The Department of Health and Human Services (HHS) and 15 other federal agencies and departments Jan. 18 issued the much anticipated finalized version of a revised Common Rule, the Federal Policy for the Protection of Human Subjects (45 C.F.R. Part 46 (HHS)).

The final rule — the result of revisions to a notice of proposed rulemaking (NPRM) released in September 2015 and the agencies’ consideration of more than 2,100 comments submitted on the proposal — was published in the Federal Register on Jan. 19 (82 Fed. Reg. 7149). Most provisions of the revised Common Rule will go into effect in January 2018.

According to HHS, the revised Common Rule “strengthens protections for people who volunteer to participate in research, while ensuring that the oversight system does not add inappropriate administrative burdens, particularly to low-risk research.” The department added that the final rule “allows more flexibility in keeping with today’s dynamic research environment” — reflecting the growth and diversification of clinical research since the publication of the Common Rule in 1991. The regulations were last amended in 2005, but those were only minor editorial changes, which did not change the rules.

“The final rule is designed to more thoroughly address the broader types of research conducted or otherwise supported by all of the Common Rule departments and agencies such as behavioral and social science research,” the preamble to the final rule said. “It also benefits from continuing efforts to harmonize human subjects policies across federal departments and agencies.”

In addition to HHS, the final revised Common Rule was released by the Departments of Agriculture, Commerce, Defense, Education, Energy, Homeland Security, Housing and Urban Development, Labor, Transportation and Veterans Affairs; the National Aeronautics and Space Administration; the Social Security Administration; the Agency for International Development; the Environmental Protection Agency; and the National Science Foundation.

‘Significant Changes’

The final rule makes a number of “significant changes” to the Common Rule, as identified in the preamble.

"Concise and focused" explanation. The new final rule sets new requirements for the information that must be given to prospective research subjects as part of the informed consent process.

In particular, consent forms generally will be required to include a "concise and focused" explanation of “key information that would be most important to individuals contemplating participation in a particular study.” The explanation, which will appear at the beginning of the consent document, must cover the purpose of the research, the risks and benefits, and “appropriate alternative treatments that might be beneficial to the prospective subject,” HHS said.

Dr. Jerry Menikoff, director of the HHS Office for Human Research Protections, said that the requirement deals with the problem of “incredibly lengthy and complex” consent forms that he said were designed “to protect institutions from lawsuits, rather than providing potential research subjects with the information they need in order to make an informed choice about whether to participate in a research study.”

Broad consent. The final rule also allows the use of broad consent — seeking prospective consent to unspecified future research — from a subject for the storage, maintenance and secondary research use of identifiable private information and identifiable biospecimens. “Broad consent will be an optional alternative that an investigator may choose instead of, for example, conducting the research on nonidentified information and nonidentified biospecimens, having an institutional review board (IRB) waive the requirement for informed consent, or obtaining consent for a specific study,” the preamble stated.

Single IRB for cooperative research. Under the final rule, beginning in January 2020, U.S.-based institutions engaged in cooperative, multi-institutional research must use a single IRB for the portion of the research that takes place in the United States.

However, the proposed requirement for a single IRB that appeared in the NPRM has been modified “to add substantial increased flexibility in now allowing broad groups of studies (instead of just specific studies) to be removed from this requirement,” HHS said.

As under the NPRM, under the final rule the single IRB requirement does not apply to the following:

  • cooperative research for which more than single IRB review is required by law; and
  • research for which any federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular study.

Exemptions based on risk profile. The new Common Rule also establishes new exempt categories of research based on the level of risk the research poses to participants. Under some of the new categories, exempt research would be required to undergo limited IRB review “to ensure that there are adequate privacy safeguards for identifiable private information and identifiable biospecimens,” the preamble stated.

For example, HHS said, there is a new exemption for secondary research involving identifiable private information if the research is regulated by and participants are protected under rules promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA).

Continuing review. The final rule removes the mandate for continuing review of ongoing research for studies that undergo expedited review, as well as continuing review for studies that have completed study interventions and are merely analyzing study data or involve only observational follow-up in conjunction with standard clinical care.

Consent for studies on stored data or biospecimens. For clinical studies involving stored identifiable data or identifiable biospecimens, researchers will have the option of relying on broad consent obtained for future research, as an alternative to seeking IRB approval for a waiver of the consent requirement. The new rule continues to allow researchers to conduct studies on non-identified stored data or biospecimens without obtaining consent.

Website posting of consent forms. The final rule requires that IRB-approved consent forms for certain federally funded clinical trials be posted on a public website. The forms must be posted by the awardee or the federal department or agency conducting the trial. The posting can occur any time after the trial is closed to recruitment, so long as the posting is no later than 60 days after the last study visit by any subject, as required by the protocol. The department or agency may permit “appropriate redactions” to the information posted and, in rare instances, may determine that no posting is required if the department or agency determines “that the very existence of a particular clinical trial should not be publicly disclosed.”

Proposed Changes Not Included in the Final Rule

The final version of the new Common Rule did not adopt a number of proposals that had been included in the NPRM, including some of the proposals that had been the most contentious among stakeholders.

Clinical trials that are not federally funded. The final rule does not extend the Federal Policy for the Protection of Human Subjects to cover clinical trials that are not federally funded.

Nonidentified biospecimens. The final rule does not adopt the proposals under which research involving nonidentified biospecimens would be subject to the Common Rule and consent would need to be obtained to conduct such research. “The final rule maintains the current practice with respect to oversight of these specimens,” HHS said. "This change alone addresses many of the public comments on the NPRM. Eliminating that proposal is intended to address concerns about the complexity of and lack of justification for the proposed changes in the rule, as well as concerns about embarking on significant changes without evidence that they would improve the system," HHS said. 

Waiver criteria for identifiable biospecimens. The final rule does not adopt the NPRM’s proposal for more stringent criteria for obtaining waivers of the consent requirements for identifiable biospecimens.

Tools and standards not yet proposed. Where the NPRM relied on tools or standards that have not yet been proposed, the final rule either does not adopt the proposal or includes revisions to the proposal to eliminate the reliance. This affects, for example, proposals dealing with a template to be used for broad consent forms or with a decision tool to be used for making exemption determinations, HHS said.

Standardized privacy safeguards for identifiable private information and biospecimens. The final rule does not include the NPRM’s proposed standardized privacy safeguards for identifiable private information and identifiable biospecimens. “Aspects of proposals that relied on these safeguards have been modified or are not being adopted,” the preamble stated.

“Excluded” activities. The NPRM proposed a set of “excluded” activities involving clinical trials. The final rule instead generally describes those activities as not satisfying the definition of what constitutes research under the regulations, or it classifies those activities as being exempt.

Exemption categories. The final rule aligns more closely with the longstanding ordering of exemption categories than did the proposed revisions to those categories. In addition, “the final rule does not include the proposed requirement that exemption determinations need to be made in specified ways,” the preamble stated.

Possible Changes by the New Congress?

Release of the rule came two days before the end of the Obama administration. There remained the possibility that under the Congressional Review Act, Congress could rescind the final rule within 60 days of its publication.

In a Nov. 15, 2016, letter, House Republicans cautioned the outgoing administration “against finalizing pending rules or regulations in the administration’s last days.” They said that, “by refraining from acting with undue haste, you will ensure that agency staff may fully assess the costs and benefits of rules, making it less likely that unintended consequences will harm consumers and businesses. Moreover, such forbearance is necessary to afford the recently elected administration and Congress the opportunity to review and give direction concerning pending rulemakings.” The letter warned that the new Congress would scrutinize any new final rules “and, if appropriate, overturn them.”