LOCI Participant Information Sheet v3.0 15-Feb-2021
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LOCI: Letrozole or Clomifene, with or without metformin, for ovulation induction in women with polycystic ovary syndrome: a 2x2 factorial design randomised trial
PATIENT INFORMATION SHEET
Local Principal Investigator: Professor Adam Balen Local Research Nurse/Midwife: Julie Glanville/Karen Meadows
Telephone number:0113 20 63470/63102 Email address: [email protected]/[email protected]
[email protected] www.birmingham.ac.uk/loci
IRAS ID: 257918 EudraCT number: 2018-004641-16 ISRCTN: 11828358 Page Sponsor Reference: RG_18-272
LOCI Participant Information Sheet v3.0 15-Feb-2021
Thank you for taking the time to read this information sheet. We understand that this might be a difficult time for you. This leaflet will explain what is happening, about the treatments available and about a research study that you can decide to take part in to try and help us find out which is the best way to help women who are in your situation. Your doctor will also talk to you about the treatment options available.
We know that women in this situation often need extra support and so at the end of this leaflet we have provided the contact details for organisations that can help you.
Brief summary We would like to invite you to take part in our research study. Joining the study is entirely up to you. Before you decide we would like you to understand why the research is being done and what it will involve for you. A member of our research team will go through this with you, to help you to decide whether or not you would like to take part and to answer any additional questions you may have. Please feel free to talk to others about this study if you wish.
The LOCI trial is informed by patient and public representation throughout the design, conduct, reporting and dissemination. This Patient Information Sheet tells you the purpose of the study, what will happen to you if you take part and detailed information about the conduct of the study. Please do take the opportunity to ask any questions you have and to ask for more information if anything is unclear.
Why have I been invited to take part? You have been invited to take part in this study because you have been diagnosed with polycystic ovary syndrome (PCOS) and you require ovulation induction in order to help you conceive naturally.
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LOCI Participant Information Sheet v3.0 15-Feb-2021
What is the purpose of the study? In order for you to conceive naturally, an egg will need to be released from your ovary. For women with PCOS, this does not always happen, and therefore we need to give medicines to help your body release an egg. There are two drugs we can give to help you release an egg; one called ‘clomifene’ and another called ‘letrozole’. There is another drug called ‘metformin’ that we can also give you at the same time as these other drugs, but we are not sure if this carries any additional benefit. Overall, we are not sure which drugs are best for ovulation induction and a successful pregnancy outcome. The purpose of this study is to test which drugs are best.
Do I have to take part? Participation in our study is entirely voluntary. If you decide to take part, we will check you are eligible and you will be asked to sign a consent form. If you do not wish to take part, you will not have to give a reason and your decision will not affect the care you will receive. Similarly, if you do decide to take part, you will be able to withdraw from the study at any time and without giving a reason, and without any effect on the medical care that you receive.
What is letrozole and what does it do? Letrozole works by suppressing oestrogen production. It is being increasingly used as a treatment by fertility specialists to aid the development of ovarian follicles and the process of ovulation induction.
What is clomifene and what does it do? Another drug frequently used for inducing ovulation is clomifene. In contrast to letrozole, clomifene works by blocking oestrogen receptors. In both cases, the action of these drugs results in the increased production of hormones needed to
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LOCI Participant Information Sheet v3.0 15-Feb-2021 stimulate the ovaries and help ovulation.
What is metformin and what does it do? Metformin is an insulin-sensitising drug used to treat diabetes and is commonly prescribed to women with PCOS who are undergoing ovulation induction. This drug was not originally designed to treat women with PCOS, but is often prescribed (called an ‘off-label prescription’) as there is some evidence to suggest that it might be beneficial. If you are already taking metformin you would need to stop this for at least 3 months before taking part in the LOCI Trial.
If I take part, which treatments will I receive? Neither you nor your doctor or nurse will be able to choose which treatment you receive. Your treatment will be decided by a computer at the LOCI Trial Office. The computer will allocate the treatment randomly, like tossing a coin. You will have an equal chance of receiving either letrozole or clomifene and either metformin or a placebo (‘dummy’ tablet). In addition, neither you nor your doctor or nurse will know your treatment allocation throughout the study. This method of research is called a “double-blind placebo-controlled randomised trial”.
