<Trust logo here> Participant Information Sheet Adults Prediction of Lupus TreAtment response Study (PLANS) Finding factors to help us treat lupus patients better and smarter. We would like to invite you to take part in a lupus research study for adults and young people. Before you decide whether or not to take part, please read this information sheet which explains what this research is about, why it is being done and how it could involve you. You may also wish to discuss taking part with your family and health care professionals such as your family doctor. Why have I been invited to take part? You have been invited to take part in this study because you are a patient with lupus (Systemic Lupus Erythematosus; SLE), your lupus is active, including in your skin and / or your kidneys, and your doctor has already decided in discussion with you to treat you with one of two types of drug: rituximab or mycophenolate mofetil / mycophenolic acid (also known as MMF /MPA). Background to the study Systemic Lupus Erythematosus (SLE; or 'lupus') can affect different parts of the body and each person has a unique set of symptoms. Patients differ in the severity of their disease and how well they respond to different drugs. On average we know that 40 60% of patients respond well to any specific drug and an even smaller proportion achieve the excellent response of no longer having any symptoms or signs of SLE (which we call remission). Patients often need to try several other treatments before their lupus is controlled. This study seeks to understand better which patients will respond well to particular drugs so that effective treatment can begin sooner. We will be looking for genes as well as chemicals and cells in the blood, urine and tissues (biomarkers) that may help us predict how well patients will respond to lupus treatment. If we can identify groups of patients who respond well to specific drugs this would help us in the future to develop tests to Page 1 of 8
help doctors treat individual patients with the drug most likely to work best for them first time. Your participation may not benefit you directly but the research aims to help us to treat lupus patients more accurately in the future. What is the study about? For this study we have decided to focus on two of the most common forms of lupus (skin and kidney involvement) and two specific treatments in routine use (mycophenolate and rituximab). With your help, we will look at how you respond to the treatment that your doctor has decided to give you for your SLE (this is called an observational study). We will try to understand the relationship between the effectiveness of the drug for you and the biomarkers we measure so that we can predict which patients are likely to respond best to each treatment. Who is doing the research? This study is organised and sponsored by the University of Manchester in collaboration with <patient's hospital trust>. The study forms part of the MASTERPLANS programme of work. MASTERPLANS is a consortium of UK universities and international companies that all have a special interest in lupus. Your study doctor and nurse will receive no personal payment for doing this study. The study is funded by the Medical Research Council and some of the research techniques are supported by companies that are developing new drugs and biomarker tests for SLE. Your eligibility for this study Your doctor will advise you on your eligibility for this study. You may not be able to take part in the study if you or your doctor thinks you are too unwell. Other things that may interfere with our measurements would also mean you may not be able to take part. These include if you have had certain drugs in the recent past, if you have active infections or recent cancer and also if you have surgery planned, or are thinking of getting pregnant, or think you might be pregnant. Do I have to take part? Taking part in this study is entirely voluntary and you are free to withdraw at any point without having to give any reason. Should you agree to take part, you will be asked to sign a consent form. Taking part or not taking part will have no effect on the type of treatment or any other care that you receive. What will I have to do if I take part and what information will be collected / needed? You will attend up to eight study visits for PLANS over a one year period at the same time as some of your routine clinical appointments with possible additional study visits if you have a lupus flare. If you decide to take part, your doctor (or a doctor who is part of the study team) will invite you to a 'screening visit'. During the visit, the doctor will explain more about the study and you can complete a form giving your consent to participate. Following consent, the doctor will record some details from you (your date of birth, gender and race / ethnicity), as well as reviewing your medical and surgical history and details of your prior and current medications to check that you match the criteria for the study. This may include taking some tests, which are necessary anyway because of starting your new drug (e.g. blood pressure, pulse rate, temperature, urine tests; and if appropriate, a pregnancy test). We may also take some blood and urine for research purposes (up to 10 ml blood (less than 1 tablespoon) and 30 ml urine (approx. 2 tablespoons)). Page 2 of 8
