Monday, July 25, 2011

Emanuel and Menikoff Explain the ANPRM

Ezekiel Emanuel, head of the Department of Bioethics at NIH, and Jerry Menikoff, director of OHRP, explain the ANPRM for readers of the New England Journal of Medicine.

[Ezekiel J. Emanuel and Jerry Menikoff, "Reforming the Regulations Governing Research with Human Subjects," New England Journal of Medicine, 25 July 2011. h/t Michelle Meyer]

The essay is a very helpful introduction to the ANPRM, clearer than the ANPRM itself. The authors conclude,

After 20 years, and the introduction of significant changes to the research landscape, many believe that the Common Rule needs revision. The ANPRM offers a rare opportunity for needed modernization that is consistent with the President’s mandate to enhance protections while simultaneously eliminating unreasonable burdens. Not everyone will agree with every proposed change. But the ideal should not be the enemy of substantial progress in achieving these two important goals. If this reform effort fails, 20 years from now, someone might write an article for the Journal to bemoan the fact that the Common Rule has undergone essentially no change in 40 years.

Fine, I'll say it. I agree with Jerry Menikoff.


Anonymous said...

The problems are not with the existing "Common Rule" - the problems are in interpretation and enforcement of 45 CFR 46. IRBs need to be educated; the regs are flexible enough to allow research to be approved as quickly as the investigators are willing to make any needed changes and clarifications. And let's not overlook the fact that many a research delay is investigator-inflicted.

The current system works very well with competent, unbiased IRBs and proficient, thorough, and ethical researchers. In fact, the only changes needed are 1) the inclusion within ‘Exempt category 4’ of data that is not in existence when the proposal was developed, and perhaps 2) requiring written consent for secondary use of biospecimens. The Common Rule already allows deferral to a single IRB for multi-site studies – it should not be mandated. Nor should the simple requirement for a status report (continuing review) once every 365 days be considered so onerous it must be eliminated. And the very notion that exempt categories are being considered for research that combines the collection of personal identifiers with sensitive data that can affect employability, insurability, reputation, or legal liability, suggests either a lack of understanding of the ‘informational’ risks associated with disclosure of such data or an undue indifference to those risks.

Anonymous said...

Establishing data security and information protection standards is both appropriate and warranted; however because such standards are neither self-implementing nor self-enforcing, nor would encompass all potential phases of the research effort, the notion that this would “eliminate the need for IRBs to review the informational risks of the research” is overly-simplistic at best and not at all representative of the review and verification of data confidentiality that IRBs have been and will continue to be responsible for. All data is vulnerable at time of collection, during conveyance to research facilities, at data entry, and during data analyses – as well as when stored on a secured computer. Further, if data is collected on a portable device (laptop, thumb drive, DVD, etc.), then that data is only as secure as is the portable device. IRBs would love to not have to be concerned with informational risks, but as long as sensitive information is being collected there will be risks associated with disclosure of that data. The notion that IRBs will not need to be concerned with data confidentiality issues once “HIPAA standards” are implemented is not borne out by the reality observable at many treatment facilities across this country that presently have such standards in place – and at which many staff are needed to implement and ensure compliance. The standards, in and of themselves, will not guarantee that no information risks will be associated with a research project.

Anonymous said...

The proposal to do away with Continuing Reviews for expedited review studies is bad policy on several different levels. Continuing Review submissions often indicate that investigators are unsure which are the most currently approved research procedures. The Continuing Review submission allows the IRB to obtain a status report on the study and re-focus investigators on what has been approved. As indicated in 45 CFR § 46.103, there is to be verification that no unapproved material changes in research procedures have occurred – the Continuing Review presents one opportune time to assess whether the conducted research is within the approved parameters.

By eliminating Continuing Reviews for minimal risk studies that received Initial Review by the expedited review process, this proposed policy change may actually make many initial reviews more burdensome/lengthy by decreasing the likelihood that the initial review will be conducted through the expedited review procedure. That is, if an IRB has to choose between 1) no continuing reviews and 2) having that initial review conducted by a convened board, they will likely choose the latter. While the proposed rule indicates that the initial expedited reviewer can “justify why continuing review would enhance protection of subjects,” the default position in the proposed rule is still no continuing review for studies initially reviewed by Expedited Review.

