New England Journal of Medicine
December 10, 2015 Vol. 373 No. 24
http://www.nejm.org/toc/nejm/medical-journal

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Perspective
Bringing the Common Rule into the 21st Century
Kathy L. Hudson, Ph.D., and Francis S. Collins, M.D., Ph.D.
N Engl J Med 2015; 373:2293-2296
December 10, 2015
DOI: 10.1056/NEJMp1512205

On September 8, 2015, the Department of Health and Human Services (HHS) and 15 other federal departments and agencies issued a proposal to revise the regulations governing the ethical conduct of research involving humans.1 The current regulations were adopted by HHS in 1981 to implement the landmark 1979 Belmont Report. Adopted by other agencies throughout government in 1991, the regulations, informally known as the Common Rule, have changed little since their inception, while the research landscape has changed radically.

In addition to revolutionary advances in scientific knowledge and technologies, society has undergone tremendous shifts in recent decades that are highly relevant to the conduct of research. Today’s studies are more likely to include multiple research sites and large numbers of participants. Research is moving toward a more participatory model, as volunteers increasingly expect to be partners in research — as exemplified by such studies as the President’s Precision Medicine Initiative (www.nih.gov/precisionmedicine). Sharing data and biospecimens can accelerate discoveries, and increasingly sophisticated information can be obtained from biospecimens. The controversy that followed the 2013 publication of the genome sequence of the HeLa cell line (derived from tumor cells from Henrietta Lacks) underscores the need for greater involvement of and respect for research participants.2

The two central goals of the proposed revisions to the Common Rule are to enhance respect and safeguards for research participants and to increase research efficiency by reducing unnecessary burdens and calibrating oversight to the level of risk. If they are ultimately adopted, the key changes will require consent for research involving biospecimens, allow participants to grant broad consent for future use of data and biospecimens, strengthen privacy and security safeguards to prevent unauthorized disclosure and use of data and biospecimens, streamline institutional review board (IRB) operations by requiring reliance on a single IRB for multisite studies conducted in the United States, and exclude some nonresearch activities and low-risk research from the rule, while exempting other low-risk research from certain requirements (see Table 1Table 1Major Proposed Changes in the Common Rule Notice of Proposed Rulemaking (NPRM).). The proposals reflect careful consideration of the public comments on proposals published in 20113 and a deeper understanding of participants’ preferences and risks4 that has been developed over the past 4 years.

One of the most significant changes will be requiring consent for the use of all biospecimens in research, whether or not they are deidentified (see Table 2Table 2Major Changes to Requirements by Research Type.). A growing body of literature indicates that prospective research participants want to decide whether their biospecimens are used in research; they want researchers to ask their permission — it is the respectful thing to do. Moreover, given the available tools and technologies, we know that biospecimens can be used to generate information unique to individuals and therefore cannot be truly deidentified4; there is thus an ethical obligation to seek permission and inform participants of risks to their privacy. The proposed change allows consent to be broad, enabling participants to grant permission for researchers to use their biospecimens and data for all kinds of downstream research questions.
No doubt, requiring consent for the use of deidentified biospecimens and allowing broad consent will pose challenges for the research community. But the proposed rule allows continued use of deidentified biospecimens collected in the past, and the new policy will be phased in over 3 years. In the beginning, there will be additional costs and effort needed to make the consent process work and to track the consent status of stored biospecimens. Enormous benefits, however, will be realized as biospecimens become more available for secondary research.

The Common Rule proposal also tackles some long-standing complaints about informed-consent documents — namely, that they are too long, too complicated, and filled with legal text designed more to protect institutions than participants. Under the proposal, the content of these forms will be limited to specific elements outlined in the rule, with nonessential information moved into a separate appendix. Furthermore, the proposed regulations strengthen privacy and security safeguards for all research involving biospecimens or identifiable information, as well as for certain research that may be exempt from other provisions of the rule. The proposal brings under the Common Rule umbrella currently unregulated clinical trials (e.g., trials of surgical procedures that do not involve devices regulated by the Food and Drug Administration [FDA] and are not funded by one of the Common Rule agencies), if they are conducted in the United States at institutions that receive human-subjects research funding from a Common Rule agency. This extension of the rule will not apply to clinical trials that are subject to regulation by the FDA or that are conducted at institutions that receive funding only for exempt research.

Multisite research now accounts for nearly half the studies funded by the National Institutes of Health (NIH). The proposal addresses inefficiencies created by the current process of redundant IRB review of multisite studies, by requiring participating U.S. institutions to rely on a single IRB of record, unless local IRB review is required by law or the federal department or agency supporting or conducting the research determines that use of a single IRB is not appropriate for the particular study. This change will help speed the initiation of research and save considerable resources.5 One concern that institutions have expressed regarding relying on single IRBs is uncertainty over whether an outside IRB or the institution would be held responsible for regulatory violations by the IRB, and the proposal addresses this concern by establishing that the IRB of record, rather than the institution relying on the IRB, will be held responsible for any IRB regulatory violations.

Several other changes will, collectively, reduce the burden on IRBs, allowing them to focus on higher-risk research. Continuing IRB review will be eliminated for studies that qualify for expedited IRB review and for most studies that have completed the interventional stages and involve only data analysis, unless on initial review it was determined that continuing review was appropriate. In addition, publication of a list of activities considered to pose minimal risk will reduce the burden on IRBs in making minimal-risk determinations. Finally, IRBs will no longer be required to review grant applications or contract proposals.

Another set of proposed changes aims to match the level of oversight to the level of risk the research poses to participants, by defining categories of research that are excluded from the Common Rule or are exempt from one or more of its requirements (e.g., IRB review). The excluded categories are activities that are deemed not to meet the rule’s definition of research (such as public health surveillance and some quality-assurance activities), to be very low-risk social science research (such as surveys, focus groups, and interviews), or to be subject to other rules with appropriate requirements (such as research involving medical records and Medicare claims data that is subject to the privacy rule of the Health Insurance Portability and Accountability Act).

Determinations of whether specific research proposals are exempt from the rule can be made with a Web-based decision tool. For example, one category of research that will be exempt from nearly all requirements includes certain types of studies involving standard educational practices, public program evaluations, or benign interventions (such as interactions that are temporary and painless with no lasting negative effects). Another category includes certain uses of sensitive information from which individuals are identifiable, if proper privacy and security safeguards are in place. Establishment of biospecimen and data repositories will be exempted from full IRB review if initial broad consent has been obtained, safeguards are in place, and to ensure that both these requirements are met, a limited IRB review is conducted. Secondary research using these repositories will be required only to have safeguards in place, and no IRB review will be necessary.

These long-overdue reforms will bring the Common Rule into the 21st century. They should help the scientific community take a giant leap forward in showing respect for research participants, without whom the biomedical research enterprise would cease to exist. Just as the Lacks family’s experience helped clarify how research needed to change, the perspectives of researchers, the public, and patients should be heard as these reforms are finalized. The NIH urges all stakeholders to closely review the proposed changes and participate in the comment process by the deadline of December 7, 2015.
Editor’s note: HHS has extended the comment period by 30 days, to January 6, 2016.

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Perspective
Reform of Clinical Research Regulations, Finally
Ezekiel J. Emanuel, M.D., Ph.D.
N Engl J Med 2015; 373:2296-2299
December 10, 2015
DOI: 10.1056/NEJMp1512463