From Oversight to Overkill: Inside the Broken System That Blocks Medical Breakthroughs—And How We Can Fix It, by Simon Whitney (Rivertown Books, 316 pp., $32.95)
Institutional review boards, or IRBs—committees charged with overseeing “Human Subject Research”—have received surprisingly little attention, given their enormous impact on medical research and innovation. In From Oversight to Overkill, Simon Whitney aims to fill that gap. His book provides a highly readable overview of the IRB system’s origins and how it blocks medical breakthroughs, and offers ideas for reform.
IRBs are supervised (mostly) by the Office of Human Research Protection (OHRP), a small agency within the National Institutes of Health that, by revoking an IRB’s license to operate, can threaten entire institutions with a research freeze. This is a major threat to institutions swollen on federal research dollars, especially because a freeze can extend to all research conducted at an institution receiving any federal funding, not just to a single federally funded program at that institution.
The original model for IRBs was the NIH Clinical Research Committee, an informal group composed of experienced researchers who met to discuss high-risk research conducted at the NIH clinical center. Outside work funded by the NIH, however, was left unsupervised.
After a series of well-publicized research scandals, Congress passed the National Research Act of 1974. Gradual scope-creep from federal bureaucrats was occasionally resisted by social scientists like Ithiel de Sola Pool but went largely uncriticized. The Reagan administration attempted some rollback of IRBs but was foiled by OHRP director Charles McCarthy. Subsequent research scandals in the 1990s (some were merely recycled stories from the 1940s) resulted in further IRB entrenchment. Whitney does an excellent job explaining these scandals and showing how, in nearly every case except the infamous Tuskegee syphilis experiments, the simplistic narrative of reckless scientists harming participants was grossly overstated or false.
A timely example, given pending legislation today aimed at improving infant health, is the SUPPORT clinical trial, which tested oxygenation strategies for extremely premature infants. It may be uncomfortable to contemplate, but much of clinical medical practice is highly contentious and based on shaky assumptions. In cases where doctors strongly disagree and the stakes are high, a well-executed randomized clinical trial is the best way to settle disputes. Thus, with good intentions, and after concluding that the existing literature “provided no reliable guidance for clinical care,” a network of expert neonatologists (the Neonatal Research Network) organized a large trial and found that a higher oxygenation strategy reduced infant mortality.
To satisfy IRB requirements for parental consent in the trial, mothers at high risk of giving birth to premature infants had to give their consent in advance. This added $200,000 in costs to the clinical trial, delaying enrollment by two years and probably having a disproportionate impact on socioeconomically disadvantaged mothers. Even with this excess of caution, “four years after SUPPORT was completed,” OHRP found that “every consent form . . . was defective.” Thus, as reward for conducting research that has subsequently saved tens of thousands of infant lives, the scientists faced lawsuits and attacks in the media and from “consumer protection” groups like Public Citizen and the Alliance for Human Research Protection. Only a supportive editorial by NIH director Francis Collins and “a summary judgment [that] . . . dismissed the lawsuit” eventually calmed the waters. The net effect: an enormous delay of medical science and no admission of guilt by OHRP for having stirred up needless controversy.
Whitney’s book remains laser-focused on pointing out that mistakes like these are the result of poor institutional design, not bureaucratic incompetence. Among other problems, IRBs have no appeal mechanism, and institutional leaders are forbidden from overruling them.
These poor design features have major consequences. In the field of social science, as law professor Philip Hamburger has argued, IRBs effectively act as censorship boards. In medicine, the cost is counted in human lives. For example, estimates of the human toll of a more cumbersome U.S. consent process for just one trial—the ISIS-2 trial of heart-attack treatments—range from 3,600 to 10,000 lives lost. And what of the trials that IRBs have discouraged from ever occurring?
In response to decades of criticism, OHRP instituted token reforms from 2011 to 2018, but the only substantive result of these efforts for biomedical researchers was to exempt a narrow category of research from the IRB review process and to allow a single IRB to supervise research over multiple institutions. The structures at the core of IRB dysfunction—its focus on risk over benefit, byzantine consent forms, and a lack of any appeal mechanism—remained untouched. Reform through the executive branch has thus proved unsuccessful.
Whitney argues that Congress should do what federal agencies apparently cannot, and he details some of the principles that reform legislation should follow. The system should be flexible enough for institutions to adapt their research oversight to various contexts, such as by letting smaller institutions assign “oversight to a single person.” IRBs should provide a clear avenue for appeals, allowing denials to be bumped upward to administrators. Instead of trying to eliminate risk to subjects entirely or to dream up fantastical hypothetical dangers, IRBs should adopt traditional risk-management practices. Burdensome consent processes should be streamlined, with acceptance of “informal or implied consent” in some contexts. Like the original NIH Clinical Research Committee, IRBs may not need to “review routine, low-risk research,” but “only experiments . . . [with] significant risk.” Research subjects’ autonomy and willingness to take risks should be respected, though “in ordinary circumstances, IRBs . . . should not permit research in which serious injury or death is likely.” Whitney’s list of IRB reforms is eminently sensible and urgently needed.
From Oversight to Overkill is a thoughtful, readable, and practically minded contribution to the IRB literature. In an era of growing popular discontent with pharmaceutical costs, reducing barriers to high-quality research will accelerate innovation and competition, improving costs in the long run. Giving IRBs fewer opportunities to stifle politically charged research should also lead to greater public trust in science. And people who don’t have the time to read ten-page consent forms will participate in research studies and trials in higher numbers, thus improving representation. IRB reform would be a win for scientists, research participants—and everyone else.