Those who are not researchers may have wondered how human research is regulated, how research subjects are protected, and how we ensure research is done correctly. Those who do human research know only too well: the Institutional Review Board.
We accept that regulations are necessary for clean water, clean air, safe food, and medicines. And our readers are familiar with complaints that regulations are based on the wrong criteria, too strict, or too lax. In the world of research, both academic and private, Institutional Review Boards, however they are titled, are the research guardrails. Telling researchers what they can or cannot do, what must be written in the consent form or advertisements, how much subjects can be paid, and many more things. Researchers sometimes chafe under these requirements but, on the whole, recognize that it protects the researchers and subjects.
The Federal Government tightly controls the makeup and functions of an IRB, specifically Health and Human Services (HHS) through the Office for Human Research Protections and the FDA (Food and Drug Administration) for drugs and devices. The Board must have at least five members, including a scientist, a non-scientist, and someone not affiliated with its institution. In practice, IRBs have a variety of researchers and clinicians reflecting the research covered and a community member as a “patient advocate.” [1] It is not required, but it is helpful to have an ethicist on board.
The IRB decides what proposals are considered covered “human research” and reviews all new proposals and all changes, problems and adverse reactions, and annually for active projects. An IRB has the authority to approve, require modifications, or disapprove research.
The History of IRBs
It’s a sad story: of cruelty, hubris, and indifference, usually with powerful people using the poor and helpless for their own ends. It started at the Nuremberg trials when Nazi doctors were convicted of experimenting on Jews and prisoners, and the Judges recommended some principles for conducting research: the Nuremberg Code. But it was not just cruel Nazis. In the United States, the Public Health Service put the attainment of knowledge above the health of poor black patients with syphilis in Tuskegee. Despite the proven efficacy of penicillin in treating syphilis, these “participants” were not given penicillin for over a decade to study the natural progress of the disease. Likewise, at Willowbrook, children with intellectual disabilities were deliberately infected with hepatitis upon admission to study its progression. (The justification was that they would all get it sooner or later anyway.) Unfortunately, there were many other examples of dangerous research being done without the patient's consent.
This was a global problem. In 1964 the World Medical Association meeting in Finland came up with the Declaration of Helsinki Ethical Guidelines for Human Subject Research. It has been updated every few years since. The revisions are not without controversy. A few years ago, a revision suggested that placebo-controlled trials were unethical. I believe it would be unethical to introduce a new drug without placebo-controlled trials demonstrating its effectiveness and side effects.
In the US, the National Research Act of 1974 created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research which produced the very important Belmont Report, which laid down three principles of human research:
- Respect for persons (both autonomy and protection of the vulnerable)
- Beneficence (maximizing the benefit-to-harm ratio)
- Justice (assigning the burdens and benefits of research fairly).
IRBs aim to apply these principles to the research they consider. Is it dangerous? Do the benefits outweigh the risks? Does the consent form explain, in an understandable way, all the procedures, risks, and benefits? Might there be coercion? Are children protected?
IRBs spend much time examining consent forms; there are many legal and regulatory requirements, but consent is not just signing forms. It involves explaining the study and making sure the subject understands it. One role of IRBs is monitoring studies to ensure that the described protocol is followed; this can include observing the obtaining of consent.
IRBs take varying approaches
I’m a member of two IRBs; a large medical school and a smaller psychiatric research institute IRB. In both, a primary reviewer and a secondary reviewer are assigned, who evaluate the proposed research and discuss any unclear issues with the research team. Both reviewers complete a check-off form indicating that the regulatory requirements for the study and the consent have been met and write a brief report to the entire IRB panel. In one of my IRBs, the investigator presents the study; in my other IRB, the primary reviewer presents the study with the investigator present. The rest of the board then asks questions. The board members discuss the research and its issues and pass a motion to approve, disapprove or require modifications after the researcher has left. Studies with minimal risks, such as those involving de-identified data already collected, may be “expedited” and reviewed only by the chair or designated members.
Over time the legal and administrative requirements of IRBs have significantly increased, so it is essential to have a good and knowledgeable director and staff. For these reasons, small hospitals combine to share an IRB or use commercial IRBs. Over time, the need for a larger research population has grown, if for no other reason than to provide increased statistical power to their conclusions. Many studies today involve multiple research centers, each with its own IRB. To reduce bureaucratic delay and confusion, the National Institutes of Health now requires its multi-center studies to use a single IRB. Local IRBs “cede” review to that IRB but may also bring local concerns to the central IRB for review.
IRBs came into being because of unregulated, abusive, and dangerous human research. Hopefully, they have made that a thing of the past. But they require conscientious and thoughtful members and staff to prevent new risks to research participants and excessive and unnecessary demands on researchers.
[1] ] For research done in a prison population, a prison worker or advocate acts on behalf of the prisoners.
