How ethics committees are organised and how they reason
An ethics committee reviews research on people on behalf of the participants, before a study starts and while it runs. In the UK it is called a research ethics committee and in the US an institutional review board. Rules set where a committee stands relative to the institution, what it protects, who sits on it and what it reviews, and who volunteers shapes its membership. A committee decides from its own past cases and its members' judgement, and it is strained by new trial designs and by having too few and too uniform members.
Where a committee stands
Institutional ethics committees are associated with the sites where studies are conducted, and central ethics committees exist alongside them. Central committees arose because, not long ago, institutional committees were found to have a potential conflict of interest with the institution's finances: employees who sat on them might be influenced by the revenue that conducting studies there could bring the institution. In most cases an institution may keep its own institutional review board but must also apply to a central ethics committee, which is dissociated from the institution itself.
A US board reviews and approves research under federal regulations and institutional policy, and the Common Rule (45 CFR 46, subpart A, in effect from 2018) requires a board to review and approve certain studies involving people. Only non-exempt studies require a board's review, and some exempt categories require a limited review. The review is two-tiered: an independent board, unaffiliated with the institution, must review the study, and a board affiliated with the institution whose staff will conduct the study, or where it takes place, may review it as well. Independent review is meant to mitigate bias and corruption, and independent boards are paid for their reviews and work on a for-profit model. Institutions, funders of research grants and various accreditation bodies require a board to approve the research and oversee it while it runs.
Most US boards sit in academic medical centres or hospitals and bring a local perspective, but some are commercial bodies that may be thousands of miles from the research. Central boards give a national perspective and local boards a local one, and the two may not dovetail.
The UK Health Research Authority is part of the National Health Service. It was created to protect and promote the interests of patients and the public in health and social care research and to enable and support ethical research in the NHS, and the Research Ethics Service is one of its core functions.
What a committee protects
Wherever a committee sits, its main objective is to protect the public in two ways: by thoroughly reviewing the background and justification for a proposed study that investigators, funders or sponsors supply, and by making sure participants can truly understand what they agree to when they sign the informed consent form.
An ethics committee serves in a sense as a surrogate for the patients enrolled in a study, and it adjudicates by looking not only at the protocol but at how information will be presented to the patient or prospective patient. That can mean reviewing screenshots, reviewing the informed consent, and evaluating the standards of the community relative to the impact on the individual taking part in the trial. Because these standards are community-based, each institution with a committee may hold different standards and expectations, and may not allow some procedures that take place in one geographical location to take place in another. Committees scrutinise all patient-facing information for understandability.
A UK committee has two main roles. It balances participants' rights, safety and wellbeing against the researchers' wishes, and when researchers seek information that may not be ethically justified, it steps in on behalf of potential participants to make the researchers reassess their goals. It also makes sure that true informed consent has been sought, checking that potential participants know everything that will happen to them during the study and what it means for their health and wellbeing.
UK research ethics committees are entirely independent of research sponsors, funders and the researchers themselves, which allows them to put the needs of research participants at the centre of their review. Their role is twofold: to protect the rights, safety, dignity and wellbeing of research participants, and to facilitate and promote ethical research that is of potential benefit to participants, science and society.
A US board's overarching role is to protect participants. Board members want to work with investigators to make sure, as far as possible, that people do not suffer unintended consequences from taking part.
Who sits on a committee
The membership represents a community, in a sense, and is very local. It usually includes:
- a medical expert, usually a clinician
- a patient advocate for the community concerned, who may have the disease, be a caregiver, or understand the patient perspective
- possibly a member of the clergy, because religion strongly influences how people are treated, at least in the United States
- people relatively sophisticated in the science and medicine of clinical research, such as someone who works in the pharmaceutical industry, a nurse, or someone with the background to understand the potential harms of taking part in a clinical trial
In 2020 there were more than 80 research ethics committees across the UK, each with between seven and 18 members, a mix of lay members and experts, an expert being a registered healthcare or social work professional or a retired doctor.
In 2023, sixty research ethics committees were active in the UK, coordinated by the Health Research Authority and made up of volunteers. Each committee must have at least seven members and can have up to 18, with about eight to ten on average. One third of the members must be lay and the rest expert. Lay members are currently defined as people who are not registered healthcare professionals and whose main professional interest is not clinical research, so a medical writer is a lay member despite extensive specialist knowledge. Expert members are specialists such as doctors, hospital medical staff, other healthcare professionals and statisticians with expertise in clinical research. No law requires the membership to be culturally diverse or to include people with varied perspectives, such as patient advocates or research staff, but a committee functions best when its membership includes people who represent the participant community and the general population.
A US board is made up of clinicians, scientists and lay members of the community. A board has at least five members of varied backgrounds and qualifications, with no legally required diversity quota. It cannot be all one gender or all one profession, and it must include at least one member who is unaffiliated with the institution and not in the immediate family of anyone who is. A member with a conflict of interest may not take part in a review, and a board that lacks the expertise for a review can bring in an expert as a non-voting member. In 2023 there was not yet any guidance on how to classify people undergoing a gender transition.
Members of US boards are often unaware of the review process and of their own impact, and they are often volunteered onto boards with little or no background in ethics. One member served on boards for nearly a decade before fully appreciating the complexity of the process and its responsibilities. The repercussions of a board's work can be wide-ranging as trials become more global, yet board certification is in many instances an afterthought.
