable candidate for radical prostatectomy surgery. Sometimes however, the disease affects only one part of the prostate, and it may be better to treat only the affected area, rather than the whole gland by using a treatment called partial ablation. This may reduce the side effects of radical treatments. This is what we are testing in the PART study. Partial ablation is not commonly used in the NHS but has previously been studied in other experimental areas. The procedures relating to this treatment have been widely used in other contexts. We are now trying to find out whether partial ablation can replace total gland treatment safely and effectively. PART aims to find the best treatment for the type of prostate cancer you have. We are comparing surgery (radical prostatectomy) and partial ablation (High Intensity Focused Ultrasound) in terms of treating the cancer, quality of life (such as sexual, urinary and renal function) and the cost of treatment. There will be two stages to the PART study: Stage 1 where we aim to recruit 100 patients (to make sure that a bigger study can be conducted comparing these treatments) and Stage 2, where we aim to recruit a further 600-800 patients. Your doctor or research nurse will let you know which stage of the study we are now in. If you take part in Stage 1 your results and data will still be included in the same way as those patients in Stage 2. WHAT IS THE PROSTATE? The prostate is an organ that forms part of the male reproductive system. It is located immediately below the bladder, just in front of the bowel. Its main function is to produce fluid that makes up part of the semen and may help enrich sperm. In younger men the prostate is about the size of a walnut. It is doughnut shaped as it surrounds the beginning of the urethra, the tube that conveys urine from the bladder to the penis. The nerves that control erections surround the prostate. A diagram of the location of the prostate is overleaf. DIAGRAM WHY HAVE I BEEN ASKED TO JOIN THE PART STUDY? You have been asked to consider joining the study because you have had a diagnosis of intermediate risk, localised prostate cancer on one side of the prostate gland only. Looking at your results, the research team think that you may be suitable for either partial ablation of the prostate to kill cancer cells, or surgery to remove the whole prostate. DO I HAVE TO TAKE PART? No. It is completely up to you to decide whether or not to join the PART study. If you decide to take part, you are still free to withdraw at any time without giving a reason. Whether you take part or not will not affect the standard of care you receive. WHAT WILL HAPPEN TO ME IF I DECIDE TO TAKE PART? In this study, we need to compare people who have partial ablation with those who have surgery. You will be given this information leaflet about PART when you visit your doctor at your routine clinic visit. You can take the information leaflet away with you, to think more about joining the study. If after routine blood tests, MRI imaging and prostate biopsies, you are considered eligible to take part in the study, you will be invited to attend an information appointment to discuss the PART study further. We have summarised what taking part in this study would involve on page 7. If you are not eligible for the PART study, you will be informed by your doctor, who will go through your treatment options with you. Partial Ablation Partial ablation works by using sound waves (high intensity focused ultrasound) to heat small areas of tissue where the cancer has been located. It is a day procedure and does not involve cuts or needles. The procedure is performed under general anaesthetic. The treatment involves a probe which will be introduced in your rectum, similar to the one you have experienced during your prostate biopsies. Since you will be under the general anaesthetic, you should not feel anything. The treatment lasts between 1-2 hours. Before starting the treatment, a tube is placed in your bladder through the skin at the bottom of your belly. This will be secured in place with a small stitch, and removed approximately 2 weeks after the treatment when we are happy that you can pass your urine well. The advantages and disadvantages of ablative therapy are included in the table on page 8. Surgery In most cases, this operation is now performed using robot assisted keyhole surgery, under general anaesthetic. The instruments are inserted through six small holes in the belly and controlled by the surgeon from a remote console in the operating theatre, with the assistant at the operating table. Sometimes it is not possible to use keyhole surgery, and the surgeon has to perform an ‘open’ procedure. In this case, the surgeon will make a cut at the bottom of your belly. The advantages and disadvantages of robotic and open surgery are included in the table on page 8. DIAGRAM TREATMENT ALLOCATION The best way to compare these two treatments is to have similar groups of patients allocated to either ablative therapy or surgery in a research study. The only way to make sure that the groups of patients are as similar as possible is to have the allocation decided by chance: a process called randomisation. This means that you will have an equal chance of having either ablative therapy or surgery. This process ensures that the treatments are compared fairly. It is important for the study that you only agree to take part if you believe you would be prepared to accept either treatment. Whichever treatment you are allocated to, you will be treated with the best possible care and the surgeon treating you will be experienced in the technique. CONSENT & RANDOMISATION During Stage 1 of the PART study, we will ask you if we can tape record your information visit with your doctor and research nurse. This will help us to make sure that you are provided with enough information about the treatments and the study. We will ask you for written permission before this happens. Your appointment will go ahead, whether or not you agree to it being tape recorded. Some people will also be invited to be interviewed by one of our researchers in more detail about their experiences. This will only happen if you are willing to do this and after you provide written permission. If after your information visit you decide to take part, you will be given this information leaflet to keep and asked to sign the PART study consent form. You will then be entered into the PART study and the research nurse or your doctor will tell you which treatment you have been assigned to straight away. The operation will then be within eight weeks from when you consented to join the study. WHAT HAPPENS IF I WANT TO CHOOSE WHICH TREATMENT I GET? At the end of the discussion, you may feel that you want to choose your treatment. However, you would not be able to select HIFU, because it is not yet a standard NHS treatment, which is the reason for conducting this study. WHAT HAPPENS DURING FOLLOW UP? Whatever group you are in, you will be under the care of your Consultant Surgeon and followed up regularly. As part of the study you will be asked to complete several questionnaires over the course of the 36 month duration. Table 1 on page 7 gives an overview of what information we would like to collect about you and when. WHAT IF THE CANCER SPREADS OR COMES BACK? You will be monitored carefully by the medical and research team, but you should always contact your GP or a member of the study team if you have any concerns. If your PSA blood test results suggests that your disease might have got worse, the doctors will organise new tests, x-rays or scans as they think are needed to assess things further. If you received HIFU and the biopsies (samples) show that you have new disease, on the other side of your prostate, we would offer you additional HIFU treatment. If however there is persistent disease after either treatment (i.e. the cancer that you had at the start that was treated has returned), we will consider that the treatment has failed, and we would discuss with you your treatment options. These may include surgery, hormone therapy and/ or radiotherapy. WHAT ARE THE POTENTIAL BENEFITS OF TAKING PART? We cannot guarantee that participating in this study will be of direct benefit to you. The main benefit of you taking part will be the information that we can gather. This would help us improve treatment options for men with prostate cancer like you in the future. WHAT ARE THE POSSIBLE DISADVANTAGES AND RISKS IN TAKING PART? The risks for each treatment are listed in Table 2. Please read through them carefully, and ask as many questions as you wish at your next appointment. WHAT IF SOMETHING GOES WRONG? The University of , as Sponsor, has appropriate insurance in place in the unlikely event that you suffer any harm as a direct consequence of your participation in this trial. If you wish to complain about any aspect of the way in which you have been approached or treated during the course of this study, you should contact the or you may contact the Clinical Trials and Research Governance office on or the head of , email . WILL MY PARTICIPATION IN THE STUDY BE KEPT CONFIDENTIAL? Yes. All information which is collected about you during the course of the research will be kept strictly confidential. You will be assigned a code number to ensure that you will not be identified in any way in any report arising from the study. As it is standard practice to inform your GP about your participation in a research study, we will ask your permission to do this. WHO IS ORGANISING AND FUNDING THE STUDY? PART is funded by the Health Technology Assessment Programme of the National Institute for Health Research, study number . The study is conducted by the . The researchers include a team of specialised doctors, scientists, technical staff and nurses. Our team is experienced and has conducted similar research in the field. WHO HAS REVIEWED THE STUDY? This study was given a favourable ethical opinion for conduct in the NHS by the Ethics Committee. This committee is responsible for making sure that research takes place in a way that protects the patients’ rights and welfare. EXPENSES AND PAYMENTS Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of receipts, or mileage allowance provided as appropriate. TRIAL RESULTS When the study results are concluded, they will be presented by clinicians and patient groups, and posted on our website for patient to access. Our website is: WHAT DO I HAVE TO DO NOW? You will be given as much time as you feel you need to discuss any issues or questions involving this research during your appointment with the researchers and study nurses. If you have any concerns or wish to discuss the study further, please contact: [ – Local Research Nurse, address, tel number] [ - Local Investigator, address, phone number] Professor , Study Chief Investigator THANK YOU FOR TAKING THE TIME TO READ THIS INFORMATION SHEET. Add Aspirin Clinical Trial Part ONE We are inviting you to take part in a research study called the Add Aspirin trial Contents 1 Why are we doing this study? 2 Why am I being asked to take part? 3 What do I need to know about the medicines used in this study? 4 What will I need to do if I take part? 5 What are the possible side effects? 6 Possible advantages and disadvantages of taking part 7 Samples and genetic tests 8 More information about taking part 9 Contacts for further information Before you decide whether to take part, it is important for you to understand why the research is being done and what it will involve. - Please take time to read the following information carefully. Discuss it with friends and relatives if you wish. Take time to decide if you wish to take part. - You are free to decide if you want to take part in this research study. If you choose not to take part, this will not affect the care you get from your own doctors in any way. - You can decide to stop taking part in the study at any time without giving a reason. - Ask your study doctor if anything is not clear or if you would like more information. - Thank you for reading this information. If you decide to take part, we will ask you to sign a form to give your consent for each part of the study. Important things that you need to know We are testing whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back. - We are testing different doses of aspirin. Some people will receive a dummy drug (placebo). - Like all medicines, aspirin can have side effects. The most common side effects of aspirin are: - irritation of the stomach - indigestion - bleeding - this a serious side effect of aspirin but it is uncommon. - We expect that most people who take part in this study will need to visit the hospital approximately 12 times over 5 years depending on your cancer type. Whenever possible, this will be at the same time as your regular check up visit. - We will also ask if you would like to donate a small amount of blood, urine and tissue from your cancer for future research. How to contact us If you have any questions about this study, please talk to your doctor at Hospital Department Hospital Address Address Tel: 1 Why are we doing this study? This study is for people who have had or have started treatment for cancer of the breast, stomach, oesophagus (food pipe), prostate or bowel. We are aiming to find out whether taking aspirin regularly after treatment for cancers that have not spread widely (early stage cancer), stops or delays the cancer coming back. This study will compare groups of people who take aspirin and those who take placebo tablets. What is a placebo? A placebo is a “dummy” tablet. It looks like an aspirin tablet but it doesn’t contain any medicine. We are using a placebo in this study so that we can make as clear an assessment as possible about the effects of aspirin. Keeping everything exactly the same apart from what is contained in the tablet allows us to study just the effects of aspirin. The placebo used in Add Aspirin contains lactose. People who are lactose intolerant will be excluded from taking part in the study. What is the usual treatment? Usually, people like you, who have had or have started treatment for early stage cancer, will come into hospital for regular check ups once the treatment has finished. People who have had prostate cancer sometimes also take long term hormone treatment. People who have had breast cancer sometimes also take long term hormone treatment or Herceptin. This will continue if you take part in the study. People who have had stomach, oesophagus or bowel cancer don’t usually take any other long term treatments. 2 Why am I being asked to take part? You are being invited to take part in the Add Aspirin study because you have had or are having treatment for cancer of the breast, stomach, oesophagus, prostate or bowel. Although your doctors believe that they are able to successfully treat your cancer, some cancers unfortunately may come back. This study will find out whether or not taking aspirin regularly after treatment can stop or delay this happening. 3 What do I need to know about the medicines used in this study? Aspirin is a common drug that is used as a painkiller and to prevent further heart attacks and strokes in some people. Some studies have suggested that people who regularly take aspirin may be less likely to be diagnosed with cancer than those who don’t take aspirin. Also, in studies testing the beneficial effect of aspirin on heart disease, aspirin appeared to reduce the number of people who developed cancer, and if people did develop cancer, it appeared to be less likely to spread. So researchers believe that aspirin may stop cancer coming back in people who have had treatment for early stage cancer. But, importantly, there is not any reliable evidence yet since previous studies were not specifically designed to answer this question. A clinical trial or study is the best way to test this. It will look at both the benefits and the side effects of taking aspirin in a large group of people who have had cancer. The study will look at two different doses of aspirin. This is because little is known about how much aspirin may be needed to have an effect, if any, against cancer. 4 What will I need to do if I take part? If you agree to take part in this study, you will have a blood test and be asked questions about your medical history to check your suitability to take part. In the study, you will be asked to take the study medicines for at least 5 years. We know that it can be difficult to take medicines every day over a long period so everyone will be asked to take 100mg of aspirin for about 8 weeks at the beginning of the study. This is called the “run in” period and will help us to identify people who may have problems taking aspirin. If you find it difficult to take aspirin regularly, it may not be recommended that you continue. After 8 weeks, if taking aspirin every day hasn’t caused you any problems, you will then be randomly allocated by computer to one of the three treatments: 1. 300mg of aspirin every day (one tablet per day) or 2. 100mg of aspirin every day (one tablet per day) or 3. A placebo tablet every day (one tablet per day). DIAGRAM If you are 75 years old or over, you will only be allocated to 100mg of aspirin or placebo. This is because you may be more likely to have side effects from aspirin. To make sure the results of this study are as reliable as possible, neither you, nor your doctor, will know which treatment you get. If your doctor needs to find out which treatment you are taking at some point during the study, they will be able to do so. Whichever treatment you get, we will ask you to take one tablet a day for at least 5 years. It is very important that you take your tablet daily. It is usually easier to remember to do this if you take the tablet at the same time each day. If you forget to take a tablet or number of tablets do not take additional tablets to catch up, you should only take one tablet a day. Please let your study doctor or nurse know if you have missed any tablets next time you see them. Who decides which treatment I will get? A computer will choose which treatment you get by a process called ‘randomisation’. This means you will have an equal chance of getting any one of the 3 treatments and ensures that the groups of people being compared in the study are as similar as possible to start with except for the treatment they take. This in turn ensures that any differences between these groups are only due to the treatments in the study. Everyone joining this study will have a two out of three chance of getting aspirin. Other medicines It is extremely important that you do not take any other medication that contains aspirin regularly and you should not buy aspirin from a chemist or shop while taking part in the study. You should also not take drugs such as ibuprofen or Nurofen (non steroidal anti-inflammatory drugs) on a regular basis but they can be used occasionally where absolutely necessary for no more than two weeks at a time. If you need to use a painkiller for more than two weeks, please discuss an alternative with your doctor e.g. paracetamol. They will also give you more information about this if you decide to take part in this study. Checks and tests Before you start taking your study treatment, you will have a blood test. After the “run in” period you will have a check up and blood test to see if you have had any problems taking aspirin. You will then have a check up, blood tests and other checks depending on your cancer type every three months until one year and then every six months after that. If you were diagnosed with bowel cancer, you will have some CT scans. These would all be part of your normal care whether or not you participate in the study. The total dose of ionising radiation from these scans is approximately the same as 30 years of natural background radiation in the UK to which we are all exposed. The risk of a secondary cancer occurring from these scans is approximately 1 in 300, which is considerably less than our lifetime risk for developing cancer which is 1 in 3. If you were diagnosed with breast cancer, you will have some mammograms. These would all be part of your normal care whether or not you participate in the study. The total dose of ionising radiation from these mammograms is approximately the same as three years of natural background radiation in the UK to which we are all exposed. The risk of a secondary cancer occurring from these mammograms is approximately 1 in 3000. Some studies have suggested that aspirin may help protect against age related changes in memory and thought processes (cognitive status). In order to find out more about this, we will ask you to complete a questionnaire at the beginning of the study, after one year and after five years. You will have your blood pressure checked at each trial visit. Your study nurse or doctor will be able to give you more information about these checks and tests. 5 What are the possible side effects? Aspirin is a common, frequently used drug and most people take it without experiencing any side effects. We will ask you some questions about your medical history to check that aspirin is a suitable treatment for you but some people might experience some side effects. Most side effects are mild but, for a very small number of people, they can be serious. Common side effects The most common side effects of aspirin include indigestion and irritation of the stomach. Between 1 in 10 and 1 in 100 people will experience these side effects. Aspirin can also make you more prone to bruising. Uncommon side effects Aspirin can cause minor bleeding from the stomach or bowel. It is very important to tell your study doctor or nurse or GP if you have any dark or black stools or any vomiting of blood. This is uncommon (between 1 in 100 and 1 in 1000 people will experience it). Aspirin can also cause severe bleeding, but this is rare and will affect between 1 in 1000 and 1 in 10,000 people. Rare side effects Irritation of the stomach or bowel can cause a small break in the lining called an ulcer. It is very important to tell your study doctor or nurse or GP if you have any dark or black stools or any vomiting of blood. Rarely, bleeding in the brain occurs. It is important to have your blood pressure checked regularly while you are taking part in the study and this will be done at each visit. Aspirin can rarely cause other areas of bleeding for example, nose bleeds or bleeding gums. Hypersensitivity reaction (allergic reaction) is also a rare side effect. Rare side effects will affect between 1 in 1000 and 1 in 10,000 people. Very rare side effects Kidney and liver impairment are very rare side effects of aspirin. Very rare side effects affect less than 1 in 10,000 people. Other side effects Some people have experienced tinnitus (ringing sound in ears) when taking aspirin. Some recent evidence has suggested that a condition called macular degeneration (age related loss of sight) may be more common in people taking aspirin. Please tell your GP or study doctor as soon as possible if you become concerned about any potential side effects at any stage, or if you are concerned about any medical problems you are experiencing. For a more detailed list of possible side effects, please see the patient information leaflet provided with your medication. If you become pregnant or decide you want to during the study, please inform your study doctor or nurse as there are risks associated with taking aspirin during pregnancy. 6 What are the possible benefits and disadvantages of taking part? What are the possible benefits of taking part in this study? We hope that you will be helped by taking part in this study, but we can’t guarantee this. However, the information we get from this study will help us to improve future treatments for people like you who have had treatment for cancer and help us find out more about the overall healthcare benefits that aspirin might provide such as preventing heart disease. What are the possible disadvantages and risks of taking part in this study? You might experience side effects from the treatment that you take in this study. Side effects of aspirin are listed in section 5. You will be asked to have a blood test before joining the study and then asked for your permission to have additional blood tests during the study. You may also be asked to have some extra appointments at the hospital if you take part in the study. During the study, you will not be able to take drugs such as ibuprofen or Nurofen (nonsteroidal anti-inflammatory drugs) on a regular basis. If you have private medical insurance or require travel insurance, your policy may be affected. You should check this with your insurance provider. 