This proposed policy change seems to confuse ‘minimal risk’ studies with ‘no risk’ studies. Under the categorization of minimal risk, the following study components can and often are approved: blood draws, nasopharyngeal specimen collection, sensitive medical data collection, surveys on drug use and or sexual habits, mild to moderate physical activities, and administration of supplements for which no IND application is required. None of these research procedures are without some real risk yet all might be classifiable as ‘minimal risk’. To think that a reviewing IRB should not be entitled to an annual status report on such studies just because the initial review was conducted via expedited review procedures is at odds with what everyone intimately involved with the IRB process knows – investigator compliance with human subject protection regulations is partially, but substantively, predicated on the fact that there is continuing oversight.

Doing away with Continuing Reviews for any study is not appropriate. Rather than change this policy DHHS would be much better served by providing (and perhaps mandating) webinars for IRBs that could provide guidance on streamlining reviews. Knowledgeable IRBs are conducting most Continuing Reviews via the expedited review process. In a nutshell, the current Continuing Review process is not overly-burdensome and works very well when both IRBs and Investigators understand their roles and duties in the research review process. Doing away with Continuing Reviews will only encourage non-compliance by investigators who will take the policy change as evidence that DHHS thinks the whole notion of human subject protections is overblown.

Anonymous said...

Periodic updating of the categories of research eligible for expedited review would be a commonsensical, if belated, policy change. However, DHHS suggests that updating expedited review categories will provide for “streamlined document submission requirements for review.” The document submission requirements should not be lessened for those studies that an IRB decides to review through the expedited review procedures versus those taken to a convened board. Expedited reviewers still need all pertinent information to make a determination about the degree of risk, whether all appropriate safeguards are in place, and whether the merits of the proposed study outweighs the potential risk. DHHS webinars and online videos for IRBs to view that discuss methods of streamlining protocols and consent documents, within the current regulatory structure, is much more appropriate.

Anonymous said...

The notion that an investigator should be able to declare their own research ‘exempt’, submit a piece of paper, and then get underway should be quickly relegated to the dustbin of bad ideas. IRBs are quite often approached by investigators seeking ‘exempt’ status for research projects that do not qualify. Investigators largely do not understand the regulations (that is not to say that all IRBs do either) and tend to misinterpret them in the light most favorable to their research effort. Further, the proposed rule indicates that investigators would submit “essential information about the study, for example information about who will be the principal investigator, and the purpose of the study” and then begin. With all due respect to the writer(s) of the proposed rule, neither the name of the PI nor the purpose of the study will supply the type of information needed to determine exempt status, much less the actual risks associated with a proposed but not defined study. The devil is in the details, not in the PI’s name or study purpose.

No research that involves specimens or data that are both sensitive (i.e., can potentially negatively impact individual’s employability, reputation, insurability, financial standing, or legal liabilities) and identifiable should ever receive an exempt categorization.

Zachary M. Schrag said...

Thanks for these comments.

You raise some interesting points, particularly about HIPAA.

But I must say that I had hoped that the ANPRM, with its 88 footnotes, had moved us past the point where anyone would expect bald assertions like these to persuade a community of scholars.

You think IRBs are competent to conduct "the review and verification of data confidentiality"? Perhaps you should read the Institute of Medicine report, Beyond the HIPAA Privacy Rule, cited by the ANPRM, which found "extreme variability in the regulatory interpretations and approval decisions among IRBs and Privacy Boards."

You think that "investigator compliance with human subject protection regulations is partially, but substantively, predicated on the fact that there is continuing oversight"? What about the findings of Keith-Spiegel and Koocher that "The efforts of some institutional review boards (IRBs) to exercise what is viewed as appropriate oversight may contribute to deceit on the part of investigators who feel unjustly treated"?

You think that "DHHS webinars and online videos" will fix the problem? Have you seen the junk they have been distributing of late?

Most importantly, you think that "Investigators largely do not understand the regulations (that is not to say that all IRBs do either)"? I'm with you there; the regulations are so poorly written no one can claim with confidence to understand them. So why defend them?

Five years ago, Menikoff would have agreed with your claim that "The problems are not with the existing 'Common Rule' - the problems are in interpretation and enforcement of 45 CFR 46. IRBs need to be educated; the regs are flexible enough to allow research to be approved as quickly as the investigators are willing to make any needed changes and clarifications." But this Panglossian view has crumbled under the weight of evidence against it.

I hope that you will engage with the body of scholarship cited by the ANPRM and on this blog.