Navigating the ethics form and the committee Dr Carl Edwards Chair of Leicester REC Why a national ethics system? • Recognition of basic rights – Nuremburg Code (1947) – Declaration of Geneva (1948) – Declaration of Helsinki (1975) • Failure of local enforcement – Willowbrook State School (1963-1966) – Guatemala (1945-1948) – Tuskegee (1932-1972) • Legislation on ethical conduct – Human Tissue Act – Mental Capacity Act – Medicines for Human Use (Clinical Trial) Regulations National Research Ethics Service (NRES) • NRES launched on 1 April 2007, merged; – Central Office for Research Ethics Committees (COREC) – Research Ethics Committees (RECs) in England • “... protect the rights, safety, dignity and well-being of research participants, whilst facilitating and promoting ethical research.” • SOPs and regulations relating to NHS Research • Health Research Authority – To be established 1st Dec 2011. [watch this space] http://www.nres.npsa.nhs.uk/ http://www.nres.npsa.nhs.uk/news-and-publications/publications/standard-operating-procedures/ IRAS • The IRAS form will gather information for: – Administration of Radioactive Substances Advisory Committee (ARSAC) – Gene Therapy Advisory Committee (GTAC) – Medicines and Healthcare products Regulatory Agency (MHRA) - Devices – Ministry of Justice (National Offender Management Service) – NHS / HSC research offices – NRES/ NHS / HSC Research Ethics Committees – Patient Information Advisory Group (PIAG) • Import/ export mechanism with EudraCT. – Medicines and Healthcare products Regulatory Agency (MHRA) for clinical trials of investigational medicinal products. What’s it all about? • Navigating the form is your best start to being able to navigate the committee. • The form is: – Is your best chance to communicate with the committee. – Is exhaustive. – May contain things you feel are not ethically relevant. – May contain things you feel are just not relevant. – Is not optional – Is the first thing the committee will know about you. The committee - 1 • Up to 18 members; Chair, Vice-Chair, plus administrator • Variety of backgrounds – Expert – Lay • System of review – Single lead reviewer – All members can read and comment – 3 decisions • Approve • Provisional opinion • Rejection The committee - 2 • What do committees look at? – What’s happening to the patient? – Do they know what’s going to happen? • Informed consent – understandable information – Is what’s happening justified? • Risk vs. Benefit • Discomfort vs. Benefit – Is there a scientific basis for the study? • Repeating existing work? • Poor research is unethical – Coercion and Inducement – Confidentiality and Dignity Review of the form • Will examine Sections of the form in it’s layout for Clinical Trials of Investigational Medicinal Product (CTIMP). • This is about as complex as the form gets. – Other types of research will have fewer questions. • This review will try to explain how the committee looks at the form. – Use this as additional help, it is not a substitute for common sense. Front page - 1 • Covering letter – Use it to elaborate any points not in the form. • MHRA request – Not an approval • Protocol – Could you do the work reading only this? • PIS/Consent – More important than the protocol to the REC? • Letter of invitation – Who is sending it? • GP letters – Really? • Letters (Sponsor, Funder, Statistician) – All help support you. • Summary/Diagram – Very important Front Page - 2 • Questionnaires – Layout and validation. • Adverts – Take time over these, need to be clear and from the right person. Project Filter page • Carefully consider this, the choices you make affect the form you end up with. • For example: – Involve adults unable to consent for themselves through physical or mental incapacity? • Important changes in the law mean CTIMPs are covered by clinical trial directive, all other research covered by the Mental Capacity Act. Section A • 2. Overview – Make sure this is in lay language. It will be published. – Be honest about the ethical issues you see • 3 Purpose and design – Keep primary objectives simple, be honest; modest expectations are not unethical. – Scientific justification need not be complicated; do not c&p from your protocol! – Keep it short, don’t include methods here. Section A • Summary of main Issues (6-2) – Never say ‘none’. – Describe them as you see them e.g. • • • • Researcher objectivity Coercion Informed consent Ability to recruit enough participants to make the study valid. – You will not ‘flag’ things for the committee. – Don’t be afraid to ask for advice e.g. • How can you ethically gain assent? • How best to approach distressed participants? Section A • A13 “Give a full summary…” – Source of some of the worst mistakes in the form. – Use lay language; • if you can’t do it here, what confidence will the committee have in you providing information to the participants? – Do a flow diagram/pictorial summary • Not everyone gets to see the full protocol. A useful way of getting extra information across. Section A • 4. Risks and ethical issues – Be consistent in the inclusion criteria (A17) • Exclusion on grounds of race, sex, age or language abilities must be explained fully. • Convenience or funding issues are weak excuses to exclude specific groups. – Make sure that you explain where the patient treatment differs