7 Samples and genetic tests Everybody that participates in this study will be asked to donate samples which may include small samples of blood, urine and tissue from their cancer. We would like to collect samples from everybody participating in the study, even if their study medication is stopped because it allows us to study the side effects of aspirin. If you choose not to give permission for this you can still take part in the study. What samples will I be asked to donate? Cancer samples: samples of your cancer may have been stored in the hospital pathology laboratory. If you decide to take part in this study, we will ask your permission to retrieve your samples. You will not be asked to have any additional samples taken for this to happen. Blood samples: we will ask your permission to take a small amount of blood when you register for the study. We will ask your permission now to do this. This part of the study is entirely optional and if you do not give your permission for this, you can still take part in the main study. What will happen to samples I give? Your donated samples will be stored in a laboratory for future research on the anti-cancer effects of aspirin and other projects aimed at improving outcomes for cancer patients. Any research using your donated samples would only be carried out after an independent research ethics committee has approved it. Will any genetic tests be done? Depending on your cancer type and your hospital, you may have routine genetic tests done. You will receive personal results from these tests. Your study doctor can tell you more about these tests. In the future, cancer researchers would like to use the blood and cancer samples that you donate (including your DNA) for separately approved research to help find out how genetics influence the risk of cancer and responses to treatments (including aspirin). You will not receive any personal results from these non routine genetic tests unless we discover genetic information which has significant implications for your ongoing care, your future health or for that of your family. If this happens, we will contact you or the doctors looking after you with this information. 8 More information about taking part Do I have to take part in the Add Aspirin study? No, it is up to you to decide whether or not to take part. If you decide to take part, we will ask you to sign a form to give your consent before the 8 week run in period and again if you decide to continue in the study after the run in period and to be randomised to one of the three treatments. You can stop taking part in the study at any time and without giving a reason. You can also decide not to take part. This will not affect the standard of care you receive. If you do decide to stop taking part, please discuss this with your doctor. If you decide to stop taking your study tablets, we would like to continue to collect some information about you. This will help us to test whether aspirin does stop cancer coming back. This is important, as it helps us to ensure that the results of the study are reliable. If you decide not to take part in this study, you will continue to have your regular checkups and any other medication that you are receiving (for example, hormone treatment if you have had breast or prostate cancer), without taking the study medications. Who is organising and funding the study? has overall responsibility for this study. It is organised by the , which has run studies of this kind for many years. at will manage the study and will collect and analyse the information. You can find out more about the here: This study is being paid for by the charity Cancer Research UK, the National Institute for Health Research’s Health Technology Assessment Programme (part of the UK Department of Health) and the at . have supplied the aspirin tablets and placebo tablets for this study. You will not be paid for taking part in this study. Your doctor is not receiving any money or other payment for asking you to take part in the study. Who has reviewed the Add Aspirin study? The study has been reviewed by international scientists on behalf of the funders. It has been authorised by the regulatory body in the UK, Medicines and Healthcare products Regulatory Agency (MHRA), as well as by Research Ethics Committee and your hospital’s Research and Development office. What will happen to information about me collected during the study? If you agree to take part in the study, your doctor will send information about you, your cancer and your progress to the . This information will be put into a computer and analysed by Add Aspirin researchers. With your permission, we will also link to your details at the NHS Central Register (NHSCR), so we can check your health status if you lose touch with your study doctor or stop visiting the hospital. To do this, we will need to keep your name and NHS number on file, but these will be kept separately from other information about you. Some participants may be asked to send a health update directly to the . You do not have to take part in this aspect of the study if you do not wish. Also, if you agree to take part in the study, your medical records may be looked at by selected hospital staff or the lead doctor for the study (or his/her nominee). Results from the study and any future research will be published but will be anonymous. We will follow all legal requirements to make sure that all information about you is treated in confidence. If you take part in this study, we will also tell your GP that you are taking part in this study so that s/he is aware that you might be taking aspirin. We would also like to keep you updated with information about the study. If you would like us to send you information, we will take your contact details and keep them separately from other information about you. You do not have to give us your contact details if you do not want us to send you updates. What will happen to the results of the Add Aspirin study? If you give us permission, we will contact you to tell you the results of this study when it is completed. We will also publish a summary of the results on the study website: www.AddAspirinTrial.org and in a medical journal, so that other doctors can see them. You can ask your doctor for a copy of any publication. Your identity and any personal details will be kept confidential. No named information about you will be published in any report of this study. What if new information becomes available during the course of the study? Sometimes during a study, new information becomes available about the medicines that are being studied. An independent committee will look at any new information and will also look at the data collected so far in the study and decide if any changes are needed. If this happens, your doctor will tell you about it and discuss whether you want to continue in the study. If you decide to stop taking part in the study, your doctor will arrange for your care to continue. Also, on receiving new information or because of a change in your health status, your doctor might consider that it is in your best interests to stop taking part in the study. Your doctor will explain the reasons and arrange for your care to continue. What if something goes wrong? If you have any concerns about the way you have been approached or treated during the study, or wish to complain, please use the normal NHS complaints process. If you are harmed by taking part, or if you are harmed due to someone’s negligence, then you may be able to take legal action. 9 Contacts for further information If you want further information about the study, contact your study doctor or nurse (see below). You can also find information about the study on the following websites: www.cancerresearchuk.org/cancer-help Thank you for taking the time to consider taking part in this study. Mammo-50: mammographic surveillance in breast cancer patients aged 50 years and over We would like to invite you to take part in a research study called Mammo-50. This information sheet explains why the research is being done and what it will mean for you. Please take time to read it carefully and discuss it with friends, your family and your GP, if you wish. Part 1 explains what will happen if you take part. Part 2 gives you further information about the study. A member of the research team will go through this with you. Please ask if there is anything that is not clear or you would like more information. Please take as much time as you need to decide whether or not you wish to take part. Your participation in this research is entirely voluntary. If you decide not to take part, you will receive usual, standard treatment and your medical care will not be affected in any way. Part 1 What is the purpose of the study? You received surgery for breast cancer approximately 3 years ago. Since then you will have seen your doctor or nurse at intervals to check that you have been well. You may have also had mammograms to try and check that the cancer has not returned. This is known as mammographic surveillance. However, we do not know the best approach to follow up women aged 50 years and over and practices vary across the UK. There is no clear evidence on how often mammograms should be carried out and for how long after surgery. Current methods of follow up care can be stressful for patients, costly for the health service and time consuming for both. These services were established when scans were less sophisticated and less women survived breast cancer. Research indicates that women aged 50 years and over may need less frequent mammograms if they are supported and monitored in other ways such as follow up programmes through GP surgeries or Hospital OutPatient Clinics. The purpose of the Mammo-50 study is to investigate the most effective and safest way of monitoring women of 50 years or over who have had breast cancer surgery. It will also consider acceptability to patients and value for money. It will eventually inform national guidelines about the best way to follow up women who have had surgery for breast cancer. What is being tested? We are testing the optimal frequency of mammograms after breast cancer surgery for women who are aged 50 years and over. This is to ensure that women receive enough mammograms to detect any cancer recurrences promptly and to offer further treatment appropriately, but not so many that they cause undue anxiety and become too costly for both individuals and the health service. We also want to find out about other methods of follow up which take place such as clinic visits to see your doctor, visits to see the breast care nurse or telephone follow up, and how these affect your quality of life. Why have I been invited? You have been invited because you are aged 50 or over, you received surgery for breast cancer approximately 3 years ago and you remain free of cancer. We do not know the best way to follow up women who are your age and who have had your type of breast cancer. We will be recruiting 5000 women over about four years from approximately 100 UK cancer centres and hospitals. Do I have to take part? No. It is entirely up to you to decide whether or not to take part and your care will not be affected in any way if you do not enter the study. If you do, you will be asked to sign a Consent Form. If you change your mind, you can withdraw at any time, without giving a reason. This Information Sheet is yours to keep whatever you decide. What will happen to me if I take part? All women who take part in Mammo-50 will be allocated to one of two types of mammographic surveillance using a process called randomisation. Randomisation is a process in which a computer is used to allocate which group you will be in and it means you have an equal chance of being in either group. This is to ensure an equal distribution of patient characteristics in both groups. Neither you nor your doctor can choose which group you will be in. Group 1: If you are in group 1 you will have a mammogram once a year for another six years. You may also see your doctor or nurse depending on your hospital’s policy. Group 2: If you are in group 2 and you have had ‘breast conserving’ surgery (also known as a wide local excision), you will have two yearly mammograms for another six years (i.e. three more). If you have had a full mastectomy, you will have three yearly mammograms for another six years (i.e. two more). . You may also see your doctor or nurse depending on your hospital policy. For both groups: You will be asked to complete a questionnaire booklet which is designed to measure your general and post treatment health. You will be required to complete a questionnaire booklet before randomisation and at the time of your surveillance mammograms. If you take part in the trial you will not be taken out of the national breast screening programme and will continue to receive a letter of invitation every three years. However, we would ask that you do not attend these screening mammograms whilst you are receiving mammograms as part of Mammo-50(Please ring the breast screening office number on the invitation letter to cancel the appointment if you receive one). This is to avoid duplication which may affect the results of the study. If you have any concerns please discuss this with your research team Optional for both groups: There are also three optional sub studies that form part of Mammo-50. By taking part in these, you will be helping to build a complete picture of the surveillance mammography and breast cancer follow up that is taking place in the UK today. This will help health policy makers to formulate recommendations for best practice in future. However, you may take part in the main study without consenting to take part in one, two or all of these. There will be an option to sign up for these or not on the consent form. The optional sub studies are: - Optional Quality of Life Study: This will help to assess how women who are receiving surveillance mammography and breast cancer follow up feel in terms overall wellbeing and concern over any long term symptom and side effects associated with cancer treatment. If you take part in this you will be asked to complete an additional questionnaire booklet which will be sent to you or given to you by a member of your hospital team if you are receiving breast cancer follow up. - Optional Qualitative Research Study: We will be interviewing a number of women who have had breast cancer to gain information about their experience and perspectives on receiving surveillance mammography and breast cancer follow up. This will help us to find out what needs you may have and how we can best deliver services in future. The interviews will take place as part of a focus group or as a one to one interview with a researcher. If you decide to take part in Mammo-50, you will also be asked if you consent to attend a focus group or be invited to be interviewed in the future. This will not commit you to taking part and you may change your mind later. If you are invited at a later date you will be asked to read an additional patient information sheet and sign a consent form for participation in the interview/focus group which, with your permission, will be recorded. - Optional Tissue Study: We will be requesting some tissue samples from women’s breast cancer surgery in order to assess the characteristics of their cancer. If you agree to donate any surgical samples, these will be a gift for future research. You will not have access to individual information generated from these samples. What are the alternatives for follow up? If you do not wish to take part in Mammo-50 you will receive the standard breast cancer follow up for your hospital. This varies from hospital to hospital. What are the other possible disadvantages and risks of taking part? We still don’t know the best and most effective way of monitoring patients after they have had surgery for their breast cancer. However, we do know that some women find regular visits to the hospital cause anxiety where as others may feel anxious if they receive less follow up visits to the hospital. By taking part in the study, you may receive more mammograms than you would normally at your hospital or you may receive less. If you have more mammograms than normal then the chance of getting a new cancer through receiving additional radiation is 1 in 6300; therefore the risk from any additional exposure is considered to be low. Women who take part will also be asked to complete questionnaires. These will take approximately 15-30 minutes to complete and will be done every time you attend for a study based mammogram, which may be an inconvenience. What are the possible benefits of taking part? There are no known benefits in taking part in Mammo-50 for you. However, depending on how you are affected by the number of visits to the hospital whether it is for a clinical follow up or a mammogram, you may find that if you receive less or more you will be less anxious. The information gained from this study should help improve follow up after breast cancer surgery for women in the future. What happens when the research study stops? After you have your last study based mammogram you should attend for mammograms offered as part of the breast screening programme. It will be made clear to you when your participation in the trial has finished. However, if you are at all unsure you should contact the research team at your hospital. We will continue to collect available information on your health for several years via agencies such as the Office for National Statistics and Public Health England. It is very unlikely that the study will end before your follow up is complete. However, if this happens, you will be offered the standard follow up for your hospital and your progress will be followed in the same way. What if there is a problem? If you have any problems or queries while taking part in the trial, let your research nurse know and they will be asked to refer you via your GP to rapid access to your hospital specialist if needed. More information will be given to you in Part 2 of this information sheet. Will my taking part in the study be kept confidential? Yes. We will follow ethical and legal practice and all information about you will be handled in confidence. There are more details about this in Part 2. This completes Part 1 of the Information Sheet. If you think you might join the study, please read Part 2 before making your decision. Part 2 What if relevant new information becomes available? We may obtain new information from other research that is important for Mammo-50 and we might want to change the study as a result. If this happens, your doctor will discuss this with you and you will decide whether or not to continue in the study. If you decide not to continue, your doctor will arrange for your future care. If you do continue, you may be asked to read a new Information Sheet. You might also be asked to sign a new Consent Form. What will happen if I don’t want to continue with the study? You can withdraw from the study at any time and without giving a reason. Information already collected may still be used unless you request that it is not. We will discuss your further treatment and follow up and your decision to withdraw will not affect your future care. What if there is a problem? If you wish to complain or have any concerns about the way you have been approached or treated by members of staff during your participation in the research the National Health Service complaints mechanisms are available to you. Please ask your research doctor if you would like more information on this. In the unlikely event that you are harmed by taking part in this study, compensation may be available. If you suspect that the harm is a result of the sponsor (University of ) you may be able to claim compensation. Please discuss with your doctor, then make the claim in writing to The Director of Delivery Assurance, Registrar’s Office, , University of , . This will be passed to the university insurers. You may have to bear the costs of the legal action initially and you should consult a lawyer about this. Will my taking part in this study be kept confidential? All personal information collected for Mammo-50 is strictly confidential and is covered under the Data Protection Act 1998. Information about you will be held on a secure database at the Mammo-50 Trial Office at Clinical Trials Unit, University of . Only authorised personnel at the Trial Office can access this. With your permission, we would like the Mammo-50 Trial Office to hold a record of your personal details. This includes your NHS/CHI number, date of birth, name and address. We may use this to send you questionnaires and other information by post. We would also like to contact the Health and Social Care Information Centre and the Office of National Statistics about you as they collect long term information about all NHS patients. However, when you join Mammo-50 you will be given a unique study number and we will use this and your initials only in any communication about you. We will not use your name. Your doctor will usually inform other doctors and nurses who look after you that you are in Mammo-50. This includes your GP. You must inform your doctor if you do not wish for this to happen. If you choose to withdraw from the study we would still like to collect information about you. This will be useful to our research. If you have any objection to this please let your doctor know if you do decide to leave the study. What will happen to the results of the research study? The results will be published in scientific journal after a number of years and presented at professional and academic conferences. If you wish, we will send you a report of the results of the study. You will never be identified in person in any report about the study or in the study results. Who is organising and funding the research? The Clinical Trials Unit at the is organising the study and the National Institute of Health Research Health Technology Assessment Programme is funding it. Who has reviewed the study? The study has been approved by the Department of Health’s National Institute for Health Research and a UK National Research Ethics Committee. It has also been approved by patient and carer representatives. What to do if you wish to take part in the study? If you wish to join this study you will be asked to sign a Consent Form. There will be further discussion with the researcher before you sign it. You will also be given a copy of this Information Sheet and your signed Consent Form. Your GP will be sent a letter telling them about Mammo-50 and that you are taking part. If you decide not to take part, your care will not be affected in any way, and there may be opportunities for your experiences of breast cancer care to be used for benefit for future care of other patients. Please feel free to discuss this with your specialist or research nurse. Thank you for taking time to read this information sheet. If you would like any independent information about taking part in research, you may find it useful to contact one of the following organisations: - Macmillan Cancer Support: (Free phone) http://www.macmillan.org.uk - Breast Cancer Care: Tel: (Free phone) http://www.breastcancercare.org.uk - Cancer Research UK Tel: (Free phone) http://www.cancerhelp.org.uk - PALS (Patient Advice and Liaison Service) Ask your GP or Phone NHS 111 for details of your nearest PALS Invitation to take part in the UKLS Trial> We would like to invite you to take part in a large national research project which we hope will benefit people at risk of developing lung cancer. Before you decide whether or not to take part, it is important for you to understand why the research is happening and what it will involve. Please take time to read this information booklet carefully and discuss it with your family and friends if you wish. What is the aim of this booklet? This booklet tells you about lung cancer, lung cancer screening and how the trial will work. It aims to give you information that will help you choose whether or not you wish to take part in the UK Lung Cancer Screening (UKLS) trial. What is the lung cancer screening trial? The United Kingdom Lung Cancer Screening (UKLS) trial is a study of lung cancer screening in the UK. We aim to recruit 4,000 people in the first stage of the trial. If the results of our trial show that CT scanning of the lungs in healthy people is worthwhile then, in the future, CT scanning may be used throughout the country for lung cancer screening. This would be similar to the breast, cervical and bowel cancer screening programmes used today. Why am I being invited to take part? You have provided details about your lifestyle and based on this information we would like to invite you to take part in the UKLS trial. We want to recruit people aged 50 to 75 years old. We have chosen this age group because we believe that if lung cancer screening is shown to be worthwhile, these