Study visits will usually be scheduled to take place in the morning so that your blood and urine can be processed on the same day. You will be asked to complete some questionnaires that will ask questions about your perspectives on your quality of life, your illness and the medicines you take. We will also record your use of healthcare resources, such as visits to the hospital and your GP as we still know very little about this aspect of healthcare for lupus patients. The brief questionnaire booklet used in some visits will take around 10 minutes to complete. At 0, 6 and 12 months, we will ask you to complete two questionnaire booklets and these will take around 45 minutes in total to complete. Your treatment with rituximab or MMF will be according to your own doctor s usual practice for administering and monitoring this treatment. The study team will not change this in any way. At the beginning of the study, your doctor will make a clinical assessment of your lupus and arrange for samples of your blood and urine to be taken. The maximum amount that will be taken for our study (over and above any blood needed for routine care) at any visit will be 115 ml of blood (approx. 8 tablespoons) and 75 ml of urine (approx. 5 tablespoons). Further blood and urine samples will also be taken at 1, 3 and 6 months, during your usual clinic or monitoring visits to your doctor. If you have a lupus flare between 6 and 12 months after entering the study, your doctor will make another clinical assessment of your flare up and arrange a further blood and urine sample. At each visit, you will have routine tests, some detailed assessments that your doctor will complete, and you will be asked to fill in forms about how the lupus affects your quality of life. The questionnaires can be completed at home or in clinic. Because we think that some factors that affect patients response to treatment may only be found in the part of the body affected by lupus, we plan, with your permission, to obtain a skin biopsy or a kidney biopsy under the following circumstances. Skin Biopsy If you have a rash as part of your condition your doctor will discuss with you about taking samples of your skin (skin biopsy) and photographs of your rash before you start treatment. Your doctor will agree with you a suitable part of the rash from which to take the biopsy. You may also be invited to have repeat biopsies at approximately 4 weeks and 6 months, though these are optional. A suitable part of the rash from which to take the biopsy will be agreed with you. A local anaesthetic will be injected around this area to make the skin numb. This procedure should not be painful. For the first biopsy, two pieces of skin tissue (approximately 4mm each) will be removed, after which stitches will be applied to promote skin healing. A dressing will then be applied, which you can remove after 48 hours. For the optional follow up biopsies, only a single 3mm biopsy is needed, and this does not usually require any stitches. These would be taken from skin in the same area as before that is either still affected by your lupus or had been affected at the time of one of the earlier PLANS biopsies. Your doctor will also take skin samples at the same visit, using tapes (like Sellotape) or a special skin washing fluid to collect chemicals from the top layer of your skin. This will help us find out whether we can find useful information without needing to perform a biopsy in the future. Up to 12 tapes will be placed in turn on the same part of your skin for 5 sec each with gentle pressure and then removed. This may cause a little discomfort but is not painful. The time between tape stripping will be about 10 sec. If your skin is too sensitive or is damaged, your doctor will use the washing fluid instead. Page 3 of 8
Your doctor will also take photographs of your skin rash. These will be close up photographs and every effort will be made to ensure you cannot be identified. Kidney Biopsy If your doctor has already planned to take a sample of one of your kidneys (termed a renal biopsy ) as part of your investigation and management (not because of the study), we will ask your doctor to provide us with further sample from the same biopsy procedure for us to analyse in our study. This does not interfere with the results of the biopsy for your clinical assessment. We use this sample to assess what is happening to your genes or chemicals/cells during kidney inflammation in lupus. If you change drug during the study If your drug is changed from MMF to rituximab or vice versa during the study, we will invite you to consent to take part in the study with the other treatment if you are agreeable to do this. If you decide not to take part again, this will not affect on the treatment and other care that you receive. Your participation in the research It is very important that you follow the study procedures and your study doctor s recommendations and medications during the study as best you can. If you have concerns about your health during the study, you should seek advice as normal from your GP or hospital doctor. We would, however, like you to tell your study doctor at the next visit if there are any changes to your lupus, general health and other treatments to help us interpret fully the results we get. What will happen to my information, photos and blood, urine, skin and kidney samples? We will use a code number for you so that you cannot be identified from any of the information (including photographs of your rash) or samples collected. Your information will be sent securely from the <hospital trust> to the University of Manchester and will be stored in a password protected and a specially coded (encrypted) PLANS database linked to a secure research database. Your samples will be collected using your unique