Writing an ethics application for the committee that reads it

An ethics committee or institutional review board decides on a submission whose documents must let every member, lay members included, judge the science, the risk to participants and whether a participant could give true informed consent. Writing that submission means choosing the route to approval and preparing early, giving a US board every required document in plain, consistent and complete detail, and writing the lay sections of a UK application to the standards its reviewers apply.

Choosing the route and preparing early

The route to ethics approval depends on the nature of the study, and research using human tissue has specific legal and regulatory requirements. ¹ When choosing the route, researchers should consult their local committee's guidelines and seek early contact with its members, so that all the necessary information and documents are available. ¹ Obtaining approval can be time-consuming and nerve-racking, and much time is often lost at this early stage because applicants are not well informed of what the planned study requires. ¹ To speed the procedure, applicants should consult someone experienced in ethics applications early. ¹

Approval by a US institutional review board can take anywhere from weeks to months, depending on how often the board meets, its workload and staffing, and the type and complexity of the research. ² It is smart practice to engage the board early in the research, because the board can be a valuable research resource. ²

A favourable decision depends on the scientific logic and persuasiveness of the proposal, and also on the clarity and completeness of the documents supporting it. ¹ Writing the study documents effectively and ethically helps the committee fulfil its objectives, which eases approval and leads to a useful and successful study. ³ An ethics application should be well written and aimed at the right audience, and medical writers can have a role in preparing it. ⁴

A US review board application

US federal regulations require board review of all research activities, to protect participants' rights and welfare during a clinical study. ⁵ To that end, a board must review every study document, among them the protocol, the consent form and, for a study conducted under investigational new drug regulations, the investigator's brochure. ⁵ The board should also review the methods and materials the investigators intend to use to recruit participants. ⁵ The same regulations codify what study documents must contain, but clinical study personnel do not understand these requirements well. ⁵ The documents the regulations name for a board's review include the study protocol; the consent forms the investigator proposes to use; recruitment materials such as advertisements; all written information participants will receive, such as instructions for use; the investigator's brochure; available safety information; information about payments and compensation; and documentation of the investigators' qualifications. ^{6, 7}

US regulations require every constituted board to include a nonscientific lay member, so a writer should make no assumptions about what the reviewers know. ² The documents must consistently give enough information to justify starting or continuing the research, in language accessible to every member. ² Details matter because they let reviewers determine the overall risk to the participant, though too much detail can be unnecessary. ² Gaps and a lack of specificity prompt the board to put question after question to the investigator until the picture is complete enough to judge the risk. ² A well-written application that follows accepted guidelines therefore eases the board's work, speeds the review and helps to ensure that the research is conducted professionally and to ethical standards. ²

The formula for a successful board submission has five parts: ²

• Simplify. Use language that is easy to understand.
• Justify. Give a science-based rationale for the study, its design and the risk to participants.
• Protect. Make sure the protocol describes clearly how participants are protected throughout, and never downplay the risk so that the research looks safer than it is.
• Be complete. Give complete, detailed information in every required document.
• Be consistent. Keep the information consistent across the sections of each document and across the study documents. ²

The lay sections of a UK ethics application

To make sure a participant can give true informed consent, meaning that they truly understand what they are agreeing to, a UK research ethics committee scrutinises the lay summary in section A6-1 of the Research Application Form, sections A10 to A13, and every participant-facing document. ⁸

The lay summary is at most 300 words, in language easily understood by lay reviewers and members of the public, and answers five questions: ⁹

• Why: the research question and why it matters.
• What: the disease, therapy or service studied and, for a therapeutic study, the drug, device or procedure tested.
• Who: who is eligible, who funds the research and who conducts it.
• Where: where recruitment happens.
• How: the duration, the design, what participants undergo and whether they must submit anything. ⁹

Sections A10 to A13 must also be written in language easily understood by a member of the general public. ¹⁰ A10 must clearly state the primary research question or objective, and A11 every secondary one. ¹⁰ A12 must give the scientific justification, answering clearly and simply what knowledge gap the research fills, why the question is important, what answering it will gain, and whether similar research has been done and, if so, why another study is needed and what is new. ¹⁰ A13 must summarise the design and methodology so that it is clear exactly what will happen to a participant, how many times and in what order. ¹⁰ Depending on the study type, A13 must also address: ¹⁰

• the null and any alternative hypotheses, and why the alternative was chosen
• the scientific and practical justification for the design and methodology and, where patients, carers, service users or the public were involved in design decisions, how their input was incorporated; committees give weight to suggestions from patient and public involvement
• the justification for control arms, especially a placebo arm
• procedures to detect and compensate for possible researcher effects and researcher bias
• how participants are identified, approached and sampled, with power and sample-size calculations
• a broad timetable for the stages of the research, such as preparation, convening meetings or conducting interviews, interpreting and analysing findings, and preparing the final report
• the sites for interviews
• any plans for interim analyses or reports. ¹⁰

Writing the UK lay sections for lay reviewers

Reviewers of the form should be able to see easily whether the research is useful, whether the study can answer its question, the state of the field, and whether the eligibility criteria are justified and as inclusive as possible. ¹¹

The language should be easily understood by a general audience, because a third of the committee are members of the public and language problems are the commonest issues committees meet. ¹¹ One committee member suggests four ways to make a lay summary easier to understand: ¹¹

• Test the text on a non-specialist not closely involved in the research, which can be part of the study's public involvement.
• Use readability scores. The Flesch Reading Ease and Flesch–Kincaid grade level in Microsoft Word are good enough for a rough estimate of the language level, and web-based applications can also analyse readability.
• Use plain-English guides and glossaries. The NIHR plain English summaries guide, published in April 2021, helps in writing and reviewing lay summaries, and glossaries such as the Multi-Regional Clinical Trials Center's Clinical Research Glossary give plain-language substitutes for technical terms and acronyms.
• Use generative AI such as ChatGPT to evaluate and rewrite the text in plain English. In that member's experience its output is not too bad, and it can serve as a good starting point.

¹¹

The form should clearly reflect the protocol and the participant information sheet, but it should not simply reproduce or refer to the protocol, above all in A12 and A13. ¹¹ Protocol text does not suit the committee, and copying it signals to members a lack of empathy and diligence, which may alter their perception of the study. ¹¹ Medical writers who work on ethics submissions should highlight this advice in their organisation's standard operating procedures. ¹¹

The form should use visuals such as flow charts, diagrams and tables to make processes and information clearer. ¹¹ A13 is especially hard to grasp in words alone and should be accompanied by well-designed visuals. ¹¹

When lay reviewers cannot understand an application

A UK application that lay reviewers cannot understand takes longer to be approved, because the committee points out the problem and has more questions and requests. ¹¹ A UK committee cannot request a resubmission of the form, though its members wish they could, but it can keep asking questions until it gets what it wants. ¹¹ Applications have been rejected for ethical concerns that arose from poor language. ¹¹ A US institutional review board, by contrast, can label an application unacceptable and request a rewrite and resubmission. ¹¹ One consultant on US boards finds that power very useful when a board reviews a decentralised trial from screenshots of interfaces, which must be understandable because the participant is isolated and has no immediate support. ¹¹