are the people most likely to benefit. Do I have to take part? No, it is up to you to decide whether or not to take part. If you decide to take part you will be given this information booklet to keep and asked to sign a consent form. You are still free to change your mind or withdraw from the trial at any time and without giving a reason. If you decide not to take part, we will not contact you again and the care you receive from your general practitioner (GP) will not be affected. We would, however, be grateful if you could fill out the attached questionnaire called ‘UKLS non participant questionnaire’ and return it to us. This information is very important and will help us to plan future screening programmes. What will happen to me if I take part? You have already been asked some basic questions about smoking, your lifestyle, occupation and known health problems. The next stage is an invitation to a recruitment clinic. At the UKLS recruitment clinic, you will be met by the receptionist and invited to watch a DVD which will give you further information about the trial. You will then be met by a UKLS research nurse who will answer any questions you may have and will then ask you to sign a consent form. At this point you will be enrolled into the trial. You will then be asked some more detailed questions about your lifestyle and family history of disease. You will be asked to give your answers on a computer by touching the screen, which will greatly assist us in developing a better way of identifying individuals for lung cancer screening programmes. You will also be asked to blow into a tube a few times (lung function tests) to look at the health of your lungs. A member of the UKLS team will take a sample of blood, a mouth swab or wash and a nose brush. The nasal sampling has a very small risk of causing a nose bleed. You will be given a pot to take home so that you can return a deep cough sample, which will be explained to you at the recruitment visit. Finally, if you are a current smoker, you will be provided with information to help you stop smoking. Your visit to the recruitment clinic should take about an hour. Your GP will be informed that you are a participant in the UKLS trial. To find out whether CT scanning of the lungs will be beneficial, we need to divide those who join our trial into two groups. Half of the people joining the trial will be offered a CT scan of their lungs and the other half will not. Both groups are equally important because we going to observe what happens in each group. Then, at the end of the trial, we shall compare what happened to the group who were scanned to what happened to the group who weren’t. To run the trial properly, people must be put into a group at random (using a computer), so neither you nor your doctor can choose which group you are put into. You will find out which group you are in about four weeks after you are enrolled. In this trial we would also like to look at the effect of screening on the wellbeing of those who take part, so you will be asked from time to time to take part in surveys about your experience of the UKLS. Regardless of whether you are in the screening or non screening group, we will check on your health through your medical records over the next 10 years. If any some reason during the trial, you lose the capacity to consent, we will retain all the previously collected data and specimens, however, we will not contact you again with any questionnaires or follow up appointments. What are lung function tests? Lung function tests (also known as pulmonary function tests) are used to look for the cause of breathing problems (like shortness of breath) and are also used to see how well treatments for breathing problems, such as asthma medicines, are working. They can be used to check for conditions such as asthma, lung tissue scarring, sarcoidosis, and COPD (chronic obstructive pulmonary disease). The tests may also be used to check whether a condition is getting worse. Lung function tests measure: • How much air you can take into your lungs. This amount is compared to that of other people your own age, height, and sex; • How much air you blow out of your lungs and how fast you do it; • How well your lungs deliver oxygen to your blood; and • How strong your breathing muscles are. What is the computed tomography (CT) scan? If you are part of the screening group, you will have a CT scan of your lungs. This scan of the chest uses x-rays and a computer to produce pictures of the lungs (it’s also known as CAT scanning). During the CT scan you lie down on the scanner and hold your breath for a few seconds while pictures of your lungs are taken. Your appointment should take about 15-30 minutes. All of the CT scan pictures are stored in a computer and read by a radiologist. You will be told about the results of your scan by a clinical member of the UKLS team within four weeks of the scan. If no abnormalities are found, you will not need any further tests but we will contact you to fill out questionnaires so that we can find out about your future health and how you felt about being screened. If any important abnormalities are found you would be given an appointment to see a chest specialist at your local NHS hospital. The specialist may advise follow up with another CT scan or other tests. If the lung specialist thinks you might have lung cancer, they will discuss treatment options with you. Your GP will be kept informed of your participation in the UKLS trial and of all scan results and any treatment recommendations, and will be able to discuss them with you. What are the possible side effects of CT scans? Because CT scanning uses x-rays to obtain pictures, you will be exposed to some radiation which you would otherwise not receive. However, the dose of x-rays used for the screening CT scan is less than you normally receive in a year from the natural surrounding environment and the risk of it causing harm is therefore very low. If an abnormality is detected, you may need follow up CT scans and if lung cancer is strongly suspected, further tests will be required. The radiation dose for follow up CT scans would be higher than for the first but the risk is still low and the benefits of detecting lung cancer at an early stage must be considered. When do I get my CT results and what do they mean? You should receive a results letter from the UKLS trials team within four weeks of having your CT scan. There are three types of results that you could receive; A normal result means no tumour or nodule was found. We expect that most people will receive a normal result. A normal result does not guarantee that you do not have or will never develop lung cancer in the future, so staying aware of any symptoms of lung cancer in the future is very important. An unclear result means that your screening CT scan was not quite normal and further tests are needed. Getting an unclear result may not mean you have cancer, just that you will most likely need a follow up CT scan. If you receive an unclear result you will be invited back to the hospital to have another CT scan. Most people will then receive a normal result. An abnormal result means that the CT scan may have found signs of a cancerous nodule in your lungs. It is not a diagnosis of cancer, but it does mean that you will be offered a follow up CT scan and other tests. Sometimes scans show other conditions that are not lung cancer but do require medical attention. If this is the case, your GP will be informed and contact you to ensure the abnormality is dealt with appropriately. What happens if my CT scan finds something? You will be cared for through the NHS and given an appointment with a lung cancer specialist doctor to discuss having a more detailed examination of your lungs. This will involve some further tests and the specialist team will explain what is required. If lung cancer is found, a doctor will discuss treatment options with you and your wishes will be taken into account. If you have to undergo any investigations or treatment procedures, we will collect any leftover tissue specimens for future research. How reliable is lung cancer screening? In some cases lung cancer could be present but may not be found by CT scanning. Cancers in the main airways in the middle of the chest may be difficult to identify on CT and not all small cancers in the lung are recognised, even by the most skilled radiologists. Are there any risks if I take part? Sometimes non cancerous abnormalities are found by screening which you would otherwise have never known about. If you need an operation to remove a lung abnormality or need to have a lung biopsy any possible risks will be fully explained to you by an NHS specialist before the procedure is undertaken. What are the possible benefits of taking part? As we do not know whether early diagnosis of lung cancer with CT scanning will be beneficial, it is not possible to tell you whether you are likely to benefit from entering the trial or not. Even If the trial is of no benefit to you personally because you have normal lungs it may benefit others taking part in the UKLS trial, as well as people in the future. Where do I need to go? There are two centres taking part in the trial: 1. 2. Both centres have dedicated rooms for the trial. When you arrive, you will be directed to a waiting room and met by the trial receptionist. If you attend the xxx clinic, you might be offered screening in our on site mobile screening unit. If you provide evidence that you receive benefits, some support may be available to you for reasonable travel expenses What happens if new information becomes available during the trial? Sometimes during the course of a research study a new technique or new information becomes available which is relevant to the study. This is unlikely to happen in this trial because the type of CT scanner being used will be up to date and of high quality. However, should such a situation arise, the research nurse will tell you about it and discuss with you whether you wish to continue in the study or whether it would be in your best interests to withdraw. What happens when the trial stops? Your records will be under the care of the trial centre for 20 years and your GP will continue your normal care during and after the trial. What will happen to the results of the trial? The main results of this trial are not likely to be available for several years but early results relating to the number of lung cancers found by screening should be known after the first two years. Once carefully analysed, the results will be published in medical journals. If you would like a summary of the results as they become available please inform the research nurse at your trial centre. Will my samples be used for any further research? If you agree to take part in this trial you will be asked to give a blood sample, a sample of spit, a mouth swab or wash and a nose brush. These samples will be stored at the University of Biobank and will be used in future research projects with ethical approval. This may allow researchers to identify biological and genetic factors that affect the risk of future lung disease. This may be useful in developing future screening tests or in understanding more about the causes of lung cancer or other lung diseases. The UKLS research team will be responsible for keeping the samples safely and making sure that any information remains confidential. Results of any studies undertaken on your sample will not be fed back to you personally or placed in your medical records, as the tests are for research only. The research results will not have any implications for you personally. All future use of the samples will have to be approved by an Ethics Committee. Will my taking part in the trial be kept confidential? If you consent to take part in this trial, your medical records and CT scan results may be inspected by authorised representatives within the trial and by the Department of Health regulatory authorities. Your name will not be disclosed outside the trial. You will not be identified in any publication or report of the trial. What happens if something goes wrong? Your legal rights are not affected by giving your consent to take part in this trial. Who is coordinating and funding the trial? The trial will be coordinated by the Cancer Trials Unit . It is funded by the Department of Health - Health Technology Agency. Who has reviewed the trial? The trial has been reviewed by the Department of Health – Health Technology Agency, the Research Ethics Committee and by the Local Research Ethics Committees of the two centres involved. I am a smoker but would like to stop smoking. Can I still take part? Yes and we would encourage you to stop smoking. Even if you stop smoking at any point in the future you are still able to take part in the trial. Just let us know the date you stopped smoking when you send back your next follow up questionnaire. The UKLS team will provide you with NHS stop smoking materials or you can contact the NHS on or go to http://smokefree.nhs.uk. Where can I get more information? Please feel free to telephone the research nurse on in the UKLS Project management office. If you would like more information or have questions you would like to ask. More information about the trial can be found on the UKLS website www.UKLS.org What should I do now? We hope that you are encouraged to join the trial. If you would like to take part, please return the enclosed ‘UKLS participant questionnaire’. If however you decide not to take part, please fill in the ‘UKLS non participant questionnaire’. Thank you for reading this UKLS information booklet and we do hope you will want to participate in this very important Lung Cancer Screening Trial, which may prevent deaths from lung cancer. MAPS Men After Prostate Surgery SIMPLE TREATMENT FOR URINARY INCONTINENCE IN MEN AFTER PROSTATE SURGERY INVITATION TO HELP WITH RESEARCH INFORMATION SHEET Simple treatment for urinary incontinence in men after prostate surgery (MAPS) 1. Title of project Conservative treatment for men with urinary incontinence after prostate surgery: multicentre randomised controlled trial of pelvic floor muscle training and biofeedback. 2. Invitation You are being invited to take part in a research study. Before you decide, it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with others if you wish. Do feel free to ask us if there is anything that is not clear or if you would like more information. Take as much time as you need to decide whether or not you wish to take part. You do not have to give a reason if you do not wish to take part. Thank you for reading this. 3. What is the purpose of the study? We want to find out if simple (physical and lifestyle) advice and treatment help men with urinary incontinence after prostate surgery. The study will take about 12 months and you will be followed up at 3, 6, 9 and 12 months by being asked to fill in a questionnaire and keep a short diary as explained in Section 7 below. We have found out that up to 10% of men have urinary incontinence after prostate surgery through the urethra and 50% after abdominal surgery. Although the problem gets better with time, there is hardly any information to show if treatment can also help. 4. Why have I been chosen? When you kindly returned the questionnaire we sent you after your prostate surgery, your answers showed that you might have this problem and be suitable for our study of treatment. We hope to study up to 800 men with the same problem. 5. Do I have to take part? No. If you do not want to take part, that is fine. You do not have to give a reason and your health care will not be affected by your decision. You can still have any treatment available locally whether or not you take part. If you decide to take part but later change your mind, you can withdraw at any time without giving a reason. The information we already have will be stored securely and confidentially, unless you request that we delete it. If you agree, we may still collect NHS information about you (such as from your hospital records), unless you request that we do not. We will specifically seek your consent (or not) to keeping this information if you choose to withdraw. 6. What will happen to me if I take part? Sometimes because we do not know which way of treating patients is best, we need to make comparisons. People will be put into groups and then compared. The groups are selected by a computer which has no information about the individual (i.e. by chance). Patients in each group then have different treatments and these are compared. In this study, you will have a 1 in 2 chance of being either in the active treatment group or in the standard treatment group. If you are in the active treatment group, you will be invited to see a hospital physiotherapist or nurse for advice about diet and exercise, such as pelvic floor muscle training, four times in three months in an outpatient clinic. They will assess you by asking questions and examining you at the first visit, which will last for an hour. The examinations at each visit will include gentle anal (back passage) testing to measure your muscle strength. This could be with a gloved finger and/or using a biofeedback machine with a small sheathed anal probe. In the second, third and fourth visits, which will each last for about three quarters of an hour, they will find out how you are getting on with following their advice, and may suggest extra ways of helping. If you are in the standard treatment group you will receive information about lifestyle changes which may help your problem, but otherwise you can continue with your normal activities. You can still have any other treatment available locally if you want it. In both groups, you are free to consult your GP or anyone else if you feel you need extra help. 7. What do I have to do? Before you enter the study, we would like you to fill in another questionnaire and sign a consent form. In both groups you will be asked to fill in two more questionnaires, at 6 and 12 months from now. Each questionnaire should take less than half an hour to fill in. You do not need to answer every question if you do not want to. Even if you are in the control group, it would be very important to return these questionnaires because otherwise we will not be able to compare the effects of the study treatment with current standard treatment. We will also ask you to keep a short diary (just for three days) at three monthly intervals (one now before you enter the study, and the others at 3, 6, 9 and 12 months from now). The diary should only take a few minutes a day to complete. There are also two short questionnaires at 3 and 9 months. These are to keep a record of how often you leak urine, and how much you use the health service. There are no extra outpatient appointments other than the four treatment appointments if you are in the active group. We may wish to find out in the future how you are after the study has finished, for example by checking your NHS records or by sending you another questionnaire. To make sure we can contact you again, we would be grateful if you could give us details of a person we could contact who would know where you are if you have moved. 8. What is the procedure that is being tested? Simple (physical exercise and lifestyle) advice and treatment. We do not propose that men in the study will have any operations, drugs or blood tests. 9. What are the alternatives for diagnosis or treatment? Alternative ways of managing your urinary incontinence include drugs or an operation, but there is also very little information about whether they work. The sorts of treatment available depend on how severe the problem is. However, it is likely that (if they work) simple methods would be recommended in the first instance, depending on the results of this study. That is why we are running this study. 10. What are the side effects of any treatment received when taking part? Physiotherapists and doctors have been giving simple advice about lifestyle and exercise for many years to individuals but we still do not know how well this works. There are no known side effects. If you do think that you suffer any symptoms, you could report them in your questionnaires. However, if you are concerned by any aspect of your treatment or health, please do not hesitate to contact the MAPS Study Office on , or your GP, who will know you are in the study. In an emergency please contact your GP or hospital Accident and Emergency Department as usual. 11. What are the possible disadvantages and risks of taking part? We do not think that there are any possible disadvantages or risks to you. If you have private medical insurance you should check with the company before agreeing to take part in the study. We do not know of a reason, however, why participation might affect your medical insurance. 12. What are the possible benefits of taking part? We hope that the treatment you receive will help you. Even if you are in the standard treatment group, you may find that your problems improve. However, this cannot be guaranteed. The information we get from this study will help us to treat men with urinary incontinence better in the future. 13. What if new information becomes available? Sometimes during the course of a research project, new information becomes available about the treatment that is being studied. If this happens, the MAPS Study Office staff will contact you to let you know about the choices available to you. However, we are not aware that any new information is likely to become available before the end of this study. 14. What happens when the research study stops? If this treatment works, we hope that the NHS will provide it in the future for all men who might benefit. However, this cannot be guaranteed and will depend on local resources. Your GP will be able to refer you for any treatments which are available. 15. What if something goes wrong? We do not expect any harm to come to you by taking part in this study. However, if you are harmed by taking part in this research project, there are no special compensation arrangements. If you are harmed due to someone’s negligence, then you may have grounds for a legal action but you may have to pay for it. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated during the course of this study, the normal National Health Service complaints mechanisms (which includes professional indemnity insurance) would be available to you. 16. Will my taking part in this study be kept confidential? If you are willing to take part, we will let your GP and your hospital Urology Consultant know that you have agreed and we will send them information about what this study is about. However, we will not send them any personal or research information about you or your part in the study. All information which is collected about you during the course of the research will be kept strictly confidential. The identification information that you give us will be separated from your answers to the questionnaires and will only be linked using a secret unique study number. We may collect some information from your hospital notes or NHS records about your surgery or use of NHS services, but again this will be confidential to the research team. Any information about you which leaves the hospital or research unit will have your name and address removed so that you cannot be recognised from it. If we have any questions about your health as a result of you participating in this study, this will be discussed with you in order to find out what you would like to do about it. Any such information would be entirely confidential, however, and would not be given to anyone else (such as your GP) without your express permission. 17. What will happen to the results of the research study? We shall publish the results of this study in the academic and popular press, and present the information at academic meetings. The information will also be sent to NHS policy makers. However, you will not be identified personally in any report or publication. 18. Who is organising and funding the research? The research is funded by the Health Technology Assessment programme of the NHS. This study is being organised by staff at the MAPS Study Office at the Research Unit, . The funds are only available for the expenses necessary for running this study, including the salaries of the researchers and staff employed. No one will benefit financially from this research. 