How do I take the trial medication? Please keep a record of your periods during treatment If you have had a period recently your doctor may tell you to start the tablets straight away. Day 1 First day of proper bleeding Day 2-3 Start letrozole or clomifene (1-3 tablets as directed by your clinical team) daily for 5 days. Start metformin or placebo (1 -3 tablets as directed by your clinical team) daily. Day 6-7 Last day to take your letrozole or clomifene tablets. Continue the metformin or placebo tablets throughout your time
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LOCI Participant Information Sheet v3.0 15-Feb-2021 in the study. If you become pregnant, we ask that you continue taking the tablets until 14weeks gestation . Please start regular intercourse 2 or 3 times a week from day 8 of your cycle.
To help confirm successful ovulation there are three main ways of doing this. One is to take home ovulation test kits, another is to check a hormone level around day 21 of your cycle (luteal progesterone test) through a blood test and the third way is to have an ultrasound scan to check for ovulation. Every hospital will have their own pathway to follow, your clinical team will guide you as to which method of confirming ovulation you should have.
If you have the day21 progesterone blood test done by your GP, please provide a copy of your result to your clinical team. No additional blood tests are required as part of the trial
If your period starts, restart your letrozole or clomifene on day 2 or 3 for 5 days and continue your metformin or placebo (Page 4).
If your period does not start then: ▪ Please do a pregnancy test. ▪ If the test is negative, a discussion may take place with your local clinical team. You will usually be given letrozole or clomifene for 6 months and a review appointment will be arranged thereafter at the fertility clinic.
What other advice can you provide to support conception? Weight and lifestyle measures The single most important factor affecting your treatment outcome is your weight. It is therefore important to ensure that you have a Body Mass Index (BMI) of less than 35. This can be IRAS ID: 257918 EudraCT number: 2018-004641-16 ISRCTN: 11828358 Page 5
LOCI Participant Information Sheet v3.0 15-Feb-2021 achieved by healthy eating and regular exercise. If your BMI is above 35.0 you will not be able to take part in the trial.
Folic acid Take folic acid (400 mcg) daily whilst trying for pregnancy, once pregnant continue folic acid until 12 weeks of pregnancy. Some women may be advised to take a higher dose.
What else will I need to do? Patient treatment diary You will also be given a Patient Treatment Diary to record your menstrual bleeding and the medicines (letrozole/clomifene and metformin/placebo) you have taken each month. You will be asked to bring this diary with you to each hospital appointment to enable a member of the clinical team to discuss your care and document the treatment you have taken.
Smartphone app Additionally, you may wish to download and use a medication tracker mobile app that allows you to easily track your trial medication intake and set reminders for when to take them. This will be optional and thus entirely up to you.
What happens next? Please continue taking the metformin or placebo tablet until 14 weeks of your pregnancy.
If you are not pregnant after 6 months of letrozole or clomifene ovulation induction treatment, your doctor will discuss further treatment options at your next clinic appointment. These may include the use of fertility injections such as Gonadotrophin or surgical treatment such as ovarian diathermy. Ovarian diathermy is a procedure which involves a general anaesthetic and use of heat or laser to destroy the tissue that producing male
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LOCI Participant Information Sheet v3.0 15-Feb-2021 hormones (reducing fertility). Alternatively, you may proceed directly to in-vitro fertilisation (IVF) treatment.
How will information about me be collected? We will collect most of our study information from your hospital notes and as part of any discussion with the care team. We will ask that you complete a short quality of life questionnaire around your first visit and at approximately 6 and 18 months.
Your Patient Treatment Diary will also be used to monitor your menstruation and intake of the trial drugs during the study.
We would also like to contact you after your participation in the study has ended to ask your permission to follow you up in the long term.
What are the benefits of taking part in this trial? At the moment there is not enough evidence to say which treatment is best for ovulation induction and a successful pregnancy outcome.
We do not know whether you will benefit personally from taking part in this study, but the knowledge gained thanks to your help will inform future treatment and potentially lead to improved treatment for ovulation induction for women in the future.
What are the risks of taking part and are there any side effects to taking these drugs? The most common side effect of taking letrozole or clomifene is hot flushes, as well as occasional fatigue and dizziness. Metformin can often cause stomach upset and sickness. Treatment with letrozole is off-license as the drug company has not applied for a
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LOCI Participant Information Sheet v3.0 15-Feb-2021 specific license to allow treatment for fertility and is therefore not approved for ovulation induction.
The risk of congenital abnormalities in babies appears to be low for both letrozole and clomifene and is comparable with babies conceived naturally. However, caution is advised to ensure these are not taken accidentally while you are pregnant.
What if new information becomes available? Sometimes new information about medicines becomes available. If this happens, we will tell you and discuss whether you should continue in the study. If you decide not to carry on with the study then we will make arrangements for your care to return to standard care. If you decide to continue in the study then we may ask you to sign an updated consent form. If the study is stopped for any other reason, we will tell you and arrange your continuing care.
