Office of Inspector General Report, July 7, 2017: “OHRP Generally Conducted Its Compliance Activities Independently, But Changes Would Strengthen Its Independence”
Background on SACHRP
SACHRP is a Federal Advisory Committee under the authority and rules of the Federal Advisory Committee Act (FACA). Per the approved Charter of the Committee,
The Committee shall consist of eleven (11) voting public members, including the Chair, who shall be appointed by the Secretary or designee. The members shall be selected from among individuals possessing demonstrated experience and expertise in any of the several disciplines and fields pertinent to human subjects protection and/or clinical research. All public members of this Committee are classified as special Government employees (SGEs) and are subject to government ethics rules.
As a practical matter, while proposed SACHRP members are approved and appointed by the Secretary, their nominations are also reviewed by the Director of OHRP and are likely to reflect, to some extent, the priorities and interests of that office. Thus, any recommendations made by the committee that pertain to OHRP and its role relative to other Federal entities involved in research on human subjects may be subject to an ad hominem critique that members are biased in favor of the importance of the mission of the Office. Nonetheless, such recommendations are within the scope of the Charter, which states:
The Committee will work to advise the Secretary on how to improve the quality of the system of human research protection programs, including the responsibilities of investigators, institutional review boards (IRBs), administrators, and institutional officials, and the role of the Office for Human Research Protections and other offices within HHS.
The OIG Report
In July 2017 the Office of the Inspector General (OIG) released a report titled: OHRP GENERALLY CONDUCTED ITS COMPLIANCE ACTIVITIES INDEPENDENTLY, BUT CHANGES WOULD STRENGTHEN ITS INDEPENDENCE. The circumstances leading to the report involved a public debate about participant protections in the NIH-funded Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT - NCT00233324). In reviewing issues related to this trial, OHRP initially found that the consent template developed by the lead institution had not properly followed the Federal Regulations regarding the required element of informed consent at 45 CFR 46.116(a)(2) - A description of any reasonably foreseeable risks and discomforts - and required the institution to “provide a plan that the IRB will use to ensure that approved informed consent documents include and adequately address the basic elements of consent as required by HHS regulations at 45 CFR 46.116(a).” After “extensive scientific and public discussions” OHRP later withdrew this requirement and signaled a hold to all compliance actions related to this issue. In response to these events, and the possibility that they could have been, or could appear to have been, the result of a lack of ability of OHRP to make independent determinations about the adequacy of human research participant protections in Federally funded research, “Congress requested that the Office of Inspector General (OIG) review OHRP procedures and make recommendations to strengthen protections for human subjects and ensure its independence.”
The OIG concluded:
Given that no law establishes OHRP’s independence and that OHRP has considerable discretion in conducting evaluations, OHRP could appear vulnerable to interference. However, our review found that OHRP has been largely able to make decisions about its compliance evaluations, obtain the information it needs, and maintain its determinations without interference.
The OIG also made the following observations:
1. Varying interpretations of OHRP’s role—whether it is oriented more toward enforcing compliance or toward setting broader policy—may limit OHRP’s ability to operate independently;
2. OHRP’s position in the HHS hierarchy and HHS’s control over its resources may limit its ability to operate independently;
3. OHRP’s practice of not reporting publicly on all of its compliance activities may give the appearance of limited oversight and independence; and made the following recommendations:
1. HHS should address the factors that limit or appear to limit OHRP’s ability to operate independently. HHS could do this by:
• Issuing guidance that clarifies (for stakeholders and the public) OHRP’s role;
• Evaluating OHRP’s position within HHS, including (1) whether to place OHRP at the same hierarchical level within HHS as the research agencies it oversees and (2) the potential advantages and disadvantages of such a change; and
• Evaluating the sufficiency of OHRP’s resources to carry out its mission and exploring with the Office of Management and Budget and congressional appropriators ways to elevate the prominence of OHRP’s budget—for example, by including it as a line item in the President’s budget.
• Finally, HHS should consider seeking statutory authority for OHRP’s independence.