19. Who has reviewed the study? This study has been approved by the Multi centre Research Ethics Committee and your Local Research Ethics Committee. The science has been reviewed and approved by the NHS Health Technology Assessment programme. If you have any questions or would like any more information, please contact the MAPS Study Office by phone: or email: You should keep this information sheet. If you agree to enter the study, please sign the enclosed consent form and we will return a copy to you. Thank you very much for reading this information sheet. COMICE: A study to compare the effectiveness of magnetic resonance imaging (MRI) in breast cancer You are being invited to take part in a research study. Before you decide, it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully. If anything is not clear, or you would like more information, please ask your consultant or one of the members of the team. Thank you for reading this. What is the purpose of this study? The usual investigations for women with breast disease are X-ray mammography, ultrasound and fine needle aspiration/ core biopsy. Occasionally, these tests may not detect the full extent of disease and some women require a second operation to ensure that all disease is removed. A new breast imaging method is now available: magnetic resonance imaging (MRI). The aim of this study is to see if MRI can provide additional information about the disease compared with X-ray mammography and ultrasound alone, and as a result reduce the number of women requiring a second operation. The full impact of this technique on the women’s lives and on the NHS will be assessed. Why have I been chosen? You have been invited to take part in this study because you are scheduled to have an operation (a wide local excision) for breast cancer. The study will involve 1840 women from several hospitals in the UK. Do I have to take part? No, it is up to you to decide whether or not to take part. If you do decide to take part you will be given this information sheet to keep and be asked to sign a consent form. If you decide to take part you are still free to withdraw at any time without giving a reason. The standard of care you receive will not be affected if you withdraw from the study at any time, or decide not to take part. What will happen to me if I agree to take part? If you decide to take part, you will be randomised either to have an MR scan or to receive no extra investigations. This decision will be made randomly by a computer, i.e. by chance. Half of the women will have no MR scan, half will have an MR scan, and the groups will then be compared. The randomisation will be performed centrally by computer and not by your Breast Surgeon. If you are to have no further investigations, you will proceed as planned to surgery. If you are allocated to have an MRI scan, this will be carried out before your operation. The appointment will be organised so that your planned surgery is not delayed. MR scanning may detect abnormalities that are not detected by X-ray mammography or ultrasound. The results of the scan will be discussed at a multidisciplinary team meeting. Any suspicious areas identified by the MR scan will be further investigated by needle biopsy. If the results of this are positive, your Consultant Surgeon will discuss this with you. However, it is possible that these abnormalities may subsequently be found to be of no importance, and you will have the operation originally planned. What does the MR scan involve? If you are allocated to have an MR scan, both breasts will be examined in addition to the tests that have already been performed. During the scan you will be asked to lie comfortably on your stomach on a special couch, which passes through the MR scanning machine. Throughout the scan you will be able to see out of the machine into the scanning room. You will be able to talk to a radiographer at all times via a two way intercom system. Before the scan a small needle will be placed in a vein in the back of your hand or in your arm. A dye will be injected through the needle during the MR scan. This is routinely used for this type of examination and causes very few problems, mostly mild allergic type reactions. During the scan you will hear knocking noises as the pictures are taken. The MR scan takes between 30 and 45 minutes. A relative or friend may come in to the scan room with you. What are the side effects of the MR scan? Our radiographers will check that you do not have any conditions such as pieces of metal in your body that may cause problems during an MR scan. The dye injected during the scan is associated with very few problems, the most common being slight pain at the site of injection and mild allergic type reaction, for example skin rash. What are the possible disadvantages and risks of taking part? It is possible that the MR scan may show abnormalities that are later found to be of no importance, and as a result you would have undergone unnecessary additional tests (needle biopsy). There is also a small chance that the MR findings will suggest that more extensive surgery should be performed than is actually necessary. What are the possible benefits of taking part? Your planned operation is a wide local excision. For some women, the pathology findings from this surgery show that a second operation is required. We hope that the MR scans will provide additional information to show which patients require more extensive surgery before the operation is carried out, to prevent a second operation. What if something goes wrong? If you are harmed by taking part in this study, there are no special compensation arrangements. If you are harmed due to someone’s negligence then you may have grounds for a legal action, but you may have to pay for it. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated during this study, the normal National Health Service complaints mechanisms should be available to you. Information about patient rights, research related questions and research related injury can be obtained from the Local Patients Action Teams or the charity CancerBACUP. Will the information obtained in the study be confidential? All information collected about you for this study will be kept strictly confidential. This information will be securely stored at the COMICE Study Offices on paper and electronically under the provision of the 1998 Data Protection Act. Anything you say will be treated in confidence, no names will be mentioned in any report of the study, and care will be taken so that individuals cannot identify you from details in reports from the results of the study. Only appropriately qualified members of the COMICE research team may confidentially review your medical records. This is to ensure that the study is carried out to the highest possible scientific standards. In order to be able to check your notes we will need to hold some information, such as your date of birth and hospital number, so that we can identify your notes accordingly. We will also hold a copy of your signed consent form. What other information will be collected in the study? With your agreement, information will be obtained about any medication you are currently taking, the findings from X-ray mammography and ultrasound, the type of operation carried out, the pathology findings from the tissue removed, and your postoperative recovery. If you agree to take part in the Quality of Life study, you will be asked to fill out four short questionnaires at baseline, 8 weeks after randomisation, and 6 months and 12 months after your operation to find out how you feel. In order to send these to you we will need to collect your full name and address. We may also contact you in 12 months’ time to ask you if you would take part in a more detailed interview about your treatment and how you have been feeling. We would contact you nearer the time and give you a separate information sheet for this part of the study. Can I withdraw from the study at any time? You are free to refuse to join the study and may withdraw at any time or choose not to answer certain questions. Will anyone else be told about my participation in this study? We will inform your GP that you are helping with this study, unless you ask us not to. Your name will not be disclosed outside of the Study Offices or GP surgery. What will happen to the results of the study? The results of this study will be published in a medical journal approximately 12 months after the last patient has been entered. The results will also be available on the following web site: http://www.hta.nhsweb.nhs.uk. Who is organising and funding the research? This study is being conducted in cooperation with the Clinical Trials Research Unit at , and the Centre for Health Economics at . It is funded by the National Health Service Research and Development Programme for Health Technology Assessment. The study has been approved by the Multicentre Research Ethics Committee. Contact for further information If you have problems or questions, please do not hesitate to get in touch. Please use one of the following contact numbers: Thank you for considering this study. Invitation to participate in the PRIME II Trial Post operative Radiotherapy In Minimum risk Elderly Patient Information Sheet Introduction You have recently been diagnosed with early breast cancer which has been completely removed by surgery. In addition, you will receive hormonal treatment in tablet form for five years. This is known to lower the risk of the cancer returning. A further treatment which is routinely offered is radiotherapy to the affected breast. This may also reduce the chances of the cancer coming back within the breast. There is some evidence that in older women radiotherapy may not always be needed and, like many treatments, it has both short and long term side effects. Apart from the existing evidence that radiotherapy might not be needed in older women, it may not be required in women such as yourself who are at low risk of the cancer returning. This is because the cancer: (1) has been removed with a generous margin of normal breast tissue; (2) did not have any bad features when examined by the pathologist under the microscope; and (3) has not spread to the lymph glands under your arm. On this basis we would like to invite you to take part in our research to help decide whether radiotherapy is necessary for women with your particular type of cancer. Your doctor has indicated that he or she thinks that you are suitable to take part in the PRIME II trial. What will happen to me if I take part? The research will involve up to 1000 women who will each be followed up for 5 years. During the study period, you will be followed up at regular intervals as an outpatient, as is standard for all patients. At annual visits, detailed information will be recorded about your progress. A mammogram will be done annually. If you agree to take part you will be given either radiotherapy or no radiotherapy. You will have the same chance of receiving radiotherapy as you will of not receiving it. Your doctor will telephone a central office, who will use a computer to randomly allocate you to one of the treatment groups. This is done so that each group has a mix of patients of different ages and state of health. If it were left to your doctor to decide who should get which treatment, he or she might be influenced by what they know about you. This would introduce bias, making the results unreliable. What does radiotherapy involve? Radiotherapy to the breast is generally carried out over several weeks, usually as an outpatient. There is some variation in the length of a course of breast radiotherapy in UK cancer centres. The number of treatments can vary from 15 to 25. The specific schedule of radiotherapy treatments that you will receive is safe and well tested and is standard at your cancer centre. For the first attendance, a series of breast measurements are done to plan your treatment. This takes around 30 minutes. The radiotherapy treatment is given to the breast in a small dose each day. Treatments are given for 10 to 15 minutes per visit. What are the possible risks of taking part? Like all treatments, there may be side effects with radiotherapy. Many patients feel tired, especially in the later weeks and sometimes extending for a few weeks beyond the end of treatment. Radiotherapy may cause skin reactions leading to breast tenderness, redness and itching in the area treated. These usually develop towards the end of the course and commonly settle within one month of the treatment finishing. Breast pain, which is usually mild and intermittent, may occur up to two years after radiotherapy, but is less troublesome thereafter. Rarely radiotherapy may cause 1) inflammation of the lung causing shortness of breath or 2) it may cause ribs to fracture but this does not often result in any discomfort. The possible risk of not being given radiotherapy is that there may be a slightly higher chance of the cancer coming back in the breast compared to women who have received radiotherapy. However, in women aged 65 or more, we know that the chance of the breast cancer returning is lower than in younger women. Also, from our knowledge of the results of your surgery and the type of your particular cancer we believe that the risk is much lower than average. If the cancer did return in your breast, further surgery would be considered. Are there any benefits from taking part? Whether or not you take part in the research you will receive the highest standards of care. Should you be allocated to the non radiotherapy group, you will not have the inconvenience of attending the treatment sessions and will be unlikely to have the side effects mentioned above. The information that we get from the research will help gain knowledge about the best way of treating patients with low risk breast cancer. You will be informed of any new information that is relevant to your treatment. You will also have the opportunity to receive a copy of the results of this trial when they are published. Do I have to take part? No, taking part is voluntary. If you agree to take part but later change your mind you can withdraw from the trial and you can be assured that your doctor will continue to look after you with the best possible medical care. If you prefer not to take part you do not have to give a reason. Your doctor will not be upset and your treatment will not be affected. If you do not take part, the standard course of radiotherapy will be recommended. With your permission, we will contact your GP if you agree to be involved in the research. Confidentiality All the research information will be confidential to the research team and will be handled in accordance with the current data protection legislation. You will not be identified in any published results. What if something goes wrong If you are harmed by taking part in this research project, there are no special compensation arrangements. However, the risks of harm are very low as the treatments are not new and your subsequent care is standard. If you are harmed due to someone’s negligence, then you may have grounds for a legal action but you may have to pay for it. Regardless of this, if you wish to complain about any aspect of the way you have been treated during the course of this study, the normal Health Service complaints mechanism is available to you. What do I do now? Please take time to read this information carefully. Once you have done so, if you wish you may contact the person named below to ask further questions. If you have private medical insurance, it may be necessary to check with your provider before agreeing to take part in the trial. If you decide to take part in the research, please complete the consent form and return it (in the stamped addressed envelope provided). You may keep this information sheet and a copy of the signed consent form. Thank you very much for considering taking part in our research. Please discuss this information with your family, friends or GP if you wish. Local investigator: Name and address of local investigator: If you would like to obtain independent advice about this research you may contact: Name and address of local independent advisor: CancerBACUP are happy to be named as independent advisors: Tel , Mon – Fri, 9am – 7pm TRAPEZE Research Trial Of Treatments For Patients With Bony Metastatic Cancer Of The Prostate Patient Information Form Your Oncologist has explained to you that your prostate cancer is no longer responding to hormonal treatment. We would like to invite you to take part in a research trial to treat you with chemotherapy. Before you decide whether to take part it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with friends, relatives and your GP if you wish. Ask us if there is anything that is not clear or if you would like more information. Take time to decide whether or not you wish to take part. Further information and a summary of the principles of clinical trials can be found on the Cancer Research UK’s patient website (www.cancerhelp.org.uk) together with information about this trial. Purpose of the trial It is believed that chemotherapy may be beneficial in treating your prostate cancer. Chemotherapy is currently a standard treatment for prostate cancer that has spread to the bone. The main aim of this trial is test the effects of combining two further known treatments for prostate cancer at different time points, with chemotherapy. The three treatments involved in this trial are described below: - Docetaxel is a chemotherapy drug and is approved in the UK for the treatment of advanced breast and lung cancer. Docetaxel has been approved for use within clinical trials for the treatment of prostate cancer. Recently published studies (including an international prostate cancer clinical trial called TAX-327) demonstrate that docetaxel improves symptom control and survival times. - Zoledronic acid is a bone strengthening agent approved in the UK for treating cancer affecting the bone. - Strontium-89 is a type of radiotherapy (given by an injection), which is also approved in the UK for treating cancer affecting the bone. Early studies show that it may provide additional pain relief when combined with chemotherapy and may improve your condition. The aim of the trial is to assess how effective and safe zoledronic acid or strontium-89 is in treating your disease when given in combination with chemotherapy. We aim to recruit 618 evaluable patients with cancer no longer responding to hormone treatment to take part in this trial. The trial will be open to recruitment for up to 5 years. A patient enrolled onto this trial will be expected to visit the hospital every 3 weeks for chemotherapy treatment for 32 weeks. After this period patients will be expected to attend the hospital on a regular basis for a maximum follow up period of 2 years. This trial may also be known under the shorter title of ‘TRAPEZE’, named after the treatments involved which include docetaxel, radioisotope and zoledronic acid. Taking part in the trial It is up to you to decide whether or not to take part. If you do decide to take part you will be given this information sheet to keep and be asked to sign a consent form. The original consent form will be stored by your hospital and a copy of the consent form will be sent to the coordinating centre. If you decide to take part you are still free to withdraw at any time and without giving a reason. This will not affect the standard of care you receive. Description of the trial When we do not know which way of treating patients is best, we need to make comparisons. Everyone who agrees to take part in this trial will be put into a treatment group. The treatment you receive will be chosen by a process called randomisation; the treatment is randomly allocated by computer, which is like making a choice by tossing a coin. This means that you have an equal chance of being treated with one of the above treatments. You and your Oncologist will know which treatment you are receiving. The four treatment groups in this trial are: (a) Docetaxel (b) Docetaxel + zoledronic acid (c) Docetaxel + strontium-89 (d) Docetaxel + zoledronic acid + strontium-89. If you agree to take part, your Oncologist will perform a number of tests and examinations before, during and after the trial. You will also be asked to complete a number of questionnaires. These are summarised below: - General medical and physical examinations - Blood tests - X-rays, CT and bone scans – to measure your cancer response to treatment - DXA Scan (bone density scans) – to measure bone density - Pain diary - Quality of life questionnaires Docetaxel, zoledronic acid and strontium-89 are given by a drip into a vein in your arm. This is called an infusion. You will receive one of the following treatments: (a) Docetaxel 75 mg/m2 as a one hour intravenous infusion every 3 weeks for a maximum of 10 cycles. (b) Docetaxel as a one hour intravenous infusion every 3 weeks for a maximum of 10 cycles with zoledronic acid every 3 weeks. Zoledronic acid will then continue alone every 4 weeks until you or your Oncologist wishes to discontinue it. (c) Docetaxel as a one hour intravenous infusion every 3 weeks for a maximum of 10 cycles and one treatment of strontium-89 given 28 days after the sixth dose of docetaxel as a short intravenous injection. Cycles 7–10 will then follow after a 28 day recovery period. (d) Docetaxel as a 1 hour intravenous infusion every 3 weeks for a maximum of 10 cycles, followed by one treatment of strontium-89 given 28 days after the sixth dose of docetaxel as a short intravenous injection. Cycles 7–10 will then follow after a 28 day recovery period. Zoledronic acid will be given every 3 weeks throughout the treatment, and will then continue alone every 4 weeks until you or your Oncologist wishes to discontinue it. You may receive less than 10 cycles of docetaxel chemotherapy cycles. The exact number of cycles that you will receive will be determined by your Oncologist after consultation with you. As part of your main treatment you will also be given steroid tablets (prednisolone) to take during your course of treatment with docetaxel. In addition, you will receive extra steroid tablets (dexamethasone) for a few days around each infusion of chemotherapy to decrease the potential side effects of docetaxel (allergic reactions and fluid retention). You will be required to visit the hospital every 3 weeks until the end of therapy. The duration of treatment will be approximately 35 weeks. After the end of treatment your Oncologist will see you monthly for 3 months and then every 3 months in order to assess the status of your disease. The flow chart below explains the visits you will make to the hospital and at which time. Restrictions It is important that you inform your Oncologist of any changes in your health, whether or not you think it is due to the treatment. You should also tell your Oncologist of any changes to your medicines, either those prescribed by your GP or those you buy at the chemist. Other treatments available Your Oncologist will discuss the different treatment options available to treat your disease. TABLE Potential side effects and risks As with all medicines of this type there may be some unwanted side effects. You should discuss these with your Oncologist. The more common side effects are listed below; there may also be other side effects that we cannot predict. Other medicines will be given to make side effects less serious and less uncomfortable. With docetaxel you may experience nausea and/or vomiting, mouth irritation, diarrhoea, fatigue, a pins and needles sensation in your hands or feet, hair loss, changes in your skin and nails, muscular pain, decrease in blood cell counts, infection, and swelling due to fluid retention. Your blood pressure may also fall while the drug is being given, and this will be checked carefully. The infusion of docetaxel may cause temporary local irritation and bruises if it is given into a small vein. All these side effects have been experienced by some patients during previous studies and most of them are reversible. (The items underlined may not be reversible). With docetaxel + zoledronic acid you may experience the same effects as stated for docetaxel above with a rise in temperature, and flu like symptoms, consisting of fever and bone pain due to the zoledronic acid. Zoledronic acid may also affect your kidney function. Blood samples will be taken prior to zoledronic acid infusion at every trial visit to check that your kidney function has not been affected. Uncommonly, zoledronic acid can cause breakdown (osteonecrosis) of the jaw. This is associated with long term use of zoledronic acid (usually over 24 months) particularly in patients who have dental disease. Zoledronic acid should be discontinued if you need a tooth extraction. With docetaxel + zoledronic acid + strontium-89 you may experience the same side effects as stated above for docetaxel and zoledronic acid. The addition of strontium-89 to docetaxel and zoledronic acid may cause some bone pain lasting 36 to 72 hours following injection. This can usually be controlled by analgesics (pain killers). Strontium-89 can also affect your blood counts following injection; these will