in the study (A18-21) • Are drugs normally withdrawn? • Is the catheter normally used? • Is the MRI scan routine? Consistency a huge problem here, double check or you’ll end up having to come back. Section A – Are you actually going to withhold normal care? • A chance to summarise what normally happens to a patient. (rarely happens but can be incredibly useful) – “Participant benefit” • Don’t be shy, extra scans, additional observations may be beneficial. – “Researcher risk” • Most often related to ‘lone worker’ risk, get hold of Trust guidelines. Section A • “Continuing care” (A25) – “At the conclusion of the study, patients entered into the study are entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits.” Declaration of Helsinki – Consider this carefully! Section A • Recruitment and consent – Make sure any patient note review will be done by part of their normal clinical team. – First approach must be by primary carer • Very few exceptions e.g. a general leaflet handed out in a clinic • Participating in care of the patient does not qualify as primary carer e.g. anaesthetists approaching patient about non-anaesthetic studies Section A • Recruitment and consent – The recruiter may not be the primary carer • They cannot know about potential participants without their consent. • Usual solution is for primary carer to give an invitation letter to participants with contact details for researcher on it. • Make sure that letter is from the primary carer. – Where recruitment takes place can be important. • Will it involve extra travel? • Is the location ‘safe’? Section A • “Informed consent” (A30) – Will you be getting consent and how informed will it be?. • If it’s a solely notes based project it’s probably audit not research. – Consent for tissue use isn’t always required. • Specific provisions in the Human Tissue Act for tissue normally discarded. – “Informed”, is there a case for a summary PIS? – Implied consent e.g. return of a questionnaire is fine. Do not over egg things. Section A • “Time to consider” – If there’s less then 24 hours for a participant to consider then explain why. • Convenience not an excuse • Minimal impact/harm or simplicity may be • Clinically it may be impossible e.g. emergency care • Complexity may preclude prior consent – consenting pregnant women into a study of pre-term labour at routine clinic visits where there is no evidence that they will go into pre-term labour (considered potentially distressing and leaves open potential administration errors) Section A • Confidentiality – Remember there’s a difference between personal data and study data! – Disclosure of coded/anonymous study data to 3rd parties is likely to be fine • Incentives – Payment to the hospital per patient is not an incentive to the researchers. • Notification of other professionals – Consider carefully if other groups really need to know? Section A • Dissemination – Make sure you complete this. Unreported research is unethical. • Do not over promise on reporting back to participants. Reporting back to the communities is probably more important. • Explain what will happen to any dissertations. • Statistical review – Make sure you have an appropriate case • Primary endpoints need to be clear to the lay person Section A • Indemnity (A76) – “Negligent harm” • NHS indemnity or 3rd party? – “Non-negligent harm” • Should be provided by external Sponsors • Is not provided by the NHS – It’s useful to get the ball rolling on getting a copy of the insurance cover asap! End Game • The form is complete, you have: – Considered the ethical issues. – Have translated your protocol into lay language. – Helped the committee understand what you intend to do (flow diagram, supporting letters). – Determined what you need participants to consent to. • Time now for a PIS and Consent form Consent form • Consent form – NRES have a standard format, use it. – Explicit consent is best for: • • • • • • Taping/videoing interviews Retaining tissue for testing Transfer of tissues to research partners Transfer of data to research partners Transfer of data outside of the EU ‘Genetic’ tests; ensure that you exclude those that may affect insurance. Participant information - 1 • Patient Information Sheet – NRES have a standard form, use it (sort of). – Standard form is good for organising thoughts. – Do not be afraid to delete irrelevant sections. – Use standard wording for indemnity, ethics approval. – Be explicit in quantifying any risks or discomforts. • Give lay examples for radiation doses or blood volumes. Participant information - 2 • Participant information sheet – Help the participant and the committee understand you. – Use diagrams where you can: • Flow charts • Examples of the size of biopsies • Photographs of equipment – The use of lay language can’t be emphasised too much. • “Get your mum to read it” test? Summary • The form may seem over complex and repetitive but it can help you. • The committee will not try to obstruct you. • 90% of the problems stem from misunderstandings • Regard the chance to speak to the committee as an opportunity, not an inquisition. Concluding thoughts • The ethics committee system is there to serve researchers. – Protecting participants – Protecting researchers – Advising research Sponsors • Please do not be put off research by the process.