Review Board Oversight and the Consent Rules

Part of Regulatory Affairs and the Jurisdiction Map: The United States under 21 CFR.

About 6 minutes. Free, in your language, no account needed.

Why this matters

In the United States the ethical review function and the consent requirements sit in their own parts of the regulations, separate from the investigational product framework. A regulatory professional who reads only the drug regulations has read half of what governs the trial.

21 CFR Part 56 governs institutional review boards: their composition, their authority, their procedures and their records. 21 CFR Part 50 governs the protection of human subjects, including what informed consent must contain.

These are not soft expectations. They are regulations, and they are inspected against directly.

What the board must be, and what it may do

Part 56 sets requirements for the board itself. It must have enough members with varying backgrounds to promote complete and adequate review, with attention to professional competence, the diversity of its members, and sensitivity to community attitudes. It must include at least one member whose primary concerns are scientific and at least one whose primary concerns are nonscientific, and at least one member not otherwise affiliated with the institution.

A member may not participate in the review of a study in which they have a conflicting interest, except to provide information requested by the board.

The board's authority is substantive rather than advisory. It may approve, require modifications to secure approval, or disapprove. It must conduct continuing review at intervals appropriate to the degree of risk, and not less than once per year. And it may suspend or terminate approval of research that is not being conducted in accordance with its requirements or that has been associated with unexpected serious harm to subjects.

That last power is worth dwelling on. A board can stop a study at its institution on its own authority, without the sponsor's agreement and without the agency's involvement.

What consent must contain

Part 50 sets out the basic elements of informed consent. In substance, a participant must be told:

That the study involves research, its purpose, the expected duration, the procedures, and which procedures are experimental. The reasonably foreseeable risks or discomforts. Any reasonably expected benefits. Appropriate alternative procedures or treatments. How confidentiality of records will be maintained. For research involving more than minimal risk, whether compensation and medical treatments are available if injury occurs. Whom to contact with questions about the research, about research subjects' rights, and in the event of a research-related injury. And that participation is voluntary, that refusal involves no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue at any time without penalty or loss of benefits.

Additional elements must be provided where appropriate, and consent may not include exculpatory language through which the subject waives or appears to waive any legal rights.

The exception people misapply

There is a narrow exception permitting research in emergency circumstances, and it is genuinely narrow. It requires that the subject is confronted by a life-threatening situation necessitating the use of the test article, that legally effective consent cannot be obtained from the subject, that time is not sufficient to obtain consent from the subject's legal representative, and that no alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject's life. These determinations must be certified in writing, and the framework requires independent concurrence except in defined circumstances.

The error is treating this as a general provision for emergency research. It is not a substitute for the separate framework governing planned emergency research with a waiver of consent, and a protocol relying on the wrong one has relied on a provision that does not cover it.

In practice

A sponsor's consent template is used across a global study and adapted per country. The US version is reviewed by the regulatory lead against Part 50 before it goes to the boards.

She finds two problems. The compensation section says the sponsor "may, at its discretion, cover reasonable medical expenses arising from study participation." The phrase creates an impression of coverage while committing to nothing, and it sits close to the line on exculpatory language.

The second is quieter. The template gives one contact for questions about the research and about subjects' rights, and that contact is the study coordinator. The requirement contemplates the subject being able to reach someone other than the research team about their rights, and a single research-team contact defeats it.

Neither problem would stop a study. Both would produce a board asking for modifications, adding a review cycle across eighteen sites. Finding them before submission is worth more than finding them well.

What this looks like when it goes wrong

A board approves a study and sets continuing review at twelve months. The study runs, the anniversary passes, and nobody submits the continuing review.

Approval lapses. Every activity after the lapse date is unapproved research, including every visit conducted, every dose administered and every datum collected.

The site does not notice because nothing stops. The system does not lock. Participants keep attending visits, and the coordinator keeps working. The lapse is discovered six weeks later during a monitoring visit.

The remedy is not retrospective approval, which does not exist. It is reporting the lapse, a board determination about the affected participants and data, and a serious conversation about whether those participants continue. A calendar entry would have prevented all of it.

Key takeaways