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Outrage of the Month: Enforcement of Federal Regulations for the Protection of Human Subjects in Research Plummets

Health Letter, September 2017

Michael Carome, M.D.

                     Image: Shutterstock.com/Castleski

The Office for Human Research Protections (OHRP), a regulatory office within the U.S. Department of Health and Human Services (HHS), purports to play a leadership role in protecting the rights and welfare of human subjects involved in research. Among the agency’s critical functions in fulfilling this role is the enforcement of compliance with the HHS human subjects protection regulations. OHRP’s Division of Compliance Oversight carries out this enforcement, in part, by evaluating allegations of regulatory violations.

A July 2017 report from the HHS Office of Inspector General (OIG) documented a precipitous drop over the past several years in the number of formal compliance evaluations initiated by OHRP in response to allegations. This decline — and the unsatisfactory explanations offered for it by OHRP staff — indicate that OHRP now routinely bypasses its own formal procedures for investigating allegations of misconduct and can no longer be trusted to meaningfully enforce the HHS human subjects protection regulations.

OHRP’s compliance oversight procedures

OHRP has long-standing written procedures, last updated in 2009, for its compliance evaluations. The procedures for for-cause compliance investigations — which historically have made up the largest proportion of OHRP’s compliance oversight activities — begin by stating that “[f]or-cause evaluations occur, at OHRP's discretion, in response to OHRP's receipt of substantive written allegations or indications of non-compliance with the HHS regulations” [emphasis added]. They further note that the agency “may choose to use other mechanisms to address allegations or indications of noncompliance rather than conducting a for-cause evaluation.”

The public reasonably expects that OHRP will exercise such enforcement discretion judiciously and that the use of other mechanisms to address substantive allegations or indications of noncompliance will be the exception, not the rule.

If OHRP determines that it has jurisdiction to evaluate allegations of noncompliance and chooses to conduct a formal for-cause evaluation, the agency sends an initial inquiry letter to the institution(s) involved in the relevant research. The letter describes the allegations and potential regulatory violations and asks the institution to conduct an investigation of the potential noncompliance, provide a written response to the allegations along with supporting documentation, and submit a corrective action plan if noncompliance is found. OHRP eventually issues one or more letters to the institution documenting OHRP’s determinations regarding whether it finds that noncompliance occurred and, if so, whether adequate corrective actions have been taken by the institution. In some cases, OHRP requires additional corrective actions.

Importantly, OHRP’s written procedures for conducting for-cause compliance evaluations include provisions to ensure the transparency of the agency’s enforcement activities for complainants and the public, including the following:

• Notifying complainants as to whether OHRP will open a compliance evaluation of the allegations raised
• Upon completion of an evaluation, informing the complainant in writing of OHRP’s determinations and any corrective actions taken by the institution
• Posting on the agency’s website each determination letter no later than 10 business days after the letter is issued to the institution
• Once a compliance oversight evaluation is closed, making available upon request under the Freedom of Information Act all documents related to the evaluation

OHRP’s written compliance procedures also stipulate an appeals mechanism under which a complainant (or institution) may request that the OHRP director reconsider any determinations from a for-cause compliance oversight evaluation. 

The OIG report’s findings

For its July 2017 report, the HHS OIG analyzed data on OHRP’s compliance activities for 2000 through 2015 as part of a Congressionally-requested assessment of OHRP’s independence.

The most striking observation presented in the report was the steep decline in the rate at which OHRP has initiated formal for-cause compliance evaluations in response to allegations of noncompliance since 2000. For the four-year period from 2000 to 2003, the agency received a total of 487 allegations and initiated for-cause compliance evaluations for 195 (40 percent) of these. In contrast, for the four-year period from 2012 to 2015, OHRP received 456 allegations but initiated for-cause compliance investigations for only 22 (5 percent) of these. 

Although this dramatic falloff is due partially to an erosion of resources as well as an increase in the proportion of allegations that are related to research deemed to be outside of OHRP’s jurisdiction, much of the decline clearly reflects a fundamental — and troubling — change in how OHRP approaches its enforcement of the HHS human subjects protection regulations.

Indeed, OHRP explained to the OIG that “it decided over the years to initiate fewer [for-cause] compliance evaluations both to better leverage its limited resources and to focus the evaluations on broad policy issues in protections for human subjects.” This explanation is disturbing for two reasons. First, deciding whether to open a formal for-cause compliance evaluation based on whether a particular allegation raises “broad policy issues” enshrines an approach to enforcement that by its very nature is arbitrary and capricious. In particular, the public, complainants and other stakeholders do not know when or on what basis OHRP has decided which policy issues are broad enough and of sufficient interest to use as a litmus test for deciding whether a particular substantive allegation warrants a for-cause compliance investigation. Nor do they know which broad policy issues OHRP is using to make these decisions at any particular time or whether the agency is applying them consistently and fairly.

Second, many substantive allegations of noncompliance do not raise broad policy issues but nevertheless often constitute the most serious types of noncompliance with the HHS human subjects protection regulations — such as conducting human subjects research without appropriate review and approval by an institutional review board or without the informed consent of the human subjects. In such cases where the potential for harm to the rights and welfare of human subjects is greatest, there is no sound basis for bypassing OHRP’s written procedures for conducting formal for-cause compliance evaluations.

The agency also told the OIG that “it increased its use of other mechanisms—for example, contacting the research institution directly—to address allegations of noncompliance.” But this explanation is nonsensical because, as noted above, under OHRP’s written procedures for formal for-cause compliance evaluations, contacting research institutions directly in writing is already one of the first steps in addressing substantive allegations.

The OIG report reveals that OHRP is abusing its discretion when deciding whether to initiate formal for-cause compliance evaluations of substantive written allegations. Use of “other mechanisms” has become the rule rather than the exception for OHRP’s approach to addressing substantive allegations of noncompliance, effectively eclipsing the agency’s procedures for conducting formal for-cause compliance evaluations. As a result, OHRP has undermined the integrity of its enforcement activities. 

For example, by routinely using “other mechanisms” to address substantive allegations, the agency and the institutions that conduct research in violation of regulations escape public scrutiny. Complainants are kept in the dark about the outcome of the agency’s review, and determination letters describing regulatory violations and any corrective actions taken by institutions are not written by OHRP or made publicly available on the OHRP website, even in circumstances where serious allegations of noncompliance are confirmed. Complainants also apparently are deprived of the right to appeal to the OHRP director the agency’s determinations in most compliance matters.

Most importantly, OHRP has signaled to the research community that there is little chance that the agency will formally investigate allegations of even serious regulatory violations.

Institutions undoubtedly are delighted to see an OHRP that is unwilling to aggressively enforce the human subjects protection regulations. Human research subjects, on the other hand, can no longer depend on OHRP to meet its obligation to protect their rights and welfare by consistently and transparently enforcing the regulations.

Note: For 10 years prior to joining Public Citizen in 2011, Dr. Carome was on the OHRP staff, serving most recently as its associate director for regulatory affairs and previously as its director of the Division of Compliance Oversight.