Background

On September 8, 2015, the Department of Health and Human Services ("HHS"), through the Office for Human Research and Protection ("OHRP"), proposed several significant changes to the Federal Policy for the Protection of Human Subjects (the "Common Rule").  In its notice of proposed rulemaking ("NPRM"), HHS and 15 other federal agencies and departments announced that the objective of these future revisions is to modernize the federal policy on human subjects research and to align the Common Rule with the many changes and advancements that have taken place in the research industry since the Common Rule was originally promulgated in 1991.  Comments on the proposed regulations will be accepted through December 7, 2015.

The long-awaited NPRM follows a July 2011 advanced notice of proposed rulemaking ("ANPRM"), in which HHS solicited comment on how to revise and modernize the Common Rule to better protect human research subjects.  If adopted, the proposals set forth in the NPRM will substantially alter how research is designed and conducted in the United States and will affect a wide range of industry stakeholders.  Among other changes, the NPRM contains proposals to expand the jurisdictional scope of the Common Rule, alter the current research review and oversight process, implement new requirements for the secondary use of biospecimens and individually identifiable information, enhance the informed consent process and add new categories of excluded and exempted research.

Human subjects research governed by the Food and Drug Administration ("FDA") will not be affected by these proposed changes to the Common Rule.  However, the FDA has stated that it intends to modify its research regulations, to the extent practicable, to be consistent with those adopted from the NPRM.  The FDA has not yet announced when those changes may be proposed or adopted.

Key Proposed Changes

Below is a summary of the key proposed changes to the Common Rule, as outlined in the NPRM.

  1. Jurisdiction. If adopted, the NPRM will significantly expand the scope of the Common Rule to cover all research studies, including those not themselves federally funded, conducted at institutions receiving federal funds for non-exempt human subjects research. As noted above, this proposed change does not extend to FDA-regulated research studies.
  2. IRB Review. One of the most noteworthy changes outlined in the NPRM is the requirement that all institutions participating in cooperative research studies to use a single institutional review board ("IRB") as the reviewing body for the study.  The federal funding agency or the lead institution would be responsible for selecting the single IRB.  A cooperative study could still be reviewed by an institution's individual IRB, though the results of such a review would not be binding nor enforced by OHRP.

III. Continuing Review of Research.  The NPRM proposes to eliminate continuing review for minimal risk research studies that qualify for expedited review. Once approved by the IRB, additional review will not be required once the study reaches the point where it involves analyzing data or accessing follow-up clinical data from standard of care procedures. The NPRM also proposes to change the default review for minimum risk research studies to expedited review.

IV. Biospecimens and the Definition of "Human Subject." The NPRM proposes to expand the definition of "human subject" to include biospecimens, whether or not the specimens contain identifiable information.  The current regulations define a human subject as "a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or identifiable private information."  Biospecimens are often used for continued research unrelated to the purpose for which they were originally collected (a "secondary use"), and it is often possible to extract DNA from biospecimens to obtain individually identifiable data. The NPRM takes the position that secondary use without consent should be prohibited because research subjects should have control over the circumstances in which personal information can be derived from their specimens.  This proposed consent requirement would only be applied prospectively and would not apply to biospecimens collected from past research subjects.  The NPRM recognizes that this definition of human subject may not be ideal and, as a result, is seeking comments on two alternative approaches. 

  1. The first alternative is to expand the definition of human subject to include whole genome sequencing data or any part of the data generated as a consequence of whole genome sequencing, regardless of the individual identifiability of the biospecimens used to generate such data. Under this approach, the Common Rule will apply to research that would generate whole genome sequencing data, the use of any part of the generated data and research involving secondary use of any part of whole genome sequencing data.
  2. The second alternative offered by the NPRM is to expand the definition of human subject to include research use of information produced using a technology applied to a biospecimen that generates information unique to an individual such that it is foreseeable that, when used in combination with publicly available information, the individual could be identified ("bio-unique information").  HHS will maintain a Secretary's List of the technologies that can generate bio-unique information, and if a researcher is using one of those technologies, then that research will be subject to the Common Rule, whether or not the researcher can identify the source of the underlying biospecimen.

Additionally, the NPRM proposes to allow researchers to obtain a one-time broad consent for the storage or maintenance of biospecimens for secondary use in subsequent research studies.  The secondary use of non-identifiable biospecimens for research that generates information already known about the individual, such as validation tests and research to develop specific diagnostic tests, would be excluded from the Common Rule.

