Tuesday, December 7, 2010

Menikoff Passes the Buck

Joseph Millum, bioethicist at the National Institutes of Health, and Jerry Menikoff, director of the Office for Human Research Protections, acknowledge the widespread dissatisfaction with present human subjects regulations and wish that "ethics review could be streamlined under the current regulations if institutions, IRBs, and researchers adhered strictly to the definition of human subjects research and used the available options for exemptions, expedited review, and centralized review—options that remain underused in biomedical research." But they put too much blame for this overregulation on IRBs and research institutions rather than on their own agencies.

[Joseph Millum and Jerry Menikoff, "Streamlining Ethical Review," Annals of Internal Medicine 153, no. 10 (November 15, 2010): 655-657.]

Millum and Menikoff call for institutions to offer exemptions and expedited review whenever possible, not just to placate researchers but to protect research participants:

Following these measures is unlikely to reduce human subject protections. The categories of research that are exempt or eligible for expedited review are unlikely to include highly unethical studies. For example, studies in these categories almost always pose no more than minimal risk to participants, which should ameliorate concerns about participant harm. Thus, the absolute probability of increased use of these measures leading to more unethical research is low.

In addition, IRBs always have constraints on their time and resources, and any time they spend reviewing one protocol takes away time from reviewing others. Institutional review boards should prioritize their time to focus on protocols that are more likely to generate ethical issues but need a way to determine whether a study will raise ethical issues without actually reviewing the full protocol. The regulatory measures we have detailed identify categories of research that are unlikely to be ethically problematic. Using them therefore frees up resources for reviewing riskier research.

So far so good. But the article overlooks four ways in which the federal government, and OHRP in particular, encourages institutions to overregulate.

1. Federal Agencies Don't Gather Data

To address the problem of overregulation, it would be nice to know how big a problem it is. The best that Millum and Menikoff can say is that "A 1998 report found that for each category of exempt or expedited research, 25% to 77% of U.S. IRBs 'practice some form of review that was more rigorous than specified by the regulations.' There appear to be no data that contradict this picture today."

While that's true enough, should OHRP be satisfied with a single, 12-year-old report sponsored by NIH? Might not a more regular system of data collection help us understand why IRBs act the way they do? And who is to sponsor this, if not OHRP and NIH?

2. OHRP Presents Exemption Determinations as Difficult, But Does Nothing to Clarify Them

OHRP's guidance on "Exempt Research Determination" claims that "an institutional policy that allowed investigators to make their own exemption determinations, without additional protections, would likely risk inaccurate determinations." So far as I can tell, this claim is based on no empirical data. But it serves to present exemption determination as a risky business, one apt to go wrong, thus discouraging institutions from applying the exemptions.

It's true that the exemptions are poorly written. For example, 45 CFR 46.101(b)(2) exempts many studies unless "information obtained is recorded in such a manner that human subjects can be identified," but 46.101(b)(4) exempts projects when "information is recorded by the investigator in such a manner that subjects cannot be identified." Why does "by the investigator" appear in (b)(4) but not (b)(2)? If a research participant takes notes during an interview, or writes about the event in his diary, is the researcher now subject to IRB review?

If OHRP were serious about getting projects exempt, it would tell everyone what the exemptions are supposed to mean. Then it would study--not guess--if researchers are capable of applying those standards.

3. Federal Officials Model Overregulation

Millum and Menikoff ignore the terrible guidance issued by the federal government over the years. For example, in June 2008 OHRP and NIH contributed to a report on Expedited Review of Social and Behavioral Research Activities. That report offered thirteen hypothetical projects it termed "eligible for expedited review," overlooking the fact that eight of the thirteen were in fact exempt from any review.

Ironically, Millum and Menikoff provide the latest example of this problem. They write that "the work of a researcher who interviewed patients with HIV/AIDS about their medications and recorded their names would not be exempt under category 2, because disclosure of the patients’ HIV/AIDS status could harm them. However, if the researcher conducted the interviews anonymously and never recorded the patients’ names or other identifying information, the study would probably be exempt."

No, if the researcher conducted the interviews anonymously and never recorded the patients’ names or other identifying information then the study would be exempt, not just probably be exempt. If Menikoff, free to invent whatever hypothetical study he wishes, and immune from OHRP sanction, still can't manage to declare this project unambiguously exempt, then how can he expect real institutions to exempt real projects?

4. OHRP Second-Guesses Exemption Determinations

Millum and Menikoff write that "regulatory bodies need to reassure the research community that their primary concerns lie not with meeting bureaucratic requirements but with genuinely protecting human participants."

Yes, that would be lovely. But in the most high-profile case concerning exemptions in recent years, OHRP rejected Johns Hopkins University's determination that Peter Pronovost's to effort reduce the incidence of catheter-borne infections in ICUs was exempt from IRB regulations. After getting slammed in the press, OHRP retreated and decided that "regulations that govern human subjects research no longer apply." Still, the lesson for IRBs was that if they err on the side of exemption, they risk the whip.

All that happened before Menikoff's arrival. But in the two years under Menikoff, OHRP has kept issuing determination letters warning not of failures of genuine protection but instead of failures to meet bureaucratic requirements:

HHS regulations at 45 CFR 46.109 require that continuing review of research be conducted by the institutional review board (IRB) at intervals appropriate to the degree of risk, but not less than once per year. The regulations make no provision for any grace period extending the conduct of the research beyond the expiration date of IRB approval. We determine that during the period from 1991-1999 when the above-referenced research was conducted at UI, continuing review for the above-referenced research did not always occur at least once per year. For example, the first continuing review occurred on February 27, 1992 and subsequent continuing reviews apparently occurred on April 1, 1993, May 12, 1994, May 10, 1995, June 27, 1996, June 26, 1997, July 9, 1998, and July 15, 1999.

The article ends with the disclaimer that "The views expressed in this commentary are those of the authors and are not necessarily those of the U.S. Department of Health and Human Services or its operating divisions, the National Institutes of Health and the Office of the Assistant Secretary for Health." No, an article designed to "to extol the virtues of [streamlining] measures" is certainly not the view of HHS and its operating divisions.

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