On 1 September 2011, the U.S. Department of Health and Human Services (HHS) extended the deadline for comment on its Advance Notice of Proposed Rulemaking (ANPRM) to modernize and enhance regulations that govern research on human subjects.1 These regulations, originally promulgated by HHS in the late 1970s, are often referred to as the Common Rule. They are applicable to research conducted, regulated or supported by federal agencies, and to other private sector entities that file an "assurance of compliance" with the regulations. Manufacturers of pharmaceutical products and medical devices, and those who conduct clinical investigations of drugs and devices that are regulated by the FDA, encounter the same requirements with slight modifications as part of FDA's regulation of clinical investigations. HHS issued the ANPRM on 26 July 2011. In response to concern that such substantial proposed revisions required additional time to review, HHS has extended the comment period by one month. Comments are now due 26 October 2011.
HHS discusses seven different areas where the provisions of the Common Rule might be modified to address various concerns that have arisen over the decades. This is not yet a proposed regulation; rather, concepts and alternatives to existing provisions are discussed. If implemented, this would substantially change the existing regulatory framework for human subjects research. In particular, rules regarding informed consent, IRB review, and data protection standards would be significantly changed for biospecimen and data research. These changes will have important implications for clinical trial sponsors, such as pharmaceutical and medical device companies, research institutions, investigators, clinical research organizations and institutional review boards (IRBs), as well as entities that maintain biospecimen repositories. HHS notes that its proposed changes to the Common Rule will likely require corresponding changes to FDA regulations, HIPAA privacy regulations, and the versions of human subjects regulations applicable to other federal agencies.
A. Extension of the Common Rule to all human subjects research. HHS proposes to extend the Common Rule to research that is not federally funded but which is conducted at a domestic institution that receives some funding for human subjects research from a Common Rule federal agency. Already, many institutions voluntarily extend the Common Rule to all non-federal research via election on the OHRP-approved Federal Wide Assurance (FWA), but not all institutions make this election.
B. Level of IRB review required. HHS proposes to refine the regulations to ensure that the level of review is commensurate with the level of risk to human subjects. Changes under consideration include:
- Elimination of continuing review for all minimal risk studies that undergo expedited IRB review.
- Regular updates to the categories of research eligible for expedited review, thereby creating a presumption that such studies are indeed minimal risk.
- Expansion of the categories of research exempt from IRB review, commencement of such studies upon filing a brief form with the IRB, elimination of routine IRB review of such studies, and a requirement for random audits of a sample of exempt studies.
- Establishment of data security standards for identifiable information and for de-identified information, consistent with the level of risk entailed by the proposed use of the information.
- Requirement for a brief written consent for research use of any biospecimens collected for clinical purposes, eliminating the current practice of treating biospecimen research as exempt once all individually identifying information is stripped from the sample. This would necessitate written consent for future research on biospecimens.
C. IRB review of multi-site studies. HHS proposes a requirement for all domestic sites in a multi-site study to rely upon a single IRB as the central IRB of record. Changes to the HHS Office for Human Research Protections (OHRP) enforcement procedures would hold an external IRB directly accountable for compliance. Issues under consideration include, among others, how a central IRB would be selected, whether the IRB would have adequate knowledge of each site, and whether a central IRB arrangement could adequately address liability concerns at each institution involved in a study.
D. Informed consent. HHS proposes to enhance the informed consent process in various ways. Modifications under consideration include new consent form requirements that would (1) specify appropriate consent form content; (2) proscribe certain content; (3) limit consent form length; (4) specify how information is presented; (5) reduce institutional "boilerplate" language; and (6) make available standardized consent forms that satisfy applicable regulations. In addition, HHS seeks to clarify criteria for waivers of informed consent and for verbal consent, and HHS would clarify the circumstances under which future research use of data would or would not require informed consent.
Informed consent for biospecimen research. HHS proposes to require institutions to provide the research subject an opportunity to choose how their biological specimens may be used in the future. Biospecimen research that is currently exempt (e.g., when the researcher does not possess information that would allow identification of the person whose biospecimen is being studied) would now require a general written consent. Importantly, HHS proposes that if data is originally collected for research purposes, consent would be required regardless of whether the researcher obtains identifiers. This consent could allow for broad future research and could be broad enough to cover all data and biospecimens at any time by the institution. But, this general consent form would permit the subject to decline participation in all future research while consenting to the research study at hand. Participation in a research study could not be conditioned on agreeing to allow future open-ended research using a biospecimen. These changes, if adopted, would apply prospectively, but not retrospectively.
E. Data security and information protections. HHS proposes that the Common Rule incorporate HIPAA standards to define individually identifiable information and de-identified information, but HHS may reevaluate and supplement these definitions. Specifically, HHS is considering:
- Creation of mandatory data security and information protection standards for all studies involving identifiable or potentially identifiable data. Specific data protection standards, modeled on the HIPAA Security Rule, would include administrative, physical, and technical safeguards, as well as data breach notification procedures.
- Adopting HIPAA Privacy Rule standards for when data is deemed de-identified, as well as categorizing all biospecimen research as identifiable information. HHS also proposes a re-evaluation of the HIPAA de-identification standard to ensure it reflects emerging technology and evolving informational risks.
- Strengthening of enforcement mechanisms under the Common Rule, such as random periodic audits. HHS poses a number of specific questions regarding implementation of data privacy and security requirements for research entities.
F. Event reporting. HHS proposes to simplify and consolidate reports on unanticipated problems or adverse events, through (1) using standardized but flexible data elements for safety reporting; (2) implementing a web-based, federal-wide portal for reporting; and (3) harmonizing terminology and reporting timelines across all agencies.
G. Consistency across federal agencies. HHS proposes to examine the extent to which regulatory uniformity across federal agencies and departments is desirable, appropriate, and feasible to address human subjects protections in diverse research populations and contexts, and in view of differing agency mandates and objectives.
Some of these proposed changes could be helpful in having informed, willing research participants. Others may seem to create needless impediments to effective communication between researcher and participant. As all of these changes would substantially affect clinical investigations, epidemiological studies and other biostatistical analyses, it is important to consider their impact on your business at this juncture before the proposed regulation is issued. Please let us know if we can assist you in preparing comments or addressing the questions on which HHS seeks input.