By Eric Krebs
Nearly two millennia ago, the Roman poet Juvenal famously asked: Quis custodiet ipsos custodes? Who will watch the watchmen?
When researchers in the United States conduct human subjects research—research that involves interacting with and observing other people to generate new, generalizable knowledge—they must submit to the watchful eye of Institutional Review Boards (IRBs).
To many researchers, especially those outside of fields typically engaged in human subjects research, IRBs are mysterious, bureaucratic entities. This week on “Proof over Precedent,” Shannon Sewards—current Administrative Director of the Dartmouth Health IRB and former IRB administrator at Harvard University—joined host Jim Greiner for the first in a series of discussions demystifying Institutional Review Boards.
Post-War Origins
Modern ethical frameworks for human subjects research trace their origin to the aftermath of World War II.
In 1947, the Nuremberg Military Tribunal decided United States v. Karl Brandt et al.—also known as the “Doctors’ Trial”—indicting Karl Brandt, the head medical official of the Nazi government, and 22 other defendants of war crimes and crimes against humanity for their organization and participation in inhumane medical experiments on civilians and prisoners during the war. The decision also included a ten-point statement on what constituted “Permissible Medical Experiments,” emphasizing the necessity of voluntary informed consent, the requirement that research yield meaningful results unprocurable by other means, and the obligation to minimize risk and suffering.
As public awareness of the dangers of unethical research grew in the 1960s, momentum for reform followed. In 1964, the World Medical Association’s Declaration of Helsinki refined these ideas for the medical profession, emphasizing the importance of patient welfare, introducing the requirement for independent ethical review, and recognizing the distinction between therapeutic and non-therapeutic research.
In 1966, the United States Surgeon General issued guidelines requiring that any institution receiving funding from the National Institutes of Health would have to certify the protection of any human subjects, and many institutions developed predecessors to modern IRBs.
The Genesis of the Modern IRB System
In 1972, Jean Heller, then a reporter for the Associated Press, broke a story that would change medical research in America forever. In 1932, Heller reported, the United States Public Health Service had misleadingly infected nearly 400 Black men in Macon County, Alabama, with syphilis. Researchers watched as the disease ravaged their subjects for four decades—even after penicillin emerged as a cure. While the government put an end to the infamous Tuskegee Syphilis Experiment shortly after Heller’s story published, the Tuskegee story and public outrage that followed catalyzed further reform.
On July 12, 1974, President Richard Nixon signed the National Research Act into law. The law required approval by an IRB of human subjects research at any institution receiving funding from the Department of Health, Education, and Welfare and created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to help establish guiding principles for IRB research.
In 1978, the Commission published the Belmont Report, which established three core ethical principles for research involving human subjects: respect for persons, beneficence, and justice. It became the philosophical foundation for U.S. federal regulations on human subjects research, guiding the work of IRBs nationwide.
The Form and Function of IRBs Today
In 1991, NIH and 14 other agencies and departments adopted the Federal Policy for the Protection of Human Subjects, today known as the “Common Rule.” These regulations set uniform baseline standards for IRB composition, review procedures, informed consent requirements, and continuing oversight of research. Moreover, under the Common Rule, institutions enter into agreements with the federal government under the Federalwide Assurance for the Protection of Human Subjects, which stipulate the terms of funding and research practices.
In 2017, the Common Rule was revised in an attempt to modernize and simplify rules while strengthening protections for research participants. Key changes included new requirements for informed consent, exemptions for low-risk research, limited IRB review for certain studies, and the requirement for single IRB review for multi-site research. Today, all agencies adhere to the baseline requirements of the Common Rule, though some have their own additional requirements.
In sum, IRBs operate as independent committees within research institutions (e.g., universities, hospitals, private organizations) and are responsible for reviewing research protocols to ensure compliance with ethical and legal standards before any study involving human subjects begins—and throughout the study’s enactment. IRBs evaluate risks and benefits to participants, ensure that informed consent is properly obtained, and monitor ongoing studies to safeguard participants.
IRBs operate as “autonomous decisionmakers,” with veto power over research at their institutions. The Boards comprise a diverse set of individuals: scientific and nonscientific experts and outside individuals alike. At the same time, Sewards notes, they are far more than a panel that serves to shoot down ideas for not fitting within predefined rules or a rubber-stamp panel. Rather, the central goal of institutional IRBs is to make sense of the tripartite puzzle of complex rules, foundational research principles, and an ever-changing set of research questions, methods, and topics. “It’s a holistic review…a gatekeeper for these ethical principles,” says Sewards.
If you’re interested in more details of this project, listen to our Proof Over Precedent podcast episode on the topic.