be monitored very closely with regular blood tests. With docetaxel + strontium-89 the addition of strontium-89 to docetaxel may cause some bone pain lasting 36 to 72 hours following injection. This can usually be controlled by analgesics (pain killers). Strontium-89 can also affect your blood counts following injection; these will be monitored very closely with regular blood tests. As with any chemotherapy it is possible that your treatment could cause problems to an unborn child. You must take full contraceptive precautions if there is any chance of you fathering a child during and for at least 2 months after the treatment. If you have a fever or bruising after receiving either of the drug combinations, it is important that you contact your Oncologist immediately. If you have a fever your Oncologist will perform some blood tests and may prescribe antibiotics. For more information about risks and side effects, ask your Oncologist. You may require one extra bone scan more than you would if you were not taking part in the trial. You may require one additional CT scan and will receive two additional bone density scans (DXA scans) more than you would receive if you were not taking part in the trial. Any potential health risk associated with these or any of the above scans is considered to be low for a patient with your medical condition. The radioactive strontium is intended to give a very high radiation dose to any parts of your bones that are involved in your cancer. The rest of your body gets a lower radiation dose and your Oncologist will explain possible side effects with you. Any potential health risk associated with the radiation is considered to be minimal for a patient with your medical condition. If you have private medical insurance you may wish to consult your medical insurers before agreeing to take part in the trial. This is to ensure that you participation will not affect your medical insurance cover. What happens when the research trial stops? At the end of the research trial, or should you withdraw, your Oncologist will assess your symptoms, discuss your options and prescribe appropriate treatment. Rarely companies sponsoring research studies may decide to stop the trial before it has finished. If this happens, your Oncologist will explain the reasons why and arrange appropriate care for you. Potential benefits The use of chemotherapy may result in a decrease in pain, improvement in the quality of life and a delay in the progression of your disease and improved survival times. This may be further improved by combining chemotherapy with zoledronic acid and/or strontium-89. The information we get from this trial may help us to treat other patients with cancer more effectively in future. Looking at blood serum samples In addition to your routine blood tests we would also like to take additional blood samples from you during your regular trial visits for additional analyses. We would like to monitor changes in protein levels in your blood during treatment to see if it can help us better predict treatment outcomes. Your participation in this part of the trial is optional and will not affect the treatment that you receive if you do not consent to providing additional blood samples for these additional tests and research. Looking at tissue samples As part of the clinical trial we would like to be allowed to have access to samples of your disease tissue, which were taken as part of your routine care and disease diagnoses. These samples will have been collected by your hospital and stored in paraffin fixed wax blocks. If you agree these samples will be collected and tested for the presence of a number of different chemicals known as biological markers by the School of Cancer Sciences at The University of and other collaborative centres. Your participation in this part of the trial is optional and will not affect the treatment that you receive if you do not consent to the research team having access to your stored tissue samples for additional research. Your rights regarding tissue/blood samples taken as part of this clinical trial The results of the analysis of your individual samples will not routinely be given to you unless it is of clinical significance and of importance to your health. You will not benefit financially if this research leads to the development of a new treatment or medical test. Any publications resulting from the collection of these tissue or blood samples will be made available to you, if requested. Please note that your participation in this part of the trial is optional and will not affect the treatment that you receive, if you do not consent to providing additional blood samples or for the research team to have access to your stored tissue samples detailed above. New information Sometimes during a trial new information becomes available about the treatment that is being studied. If this happens your Oncologist will tell you about it and discuss with you whether or not you want to continue. If you decide to withdraw your Oncologist will ensure the continuation of your care off trial. You may be asked, if you decide to continue in the trial, to sign a new consent from. Voluntary participation and discontinuation Your participation in this trial is voluntary. If you agree to take part and then change your mind and wish to withdraw, you may do so at any time without this decision affecting your future care. If you decide not to take part your Oncologist will discuss your future care with you. Your legal rights will not be affected by your giving consent to participate. At the end of the trial your Oncologist will discuss future treatment options. It is not anticipated that patients will be switched routinely to the alternative treatment in the trial. Confidentiality and patient rights If you agree to take part in the trial you will need to sign and date the Informed Consent Form attached. Your medical notes will need to be seen by authorised members of our research team so they can collect information needed for this research trial and also to check that it is correct. Your unique registration number will be used to make sure you cannot be identified outside the trial. All information collected about you during the course of the research will be treated as strictly confidential. The confidentiality of your medical records will be respected at all times. We will continue to contact your hospital in the future to find out how you are getting on. Ideally, we would like to do this for life, but patients often change address or can lose touch with their hospital. If this happens we would still like to be able to collect important basic details (e.g. full name, date of birth, hospital number and NHS number). The Office for National Statistics (ONS) keeps records that can easily provide the information we need, so we would like your permission to ask ONS to pass on this information to us. Any information received in this way remains confidential and is used only for the purposes of that particular trial. Please initial the consent form to indicate you are happy for us to do this. The information that will be collected from ONS will relate only to the status of your disease and current health. The ONS system will not be used to collect information such as your home address. With your consent your GP will be informed that you wish to take part in a clinical trial. Your GP may be asked to provide information from your records, which are required for the trial. Anonymised data from the trial may be provided to third parties (e.g. pharmaceutical companies or other academic institutions) for research, safety monitoring or licensing purposes. Your legal rights will not be affected by agreeing to take part in or withdrawing from the trial. You are free to withdraw from the trial at any time without giving a reason. If you decide to withdraw from the trial, this will not affect the standard of your routine care in any way. Your Oncologist will continue to treat you with the same level of care. The trial has been reviewed and approved by the Multicentre Research Ethics Committee, one of 13 national Research Ethics Committees. You will be informed of any significant new findings that occur during the trial as this may change your decision to continue. What if something goes wrong? You will be closely monitored both during and after therapy and any side effects will be treated as appropriate. If you are harmed by taking part in this research project, there are no special compensation arrangements. If you are harmed due to someone’s negligence, then you may have grounds for legal action but you may have to pay for legal advice. Regardless of this, if you wish to complain about any aspect of the way you have been approached or treated during the course of this trial, the normal National Health Service complaints mechanisms are available to you. Results of the trial At the end of the trial the information collected will be analysed and published in recognised medical journals. Your Oncologist will be informed of any publications and will be able to supply a copy of these publications to you on request. The identity of the patients who took part in the trial will remain confidential. Your Oncologist and trial nurse will also be informed of any results throughout the duration of the trial. Organisation and funding of the trial The research trial is being carried out by the Cancer Research UK, School of at . The research is funded by grants from the Health Technology Assessment (HTA) programme (a governmental funding body which funds clinical research), and pharmaceutical companies and . During your involvement in this trial no travel costs incurred by you or your family will be paid. Your Oncologist or any other members of staff that are involved in your treatment and care have not been paid for entering you into this clinical trial or receive payment for conducting the trial. Time to consider You should take at least 24 hours to decide if you wish to take part. Who should you contact with questions? You will be given a copy of this information sheet and the signed consent form to keep. If you have any problems or questions about this trial or your rights as a patient in clinical research you should contact: Oncologist Tel No Trial Nurse Tel No 24 hour contact number: The 24 hour contact number can be used out of working hours (9am – 5pm) in the event where you need you contact a hospital doctor immediately. We would like to thank you for reading the Patient Information Sheet and for considering taking part in this Clinical Trial. If you have any further questions please talk to the trial doctor before considering entry into this clinical trial. A study to find out the best form of follow up after surgery for bowel cancer Ethics committee number: Introduction You are being invited to take part in a research study. Before you decide whether to take part, it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with friends, relatives, and your GP if you wish. Ask us if there is anything that is not clear, or if you would like more information. Take time to decide whether or not you wish to take part. Thank you for reading this information sheet, which is yours to keep. Cancerbackup are an independent patient advisory group that you can contact if you would like to ask further questions about medical research or this trial. Cancerbackup produce a booklet titled “Understanding cancer research trials (clinical trials)” which discusses what trials are and why they are needed. This booklet may be ordered from their website www.cancerbackup.org.uk. Alternatively the United Kingdom Clinical Research Network is another organisation that you can contact if you have any questions about cancer trials (www.ukcrn.org.uk). Your cancer and its treatment Bowel cancer is a common condition. Doctors usually treat bowel cancer with surgery, chemotherapy, radiotherapy or a combination of these. Treatment is often very successful, but sometimes the cancer starts to grow again. If this happens you can have more treatment. Some patients are followed up after bowel cancer surgery, but some aren’t. Some patients have scans and blood tests to detect recurrent cancer. Others simply go to see their family doctor/general practitioner (GP) if they have symptoms. At the moment we don’t know which approach is best. If cancer comes back (recurs) it will eventually cause symptoms. Tests may pick this up earlier, but there is no evidence so far that this will help in the long term. Some patients find going backwards and forwards to the hospital stressful and inconvenient, and it is expensive. There are also very small risks from the radiation from scans, and there is more information about this below. On the other hand there may be some as yet unidentified benefit in picking up recurrent cancer before symptoms develop. Because we do not know what is best for you or for the NHS in general, we are performing a research study which is supported by the NHS. The research study The aim of this study is to find out the best follow up for patients who have had successful treatment for bowel cancer. We have asked you to take part in this study because we believe that it is unclear what follow up schedule would be best for you. We aim to recruit about 1000 patients in total. It is up to you to decide whether or not to take part. If you do decide to take part you will be given this information sheet to keep and asked to sign an informed consent form. If you decide to take part, you are still free to withdraw at any time without giving a reason. This will not affect the standard of care you receive. If you withdraw from the study, the study team may want to ask your nurse and /or hospital doctor for information about your treatment and care in the future. Because we do not know what form of follow up is best, we need to compare different types of follow up. Patients will be put (randomised) into one of 4 groups by a computer which has no information about you and so is entirely by chance – neither you nor your doctor will be able to decide which group you go into. Patients in the 4 groups will have different forms of follow up and then the information from the 4 groups will be compared. All patients will have a blood test before they go into the study, to measure a tumour marker called CEA. This blood test is often (but not always) part of routine care. All patients will be seen by their surgeon about 6 weeks after their operation or after their course of chemotherapy (if they have it). All patients will be given a booklet (called the Handbook for Patients) which has written information about symptoms to look out for, which may suggest that the cancer has come back. All patients will complete a simple quality of life questionnaire once a year. All patients will have a colonoscopy 5 years after they go into the study. You may have had a colonoscopy before your surgery - it involves passing a small telescope along the whole length of the large bowel and is done to make sure that your cancer has not returned and that there are no tumours or polyps growing in the bowel. Group 1 - if you have any of the symptoms listed in the Handbook for Patients, your GP will decide whether you need more tests or not, and may refer you back to your hospital doctor. You may have a body (CT) scan 12-18 months after you go into the study, depending on whether or not your hospital doctor feels this is appropriate. Group 2 - if you are randomised to Group 2, you will have the follow up described in Group 1. You will also have a blood test every 3 months for the first 2 years and then every 6 months for another 3 years. When the blood test is due, the team organising the study will write to you asking you to make an appointment at your GP’s surgery for the blood test. This blood test will measure CEA, as an increased level of CEA can sometimes mean that the cancer has started to grow again, but it can also become raised for other reasons. If your level of CEA rises, the study team will write to you again, asking you to make another appointment at your GP’s surgery, for a second blood test. If your CEA level remains high, your GP will refer you to the hospital for other tests. You may have a body (CT) scan 12-18 months after you go into the study, depending on whether or not your hospital doctor feels this is appropriate. Group 3 – if you are randomised to Group 3, you will have regular follow up at the hospital either by a doctor or a specialist nurse. You will have a body (CT) scan every 6 months for the first 2 years and then every year for 3 years. You will have a colonoscopy 2 years after your original operation. Group 4 – if you are randomised to Group 4, you will have blood tests based in the GP’s surgery (as for Group 2) and hospital follow up with regular CT scans (as for Group 3). You will also have a colonoscopy 2 years after your original operation. Group 4’s follow up is therefore a combination of the follow up in Groups 2 and 3. Additional information In addition to the study described above, we are also interested in other factors in the outcome of bowel cancer surgery, such as your genetic make up. We would therefore like your permission to keep a sample of your blood and cancer tissue in a “bank”, so we can do more research in the future. These samples will be stored in designated secure laboratories in your local hospital centre and in and following Medical Research Council (MRC) guidelines. The samples will be kept under the care of your doctor or researchers from the study team. Any future research will be done anonymously, but the result may be linked to other information on your case. It is possible to participate in the main study but not in this additional study, if you wish. Potential advantages and disadvantages of the treatment options Whichever follow up group you are in, you will be managed by a team of health professionals and you will be offered appropriate treatment if your cancer comes back. The more intensive follow up schedules may find any recurrent cancer at an earlier stage which may or may not be an advantage. They may also find other changes that are not cancer and which don’t need treatment. This may mean that you have more investigations than necessary and this can cause inconvenience and anxiety. There is also a small risk from the radiation from the body (CT) scans. A body scan uses X-rays and hence has a small radiation dose associated with it. Any abnormality shown by the scans will be followed up and this may involve further tests. The dose of radiation you receive from a single CT scan is equivalent to that which you would normally receive from the environment in 4½ years. Radiation may sometimes be associated with the development of cancer and it can be estimated that the risk of the CT scan schedule across the whole study is around 1 in 2000. For some patients there is no risk at all. For a small and younger group of patients completing all 7 scans, the risk may be estimated to be in the region of 1 in 300. Even this is extremely small compared to the risk that your own cancer may come back. Many hospitals use this number of scans routinely on their patients already. It is exactly this balance of risks that we are trying to evaluate. The less intensive schedules are much simpler and are associated with less anxiety and inconvenience. This may lead to any recurrence of the cancer being picked up at a later stage, but we are not sure if this makes any difference in the long term. Many bowel cancer units use these simpler schedules as routine. There are no lifestyle restrictions for this study, you should continue as normal. Depending on which group you are randomised to, you will be notified when a blood test or hospital appointment is due. We know that everyone experiences occasional digestive upsets such as indigestion or wind and these are perfectly normal. However if these symptoms persist for more than 2 weeks or if they worsen, you should contact your GP. If appropriate, your GP may then refer you to your hospital doctor. This applies to all patients, regardless of which group you are allocated to. Other information If you decide not to participate in this study you will still be given the best possible treatment. You will have the follow up that is standard practice at your hospital. During the course of any study it is possible that something may go wrong. Such events may not specifically be the fault of any of the doctors or nurses managing you. As all the treatment schedules given are conventional, there are no specific arrangements for compensation in this situation. Your right in law to claim compensation for injury where you can prove negligence is not affected. If you consent to take part in the study, your records may be inspected by doctors, nurses or other study staff associated with the study. Some of your details will be known to the coordinating team as they will need to contact you directly, e.g. to ask you to arrange blood tests, and to send you quality of life questionnaires. Your study details will be recorded on computers in (where the study is being coordinated), but will only be available to authorised members of the team. Ultimately the results of this study will be published in the medical literature. Any published information will remain anonymous, and your confidentiality will be safeguarded. In the future, the results may affect the treatment of patients with your condition. This study is being supported by the NHS Research and Development Health Technology Assessment (HTA) Programme, the main research arm of the NHS. The study has been reviewed by the Research Ethics Committee. If you agree to take part in the study you will be asked to complete an informed consent form and you will be given a copy of the informed consent form to keep. How to contact us For any problems related to the study, help is always available. Your local hospital contact is: Prof / Dr / Mr / Ms and they can be contacted on Tel: Help is also available 24 hours a day, 7 days a week via your usual GP services or via Tel, in addition to your normal emergency services. Thank you for considering taking part in this study. The ARTISTIC Trial You signed a consent form between 2001 and 2003 to participate in the ARTISTIC trial, a randomised trial of HPV (Human Papillomavirus) testing in primary cervical screening. HPV is a common virus which can affect the cervix. It is thought to be sexually transmitted. It does not produce any symptoms and can lie dormant for years, so there is no way of knowing how long it has been present in the cervix. Up to 70% of women who ore, or have ever been sexually active have had this infection at some time in their life, and in most cases it is cleared up by the immune system. It has been shown that if this virus infection persists, it can be associated with pre-cancerous changes in the cells of the cervix, resulting in an abnormal smear test result later on. HPV testing may identify abnormal cells not detected by the smear test, or it may indicate the need for another smear sooner than the normal 3-5 year interval for smears. We have now obtained additional funding from our sponsor, the Health Technology Assessment Programme, to enable us to extend the ARTISTIC trial until 2009. To enable us to access your screening results and HPV test your smear sample, we require your consent. What will I have to do if I want to remain in the study? Please sign the enclosed consent forms to say that you understand the trial, wish to participate and allow us to use the information collected – all information given will be treated confidentially. Return both consent forms to the Trial Office in the postage paid envelope, we will then send one to your GP practice and keep the other for our records. You will be reminded by letter when your next smear and HPV test are due and you can make an appointment for the test with your GP or Family Planning Clinic. Your next smear test will be taken in the normal way, using Liquid Based Cytology (LBC), but will also be tested for Human Papillomavirus. In order to see how effective the HPV test is we need to compare a group of women in whom the HPV result is known with a group of women in whom the HPV result is not known. You will keep the same trial number and remain in the same group (HPV result revealed or concealed) to which you were originally randomized. You will receive a result letter from the Trial Office as well as the Health Authority. Do I have to continue to take part? Continued participation in the trial is voluntary. If you decide not to participate you will still have your smear taken in exactly the same way. This will not affect your treatment. Furthermore, if you reconsent to participate in the trial but wish to withdraw at any time, then you are entirely free to do so. Smear takers will be provided with