2. OHRP should post the following on its website: (a) a description of its approach to oversight and (b) data (in aggregate) on the full array of its compliance activities
Charge to SACHRP
OHRP agreed to OIG recommendation (2), and SACHRP is now asked to make recommendations regarding the four specific ways identified in the OIG report that HHS could address the factors that limit or appear to limit OHRP’s ability to operate independently.
It is important to note that how OHRP chooses to use its resources is not within the scope of this charge. In particular, the OIG report describes inconsistent stakeholder perceptions of OHRP’s role and describes its possible activities on a continuum between compliance and policy orientations. The report does not make recommendations regarding the proper balance of activities and implies that this decision is one properly made by OHRP and its Director.
Issuing guidance that clarifies (for stakeholders and the public) OHRP’s role
As described above, the OIG report notes that OHRP’s role lies on a spectrum between enforcing compliance and developing policy. While both policy and compliance are within the mission of OHRP, the authority of its policy recommendations and findings depends on the possibility of non-compliance findings and consequent actions. No policy will be fully implemented in an environment where its enforcement is unlikely or impossible.
SACHRP recommends that OHRP make its dual responsibilities of policy development and compliance enforcement explicit, and that the explicit description reassert its authority to act against entities found out of compliance with 45 CFR 46 regulations for the protection of human research subjects in HHS funded research.
Evaluating OHRP’s position within HHS, including (1) whether to place OHRP at the same hierarchical level within HHS as the research agencies it oversees and (2) the potential advantages and disadvantages of such a change
The OIG report makes the observation that:
OHRP is under the Assistant Secretary for Health, whereas the agencies that fund research—such as NIH—are directly under the Secretary of Health and Human Services. This means that OHRP is at a lower level in the HHS organizational hierarchy than the research-funding agencies and may face greater pressure in arguing its decisions because it does not have an equal voice with those agencies
The practical consequences of elevating OHRP’s hierarchical level within HHS to the level of the Secretary are unclear, but the symbolic importance of positioning the office responsible for compliance at the same level as the entities it oversees would be significant, as suggested by the OIG report. It is worth remembering that OHRP’s functions have already been elevated once, when it was moved from within the NIH, where it reported to the Director, to the Office of the Assistant Secretary for Health, to avoid the appearance of a conflict of interest. As the debate around the SUPPORT trial shows, that appearance of conflict remains.
SACHRP recommends elevating OHRP’s position within HHS to be commensurate with that of the entities it regulates.
Evaluating the sufficiency of OHRP’s resources to carry out its mission and exploring with the Office of Management and Budget and congressional appropriators ways to elevate the prominence of OHRP’s budget—for example, by including it as a line item in the President’s budget.
The OIG notes that the Office can independently decide how to best fulfill its mission through a balance between its compliance and policy development activities. The description of such decision-making as independent may be disingenuous in the face of shrinking budget and resources, particularly when compared to the growth of regulated entities.
The OIG report notes that OHRP’s budget “has generally been flat, averaging about $6.9 million annually since 2000.” Since that report was published, OHRP’s budget has been less than $6.5 million annually, and with adjustment for inflation, it is only about 63% of what it was at its peak in 2003. For comparison, the NIH budget has risen from $27 billion to $37 billion annually over the same period, although it has remained essentially flat when adjusted for inflation. While the NIH budget does not translate directly into the volume of NIH-funded research studies with human participants, these trends raise the possibility that OHRP’s resources and capabilities are shrinking while the major source of Federally-funded research funds expands.
In addition to possible changes in the volume of regulated research, the past several years have brought major changes in research regulations and in the research enterprise, significantly increasing the policy and advisory obligations of OHRP. These changes include:
• a substantive revision to the Common Rule, released on 1/18/2017, and additional rules regarding its implementation and transition dates;
• the 21st Century Cures Act, passed in 12/2016;
• updates to NIH policies requiring, among other things, single IRB review of multi-site NIH trials and changes to certificates of confidentiality;
• a new European Union General Data Protection Regulation, with extensive but poorly understood implications for research funded in the United States but with sites or participants in the EU;
• increasing awareness of the ubiquity and vulnerability of personal digital data, both medical and other;
• an increasingly sophisticated appreciation of the confidentiality risks of research with genetic information, with resulting divergent local and national regulations.