What a committee reviews
A UK committee reviews seven aspects of a study:
- its social or scientific value: whether the research supports the study objectives, whether the study is necessary and whether its outcomes will be useful
- the fairness of recruitment, including any excluded community, barriers such as language or technology, and the reasons for recruiting or not recruiting a vulnerable group such as children, pregnant people or people with cognitive problems
- the adequacy and completeness of the consent information
- the risk–benefit ratio: the anticipated benefits, the risks and whether they are clearly explained, and whether adverse effects are explained in clear, accurate language
- the care and protection of participants: whether their welfare and dignity are prioritised, whether study expenses will be paid, whether the language is coercive and whether they will receive the trial results
- the suitability of the applicant and supporting staff: whether capable and competent people will conduct the trial
- the suitability of the supporting information, such as the patient information sheet, posters and participant diary: whether its language is appropriate and understandable, a point committees commonly object to because the language often is not appropriate
A UK committee looks at all the clinical research studies that come to it from a purely ethical perspective, to make sure participants are looked after safely and their safety, wellbeing and rights are maintained throughout. It examines:
- the scientific design and conduct of the study
- the recruitment arrangements, and whether participant selection is fair
- the informed consent: whether participants actually understand what they are committing to, and whether the documentation in front of them is complete
- the balance of benefit and risk: whether participants are exposed to too much risk for the information the study will yield
- everything used to support the study alongside the consent documents, such as posters, recruitment material and diaries
- the suitability of the applicants and their supporting staff
US boards are heavily regulated and follow the FDA's criteria for approval (21 CFR 56.111), and their review is continuous. To approve a study, a board must find in its initial review that all of the following are met:
- risks are minimised and reasonable against the anticipated benefits and the importance of the resulting knowledge, since participants give their time and put their wellbeing at risk for benefits that may not be realised
- selection is equitable and considers language, socioeconomic and technological barriers to taking part
- consent is sought and appropriately documented, with an understandable form
- the research plan includes a data monitoring plan to record signals of risk
- participants' privacy is protected
- vulnerable participants are protected by appropriate safeguards
When new information affects its earlier findings, a board conducts a continuing review against the same criteria (21 CFR 812.64).
A board reviews these materials:
- the protocol and consent documents in use at the study site, and any proposed changes to them
- a summary of amendments since the last review
- the investigator's brochure and its modifications
- new information, especially about risk, from sources such as competitors' products, newly described syndromes and other published or unpublished sources
- relevant regulatory actions that could affect safety and risk
- other significant information, such as reports from data monitoring committees
- a summary of participants' withdrawals since the last review
- a summary of participants' complaints since the last review
How committees reach their decisions
US institutional review boards operate by case-based learning, using previous decisions as the basis for new ones, rather than by applying a general set of rules or principles. So different boards reach different judgements, which can be a big problem for a multi-site study, where the boards covering different sites may request different amendments. Training board members on a common set of real cases has been proposed as a way to make decisions more consistent.
In three boards whose meetings were observed, the members' backgrounds, biases and prejudices greatly affected how the boards operated, and researchers were judged on the writing of their applications, including typos and inconsistencies.
Because board meetings are closed, subjective experience, such as members' experiences of family members and acquaintances, can weigh more heavily in decisions than it might in an open meeting. The minutes give a selective picture: they obscure disagreement, give the impression of consensus, and shield individual members from being linked to particular requests for changes, which lets members make those requests without fear of reprisal.
The federal guidelines boards must follow are highly subjective, and members try to do the right thing for participants even when they are uncertain about the effects of a proposed intervention. Risk to patients is a fundamental consideration in every protocol a board reviews, yet minimal risk does not mean the same thing to every member, every board or every oversight or accreditation agency.
Boards also find the appropriate payment of participants difficult: what amount is fair, reflecting invasiveness or inconvenience, and what is excessive or possibly coercive is often unclear. Coercion, the idea that people might do something not in their best interest solely for money, could undermine informed consent. A framework for fair payments proposed in 2018 illustrates the continuing lack of consensus in the research community.
Decentralised trials
Decentralised trials use technology, processes or services that create the opportunity to reduce or eliminate participants' need to visit a traditional research site, which raises the question of what information an ethics committee reviews when participants do not visit a site. Good clinical practice (ICH E6(R2)) requires the written information given to patients to be submitted for ethical review, which would include the electronic consent form and screenshots of the patient-facing screens. Under an adaptive design, however, the screens can change from one day to the next, and reviewing every possible screen would greatly increase the effort and time committees need, so the initial library of screenshots submitted may not be complete.
US boards get only screenshots, not a software demonstration, and screenshots are not enough to understand the patient's view. UK committees lagged behind in how to review such trials carefully: they are sometimes sent weblinks to help them experience a platform, but there is no clear guidance on how to submit them.
Committees also ask about equity and digital literacy in a decentralised trial: whether participants will be given a device, know how to use it, can get online, or have the option of using a facility instead. Providing such options is good practice, so as not to hinder participation inadvertently.
Diversity of participants and members
One of the main problems ethics committees face is diversity, both in recruitment and in their own membership. In recruitment, the participant population should be representative, but taking part is hindered by cultural norms and historical injustices that have eroded some communities' trust in clinical research, and it is hard to balance benefit and risk in deciding whether to recruit vulnerable participants. A committee that represents the participant community would help with both, but such a committee has proved hard to build.
Too few people volunteer, because membership takes a large time commitment, a good understanding of clinical research and possibly some qualifications. It also means much reading and may mean travel, though most meetings are now held online. Even so, members are mainly White, older people with the time and luxury to take part. Because neither the UK nor the US legally requires a diverse membership, there is less motivation to persuade people from under-represented communities to volunteer.
Committees run on small budgets and cannot pay their members, and they need to be careful about making and receiving payments, which may lead to conflicts of interest. Members take part out of the goodness of their heart, though a UK committee's chair and vice-chair receive a small annual payment for their extra work.