spare copies of the consent forms in case you have not already returned yours to the Trial Office. You can sign it when you attend your next smear, or you can let them know that you wish to opt out of the trial. What happens if I am in the group where the HPV result is revealed? You will be told both you HPV and smear result. If your smear is abnormal, you will be managed under current NHS guidelines, the same as if you were not participating in the study. If the smear is normal, but the HPV result is positive we will repeat the HPV test when your next smear is due. In many cases the infection clears up on its own. If it is still positive, you will be referred for a colposcopy examination of the cervix to detect any possible underlying abnormalities. N.B. This will replace the current arrangements whereby women who test HPV positive with a negative smear are recalled for an HPV only test after 12 months. What happens if I am in the group where the HPV test is not being revealed? One quarter of the women who take part will not be told of their HPV result. If you are in the concealed arm of the trial, management of any abnormal results will remain exactly as it is under routine NHS Cancer Screening Programme guidelines. You will be notified of your smear result and informed of any follow up where required. Are there any benefits in participating in this study? By continuing to take part in this trial you will be assisting in providing evidence as to whether or not HPV testing in the future might mean that those women with normal smears and negative HPV results would only need to attend for a smear say every 10 years. Before any changes can be made to the programme studies such as this one need to be carried out. Finally, THANK YOU for your participation in the ARTISTIC trial so far, it has been very helpful. We hope that you will continue to participate, and if you have any queries please don’t hesitate to get in touch. For further information please contact: – Trial Coordinator – Trial Secretary OPTIMA prelim Optimal Personalised Treatment of early breast cancer using Multi parameter Analysis - preliminary study Patient Information Sheet We would like to invite you to take part in a research study called Optima prelim. This sheet explains why the research is being done and what it will mean for you. Please take time to read it carefully and feel free to talk it over with friends, your family and your GP. Part 1 explains what will happen if you take part. Part 2 gives you more information about the study. A member of the research team will go through this with you. Please ask us if there is anything that is not clear or you would like more information. Please take as much time as you need to decide whether or not you wish to take part. Your participation in this research is entirely voluntary. If you decide not to take part, your decision will be respected and your medical care will not be affected in any way. Part 1 What is the purpose of this study? Chemotherapy and hormone treatment are standard treatment for women with your type of breast cancer. This is to reduce the chances of the cancer coming back. Chemotherapy is given as an injection usually every three weeks over a few months. Hormone therapy is a daily tablet such as tamoxifen for five years. Younger women may also have a monthly injection to stop menstrual periods. Recent research indicates that some women with your type of breast cancer may not benefit from chemotherapy, and would do just as well with hormone treatment only. The decision to give chemotherapy, or not, is currently made using simple measurements such as the size of the tumour and the number of lymph glands affected. These methods are not as good as we would like, and means that sometimes patients are given chemotherapy unnecessarily. Tests have been developed to try to predict which women could avoid chemotherapy. The tests are carried out on a sample of the tumour removed by the surgeon. There are several existing tests and new ones in development. The best known of these tests is called Oncotype DX. The aim of this study is to investigate whether a personalised decision about chemotherapy using tests like Oncotype DX can be made safely and effectively. Initially we want to include 300 patients in the study from about 30 hospitals. If it works well, we want to extend this to a much larger study throughout the UK. Can you explain the Oncotype DX test? In the past ten years, there has been a lot of research into new ways to look at breast cancer. Tests have been developed that make lots of measurements in tumour cells. These tests are sometimes called multi parameter assays. They look at the genes in the breast cancer cells. A number of these new tests are now available. They promise to change the treatment of breast cancer. The first of these tests was Oncotype DX. It was developed by a company in the United States. It measures 21 genes in the tumour cells. The Oncotype DX test was first carried out on stored samples from patients treated many years ago. The results suggested that Oncotype DX could show whether or not chemotherapy is needed. The Oncotype DX test is done in a central laboratory. The test is widely used in the United States. The National Institute for Health and Care Excellence has approved its use for some NHS patients with breast cancer that has not spread to lymph glands. Your doctor has discussed OPTIMA with you because the test is not available to you through the NHS. More research is needed to help the NHS decide how best to use tests like Oncotype DX, especially for patients with cancers that have spread to lymph glands. You may find the Oncotype DX website helpful for further information about the Oncotype DX test (aimed at American patients): http://www.oncotvpedx.com/en-US/Breast.aspx What will happen after joining OPTIMA prelim? If you decide you would like to take part in this study, you will need to sign a consent form. Your medical team will be asked to send some information about you to the OPTIMA Trial Office at the Clinical Trials Unit, . Your doctor will be asked to send a sample of your tumour to our central laboratory in London. This is so we can check that you are suitable to join the study. OPTIMA prelim is a 'randomised controlled' trial. This means that doctors are not sure which of two treatment options would be best. The best way to compare the two treatment options is to use each of them in two similar groups of patients. This allows us to be sure that if there is a difference between the two groups, it is because of the treatment option, and not because the groups are different from each other in some way. Everyone who agrees to take part in this study will be allocated to one of two groups of patients. The only way to make sure that the groups of patients are as similar as possible is to have your treatment option decided upon by chance: a process called randomisation. Randomisation will be done by the OPTIMA Trial Office using a computer. This process ensures that the two options are compared fully and fairly. You will have an equal chance of your treatment being assigned according to one of two options. Option 1: A sample of your tumour tissue will be sent to our laboratory where it will be checked and stored. After 3 to 4 weeks, you will start chemotherapy followed by hormone treatment. This is the current standard treatment, and will not be decided according to the Oncotype DX test. All patients will receive both chemotherapy and hormone treatment. Option 2: A sample of your tumour tissue will be sent to our laboratory where it will be checked. It will then be sent on to a second laboratory where the Oncotype DX test will be performed. The test result will come back in 3 to 4 weeks. The result will indicate whether you should benefit from chemotherapy or not. You will then receive hormone treatment, with or without chemotherapy. Most patients in Option 2 will not need chemotherapy and will just have hormone therapy. DIAGRAM Your doctor will discuss chemotherapy with you. If you do receive chemotherapy we will not tell you or your doctor whether you are in Option 1 or Option 2. Therefore you will not know if your treatment has been decided using an Oncotype DX test. You may be having chemotherapy because you are in Option 1 (standard treatment), or one of those in Option 2 recommended to have chemotherapy. We are doing this because we do not want either you or your doctor to be influenced by the test result. It will take between 3 and 4 weeks to decide your treatment if you join OPTIMA prelim. We know that this length of time is safe. We have asked your doctor to discuss chemotherapy with you now. Then you can start treatment as soon as you get the decision. All patients will receive hormone therapy. Your hormone treatment is a daily tablet. It is the usual treatment used in the NHS and is normally for 5 years. If you have not had your menopause we will ask you to have monthly injections for at least 3 years. This is to stop your menstrual periods. We will do this even if you have chemotherapy and your periods stop or if your doctor is not sure whether you have had your menopause. These injections are not widely used as part of usual NHS treatment but we believe they improve hormone treatment. The reason for giving the injections is to make sure that everyone within OPTIMA study receives the same hormone treatment. During and after your treatment, you will continue to be followed up by your doctor to assess your progress. This will be every three months during the first year and once a year after that up to 10 years. Your research doctor or nurse may contact you by telephone instead of asking you to come to the hospital. We will ask your doctors how you are, including your GP. We would also like to collect information about you from central NHS databases. We want to find out whether tests such as Oncotype DX are acceptable to patients and their doctors. Researchers in our team will ask some patients and their doctors what they like and dislike about OPTIMA prelim. We may change the way we explain the study to patients in the future. This is why we would also like to talk to some women who decide not to join OPTIMA. Whether you decide to enter the study or not, you may be asked if you would agree to being interviewed by one of our researchers to discuss reasons for your decision. However, you are under no obligation to do so. Why have I been chosen? We are asking women with breast cancer who would usually receive both chemotherapy and hormone treatment to take part. This means women with cancers 3 centimetres or larger, or with cancer which has spread to the lymph glands. The Oncotype DX test has been used for some women in other countries with good results but we want to study the test in more women before bringing it into routine use in the NHS. The test is mainly used for tumours which have not spread to lymph glands. We especially want to study women who usually get chemotherapy because the cancer has spread to lymph glands or who have larger tumours. The information we have suggests that the test works equally well for such women but we need to prove this. Do I have to take part? No. It is entirely up to you to decide whether or not to take part. If you do, you will be asked to sign a Consent Form. If you change your mind, you can withdraw at any time, without giving a reason. This Information Sheet is yours to keep whatever you decide. Your care will not be affected in any way if you do not enter the study. What are the side effects of any treatment received when taking part? With any cancer treatment, some side effects may occur. Your doctor will discuss these with you. If you join the study and have chemotherapy, the side effects would be the same as if you were treated outside the study. This is because we expect you will be offered the same chemotherapy outside the study. You may experience symptoms of the menopause if you have injections to stop your menstrual periods. These symptoms will sometimes go away when you stop the injections. It depends on how old you are. Many women will get these symptoms anyway if they have chemotherapy. If your periods stop early, you are more likely to develop osteoporosis as you get older. This is also true for women whose periods stop because of chemotherapy. The doctors and nurses looking after you are very aware of this risk. They will monitor your bone health carefully. If signs of bone thinning develop, this can be treated at an early stage. All other treatment is the same whether you are in the trial or not. What are the possible benefits of taking part? The Oncotype DX test may show that you do not need chemotherapy. This means that you would avoid any chemotherapy side effects and start hormone treatment straight away. The test could also show that you do need chemotherapy. If you are given chemotherapy as well as hormone therapy, you will be receiving the current standard treatment. We are doing this study to work out who can safely avoid chemotherapy and be treated with just hormone treatment, and those who need chemotherapy. We believe that using tests to help make decisions about chemotherapy treatment will become normal in the future. Everyone in this trial will be closely followed. You will have a research nurse or researcher to help monitor you. What are the potential disadvantages of taking part? We are still in the early years of learning the best way to use these tests. So far, the Oncotype DX test has mainly been used for tumours which have not spread to lymph glands. The test might not work so well for patients with larger tumours or involved lymph glands. We do not believe this to be the case. However we might find out in the future that chemotherapy could have offered additional benefit to a few women receiving hormone treatment alone. If you join the study, it will take 3 to 4 weeks to complete the additional tests on your original tissue sample. There is good evidence to show that this time period does not increase the risk for women with your form of breast cancer. You will be asked to complete questionnaires, which will take some extra time. As indicated above, we are doing this study to work out who can benefit most from chemotherapy, in addition to hormone treatment. What happens if the research study stops? The study might end before your treatment is complete. This is unlikely. If it happened, you would get the normal treatment for breast cancer. However, you will be able to discuss this with your doctor. Your progress will be followed in the same way. If you would like further information, please ask: • Principal Investigator (Name/contact.no.) • Research Nurse/coordinator (Name/contact.no.) If you would like some independent advice, you can contact either of the following: Suggestions: Breast clinical nurse specialist + contact number Macmillan Cancer Support a useful source for further information. They can provide information on breast cancer, its treatment, and clinical trials. You can find this at http://www.macmillan.org.uk Alternatively, you can call them on (freephone), and they will send you information leaflets in the post free of charge. Other contacts you may find helpful are: Breast Cancer Care: Tel: (freephone) Web: http://www.breastcancercare.org.uk Cancer Research UK Tel: (freephone) Web: http:www.cancerhelp.org.uk This completes Part 1 of the Information Sheet. If you think you might join the study, please take time to read Part 2 before making your decision. Part 2 What if new information becomes available? We may get new information from other research that is important for OPTIMA prelim. We might want to change the study as a result. If this happens, your doctor will discuss this with you. You will decide whether or not to continue. If you decide not to continue, your doctor will arrange for your future care. If you do continue, you may be asked to read a new Information Sheet. You might also be asked to sign a new Consent Form. What happens if I don't want to carry on with the study? If you do not want to carry on, we will only use details that we already have. You can ask for all information about you to be removed. We will not use any of your personal information. You may be asked to sign an extra form to confirm your wishes. What if there is a problem? If you wish to complain, or have any concerns about any aspect of the way you have been approached or treated by members of staff you may have experienced due to your participation in the research, the National Health Service or complaints mechanisms are available to you. Please ask your research doctor if you would like more information on this. In the unlikely event that you are harmed by taking part in this study, compensation may be available. If you suspect that the harm is the result of the Sponsor's or the hospital's negligence then you may be able to claim compensation. After discussing with your research doctor, please make the claim in writing to Dr who is the Chief Investigator for the research and is based at xxxxx. The Chief Investigator will then pass the claim to the Sponsor's Insurers, via the Sponsor's office. You may have to bear the costs of the legal action initially, and you should consult a lawyer about this. Will my taking part in this study be kept confidential? All personal information collected for OPTIMA is strictly confidential and is covered under the Data Protection Act 1998. We will ask your doctor and nurse to provide information about you and your disease to the OPTIMA Trial Office at Clinical Trials Unit, . This will be entered on to a secure database. Only authorised personnel at the Trial Office can access this. When you join OPTIMA we will give you a unique study number. Information about you that leaves the hospital will refer to you by your study number, and by your initials only. We will not use your name. With your permission, we would like the OPTIMA Trial Office to hold a record of your personal details. This includes your date of birth, name and address. We may use this to send you questionnaires and other information by post. We would also like to contact the Office of National Statistics about you as they collect long term information about all NHS patients. Your doctor will usually inform other doctors and nurses who look after you that you are in OPTIMA prelim. This includes your GP. You must inform your doctor if you do not wish for this to happen. If you choose to withdraw from the study we would still like to collect information about your treatment. This will be useful to our research. If you have any objection to this please let your doctor know if you do decide to leave the study. What will happen to any samples I give? We plan to compare the Oncotype DX test to other new tests. Many research labs have been working on this over the past few years. As a result several tests are now available. Some of them are much simpler and less expensive than the Oncotype DX test. We will be relying on Oncotype DX for your treatment decision. We would like to see how other tests would have performed. We are asking your permission to use these other tests as well, although we will not be able to tell you the results. When we have analysed the data at the end of OPTIMA prelim, we may choose to use a different test in the main study. All samples will be stored with your study number, initials and date of birth, and will not have your name or other details. They will be kept in a secure place by the Chief Investigator or his deputies. Information given to any researcher will not include your personal details. Some of our research may take place in laboratories in other countries. It is possible that some of the research results from this trial might be used by companies. If this happens, neither you nor your doctors will benefit financially. None of the doctors or scientists involved in this trial has any financial interest in it. We may also want to use your samples for other research in the future. We ask if you will give us the remainder of your tumour sample for this. It would be returned to your hospital if you or your doctor ever needed it. Will any genetic tests be done? We may want to do genetic tests on your cancer sample in the future. The genetic tests are performed on the cancer cells, not on you. They do not predict risk of inheritance. They will not affect insurance. The tests are usually those that help us understand how cancers develop and how we can treat them. You can refuse permission to have your samples used in this way at any time. It will not affect your part in this study. Data from your samples might be shared to help other scientists. There is a very small risk that a skilled scientist could work out that the sample came from you. We think it is highly unlikely that this would happen. Scientists have talked about it so we are including it in this information sheet. What will happen to the results of the research study? The results of the research will be published in scientific journals. We expect that some results will be ready for publication in about 2 years. The results of the main OPTIMA study will take more than five years before they are ready. You will not be identified in any report of this study. If you wish, you can ask your doctor to send you a copy of the report when it is published. Who is organising and funding the research? This research is run by . Clinical Trials Unit is supporting . is Sponsor for the research. The study is funded by the National Institute for Health Research (NIHR). Their Health Technology Assessment Programme is paying for it. Who has reviewed the study? The study has been approved by the Department of Health's National Institute for Health Research and a UK National Research Ethics Committee. It has also been approved by patient and carer representatives. What to do if you wish to take part in the study? If you wish to join this study you will be asked to sign a Consent Form. There will be further discussion with the researcher before you sign it. You will also be given this Information Sheet and a signed Consent Form. If you decide not to take part, your care will not be affected in any way. Thank you for taking time to read this Information Sheet. Strategies to Increase Cervical Screening Uptake at First Invitation (STRATEGIC) Patient Information Sheet You have been invited to take part in a research study which aims to find ways of improving cervical screening uptake amongst women receiving their first invitation from the NHS Cervical Screening Programme. This information sheet will describe what will be required of you if you agree to participate. Why have I been invited? You have been invited to take part because you are due to attend for your first cervical screening test. It is your choice whether you wish to contact the trained nurse. What is the purpose of a trained nurse? The trained nurse has been trained to answer any questions about cervical screening and discuss what options are available to you. We are offering you flexible ways of asking any personal or practical questions to obtain factual information. What will I have to do? If you would like to discuss cervical screening with the trained nurse please use the contact details overleaf. After you contact the trained nurse we will send you a consent form to complete and a postage paid return envelope. What will happen to me if I take part? We would like your permission to check the national screening database to see whether you attend for cervical screening after having a discussion with the trained nurse. In order to do this, we would also ask that we could store your personal details (name, date of birth and address) on a secure trial database. You are free to withdraw your consent at any finite and your further medical care will not be affected. What are the alternatives? If you do not wish to contact the trained nurse, we recommend that you attend for your cervical screening test at either your GP or sexual health clinic. What will happen to the results of this study? The results of the study will be used to measure the effectiveness of offering women our research interventions on the uptake of cervical screening. Who is organising and funding this research? The study is being organised by the who have received funding from the NHS National Institute for Health Research Health Technology Assessment Programme (www.hta.ac.uk). Who has reviewed the study? All research in the NHS is reviewed by an independent group: called a Research Ethics Committee to protect your interests. The study has been reviewed and given a favourable opinion by the Research Ethics Committee. Where can I find further information? If you have any additional questions please contact our trained nurse with the contact details overleaf. For more information on cervical screening please contact