code number but not your name. Some of your samples of blood, urine, skin and kidney may be processed at the hospital where they were collected and some will be sent for processing at laboratories at the University of Manchester and/or other MASTERPLANS university partners. We will extract cells, chemicals and genetic materials (DNA, RNA) in order to look for biomarkers. Samples will be handled and stored in accordance with good practice and legal agreements overseen by the University of Manchester. Your skin photographs will only be accessible to researchers at the University of Leeds, who are leading the skin part of the PLANS study, and to the Chief Investigator and study coordination team at the University of Manchester. So that we can contact you about the study, we will keep your name and contact details on a secure server at the University of Manchester, separately from the research databases. Only the Chief Investigator and study coordination team at the University of Manchester will have access to these data. Page 4 of 8
Sharing of data and samples with other collaborators Your research data and samples may be shared anonymously and securely with other researchers, in accordance with national standards for data security and Good Clinical Practice. Data and samples will primarily be shared with academic and life sciences industry members of the MASTERPLANS Consortium. All of these partners have signed a common agreement to respect your anonymity. Our Consortium includes partners located in the UK and abroad, including outside the European Economic Area (EEA). Your data and samples may also be requested by other collaborators who are authorised researchers in the UK and potentially, centres abroad, including outside the European Economic Area. Requests for use of data and samples will be considered by a MASTERPLANS committee that includes patients on the panel. The committee will require ethical approval for all studies involving your data or samples. We will ask you for your consent to share data / samples with other collaborators. A complete list of partners with whom we share data and samples is available on the MASTERPLANS website www.lupusmasterplans.org. This comprises the organisations in the MASTERPLANS Consortium (academic institutions and life science industry organisations) and other research teams that have been approved by the MASTERPLANS Consortium. The website also provides the purpose of the research for which MASTERPLANS data and / or samples are being used. In order to benefit from new and future research techniques, we also would like to store your data, blood, urine, kidney and skin tissue samples, confidentially and anonymously, at the end of the study for possible use in further medical research at a later date. You are free to change your mind at any time and can ask your study doctor for your samples to be destroyed. This will have no effect on your standard care. What are the possible disadvantages and risks of taking part? Time in clinic: Because we are looking in depth at many different aspects of your response to MMF or RTX, there are a number of PLANS activities at each visit. These have been minimised so far as possible. Questionnaire booklets can be filled in while waiting for tests in clinic or if necessary, at home afterwards. We may contact you to remind you to complete any booklets taken home. Blood samples will be taken at the same time as routine blood samples by inserting a needle into a vein. This can cause discomfort and may result in bruising or bleeding that may take a few minutes to stop. Any discomfort and bruising should resolve in a few days. Skin biopsy: The risks include development of some type of scar, an infection which occurs in less than 3 per 100 patients, and other rare complications such as bleeding which may take a few minutes longer to stop, wound opening (dehiscence) and nerve damage resulting in numbness which may be permanent (less than 1 per 100 cases). You will be given a leaflet about wound care with a contact number for any concerns or problems after the biopsy is done. Kidney biopsy: You will be having the biopsy anyway as part of your care and the risk of complications from taking additional tissue remains low. Around 1 in 100 patients may have blood in their urine and a blood transfusion may be required around 1 in 1000 patients. Your clinical team will advise you in this as part of your routine care. Page 5 of 8
Withdrawal from the study You are free to withdraw from the study at any point without having to give a reason, by informing your study doctor or the contacts at the end of this leaflet. This will have no effect on your standard of care. If you become incapacitated and can no longer provide your on going consent, you will be withdrawn from the study and no further data or samples will be collected from you. Following your withdrawal from the study, we will continue to use the anonymised data and samples that you have already provided with consent, though we will destroy your name and contact information. What are the possible benefits of taking part? The research will not be of direct benefit to you but we hope that it could benefit other lupus patients in the future by guiding doctors to the most effective drug, so that patients can be put on the drug most likely to work for them at the beginning of their treatment. You will not receive any financial compensation for taking part in this study or from any commercial or other use of MASTERPLANS results. What happens when the research study stops? We will securely store your