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Human Subjects Research RegulationPerspectives on the Future$

I. Glenn Cohen and Holly Fernandez Lynch

Print publication date: 2014

Print ISBN-13: 9780262027465

Published to MIT Press Scholarship Online: January 2015

DOI: 10.7551/mitpress/9780262027465.001.0001

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Introduction to Part I—Regulation of Risk

Introduction to Part I—Regulation of Risk

(p.27) Introduction to Part I—Regulation of Risk
Human Subjects Research Regulation

Nir Eyal

The MIT Press

Participation in some studies is medically far safer than in the studies that defined research ethics and inspired its regulatory framework. Consider post-approval drug follow-up; observational studies that use publicly available data; many surveys; secondary studies of stored tissue. These studies do not test unapproved biomedical substances on any person. Do they require the protections suitable for paradigm clinical studies? Or can their regulation be lighter?

On the face of it, Rosamond Rhodes's and Ana Iltis's contributions to this volume present opposing approaches to this question. Rhodes la-ments the red tape of so much research review, and proposes a new category of research, which she calls “de minimis risk.” Research falling in this rubric involves less risk than what we already categorize as “minimal risk.” One example is secondary studies on stored tissue. Normally they pose absolutely no physical risk to the body. The regulation of such studies, Rhodes argues, ought to be dramatically relaxed. Rarely should they require informed consent or independent review—except for brief initial review to confirm that they are de minimis risk. Recognizing that some studies are de minimis risk would also highlight the rationale behind the already relaxed regulation of “minimal risk” and “exempt” studies. The point of the light regulation of all is that research regulation is necessary only inasmuch as risks are substantial.

One proposal within the 2011 ANPRM is to eliminate continuing re-view of minimal risk research (as determined by brief initial review). Iltis criticizes this proposal. Her position might initially seem diametrically opposed to Rhodes's position on de minimis risk research. Iltis accuses the ANPRM proposal of several fallacious assumptions, namely that there are (virtually) no errors in the initial classification of studies as minimal risk; that a study's risks cannot increase over time; that the value of a study cannot decrease in its course, thus altering its risk to value ratio; (p.28) that potential participants' perceptions of these matters are unimportant or insensitive to whether active oversight continues; and finally, that when a study, even a low-risk study, fails to recruit enough participants for its successful completion, it remains permissible to pursue.

On the face of it, Rhodes's and Iltis's contributions are at opposite ends of a logical spectrum regarding minimal risk study regulation and oversight. While Rhodes supports deregulation and lighter oversight for these studies, Iltis supports persisting, active oversight for all studies. However, for the most part, both Rhodes and Iltis could agree that if a study were known to be and expected to remain very minimal risk, then much of the need for oversight would vanish. The difference between their conclusions may stem primarily (though not entirely) from the fact that Rhodes speaks at the level of objective obligations and Iltis, at the level of subjective or epistemic ones. Rhodes supports light regulation for objectively safe experiments and Iltis, heavy regulation for experiments that initially seem objectively safe but that may turn out to be objectively unsafe.

Consider, as an analogy, a pill that would cure patient Joe of his mild disease with no side effects, but that his physician erroneously takes to be unsafe because that pill often kills patients. What the physician fails at the time to appreciate (and any colleague would also fail to appreciate given the state of medical knowledge) is that the active ingredient that kills patients works through interaction with a certain enzyme, which Joe happens to lack. Therefore, objectively, Joe would be cured safely if he took the pill.

What should we say, then: ought Joe's physician to prescribe the pill to Joe? There is a sense in which the physician ought to prescribe it—because it would cure Joe safely; and a sense in which the physician ought not to prescribe it—because according to physicians' best knowledge at the time, the pill may well kill Joe. Both senses matter. One sense is objective: the pill is objectively safe and helpful, and should be prescribed. Another sense is subjective or epistemic: contemporaneous evidence suggests that the pill is unsafe, so (in that evidence-dependent sense) it should not be prescribed.

Applying the analogy to minimal risk research, Rhodes and Iltis might be talking about different things, rather than engaging each other's positions. Rhodes might be focused exclusively on objectively de minimis risk research and Iltis, on research that initially, based on the evidence available at the time, seems safe, but that might still turn out to be risky.

To identify the appropriate level of regulation and oversight for (ob-jectively/subjectively) very low-risk research would have both practical (p.29) and philosophical importance. Coming years are expected to see a rise in post-approval drug research, observational research on electronic health records, and other (seemingly) physically low-risk studies.

In addition identifying the appropriate level of regulation and over-sight for very low-risk studies may help research ethicists explore a surprisingly neglected question: What is the exact goal or purpose of human subject research regulation and oversight, in general?

Let me clarify the question. Obviously research participants usually should be offered protections against very dangerous or very disrespectful studies, even when these studies would have otherwise advanced scientific, medical, and public health knowledge, and the public's health. What is the reason that often we should forgo these opportunities to promote knowledge and health?

The main justifications to date assume that in the pursuit of collective goals such as knowledge and population health it remains morally wrong to subject identified individuals, even volunteers, to high medical risk from active intervention in their bodies. But any justification founded on this assumption seems moot in the case of minimal risk studies. They do not subject anyone to high medical risk. That makes minimal risk studies good test cases for the view that what research regulation and oversight are responding to is in part altogether different concerns. Take concerns about the sheer invasion or intervention in someone's body without her consent, or about the use of her “own” body to profit without sharing benefits with her. These concerns may arise about low-risk research as well, for example, about unauthorized studies on donated body tissue and patient information, and about studies of safe and approved sub-stances that do not share financial profits with those whose bodies were used in the investigation. Do we want to insist that even in these minimal risk studies, and assuming that they were bound to remain minimal risk, intense regulation and review remain necessary? If they are unnecessary, that may suggest that non–risk-related ethical concerns about reciprocity, autonomy, and so forth, are more imagined than real.

This way whether regulation and oversight are needed for low-risk studies is a clue to identifying the exact problem for which research regulation and oversight are appropriate policy responses. If intuitively there is no problem with a minimal risk study that is performed without benefit sharing and without informed consent, then reciprocity and autonomy might lack the general value that many (bio)ethicists have assigned them. The ethics of minimal risk research could thus shed light on the general point of research ethics and on the best ways to conduct, regulate, and oversee high-risk medical investigations as well. (p.30)