Regulating Human Subjects Research

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A changing research environment means regulators and institutional review boards must adapt.

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Institutional review boards (IRBs) protect the health, safety, and privacy of people participating in biomedical and behavioral research. Although regulators have sought to protect human subjects as early as the 1960s, they did not codify the IRB as an independent oversight mechanism until 1974. In 1981, American regulators instituted sweeping protections for human research subjects following calls for accountability from the international research community—called the Common Rule—as well as controversy surrounding experiments such as the Tuskegee syphilis study

Organizations that receive federal funding for research, such as universities, house at least one IRB to review the institution’s research proposals. The committee can approve, disapprove, or require modifications to a research proposal to ensure potential human subjects are protected according to “ethical principles and federal regulations.” 

In this way, IRBs possess responsibilities that go above and beyond checking for compliance with federal regulations, including “review of conflicts of interest,”  “training of investigators,” and “monitoring of clinical trial registration.” 

As research involving human subjects moves from single site studies to research with a larger institutional footprint, researchers and others interested in the IRB process face both calls to add protections for study participants and complaints that the current regulatory framework is too difficult for researchers to navigate. To deal with this changing landscape, the U.S. Department of Health and Human Services (HHS) has reformed regulations to allow a single “IRB of record” to review research involving multiple institutions. 

This week’s Saturday Seminar explores the regulatory landscape surrounding the use of IRBs in studies that involve human subjects.

On Systemic Change

  • In one of The Regulatory Review’s top essays of 2019, Philip E. Rubin of Haskins Laboratories argues that human-subjects research requires close regulatory attention because it is critical to scientific development. Due to decades of research regulation development, most human subject research studies today maintain high ethical standards, but “the scientific, medical, and technological landscapes are constantly changing and often engender challenges in research ethics and regulation,” Rubin writes. As regulations continue to modernize, Rubin argues that the opinions and preferences of a wide range of stakeholders must be heard.
  • “It is past time for a Belmont 2.0.” In an article for Nature, Yale’s Nathaniel Raymond advocates updating the Belmont Report, a document commissioned by Congress over forty years ago that outlines key ethical considerations for conducting human research. Raymond asserts that the Belmont principles are ill-suited to the digital age. For example, Raymond notes that data that permit researchers to track people based on factors like ethnicity, religion, gender, and health status are exempted from IRB requirements. Rather than merely revising the current guidelines, Raymond urges Congress to commission a new Belmont Report “to deal holistically with applications of data science that will only become more complicated as technology progresses.”

Recent Reforms

  • In a recent essay in Health Affairs, Alison Bateman-House explores the differences between U.S. Food and Drug Administration’s (FDA) Expanded Access program (EA)—which has been in place for decades—and the Right to Try (RTT) law signed into law by President Donald J. Trump in 2018. The main difference, Bateman-House argues, is oversight procedure between these two systems. Bateman-House explains that “in EA, the treating physician, drug company, FDA, and IRB work together” to ensure legal and ethical requirements, among other requirements, are met. In contrast, “under RTT, only the treating physician and the drug company — neither of whom is a neutral party — provide oversight,” Bateman-House argues.  
  • When multiple institutions collaborate on a human research project, each institution’s IRB reviews the project, resulting in potential delays and duplicative administrative work that can slow research. For the Harvard Catalyst Regulatory Foundations, Ethics, and Law Program, Sabune Winkler, Elizabeth Witte, and Barbara Bierer describe the Master Reciprocal Common IRB Reliance Agreement (MRA). They propose the MRA framework to “streamline IRB review processes and reduce administrative burden and barriers to collaborative, multi-institutional research.” Using the MRA, institutions may rely on another institution’s IRB to review a particular research protocol for a multisite-study. The article appears in the journal, Clinical and Translational Science.
  • In a recent article, Cynthia Hahn, Petra Kaufmann, Soo Bang, and Sara Calvert describe resources made by the Clinical Trials Transformation Initiative (CTTI) and National Center for Advancing Translational Sciences (NCATS) to facilitate the adoption of single IRBs of record (sIRBs) to oversee most U.S. multi-site studies with federal funding. Because the sIRB requirement and related amendments to the Common Rule are so new, the authors suggest that researchers work together to “share best practices, improve standardization, and fill remaining information gaps.” Hahn and her co-authors indicate that they hope that once implemented, this new regulatory framework will “ensure participant protections while facilitating more efficient conduct of multisite trials.”

The Saturday Seminar is a weekly feature that aims to put into written form the kind of content that would be conveyed in a live seminar involving regulatory experts. Each week, The Regulatory Review publishes a brief overview of a selected regulatory topic and then distills recent research and scholarly writing on that topic.