Can I decide not to carry on with the study? If you decide to take part in the study but then change your mind, you will be free to withdraw at any time and stop taking the study treatment, without giving a reason (although we will appreciate it if you tell us why you changed your mind). Your care will not be affected in any way.
If you decide to not take any of the treatment, we would still like to find out what happens to you, and to use all the information already collected from you, unless you tell us that you are unwilling for us to do so.
How will my GP know I am participating? With your consent, we will inform your General Practitioner of your participation in the study.
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LOCI Participant Information Sheet v3.0 15-Feb-2021
What will happen to the results of the study? When the results of the study are known, we will inform you of the overall findings by email and/or via our website. We will also publish the overall findings of the study in medical journal(s), for consideration by the National Institute for Health and Care Excellence (NICE).
Who has organised and reviewed the research? This study has been funded by the National Institute for Health Research (NIHR). It is organised, managed and coordinated by the University of Birmingham, and data will be collected and stored by this institution. The study is also sponsored by the University of Birmingham.
The LOCI trial has been reviewed by the West Midlands— Edgbaston Research Ethics Committee. Additionally, the study will be supervised on a regular basis by an independent Data Monitoring and Ethics Committee (DMEC) and Trial Steering Committee (TSC) to ensure the safety of all participants in the study.
The doctors and nurses/midwives caring for you will not receive any payments for recruiting women into the study. Our study participants will not be paid to take part. Your involvement would be greatly appreciated and will help us understand how best to optimise ovulation induction in women with PCOS and infertility.
What if there is a problem? If you take part in the study, then you will retain the same legal rights as any other patient within the National Health Service. If you are not satisfied with any aspect of the way in which you have been approached or treated during the course of our study, then please speak first to the researchers (our contact details are
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LOCI Participant Information Sheet v3.0 15-Feb-2021
on the front cover of this information leaflet).
If you wish to complain formally, then the normal National Health Service complaints mechanisms will be available to you: please ask to speak to Patient Advice and Liaison Service (PALS) and Complaints Please contact the PALS team: Tel: (0113) 2066261 - Available during normal working hours only (9:00am to 4:30pm Monday to Friday). Tel: (0113) 2067168 - For queries outside of normal working hours, please leave a voicemail. E mail: [email protected]
The Sponsor (University of Birmingham) has insurance in place for the duration of the research project including legal liability cover.
Data Protection Essentials In order to carry out the research project described above, we will need to collect information about you, and some of this information will be your personal data. Under the data protection law, we have to provide you with very specific information about what we do with your data and about your rights. We have set out below the key information you need to know about how we will use your personal data. More information on how the University processes personal data can be found on the University’s website on the page called ‘Data Protection - How the University Uses Your Data’ (https:// www.birmingham.ac.uk/privacy/index.aspx).
Who is the Data Controller? The University of Birmingham, Edgbaston, Birmingham B15 2TT is the data controller for the personal data that we process in relation to you.
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LOCI Participant Information Sheet v3.0 15-Feb-2021
What data are we processing and for what purpose will we use it? We will collect and process your personal data to conduct the research project, as explained in this Participant Information Sheet. What is our legal basis for processing your data? The legal justification we have under data protection law for processing your data is that the sponsor is undertaking medical research in the public interest.
We do not envisage any problems occurring as a result of your participation in the study. However, all patients are covered for negligent harm according to NHS indemnity guidelines. If you have a concern about any aspect of this study, you should ask to speak to a member of the research team who will do their best to answer your questions (our contact details are on the front cover of this information leaflet).
How will we use information about you? We will need to use information from you and your medical records for this research project and any potential future follow on studies.
This information will include your initials, NHS number and contact details. People will use this information to do the research or to check your records to make sure that the research is being done properly. People who do not need to know who you are will not be able to see your contact details. Your data will have a code number instead. We will keep all information about you safe and secure.
Once we have finished the study, we will keep some of the data so we can check the results. We will write our reports in a way that no-one can work out that you took part in the study.
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LOCI Participant Information Sheet v3.0 15-Feb-2021
Who will my personal data be shared with? Leeds Fertility at Seacroft Hospital will use your name, NHS number and contact details to contact you about the research study, and make sure that relevant information about the study is recorded for your care, and to oversee the quality of the study. Individuals from the University of Birmingham and regulatory organisations may look at your medical and research records to check the accuracy of the research study. Leeds Fertility at Seacroft Hospital will pass these details to The University of Birmingham along with the information collected from you and your medical records. The only people in The University of Birmingham who will have access to information that identifies you will be people who need to contact you to confirm any information or audit the data collection process. The people who analyse the information will not be able to identify you and will not be able to find out your name, NHS number or contact details. Leeds Fertility at Seacroft Hospital will keep identifiable information about you from this study for 25 years after the study has finished. We will not share your personal data with any third party.