your GP or visit www.cancerscreening.nhs.uk/cervical (Barrett’s Oesophagus Surveillance Study) A randomised controlled trial of surveillance for patients with Barrett’s oesophagus You are being invited to take part in a research study. Before you decide it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with others if you wish, for example family and friends or your family doctor (GP). Ask us if there is anything that is not clear or if you would like more information. Take time to decide whether or not you wish to take part. Thank you for reading this. What is the purpose of the study? Barrett’s oesophagus is a change in the lower gullet (oesophagus) brought about by the frequent reflux of gastric juice from the stomach into the oesophagus. The lining of the lower oesophagus has changed to become like the lining of the small intestine. You have had an endoscopy that has diagnosed Barrett’s oesophagus and for most people it is not a life threatening condition but it can cause troublesome indigestion like symptoms. It occurs in about 1% of the adult population and can lead to oesophageal cancer in some people. Once you have Barrett’s oesophagus the life time risk of it developing into cancer is about 5 10%. The risk of developing cancer from Barrett’s oesophagus has led to the development of guidelines that recommend that patients with Barrett’s oesophagus have an endoscopy every 2 3 years to detect cancer early when the benefit of treatment is much more favourable. The use of regular endoscopy to review the progress of Barrett’s oesophagus commonly causes minor complications in between 1 10% of patients. These include discomfort, pain, breathing difficulties which should settle down in a few days. It is also inconvenient for patients and causes anxiety. In very rarely can result in perforation of the gullet (oesophagus) or death. The guidelines for managing Barrett’s oesophagus acknowledge that the information to support endoscopy surveillance is relatively weak and the value of regular endoscopy is still subject to considerable debate. The most appropriate method of establishing whether regular endoscopy reduces the number of people dying from cancer of the gullet (oesophageal adenocarcinoma) is through randomised controlled trials. At the moment there are no trials published or being conducted in this area. We are conducting this study because we are not sure whether regular endoscopy, with the risks described, is beneficial to patients with Barrett’s oesophagus or whether using patient’s symptoms could be just as good. It should be important to find out if regular endoscopy benefits patients before routinely offering it to patients. Why have I been invited? As a patient with Barrett’s oesophagus you have been invited because you have been diagnosed with Barrett’s oesophagus. A total of 2,500 Barrett’s patients will be recruited from across the UK during a 2 year period and followed up for a further 10 years. What will happen to me if I take part? Since we do not know the best way of managing patients with Barrett’s oesophagus we need to make comparisons. If you agree to go into the study you will be randomly allocated to either have an endoscopy every 2 years and a questionnaire once a year asking about your condition or to just receive a questionnaire once a year. The groups are selected by a computer, i.e. allocation is by chance, like tossing a coin. Patients in each group then have different management and these are compared. The Trial is much fairer if people are assigned to groups by chance, not by choice. You will also be registered with the Office of National Statistics (ONS) so that in the event of your death or diagnosis with cancer, during the ten year study the trials centre will be automatically notified, even if you have moved away and we haven’t got your address. We will send the biopsy samples from a randomly selected group of patients to a second laboratory so that the findings from laboratories can be compared. If your samples are chosen, the samples will be sent to the second laboratory with only a number to identify them. They will not have your name on them. You will not be made aware of the results unless your research doctor thinks that they are important to your future care. What do I have to do? Everyone taking part in the study will receive a questionnaire each year for ten years. The questionnaire will ask you about your current symptoms and general wellbeing. This will be sent to you by the BOSS study office. Any additional information we might need about your condition will be provided by your local hospital doctor. If you are randomly chosen to have an endoscopy every 2 years, this will be arranged by your local hospital, in the same way that your recent test was arranged. You will be able to claim travel expenses to attend for your endoscopy if your hospital does not normally carry out regular endoscopy checks on patients with Barrett’s oesophagus. This is because this visit would be considered to be an extra one that would not have taken place if you were not in the research study. If you want to claim, please ask your research doctor or nurse how to go about it. Regardless of which group you are in you can still be referred back to the hospital consultant for further tests and investigations if your GP considers it to be necessary. What are the possible benefits of taking part? We cannot promise that taking part will benefit you. However, the information we get from this study may help us to treat future patients with Barrett’s oesophagus more effectively and given the long term nature of the condition this might include you. What if I don’t want to take part? Your hospital doctor will discuss the most appropriate way of monitoring your Barrett’s oesophagus and treating the symptoms. What if new information becomes available? Sometimes during the course of a research project, new information becomes available about what is being studied. If this happens, your research doctor will tell you about it and discuss with you whether you want to continue in the study. If you decide to withdraw your research doctor will make arrangements for your care to continue. If you decide to continue in the study you will be asked to sign an updated consent form. Also, on receiving new information your research doctor might consider it to be in your best interests to withdraw you from the study. He/she will explain the reasons and arrange for your care to continue. What happens when the research study stops? If the project were to stop early then your care will return to the best available at that time. At the end of the project we will look at the findings and then make recommendations about what changes in care there should be. What if something goes wrong? We believe that this study is basically safe and do not expect you to suffer any harm or injury because of your participation in it. The NHS indemnity scheme will compensate you if you are harmed due to someone’s negligence but there is no compensation scheme for harm that was not caused by negligence. Will my taking part in this study be kept confidential? If you consent to take part in the research any of your medical records may be inspected by the trials centre for purposes of analysing the results. They may also be looked at by people from the regulatory authorities to check that the study is being carried out correctly. Your name, however, will not be disclosed outside the hospital. If you agree your general practitioner will be informed of your participation in the trial. What will happen to the results of the research study? The results of the research will be published in one or more papers in medical journals so that they are available to all doctors. At the end of the study you can request a copy of the results from your GP. No individual patients will be identified in any publication or report. Who is organising and funding the research? The trial has been organised by Prof , a surgeon specialising in Barrett’s oesophagus at . The study is funded by the NHS Health Technology Assessment Programme. The doctor conducting the research is not paid for including patients in the study and for looking after them. These costs are borne by the NHS. Do I have to take part? No, it is up to you to decide whether or not to take part. If you do decide to take part you will be given this information sheet to keep and be asked to sign a consent form. Once you have decided to take part you are still free to withdraw at any time and without giving a reason. Your decision to withdraw at any time, or a decision not to take part, will not affect the standard of care you receive. What if I have any further questions? Please contact the doctor who is conducting the study in your local hospital: Thank you again for considering taking part in this study. If you decide to go ahead please sign and date the accompanying consent form. You should retain a copy of this information sheet and the signed consent form. Virtual colonoscopy compared with conventional colonoscopy for diagnosis of bowel disease We are inviting you to take part in a research study. Before you decide, you need to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with others if you wish. Ask us if there is anything that is not clear or if you would like more information. What is the purpose of the study? We want to compare the effectiveness and convenience to you of two procedures that are used to diagnose bowel disease. The method that we have been using up to now at St Marks Hospital is called colonoscopy. Colonoscopy involves inserting a tube into the bowel so that the doctor can see inside in order to see any abnormalities. Recently, a new type of x-ray CT scan called ‘virtual colonoscopy’ has been developed that is as good at diagnosing disease and may be more convenient for the patient. A few NHS hospitals are already offering virtual colonoscopy to patients instead of conventional colonoscopy. The NHS has sponsored this research project in order to find out if this test should replace conventional colonoscopy. The research is being carried out in 15 NHS hospitals and will involve 2,000 patients who will be allocated randomly to receive either conventional colonoscopy or the virtual colonoscopy. This way we will be able to find out which works best both for doctors and patients. Why have I been chosen to take part in the study? You have been chosen because your doctor has referred you for a bowel examination to find out the reason for your symptoms. Do I have to take part? No. It is up to you to decide whether or not to take part in this research. If you decide not to, you will get conventional colonoscopy. If you do decide to take part then there will be a random decision to give you either conventional colonoscopy or the virtual colonoscopy. We recommend that you keep this information sheet. You can withdraw at any time, or decide not to take part, which will not affect the usual standard of care you receive. What will happen to me if I take part? One third of our patients will be given the virtual colonoscopy and two thirds will have the conventional colonoscopy, which is the same test you would have if you did not take part in this research You will therefore have a one in three chance of having a virtual colonoscopy. The test you will be offered will be decided by a computer, like in a lottery – you cannot decide what test you will have. Both tests involve taking laxative medicines the day before in order to clear the bowel out. Both tests are performed with you lying down and both involve an injection to relax your bowel. - For conventional colonoscopy a doctor places the colonoscope tube inside your back passage and looks around while moving it along the bowel. You may be given a sedative injection to make you a little drowsy. The whole examination usually takes about 20 minutes but can take longer. If you have been given a sedative you will need to wait for this to wear off before you can go. This usually takes about an hour. - During virtual colonoscopy a smaller tube is placed just inside your back passage. Some carbon dioxide is introduced through this in order to inflate the bowel. One difference for you is that no sedative is given. Two x-ray CT scans are then taken, one with you lying on your tummy and one with you lying on your back. Each CT scan takes about 20 seconds and you will be asked to hold your breath during this. The whole examination takes about 20 minutes. You will then be free to go. Whichever test you have, you will need to come back for your outpatient appointment with your doctor to get the results. Whichever test you have, the results will be handled by your doctor exactly as normal and will also be transferred to a research office at . At various stages up to three months after, we will ask your opinion of the test that you received. We will ask you to fill in some short questionnaires that we will send to you along with a stamped addressed envelope for return. What are the side effects of taking part? Neither procedure has any common serious side effects. However, very rarely, patients having conventional colonoscopy may become over drowsy with the sedative. Even more rarely, the bowel can be torn by the colonoscope tube. This is very uncommon. What are the possible disadvantages and risks? The virtual colonoscopy use x-rays but is well within official safe limits for medical procedures. The virtual colonoscopy also looks at organs outside the bowel. This has possible advantages (e.g. disease elsewhere may be detected earlier) and disadvantages (e.g. you may need further tests if the virtual colonoscopy shows something elsewhere that you doctor thinks is important). What are the benefits? Both tests are well established and you will get the best possible care whichever test you have. What if new information becomes available? If the virtual colonoscopy test comes out as being better for diagnosis, or more convenient for patients, then we will be able to switch to this test for future investigations. What if something goes wrong? If taking part in this research project harms you then usual NHS compensation arrangements apply. If you are harmed due to someone’s negligence then you may have grounds for legal action. If you wish to complain about any aspect of the way you have been approached or treated during the course of this study, then we would like to hear from you and would ask you to contact us directly. Also, the normal National Health Service (NHS) complaints mechanisms are available to you. Will my taking part in this study be kept confidential? All information about you collected during the course of the research will be kept strictly confidential and available only to your hospital doctor and the study researchers. During the trial period, your contact details and the results for your investigations will be held on a secure database at . Any information about you that leaves your hospital will comply with the Data Protection Act and only authorised study researchers will have access to this information. Your GP will be notified of your participation in the trial. What will happen to the results of the research study? The results following completion of the study will be published in medical journals. Further information can be obtained from . You will not be identified from the publication. The results of this research will be used by the NHS to decide whether to use the virtual colonoscopy test instead of conventional colonoscopy. Who is organising the research? This research is being organised by , a consultant radiologist at , in association with other doctors across the United Kingdom, including many working at Cancer Research UK. The research is happening at 15 hospitals. The study has been reviewed by the Research Ethics Committees and the NHS Health Technology Assessment (HTA) Programme is funding this research. The doctors and nurses are not being specially paid to do this research. If you have further questions or require further information please contact Thank you for reading this and taking part if you agree. Study Title: The use of cardiac rehabilitation services to aid the recovery of bowel cancer patients You are invited to take part in this rehabilitation programme. This sheet is to provide you with the information you need to see if you would like to take part in the study. Please ask if you have more questions or need more information. What is the purpose of the Study? Studies have shown that exercise is likely to reduce the risk of the bowel (colorectal) cancer returning and to reduce fatigue and depression. Often patients don’t know if it is safe to exercise. Cardiac rehabilitation, which involves exercise and health advice, is already offered to people recovering from a heart attack. Cardiac rehabilitation gives people confidence to exercise and improves wellbeing. This study is to see if people recovering from bowel cancer can also benefit from this programme. Why you? You have been asked to join the study as you are recovering from surgery for bowel cancer. We have also asked others who have come in for similar surgery. Ethical Approval The Research Ethics Committee has reviewed the study. There will be monitoring from the that this research project is being properly conducted. What happens next? You will be asked to complete a consent form to confirm your willingness to take part in the study. This will take place in hospital, the rehabilitation facility or your own home. A member of the research team will witness your signature. You will then be contacted by a rehabilitation physiotherapist, who will meet you and assess if the programme is suitable for you. If the programme is suitable, you will be given an appointment for the next available weekly rehabilitation class. We will ask you to come in to answer some questions for us. When we have done this, you will be allocated to either take part in the study and attend the rehabilitation group, or you will be part of our control group, and will not be required to attend the classes. Please keep a copy of this information sheet. Do I have to take part? No. It is up to you to decide if you want to take part. If you do decide to join the study you can stop at anytime without giving a reason. If you do stop you may be asked if you are willing to give a reason as this may help plan future studies. If you do not want to join the study, or leave the study, you will continue with all normal follow up care. What if I wish to complain about the study? You can submit a written complaint about any part of the study to: . If you believe you have been harmed by taking part in the study you can make a complaint and seek compensation through the (see below). You can also complain through the usual NHS process. If you are harmed due to someone’s negligence you may have grounds for a legal action, but you may have to pay your legal costs. The NHS has no legal liability unless the harm is caused by someone’s negligence. Who do I contact for further information about the study? Dr is the Principal Investigator for the study. If you wish independent advice please Contact . Dr Tel: Email: Independent contact: Professor Tel: Email: Thank you for taking the time to read this and to consider taking part in the study. Information for patients eligible for registration into the FOCUS4 Trials Programme in colorectal cancer 1. Why am I being given this patient information sheet? - You are being invited to take part in a research study called FOCUS4, because your oncology doctors are recommending or have already started you on a course of chemotherapy for colorectal (bowel) cancer. - Participation in the research is entirely voluntary. If after considering it, you decide not to participate, this will not affect your care in any way and your oncology doctor will explain the best alternative standard treatment available. 2. Why am I being asked to participate in this research? - When cancer of the bowel is not completely removable by surgery or when it has spread to elsewhere in your body, chemotherapy may be given. This is a form of drug treatment which aims to kill cancer cells. Your oncology doctor is recommending that you have 16 weeks of chemotherapy to try and stabilise or reduce the size of your tumour. - Usually, the type of chemotherapy that is offered to a patient depends on how well it works on average in patients with bowel cancer. - However, there are now some specific tests that can be done on the tumour which may help us to choose more accurately which sort of treatment might be best for you when you reach the end of your 16 weeks of chemotherapy. - After the first 16 weeks we will offer you entry into a trial of a new form of treatment for your type of bowel cancer. 3. What am I being asked to consent to? - To take part in this research study you will be asked to consent to two separate steps. We have provided a flow chart at the end of this information sheet to show the steps more clearly. The first step is explained here and step 2 is described in section 5 of this information sheet. Step 1 asks for your permission to send a piece of your tumour (already stored in the local hospital pathology department where your cancer was diagnosed) to a central laboratory. A copy of your consent form will be sent to your local hospital pathology department (where it will be kept in a secure location), to authorise the release of your pathology block to the central laboratory. - This central laboratory will run specific tests (known as ‘molecular markers’) on the tumour sample. These tests will identify your cancer as one of four ‘types’. This process will take several weeks. In a few patients (about 2%), the tests do not work properly and the tumour is considered as a fifth type (unclassified). These test results will be made available to your oncology doctor for this research study. However they may help determine whether there are other future studies that you should consider following your participation in FOCUS4. - Following the specific tests, we would like your permission to store the piece of your tumour that was used to perform these tests. It will be stored at a central laboratory to be used for other studies for future bowel cancer research. This research will help us understand more about bowel cancer and the type of treatment that might be more effective for other patients in the future. It will involve extracting DNA or other material from the piece of your tumour. This research is based in UK Universities but may involve collaboration with commercial companies or other institutions. All such work is anonymous: your specimens will be identified by your unique trial number, not your name. These additional studies will not affect your treatment in any way, and you are free to withhold this permission without affecting your participation in FOCUS4 or your relationship with your doctor. - In addition to the blood samples that will be taken as part of your standard care, we would also like your permission to take some further blood for other bowel cancer research purposes. This will help us find substances in your blood which might help us understand more about bowel cancer and the type of treatment that might be more effective for other patients in the future. It will not help us with your own treatment. There are two types of blood sample collection required for two different areas of bowel cancer research. One area of research just requires one blood sample. The other requires a sample at the start and some additional samples later during the study. Your consent form will ask whether you are happy to provide the initial blood samples for these areas of research. We will ask you in the second stage of the trial about the later samples. - A copy of your consent form will also be sent to the Clinical Trials Unit () who are responsible for running this trial. They will destroy their copy of the consent form once they have checked it. - We are also asking if we may collect future routine information about your health status after participation in the trial. This will be collected by adding your name to government national registers such as the Office for National Statistics (ONS) and the NHS Strategic Tracing Service. The is registered to store this information according to the requirements of the UK Data Protection Act (DPA). There is a question about this on the consent form that we will ask you to sign before you agree to be registered into FOCUS4. 