Advanced Notice of Proposed Rulemaking (ANPRM): Enhancing Protections for Research Subjects & Reducing Burden, Delay & Ambiguity for Researchers

by Yvonne Higgins, AB, CIP, Director, Quality Management

On July 22, 2011, the U.S. Department of Health and Human Services (HHS) announced a proposal that may result in significant changes to federal regulations on the protection of human research subjects. In the notice, published in the federal register, HHS acknowledged that “the landscape of research activities has changed dramatically” and that there are “many questions about whether the current regulatory framework is adequate and appropriate for the protection of human subjects in the 21st century.” A key purpose of the proposed change is to “…better focus oversight resources on higher-risk research studies.” 1

The Rulemaking Process

The rulemaking process involves two phases: an advanced notice of proposed rulemaking (ANPRM) followed by a notice of proposed rulemaking. Each phase requires an extended public comment period and subsequent analysis by the government of the comments before publication of the final rule.

The rulemaking process is outlined as follows:

This process presents an invaluable opportunity for IRBs, academic institutions, CROs, pharmaceutical and medical device companies and other stakeholders to provide HHS with initial comments on the proposed changes. Commenters are invited to provide general feedback or to respond to any of the 74 specific questions raised by the authors of the advanced notice.

Key features of the proposed rule
Single IRB of Record for Multi-site US trials
One proposed requirement would be for a single IRB of record for all of the U.S. sites in a multi-site study. This would replace the current practice of multiple and redundant IRB reviews at participating sites.

This proposed streamlined approval process addresses a concern of sponsors and investigators – that a delay in IRB approvals mean delays in the impact of research findings. The ANRPM also suggests that duplicative IRB reviews of multi-site studies not only increases burden, but may also result in weakened protections. Thus, the ANRPM proposes the requirement for a single IRB of record for multi-site studies.

In the discussion of possible solutions, the ANPRM describes two current alternative models of IRB review: the use of central government run IRBs (specifically, the Veterans Affairs CIRB and the National Cancer Institute’s CIRB) and the use of academic consortia. The advanced notice does not acknowledge the existence or merit of other alternative models of IRB review such as review of industry sponsored research by independent IRBs.

Calibrating IRB review based on research risk
A series of changes to the review of research that poses no more than minimal risks to research participants including:

  • Expanding the list of research categories eligible for expedited review
  • Eliminating the requirement for continuing review of minimal risk studies
  • Expanding the categories of research currently reviewed as exempt

Enhancing Informed Consent
The advanced notice calls for greater specificity about how consent forms are written and what information they contain. The document proposes that researchers, sponsors and IRBs adopt strategies to shorten and simplify informed consent documents. The notice invites comment on the value of standardized consent language and the use of oral consent for any research involving surveys, focus groups and interviews conducted with consenting adults, even if identifiers are kept.

The proposed changes would also require written informed consent for collection of biospecimens for research purposes even if no identifiers are kept – but would allow consent to be obtained by the use of a standardized form allowing for unspecified future research. The requirement for written informed consent would not apply to specimens collected prior to the effective date of the new rules.

Establishment of an electronic reporting system for adverse events and unanticipated problems
The advance notice suggests the establishment of a single government-owned website for reporting, storage, and dissemination of adverse events. The notice seeks comment on the use of a set of harmonized definitions and reporting requirements that would fulfill multiple federal reporting requirements.

Data security standards
The advanced notice also proposes mandatory standards for data security and information. The proposed rule would replace the IRB’s authority to evaluate risks to privacy and confidentiality with mandatory data security standards and requirements for all human research. This suggested approach mirrors the current HIPAA Privacy Rule data security requirements including encryption and audit trails.

To submit comments, visit and search for docket number HHS OPHS-2011-0005. The comment period closes October 26, 2011.

1 Reforming the Regulations Governing Research with Human Subjects, Ezekiel J. Emanuel, MD, PhD & Jerry Menikoff, MD, JD; New England Journal of Medicine, July 25, 2011