Sometimes, external organisations assist us with processing your information, for example, in providing transcription services. These organisations act on our behalf in accordance with our instructions and do not process your data for any purpose over and above what we have asked them to do. We make sure we have appropriate contracts in place with them to protect and safeguard your data. If your personal data are transferred outside the European Union (for example, if one of our partners is based outside the EU or we use a cloud-based app with servers based outside the EU), we make sure that appropriate safeguards are in place to ensure the confidentiality and security of your personal data.
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LOCI Participant Information Sheet v3.0 15-Feb-2021
When you agree to take part in a research study, the information about your health and care may be provided to researchers running other research studies in this organisation and in other organisations. These organisations may be universities, NHS organisations or companies involved in health and care research in this country or abroad. Your information will only be used by organisations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research.
This information will not identify you and will not be combined with other information in a way that could identify you. The information will only be used for the purpose of health and care research, and cannot be used to contact you or to affect your care. It will not be used to make decisions about future services available to you, such as insurance.
How will my personal data be kept secure? The University takes great care to ensure that personal data is handled, stored and disposed of confidentially and securely. Our staff receive regular data protection training, and the University has put in place organisational and technical measures so that personal data is processed in accordance with the data protection principles set out in data protection law.
The University has an Information Security Management System based on ISO27001 with a range of controls covering the protection of personal information. Annual security awareness training is mandatory for staff and the University is accredited under the NHS Information Governance Toolkit, the Payment Card Industry Data Security Standard and is in the process of gaining Cyber Essentials Plus for defined services. In relation to this project, electronic data will be kept on secure, encrypted IT servers within the University of Birmingham and also securely stored on a trusted external database provider, MedSciNet. Any physical paperwork containing
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LOCI Participant Information Sheet v3.0 15-Feb-2021 identifiable data will be kept in an access-controlled, secured room inside a locked filing cabinet at all times.
How long will my personal data be kept? Your data will be retained for 25 years after the publication of the research outcomes. If you withdraw from the project, we will keep the information we have already obtained but, to safeguard your rights, we will use the minimum personally-identifiable information possible. Your rights in relation to your data You may have the following rights in respect of your personal data: The right to access your data (often referred to as a Subject Access Request). The right to rectification of inaccuracies in your data. The right to erasure your data (in certain circumstances). The right to restrict processing of your data (in certain circumstances). The right to object to the processing of your data (in certain circumstances). The right to ask for your personal data to be transferred electronically to a third party. The right to withdraw consent.
However, your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the project, we will keep the information we have already obtained but, to safeguard your rights, we will use the minimum personally-identifiable information possible. If you would like more information on your rights, would like to exercise any right or have any queries relating to our processing of your personal data, please contact:
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LOCI Participant Information Sheet v3.0 15-Feb-2021
The Information Compliance Manager, Legal Services, The University of Birmingham, Edgbaston, Birmingham B15 2TT Email: [email protected] Telephone: +44 (0)121 414 3916 If you wish to make a complaint about how your data is being or has been processed, please contact our Data Protection Officer: Mrs Carolyn Pike, OBE, The Data Protection Officer, Legal Services, The University of Birmingham, Edgbaston, Birmingham B15 2TT Email: [email protected] Telephone: +44 (0)121 414 3916
You also have a right to complain to the Information Commissioner's Office (ICO) about the way in which we process your personal data. You can make a complaint using the ICO’s website https://ico.org.uk
Where can I find more information? Sources of further support
Tommy’s [email protected] www.tommys.org 0800 014 7800 Monday-Friday, 9-5pm
Fertility Network UK 01424 732361 www.fertilitynetworkuk.org Mon-Fri, 9am-5pm
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LOCI Participant Information Sheet v3.0 15-Feb-2021
Contact Information If you would like to speak to someone about the study please contact the trials team at: [email protected]
www.birmingham.ac.uk/loci
Support can also be found through the NHS Patient Advisory and Liaison Service (PALS) Patient Advice and Liaison Service (PALS) and Complaints Please contact the PALS team
Tel: (0113) 2066261 - Available during normal working hours only (9:00am to 4:30pm Monday to Friday).
Tel: (0113) 2067168 - For queries outside of normal working hours, please leave a voicemail. E mail: [email protected]
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