V. Informed Consent.  The NPRM proposes to modify the informed consent regulations in an effort to shorten consent forms and make it easier for research subjects to locate the key information necessary to make informed decisions regarding their participation in research studies. 

  • Presentation of Information. The NPRM proposes that all information required by the Common Rule must be presented first in the informed consent document.  This includes the information that a subject would need to know to make an informed decision about whether to participate in the study.  All other information provided to the subject by the principal investigator as part of the informed consent process must be attached in an appendix.  If a HIPAA authorization is combined with a consent form, the authorization must be included in the primary document and not the appendix.
  • New Basic Elements of Informed Consent. Under the proposal, subjects will have to be informed that their identity could be removed from collected data or specimens and the non-identified data used for secondary research studies. The consent will need to inform subjects that:
    • Their non-identified data could be used for future research studies without additional informed consent; or
    • The subject's data will not be used for future research studies, even in a non-identified form.
  • New Additional Elements of Informed Consent.  The NPRM proposes to add three additional elements to the informed consent process by requiring principal investigators to inform subjects:
    1. That their biospecimens may be used for commercial profit and whether or not the subject will share in that profit;
    2. Whether they will be informed of clinically relevant research results, including individual research results, and under what conditions; and
    3. That they have an option to consent, or refuse to consent, to investigators contacting them to seek additional information or biospecimens or to discuss participation in another research study.
  • IRB Waiver of Informed Consent Requirements.  Under the NPRM, if an individual refuses to sign a broad consent for biospecimen use in secondary research, an IRB may not waive this consent, absent extreme circumstances such as when the research "could not be conducted with other biospecimens for which informed consent was or could be obtained."  For research using identifiable information, the research must not be able to be "practicably" carried out in the absence of these identifiers.  The NPRM requires IRBs to use the following elements to determine "practicability":
    • Scientific validity would be compromised if consent were required;
    • Ethical concerns would be raised if consent were required;
    • There is a scientifically and ethically justifiable rationale why the research could not be conducted with a population from whom consent can be obtained; and
    • Practicability should not be determined solely by considerations of cost, convenience or speed.
  • Informed Consent Template.  The NPRM will create a Secretary's Template that researchers could use to collect broad consent from subjects for the secondary research use of biospecimens and identifiable private information.
  • Public Availability of Informed Consent Documents.  To increase transparency and accountability, the NPRM proposes that consent documents for trials conducted or supported by a Common Rule agency must be posted on a public federal website within 60 days after the close of the trial's recruitment.

VI. Excluded Research. The NPRM will exclude 11 activities from regulation under the Common Rule. Investigators self-determine whether a research study is excluded. Such research must still be conducted with the principles outlined in the Belmont Report. Excluded research will include the following:

  • Activities not considered research such as program improvement activities, quality assurance and quality improvement programs and public health surveillance;
  • Activities that are sufficiently low risk and subject to other independent controls such as collection or study of publicly available or non-identifiable information; and
  • Activities that are low-risk and do not meaningfully diminish research subject autonomy.

VII. Exempted Research.  If adopted, the NPRM will help investigators and research institutions determine whether their research is exempted through the development of tool.  This exemption determination tool will allow investigators to input study information into an algorithm to determine whether or not a particular study is exempt.  If information is input correctly, the use of the tool will qualify as a safe harbor from the Common Rule. The following additional exemptions were proposed in the NPRM:

  • Low-Risk Interventions.  This exemption includes benign interventions involving the collection of data from an adult subject that are brief, harmless and not physically invasive.  The subject will have to consent to the intervention and data collection, and the information must be unidentifiable or cannot place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement or reputation if disclosed. 
  • Collection of Sensitive Information Subject to Documentation and Security Standards.  This exemption includes secondary research use of identifiable private information collected for non-research purposes if the individual was notified that the information may be used in research.
  • Research Involving Biospecimens.  This exemption requires that consent be obtained for the research use of biospecimens but allows for broad consent for those future uses, provided that the principal investigator uses the Secretary's Template.

Practical Takeaways

These changes, if adopted as proposed, will require those participating in human subjects research to evaluate and revise many of their research processes, procedures and policies. If adopted, the effective date of the final rule will be one year following its publication in the Federal Register.  Compliance with the new Common Rule regulations will be required upon that effective date with the exception of the rules covering biospecimens and the mandate for oversight of cooperative studies by a single IRB, which will require compliance within three years following publication of the final rule.

The NPRM seeks public comment on numerous proposals and questions outlined in the NPRM.  The 90-day comment period closes on December 7, 2015. A copy of the NPRM can be found here.