Among the direct consequences of these social, statutory and regulatory changes are:• the requirement that FDA and OHRP harmonize their regulations and guidance;
• An increased focus on use of “real world evidence” in medical research, with consequent challenges to models of consent and autonomy;
• increased focus on trial designs other than randomized clinical trials, including cluster-randomization and pragmatic, or “in place” trials taking place in the context of care;
• the requirement that HHS convene regular reassessments of identifiability and privacy in the context of evolving technology;
• the requirement that HHS revisit the list of research that qualifies for expedited review on a regular basis;
• the requirement to develop, maintain and support a web site and submission standards and processes for consent form that are required to be posted by the updated common rule;
• a need for guidance on the interpretation of changes in the updated common rule, including fundamental changes to the consent document and process, changes to exempt categories, implementation of “broad consent,” and the requirement for single IRB review of multi-site trials;
• Need for education and outreach around the changing and increasingly complex research environment.
It is beyond the expertise of SACHRP to evaluate whether OHRP’s existing resources are sufficient to address its ongoing policy and compliance obligations, while also addressing these additional needs, but the complexity of the current environment suggests the need for a formal planning and budgeting exercise for the Office.
SACHRP recommends that HHS undertake a strategic planning and bottom-up budgeting exercise to assess the adequacy of OHRP’s current resources and potentially to establish a new baseline budget that reflects the evolving research environment.
As implied by the OIG report, the most definitive way that regulated entities can affect OHRP’s compliance function is by arguing for a decrease in its budget. Once an appropriate budget is established, ensuring independence requires that this budget be protected from inappropriate reactive pressures or from real or apparent conflicts of interest.
SACHRP recommends that OHRP’s budget should be shielded from inappropriate changes unrelated to changes in mission, scope or responsibilities. One way to achieve such independence would be to index the budget to Federal research expenses, perhaps as indicated by a surrogate like the NIH budget.
Finally, HHS should consider seeking statutory authority for OHRP’s independence
In both the current report and a previous report from 2014 (Report of OIG Review of Allegations of Interference in OHRP Compliance Determination for SUPPORT), the OIG concluded that OHRP had been able to act independently, but also noted that “no law establishes OHRP's organizational independence.” While offering the model of the Inspector General (IG) Act as a way to create such statutory independence, the OIG observed that “Federal OIGs routinely consult with experts in the programs they review,” implying that statutory independence would not preclude the kind of debate that developed around SUPPORT.
The IG Act creates offices that have oversight of Federal program. The oversight function of OHRP, in contrast, is focused on regulatory compliance of entities receiving Federal funds for research. As illustrated by SUPPORT, the concern for OHRP is not necessarily direct influence or interference by research entities in its compliance activities, but rather the influence or interference by other Federal entities that disagree with its findings and feel they have an equivalent expertise or authority.
Despite this difference in scope, there are several aspects of the IG Act that could serve as useful models:
• establishment of authority (§ 6);
• requirement for transparency (§ 5), specifically the requirement for disclosure in its semiannual reports:
§5(21) a detailed description of any attempt by the establishment to interfere with the independence of the Office, including (A) with budget constraints designed to limit the capabilities of the Office; and (B) incidents where the establishment has resisted or objected to oversight activities of the Office or restricted or significantly delayed access to information, including the justification of the establishment for such action;
Documenting and disclosing improper interference might be more difficult for OHRP, given the complexity of its relationship to Federal funding entities and institutions or other entities receiving such funds. Identifying such interference would be more likely if OHRP was at the same hierarchical level as the research agencies it oversees (see preceding recommendation).
The OIG report concluded that some of the problems around SUPPORT that led to concerns about OHRP’s independence arose because OHRP’s role and authority to interpret regulations was not clear to Federal research agencies. This role and authority are currently not defined by statute, but are reflected in the Office’s mission.
SACHRP recommends that HHS consider seeking statutory authority for OHRP to directly collect, on its own authority, all documents related to its investigations.
SACHRP recommends that HHS consider seeking statutory clarification of the role and authority of OHRP as the primary interpreter of the regulations in 45 CFR 46 for the protection of human participants in HHS funded research,