4. What will happen to me during my initial chemotherapy treatment? - Your initial treatment will include a 16 week standard course of chemotherapy as recommended by your oncology doctor. It is routine practice to see how the tumour is responding by having a CT scan and this will be arranged about half way through, and again at the end of your 16 weeks of chemotherapy. CT stands for computerised tomography. The CT scanner uses X-rays to take a series of very detailed pictures of the body and is a painless procedure. The pictures are taken while you lie on a couch, which moves backwards and forwards through the hole of the machine. This procedure involves some exposure to ionising radiation. Like all medical procedures, this does entail some risk, but in this case the benefits outweigh any such risk. - If the CT scan half way through your chemotherapy shows that you are responding to treatment (your cancer has not grown or even shrunk), you will continue on treatment to the 16 week scan. If your tumour has got bigger at this half way scan, your oncology doctor will discuss with you about other treatment options at that time. 5. What will happen to me at the end of my initial chemotherapy? - The second step of this research study will start at the end of your 16 weeks of chemotherapy when we will have the results of your specific tests back from the central laboratory. If at the end of your 16 weeks of chemotherapy your cancer has shrunk or at least not grown, for many people this would be a time when they might take a break from the chemotherapy. In our last trial called The COIN Trial we showed that having a break from chemotherapy after this initial course of chemotherapy, is a safe thing to do for most patients. - The aim of the FOCUS4 is to find a good treatment for your particular type of cancer after you have finished your first 16 weeks of chemotherapy. We will be doing it by comparing how patients get on with either a new treatment tablet or a dummy tablet. - The new treatments that we will be testing will be selected because they may offer a possibility of benefit for patients with the type of bowel cancer that we will identify by your specific tests. When we know the results of your specific tests, we will provide you with more detailed information on the trials that will be available to you at that time. Please look at the flow chart at the end of this information sheet to see where step 1 ends and step 2 starts. - If you want to get information on all the trials that we will be conducting, we can provide you with patient information sheets for all of them now, but we feel it would be easier for you to wait until we know the results of your specific tests and give you the relevant information at that time. 6. What if I do not want to participate in one of these trials at 16 weeks? - By consenting to sending your piece of tumour for specific testing, you are under no obligation to consent to participate in any of these trials. If you decide not to consent into these trials, we would hope to be able to use the results from your specific tests from the central laboratory for other research. However, you can ask for the results not be given to anyone else or used in any way. DIAGRAM Please use this space below to record any questions you might have for your oncology doctor at your next visit. Contact Details for further information: Local Investigator: Dr. Telephone no: Research Nurse: Telephone no: CONVERT (Concurrent ONce daily VErsus twice daily RadioTherapy) A 2 arm randomised controlled trial of concurrent chemo radiotherapy comparing twice daily and once daily radiotherapy schedules in patients with limited stage small cell lung cancer (SCLC) and good performance status PART 1 Invitation to participate in the study You are being invited to take part in a research study. Before you decide if you want to take part, it is important for you to understand why the research is being done and what it will involve. Please read the following information carefully and if you wish, discuss it with friends, relatives and your General Practitioner. Ask us if there is anything that is not clear or if you would like more information. It is important to take time to understand this information and decide whether or not you wish to take part. Why is this research taking place? Your type of lung cancer can be treated with a combination of chemotherapy drugs and chest radiation therapy, called concurrent chemoradiotherapy treatment. Doctors agree that combining radiotherapy and chemotherapy improves the outcome of treatment, but some questions remain unanswered about the best way to combine radiotherapy with chemotherapy. The optimal dose, duration and number of daily fractions of radiotherapy are still to be defined. What is the purpose of this research study? The purpose of this research study is to find out: - What is the best total dose of radiotherapy to prescribe for small cell lung cancer - What is the most effective way of giving the radiotherapy? Is it once or twice a day? Why have I been chosen? You have recently been diagnosed with small cell lung cancer and your doctor has recommended chemotherapy and radiotherapy treatment. Your doctor feels that you are suitable to take part in this trial. This is a research study, and other patients similar to you are also being asked if they would be willing to take part. In total approximately 530 patients will take part. Do I have to take part? You do not have to take part in this research, your doctor will continue to treat you whatever you decide. However, if you decide to take part you will be asked to sign a consent form. You will be given a copy of this to keep, together with this information sheet. It is routine for your GP to be kept informed about your treatment, so your GP will be told if you are taking part in this research. If you agree to join you will still be able to withdraw at any time without giving a reason. If you withdraw from the study this will not affect the standard of care you receive. What will happen to me if I take part? If you agree to take part, you will be asked to sign a consent form and your doctor will organise a number of tests to check if you are eligible for this study. The tests will include a physical examination, a chest x-ray, a CT scan of the brain, thorax and upper abdomen, a radiotherapy planning scan, blood tests and lung function tests. These tests are normally done as part of the routine tests for patients who are to be treated with concurrent chemoradiotherapy. Some patients may also require a bone scan or a pregnancy test. If you are eligible you will be randomly allocated to once or twice daily radiotherapy. This is done by a computer, you or your doctor cannot choose the treatment. Once you have started the treatment you will be assessed weekly for any changes in your symptoms, any side effects of treatment and any changes in your blood tests. A CT scan will be repeated after chemoradiotherapy, then 6 and 12 months after the date you enrolled in the study. After completing treatment, you will be reviewed weekly until any side effects have resolved then 3 monthly until 1 year and 6 monthly thereafter. Follow up visits at more frequent intervals will be decided by your doctor. TABLE Blood and tissue samples for research You will also be asked to consent to storage of tissue and blood samples for use now and in the future for research aiming to improve knowledge and treatment of small cell lung cancer. Consent to the storage of samples is optional, so if you prefer not to consent to this you may still take part in the research. If you consent to collection of tissue and blood samples for storage these will be taken as follows: 1. You will be asked to donate tissue left over from the biopsy (biopsies) or operation(s) performed as part of your routine clinical care. No additional procedure(s) will be necessary. 2. You will be asked to donate blood before you start treatment (day 1), on day 22 of treatment and when treatment is completed. The amount of blood taken will be 10 - 30mls (two to six teaspoons) each time. Every effort will be made to take the blood samples at the same time as your routine blood tests are taken. The extra blood samples will not increase the amount of time you spend in the hospital. What do I have to do? You will be expected, if you take part in the study, to attend the scheduled visits. What are the treatments that are being tested? The treatment being tested is the radiotherapy. The trial is to compare a short course of radiotherapy given twice a day with a longer course given once a day. - Short course radiotherapy Radiotherapy treatment will be delivered twice a day, Monday to Friday (excluding weekends) for three weeks. There will be an interval of 6 to 8 hours between each treatment, for example treatment will be given at 09.00hrs and 15.00hrs. - Long course radiotherapy Radiotherapy treatment will be delivered once a day, Monday to Friday (excluding weekends) for six and a half weeks. - Chemotherapy The chemotherapy (cisplatin and etoposide) treatment you will receive is standard. It will be administered by a drip for 3 consecutive days every 3 weeks for a total of 4 to 6 cycles. The way the chemotherapy is administered and the number of chemotherapy cycles that you receive will be decided by the doctor in charge of your treatment. The first course of chemotherapy will be given 3 weeks before the start of the radiotherapy treatment. If you receive short course radiotherapy the second cycle of chemotherapy will be administered during the first 3 days of the radiotherapy treatment and subsequent cycles will be administered after completion of the combined treatment. If you receive long course radiotherapy, the second, third and fourth cycles of chemotherapy will be administered during the weeks when you are receiving radiotherapy treatment, and subsequent cycles will be administered after completion of the combined treatment. The radiotherapy treatment will take around 15 minutes each time. Your doctor will discuss the length of time that the chemotherapy takes to administer. After chemotherapy and radiotherapy to your chest have been completed you may be offered a short course of radiotherapy to your brain. This is to prevent cancer developing in your brain, as this type of lung cancer can sometimes spread to the brain. If your doctor thinks this would be appropriate for you he/she will explain more about the treatment and any possible side effects. What are the alternatives for treatment? If you do not wish to take part in this study your doctor will tell you what alternatives are available. The alternative treatment will vary depending on your lung cancer doctor. What are the potential risks and side effects of taking part? You may experience some of the following side effects during treatment. These are usually temporary. It is important to tell your hospital doctor about any side effects so they can be monitored and, where possible, treated. The side effects are similar with both treatments, and will vary from person to person. It is possible you will experience very few of these side effects however staff will be able to advise you if any side effects become problematic. Prior to starting this research study a smaller study of the same treatments was carried out and patients in that study did not experience any major toxicities leading to long term side effects. Common chemotherapy side effects: - Kidney function: Because cisplatin can affect your kidneys, it is important to drink plenty of fluids (at least 8 cups) the day before and for a few days after chemotherapy. We may ask you to bring in a 24 hour urine collection to monitor your kidney function. - Extravasation is when chemotherapy leaks outside the vein. If you develop redness, soreness or pain at the injection site at any time please let us know straightaway. - Bone marrow suppression. Your bone marrow is where your blood cells are made (these are the red cells, white cells and platelets) to replace those naturally worn out within the body. Chemotherapy interferes with this process and the number of cells in your blood can become low. This means that following treatment you could become: Prone to infection: Your white cells can become low, this is most common the week after treatment. You may develop a sore throat, cough, fever, shivering or other symptoms which may be due to infection. A normal temperature is between 36C and 37C. If your temperature is above 37.5C, contact this hospital straightaway without delay. Minor infections can become serious over a matter of hours. Anaemic: If your red cells become low you may experience excessive tiredness, feel dizzy, breathless and/or look pale. Prone to bleeding: If your platelets become low, you may get nose bleeds, bruising or bleeding gums. You will have a routine blood test before each treatment to monitor the effects of the chemotherapy, BUT please contact this hospital if you experience any of the symptoms listed above. - Hair Loss. Hair loss is usually total. The hair falls out gradually 10 to 14 days following your first course of treatment. The time scale varies from person to person. Please remember that this is a temporary side effect and your hair will grow back when you treatment is completed. - Nausea and vomiting (sickness). The severity of this varies from person to person. Anti-sickness medication will be given along with your chemotherapy to prevent this. You will also be given anti-sickness tablets to take at home. Occasionally your anti-sickness medication may need to be changed or increased and you may need extra fluid through a drip. - Lethargy (fatigue). Some chemotherapy may make you feel tired and lacking in energy. - Strange taste. Occasionally during treatment you may experience a strange taste, sometimes described as metallic or bitter. - Tinnitus & high frequency hearing loss. You may develop tinnitus (ringing in the ears), this sensation should subside when your treatment finishes. High frequency hearing loss can also occur with this chemotherapy, this may be permanent. - Tingling & numbness in the fingers or toes. Usually only mild and temporary. Please report these symptoms to your doctor on your next hospital visit. On rare occasions, this may be permanent. - Upset bowels. You may get upset bowels with this chemotherapy: Diarrhoea. If this becomes a problem while you are having treatment, anti-diarrhoea tablets can be prescribed for a temporary period until this is resolved. Constipation. This occasionally occurs in the long term. Try to drink plenty of fluids and eat foods high in fibre. Tell your doctor who may prescribe a suitable laxative. - Sore mouth. You may develop a sore mouth during your treatment but this can often be prevented by doing regular mouth washes. - Loss of Appetite. Loss of appetite is a common side effect. You should take plenty of fluids and try to ensure that you take in enough calories. Your doctor or nurse can advise on dietary supplements if needed. - Contraception & Fertility. If you are fertile, you should use effective contraception while on chemotherapy. Effective contraception means one of the following methods: For female patients: 1. Tubal ligation 2. Physician documented placement of an intra uterine device (IUD) 3. Diaphragm with spermicidal foam/gel/film/cream/pessary 4. Condom with spermicidal foam/gel/film/cream/pessary 5. Male partner who has had a vasectomy 6. Hormonal contraceptives For male patients: 1. Use of condom. 2. In addition to a condom: male subjects without a vasectomy must ensure that their female partner uses another form of contraception such as an IUD, spermicidal foam/gel/film/cream/suppository, diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant or a tubal ligation if the female partner could become pregnant from the time of the first dose of trial medication until completion of follow up procedures. 3. The female partner would not be required to use another form of contraception if they are of non childbearing age. If you suspect that you may be pregnant please tell your doctor immediately. Chemotherapy may also affect your ability to have children in the future. Common radiotherapy side effects Acute side effects are temporary and affect all patients. They will vary depending on the volume of normal tissue which is being treated and your general fitness. The early side effects of concurrent chemo radiotherapy may include: - Some pain in the chest in the 24 hours after the first treatment. This is usually mild and settles down fairly quickly. - Increase in your cough and sputum (spit) which may contain a little blood. Don’t worry, this is quite normal. If you are having difficulties with this during treatment, let your doctor know. Coughs can sometimes worsen when treatment finishes. - Tiredness. Tiredness related to radiotherapy varies a lot from person to person. - Difficulty in Swallowing. Inflammation of the gullet (oesophagitis) can cause discomfort when swallowing (dysphagia). Your doctor can prescribe medicines to alleviate this symptom and the hospital dietician can advise about modifications to your diet and supplements. You should concentrate on maintaining a good fluid intake. - Shortness of Breath. Inflammation of lung tissue (pneumonitis) can cause a dry cough and a degree of breathlessness during or shortly after radiotherapy. A variant of this side effect can cause troublesome breathlessness about six weeks after radiotherapy is completed. This side effect is usually treated with a course of steroid tablets. - Skin Rash. Skin reaction can be caused by radiotherapy treatment, similar to sunburn. On rare occasions a cream may be needed. These side effects tend to build up during treatment and are at their worst in the last week of treatment or in the first 2 weeks after treatment is completed. They then recover 3-6 weeks after treatment. The late side effects of concurrent chemo radiotherapy may include: - Difficulty in Swallowing. Narrowing of the gullet may require a minor operation to stretch the gullet (dilatation) or in rare cases surgery. If you experience swallowing difficulties months after completion of the combined treatment further investigations (gastroscopy – tube into the stomach) may be necessary. - Shortness of Breath. Damage to the normal lung tissue may occur from radiotherapy. This can result in shortness of breath and increased risk of infections. Radiotherapy may leave the lung with some scarring (fibrosis). This can mean that your lung does not work quite as well as it did before, and you may notice a slight increase in breathlessness. - Rare late side effects. They include thinning of the ribs (following a severe cough, this can result in chest pain and/or minor rib fracture) and injury of the spinal cord (in extremely rare cases). An injury to the spinal cord can cause permanent difficulties in walking and loss of sensation in the lower body. Every effort is made to carefully plan your treatment so as to avoid this problem. The risk of these late side effects is generally small as the treatment is planned carefully to try to avoid them. If you do have late side effects they will become noticeable 6-18 months after radiotherapy is completed and are generally permanent. Other possible risks of taking part Risks of blood tests: in most cases taking blood does not cause any problems, however there is a risk of some bleeding, bruising, discomfort, dizziness, infections and/or pain at the site where the blood is taken. Risks of scans: in addition to radiotherapy you will be exposed to some radiation as a result of x-rays and CT scans. There is a small chance that being exposed to radiation could result in the development of a cancer several years later, but the actual risk is very small compared with the benefits of diagnosing and treating your existing cancer. What are the possible benefits of taking part? We hope that both treatments will help you. However this cannot be guaranteed. The information we get from this study will help us to treat future patients with the same disease better. Who can I contact for further information? If you have any concerns with your treatment and need to contact someone out of hours (after 5pm and before 9 am) please contact This completes Part 1 of the information sheet. If the information in Part 1 has interested you and you are considering participation, please continue to read the additional information in Part 2 before making any decision. PART 2 What if relevant new information becomes available? Sometimes during the course of a research project, new information becomes available about the treatment that is being studied. If it happens your doctor will tell you about it and discuss with you whether you want to continue in the study. If you decide to withdraw your doctor will make arrangements for your care to continue. If the study is stopped for any other reason, you will be told why and your continuing care will be arranged. What will happen if I don’t want to carry on with the study? You can withdraw from the study at any time. If you withdraw from the study, you will be able to choose either: - To allow us to use samples and information collected up to the time of withdrawal and to continue obtaining information from your health records so that we can record what has happened to you since you withdrew from the study OR - You can request that we destroy all your identifiable samples and/or that we do not collect any further information from your health records. What if something goes wrong? The study is being performed by your doctor and insurance against injury will be provided against the hospital that is looking after you. If you are harmed due to someone’s negligence, then you will have grounds for legal action but you will have to pay for it. Regardless of this, if you wish to complain about any aspect of the way you have been approached or treated during the course of this study, the normal NHS complaints mechanisms will be available to you. By signing a consent form you are NOT waiving any of your legal rights. Confidentiality If you join the study, some parts of your medical records and the data collected for the study will be looked at by authorised persons involved in the research. The ethics committee that approved this study and regulatory authorities may also ask for access to your records. All will have a duty of confidentiality to you as a research participant. What will happen to any samples I give? We are intending to carry out analysis on any blood samples and tissue that you donate. These samples will be used for research to determine groups of patient more likely to respond to treatment or more likely to develop side effects to treatment. The samples may be shared with other research groups who have the same field of interest in the UK or outside the UK. All blood samples or tissue collected will be stored anonymously. All information which is collected will be kept strictly confidential. Procedures for handling, processing, storage and destruction of data will be compliant with the Data Protection Act 1998. Only the Chief Investigator () and personnel authorised by the Chief Investigator will have access to break the study codes and identify the donors of the samples. Any unused samples will be retained indefinitely for use in future projects designed to identify genes and proteins that are involved in small cell cancer; and genes and proteins that predict for benefits or side effects of treatment. Samples may be transferred within or outside the UK to collaborators in other academic or commercial research settings. Nothing that could reveal your identity will be disclosed to collaborators elsewhere. You may choose to participate in the study but not to have your blood or tissue stored for research purposes. If you choose to donate blood or tissue you have the right to have the sample(s) destroyed at any time by contacting your study doctor. If you decide to have your sample(s) destroyed, any analysis done and data gathered before the request cannot be removed, however no additional analysis will be done on your samples and the rest of your remaining samples will be destroyed. Will any genetic tests be done? Genetic analyses will be performed to study the genetic influences on small cell cancer and so the results will not affect you directly. No clinical genetic tests will be done for specific known inherited diseases. What will happen to the results of the research study? Independent experts will review the progress of the research, and the results will be published in a respected medical journal. The results will help to decide how to treat small cell lung cancer in the future. Studies like this are often used in cancer research. Who is organising and funding the research? The CONVERT study is being funded by Cancer Research UK and sponsored by the NHS Foundation Trust. Who has reviewed the study? The CONVERT study was given a favourable ethical opinion for conduct in the NHS by the Research Ethics Committee. Thank you for taking time to read this information sheet. You will be given a copy of the information sheet and a signed consent form to keep if you decide to take part in the study.