consent form and anonymised information about your health at the University of Manchester for a period of 10 years after the study ends and will then destroy them. Your samples will be stored in a secure storage facility (biobank) approved under the Human Tissue Act for 10 years from the end of the study, and will then be destroyed. Will my taking part in the study be kept confidential? Yes, your data will be kept confidential and secure during its electronic transmission and in the research databases at the University of Manchester and other academic and industrial partners in the MASTERPLANS consortium. This is in accordance with Good Clinical Practice and national standards for data security. Your clinical data held at the University of Manchester will not contain your real name or any other means of identifying you. Your real name will not be used in anything we write or publish. We will, with your signed consent, wish to contact your GP to inform him/her that you are involved in this research. Individuals from the University of Manchester, your NHS Trust or regulatory authorities may from time to time need to access data collected during this study to monitor or audit the research to ensure it is being conducted appropriately. With your consent, this will include data from which you could be identified, as this is necessary to ensure appropriate conduct of the research. All individuals have a duty of confidentiality to you as a participant in this research. What if there is a problem? If you have a concern about any aspect of this study that your clinical care team cannot resolve, you need first to contact the PLANS STUDY COORDINATOR (see Contact Details at the end of this leaflet), who will do his/her best to answer your questions. If he/she is unable to resolve your concern or you wish to make a formal complaint regarding the study, please contact the Research Governance and Integrity Manager, Research Office, Christie Building, University of Manchester, Oxford Road, Manchester M13 9PL by phoning 0161 275 2674 or 0161 275 2046 or by email to research.complaints@manchester.ac.uk. Alternatively you Page 6 of 8
may contact your local NHS Patient Advice and Liaison Service (PALS) on <telephone no.> or email: <email address>. In the event that something does go wrong and you are harmed during the research you may have grounds for a legal action for compensation against the University of Manchester or <hospital trust> though you may have to pay your legal costs. The normal National Health Service complaints mechanisms will still be available to you through your local NHS Patient Advice and Liaison Service (PALS) on <telephone no.> or email: <email address>. Future research studies Lupus is a rare disease and this project will provide the opportunity to collect information on a large group of patients who have lupus. There is still a lot we don t know about lupus and we would therefore like to ask your permission to contact you in the future about other research studies that are being carried out. You do not have to agree to be contacted about future research but if you do agree to be contacted, your details will be kept securely in a register of participants interested in being contacted. If a new research project does come up, we will not pass your details on to anyone else. Instead we will write to you to inform you about the research. BILAG BR study (British Isles Lupus Assessment Group Biologics Register) If you are taking part in both PLANS and BILAG BR, we can collect information just once for the two studies. We will ask your permission to record your BILAG BR unique code number (study ID) so we can do this. What will happen to the results of the PLANS research study? We will make the results of our research available to the public and lupus patients via the MASTERPLANS and LUPUS UK websites (www.lupusmasterplans.org and www.lupusuk.org.uk) and social media, and through LUPUS UK's newsletter for members. We will make the findings known by publishing the results in research publications and at conferences. In the unlikely event that we wish to use a photograph of your rash to illustrate our research findings, we will contact you to ask permission to include the photo. If we find biomarkers that predict response to different drugs in different patient groups, we intend to conduct one or more further studies ('clinical trials') to make sure that the biomarkers are reliably effective in particular patient groups. Who has reviewed the study? This study has been reviewed by the Health Research Authority (approval dated <date>; IRAS ref. 198463) and the Research and Development Department situated at your hospital prior to the start of the study. If you have any questions or would like to find out more about this study, please contact your hospital care team or the PLANS research team, whose details can be found below. For general information on taking part in research, see the NIHR website www.nihr.ac.uk/get involved or contact your local NHS Patient Advice and Liaison Service (PALS) on <local number> (email: <local email>). Thank you for taking the time to read this information sheet and for considering joining the study. Page 7 of 8
Contact Details: <contact at hospital Trust> <Tel. <hospital telephone>> Email: <hospital email address> The PLANS Study Coordinator <name> Tel. 0161 275 <xxxx> Email: masterplans@manchester.ac.uk Division of Musculoskeletal and Dermatological Sciences School of Biological Sciences University of Manchester Stopford Building Room <room> Oxford Road Manchester M13 9PT Page 8 of 8