Clinical Research Policy

Research Involving Human Subjects

The Office of Science Policy (OSP) is working to meet the needs of NIH's various stakeholder communities as the Department of Health and Human Services considers possible reforms in the federal regulations to protect human subjects in research and other related issues and challenges.

OSP is contributing to these efforts in many ways. This includes collecting and coordinating the NIH response to important policy matters; serving as NIH representatives for interagency policy development activities; and promoting consistency in the interpretation of regulations, policy, and guidance by working within NIH and other agencies. The CR Policy program is a resource for communication and sharing of best practices within the NIH community regarding ethical, regulatory, and scientific challenges in human subject research.

 

Common Rule Advanced Notice of Proposed Rulemaking (ANPRM).

Initially published in 1974, the DHHS regulations for the protection of human subjects in research were developed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The National Commission was created after the enactment of the 1974 National Research Act (Public Law 93-348), in response to a number of highly publicized abuses in research. Among other responsibilities, the National Commission was charged with identifying the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines to assure that such research is conducted in accordance with ethical principles.

The ethical principles are described in the Belmont Report, and include respect for persons, beneficence, and justice. These three principles are applied through regulations. The DHHS regulations, 45 CFR 46 consist of Subpart A, often called the “Common Rule“ and Subparts B through D, and were written to describe appropriate protections for human subjects in research. In 1991, the Common Rule was adopted by 14 additional Federal departments and agencies. Subsequently three more Agencies signed on to the Common Rule, bringing the total to 17.

Since the promulgation of the Common Rule, the research landscape has undergone significant changes. The volume of clinical research and the number of multi-site studies have increased. In addition, new and improved technologies make it possible to do research with databases, the internet, archived biospecimens and data, as well as research on genomics, bio imaging, and informatics. These changes have raised questions about whether implementing the current regulations adequately protects human subjects against risks associated with the evolving research enterprise.

In response to concerns about the adequacy of the Common Rule, in July, 2011 DHHS and OSTP issued an Advanced Notice of Proposed Rulemaking (ANPRM) that proposed enhancing human subjects protections and reducing burdens for researchers. The ANPRM proposed seven possible regulatory reforms:

  1. Refinement of the existing risk-based regulatory framework;
  2. Utilization of a single IRB review of record for domestic sites of multi-site studies;
  3. Improvement of consent forms and the consent process;
  4. Establishment of mandatory data security and information protection standards for all studies that involve identifiable or potentially identifiable data;
  5. Establishment of an improved, more systematic approach for the collection and analysis of data on unanticipated problems and adverse events;
  6. Extension of Federal regulatory protections to all research regardless of funding source, conducted at institutions in the U.S. that receive some Federal funding from a Common Rule agency for research with human subjects; and
  7. Improvement in the harmonization of regulations and related agency guidance.

More than 1100 comments were received during the public comment period which ended in October, 2011. Using input provided by the NIH ICs, CR Policy program staff supplied information to NIH leadership to inform them about stakeholder interests relating to these issues.

 

Common Rule Notice of Proposed Rulemaking (NPRM)

The NPRM was issued on September 8, 2015 for public comment by the Office of the Federal Register. The U.S. Department of Health and Human Services and fifteen other federal departments and agencies have announced proposed revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991. The NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. The Office for Human Research Protections (OHRP) held a public Town Hall Meeting to respond to questions related to the NPRM on October 20, 2015. OHRP has also developed a Webinar Series on the NPRM to help the public better understand the goals and impact of the new proposals. The public comment period in response to the NPRM closed on December 7, 2015.

The following list encompasses the most significant changes to the Common Rule proposed in the NPRM:

1) Improve informed consent by increasing transparency and by imposing stricter new requirements regarding the information that must be given to prospective subjects, and the manner in which it is given to them, to better assure that subjects are appropriately informed before they decide to enroll in a research study.

2) Generally require informed consent for the use of stored biospecimens in secondary research (for example, part of a blood sample that is left over after being drawn for clinical purposes), even if the investigator is not being given information that would enable him or her to identify whose biospecimen it is. That consent would generally be obtained by means of broad consent (i.e., consent for future, unspecified research studies) to the storage and eventual research use of biospecimens.

3) Exclude from coverage under the Common Rule certain categories of activities that should be deemed not to be research, are inherently low risk, or where protections similar to those usually provided by IRB review are separately mandated.

4) Add additional categories of exempt research to accommodate changes in the scientific landscape and to better calibrate the level of review to the level of risk involved in the research. A new process would allow studies to be determined to be exempt without requiring any administrative or IRB review. Certain exempt and all non-exempt research would be required to provide privacy safeguards for biospecimens and identifiable private information. New categories include:

            a. certain research involving benign interventions with adult subjects;

            b. research involving educational tests, surveys, interviews or observations of public behavior

                when sensitive information may be collected, provided that data security and information privacy protections policies are followed;

            c. secondary research use of identifiable private information originally collected as part of a non-research activity, where notice of such possible use was given;

            d. storing or maintaining biospecimens and identifiable private information for future, unspecified secondary research studies,

                or conducting such studies, when a broad consent template to be promulgated by the Secretary of HHS is used, information and biospecimen privacy 

                safeguards are followed, and limited IRB approval of the consent process used is obtained.

5) Change the conditions and requirements for waiver or alteration of consent such that waiver of consent for research involving biospecimens (regardless of identifiability) will occur only in very rare circumstances. 

6) Mandate that U.S. institutions engaged in cooperative research rely on a single IRB for that portion of the research that takes place within the United States, with certain exceptions.  To encourage the use of IRBs that are otherwise not affiliated with or operated by an assurance-holding institution (“unaffiliated IRBs”), this NPRM also includes a proposal that would hold such IRBs directly responsible for compliance with the Common Rule.

7) Eliminate the continuing review requirement for studies that undergo expedited review and for studies that have completed study interventions and are merely analyzing data or involve only observational follow-up in conjunction with standard clinical care.

8) Extend the scope of the policy to cover all clinical trials, regardless of funding source, conducted at a U.S. institution that receives federal funding for non-exempt human subjects research.