HHS Proposes Changes to Rules Governing Human Subject Research

 For the first time in 20 years, the Department of Health and Human Services (HHS) “proposed sweeping revisions to rules governing scientific research involving human subjects with the intent of extending protections to a larger number of people while simultaneously streamlining the oversight and paperwork required of scientists.”

According to the Washington Post, “the proposed changes would be the first in two decades to the “Common Rule” (45 CFR 46) that governs nearly all human-subject research financed by American taxpayers.” The Common Rule has been in place since 1991.

The Common Rule dates back to a the 1978 “Belmont Report,” which was prompted by the infamous Tuskegee syphilis study, in which impoverished African-American sharecroppers in Alabama who had syphilis were enrolled in a study to monitor the natural progress of syphilis. They were given free medical care, meals, and burial insurance, and never told they had syphilis.

The Belmont Report laid the ethical framework for the government’s stance on human research and includes principles such as treating all participants with courtesy and respect, allowing for informed consent, and adhering to the philosophy of “do no harm” while maximizing research benefits and minimizing risks to the subject.

Proposed Changes

The changes would try to address features of the research landscape that were uncommon 20 years ago, such as:

–       The proliferation of clinical experiments conducted at multiple sites;

–       The growth of research by drug companies; and

–       The collection of biological specimens for permanent archiving.

In an ANPRM Frequently Asked Questions (FAQs) produced by HHS, the agency asserted that they are considering changes for two reasons:

–       The human subject research landscape has changed dramatically since the early 1980s when the current regulations were first being formulated and

–       In light of that, there is a need to address effectiveness and the efficiency of the regulations for human subject protections in the current research environment.

Howard K. Koh, MD, MPH, an assistant secretary of HHS asserted that, “these proposals are designed to modernize, simplify and strengthen the current system.” Dr. Koh added that, “this regulatory review effort is primarily about enhancing protections for human subjects” and “the changes under consideration offer the promise of updating and enhancing those protections to keep pace with current challenges.”

The changes, which can be revised after 60 days of comment by the public, got an early warm welcome according to the Post. Accordingly, the government is seeking the public’s input on an array of issues related to the ethics, safety, and oversight of human research. Comment is sought on the following:

1. Revising the existing risk-based framework to more accurately calibrate the level of review to the level of risk.
2. Using a single Institutional Review Board review for all domestic sites of multi-site studies.
3. Updating the forms and processes used for informed consent.
4. Establishing mandatory data security and information protection standards for all studies involving identifiable or potentially identifiable data.
5. Implementing a systematic approach to the collection and analysis of data on unanticipated problems and adverse events across all trials to harmonize the complicated array of definitions and reporting requirements, and to make the collection of data more efficient.
6. Extending federal regulatory protections to apply to all research conducted at U.S. institutions receiving funding from the Common Rule agencies.
7. Providing uniform guidance on federal regulations.

Discussion

Heather Pierce, an official at the Association of American Medical Colleges (AAMC) noted that the proposed changes “will have quite a significant response from the research community,” and will “be seen as moving human-research oversight into the 21st century.”  The proposed rule “acknowledges that biospecimens are inherently identifiable,” explained Kathy Hudson, PhD, deputy director for Science, Outreach, and Policy at the National Institutes of Health (NIH).

The Common Rule lays out a single set of requirements for informed consent, ethical oversight and human-subject protection at 15 federal departments and agencies, such as the National Institutes of Health (NIH), the Department of Defense (DOD) and the U.S. Agency for International Development (USAID).

The rule must also be followed in research funded by those agencies but done elsewhere, such as at universities and medical schools.

Under the proposed changes, the Common Rule would cover all research at institutions that get money from one of the 15 federal agencies, even studies paid for entirely by other sources, such as drug companies or private foundations. The effect would be to capture nearly all the biomedical experiments not already covered.  HHS provided a full table of the regulatory changes they are proposing, comparing the current rule to changes being considered, and describing the rationale for the proposed change.

The rule would also require that a single “institutional review board” (IRB) oversee a study that enrolls subjects at many hospitals and clinics (as is the case with most big clinical trials of drugs and procedures). Currently, each hospital’s board generally reviews the experimental protocol and makes suggestions — a process that researchers call burdensome and government overseers find confusing.

However, boards in foreign countries would still review proposals for research enrolling their own citizens because, according to an HHS document, “it might be difficult for an IRB in the U.S. to adequately evaluate local conditions in a foreign country that could play an important role on the ethical evaluation of the study.”

“Being able to shrink the time from having a protocol in hand and being able to recruit patients is key,” Hudson said.

The proposal would also exempt from board review research that involves surveys and interviews that poses little or no risk to people — a change expected to be especially welcomed by social scientists. The revisions intend to make the consent forms that lay out a study’s risks and possible benefits clearer, shorter and more standardized.

Last week’s announcement acknowledges the revolution in computer information technology and in understanding the human genome that’ has marked the last 20 years of medical research.

A single Web site would be created where all “adverse events” from clinical studies would have to be reported. Today, notification of such problems is sent to various agencies on different schedules. Having a single database would not only be more efficient, it might increase the chance of catching rare and severe complications more quickly.

Volunteers in studies in which biological material, such as blood or tissue, is collected would be asked whether they agree to have the material used in future research. Today, archived blood can be studied long after collection as long as researchers strip it of information that identifies the donor. But the concept of “anonymity” has changed in an era of cheap and easy gene sequencing.

“This acknowledges that with today’s technology that biospecimens are inherently identifiable,” said Hudson. Asking permission to use their specimens — including their DNA — in future research “expresses a very high level of respect to those research participants,” she said.

Information and to Respond

The Advance Notice of Proposed Rulemaking can be found here.  Comments are due no later than 5 p.m. on September 26, 2011. Comments can be submitted online through http://www.regulations.gov. Be sure to enter Docket No: 2011-18792. Click here for instructions on how to submit comments.  

For further information contact Jerry Menikoff, M.D., J.D., Office for Human Research Protections (OHRP), Department of Health and Human Services, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852; telephone: 240-453-6900 or 1-866-447-4777; facsimile: 301-402-2071; e-mail: jerry.menikoff@hhs.gov