Significant Changes Proposed for Human Research Studies

Classic Anthology of 101 Charts

Clinical researchers cannot afford to ignore this.

RESEARCH If you are involved in clinical research, you cannot ignore the 92-page Advance Notice of Proposed Rulemaking (ANPRM) from the United States Department of Health and Human Services (DHHS) that impacts future human research. [1] This does not spell imminent disaster but it does require active intelligent responses to 74 categories of questions.

In a nutshell, the ANPRM, released July 22, 2011, focuses on streamlining approval review and approval processes as well as participant consent of inherently identifiable blood, DNA, and tissue samples for perennial research in a manner that does not conflict with HIPAA regulations. Patients and researchers are encouraged to read the proposal in its entirety. The following excerpts should provide you with impetus to become actively involved in shaping future research with direct responses to DHHS.

The "Common Rule," requires that federally funded investigators in most instances obtain and document the informed consent of research subjects, and describes requirements for institutional review board (IRB) membership, function, operations, research review, and recordkeeping. Currently, except for human subjects research that is determined to be exempt from the regulations, federally funded research involving human subjects is reviewed by an Internal Review Board (IRB) in one of two ways: 1) by a convened IRB, or 2) through an expedited review process. [2]

The President's Executive Order requires Federal agencies to review existing significant regulations.

Since the Common Rule was developed 25 years ago, the landscape of research activities has changed dramatically. While traditional biomedical research conducted in academic medical centers continues to flourish, many studies are now also conducted at community hospitals, outpatient clinics, or physician-based practices. Clinical research is regularly conducted at multiple institutions across the U.S. and other countries. The advent of sophisticated computer software programs, the Internet, and mobile technology have created new areas of research activity, particularly within the social and behavioral sciences, exponentially increasing the amount of information available to researchers, while providing the means to access and analyze that information.

The President's Executive Order requires Federal agencies to review existing significant regulations to determine whether they should be modified, streamlined, expanded, or repealed to make the agency's regulatory program more effective or less burdensome.

  1. The system has been criticized as not adequately calibrating the review process to the risk of research. While physical risks generally are the greatest concern in biomedical research, social and behavioral studies rarely pose physical risk but may pose psychological or informational risks.
  2. Critics have commented about the inefficiencies of review by multiple IRBs for multi-site studies, which add bureaucratic complexity to the review process and delay initiation of research projects.
  3. Questions have been raised about the extent and quality of the protections afforded by current informed consent requirements and practices. In some research studies, consent forms have become lengthy and are often written in highly technical terms.
  4. Increasing use of genetic information, existing (i.e., stored) biospecimens, medical records, and administrative claims data in research has changed the nature of the risks and benefits of research participation.
  5. There is concern that current regulations do not provide an ideal mechanism for the collection of information that would allow evaluation of the effectiveness of the research oversight system in protecting human subjects.
  6. Concerns have been expressed that the current regulatory system does not adequately protect all research subjects.
  7. The multiple, differing regulatory requirements that can apply to a single research study have been criticized as complex, inconsistent, and lacking in clarity.

Changes are proposed to the following seven aspects of current regulatory framework:

  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
  5. Establishment of an improved, more systematic approach for the collection and analysis of data on unanticipated problems and adverse
  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
  7. Improvement in the harmonization of regulations and related agency guidance

Five of the most significant changes being considered are summarized below:

  1. Establishing mandatory data security and information protection standards for identifiable information and rules protecting against the inappropriate re-identification of de-identified information that is collected or generated as part of a research study.
  2. Continuing review would be eliminated for all minimal risk studies that undergo expedited review, unless the reviewer explicitly justifies why continuing review would enhance protection of research subjects.
  3. Revising the regulations regarding expedited review to provide for mandatory regular updating of the list of categories of research that may be reviewed under this mechanism.
  4. Revising the regulations regarding studies currently considered exempt. Add a new category for certain types of behavioral and social science research that goes beyond using only survey methodology. Expanded category 4 exemption would apply to the secondary use of identifiable data and biospecimens even if such data or biospecimens have not yet been collected at the time of the research proposal.
  5. Generally requiring written consent for research use of any biospecimens collected for clinical purposes after the effective date of the new rules.
Proposal for the Excused Category of Research
Involving Pre-Existing Information or Biospecimens
Identifiable Information
and All Biospecimens
Limited Data Set (As defined in the HIPAA Privacy Rule) De-identified Information (As defined in the HIPAA Privacy Rule)
Written consent required for future research with material collected for non-research purposes? Yes, which could be obtained in connection with the initial collection. No consent required No consent required
Consent for future research with material collected for research purposes? Yes. Consent for future research typically obtained at the same time as consent for initial research (which, for data, could be oral when oral consent was permissible for the initial collection). Yes. Same rule as for "Identifiable Information and All Biospecimens." Yes. Same rule as for "Identifiable Information and All Biospecimens."
Standardized Data Protections?* Yes. Protections would include encryption, use only by authorized personnel with audit tracing, prompt breach notification, and periodic retrospective random audits. Yes. Same rule as for "Identifiable Information and All Biospecimens" plus a prohibition against re-identification. Yes. Protection would include prohibition on re-identification.
Registration of research with IRB or research office? Yes. Yes. No.
Prior Review by IRB or research office? No, unless investigators plan to re-contact subjects with their individual research results. No. No.

* These data protections are discussed in the context of secondary research uses of biospecimens and data, which present mostly informational risks, rather than physical risks, to participants. However, as indicated elsewhere in this ANPRM, informational risks will always be present where data and biospecimens are collected, thus requiring these data protections to be applied to any such research.

The table above is from pages 73 and 74 of the ANPRM. Compilers of the proposal are earnestly requesting responses from the public and professional sector. It would be a shame to lose out on an opportunity to shape your personal privacy and future research. When submitting responses to the specific questions asked in the ANPRM, please cite the specific question by number (1-74). [2]

Tags: healthcare reform, pathology, physicians

  1. HHS announces proposal to improve rules protecting human research subjects. Press Release,
  2. ANPRM for Revision to Common Rule. Download PDF,