Sweeping changes coming to human research field: Are you ready?

National Bioethics Advisory Commission’s report set to debut

For IRB administrators and researchers, only one thing is certain for the immediate future: change, dramatic change. The National Bioethics Advisory Commission (NBAC) and other groups have come out with sweeping recommendations. One of the most controversial — and potentially life-changing for anyone involved with an IRB — is the creation of a single, independent federal office to lead and coordinate the oversight system for all human research: the National Office of Human Research Oversight (NOHRO).

"The current oversight system is difficult to maneuver through. There’s no single entity in charge with any clear authority, and NOHRO would provide for a single mechanism where IRBs could get definitive answers," Eric M. Meslin, PhD, executive director of the NBAC. Individual federal agency roles under the proposed structure would still need to be defined, he notes.

The NBAC put polishing touches on its highly anticipated report on human research ethics at its 47th meeting March 15-16 in Atlanta. Included in the 296-page report are 17 recommendations specifically for local oversight systems, which, if enacted, will streamline the behemoth known as IRB management.

The report, titled Ethical and Policy Issues in Research Involving Human Participants, is slated to be finalized in May. "Our goal is to have the report sent to President Bush by July," adds Meslin.

"We’re here to provide a basic groundwork for the people out there doing research because it’s not the same field as it was 10 years ago. Now, people are too afraid to do anything, and they’re looking for this kind of guidance," says David R. Cox, MD, PhD, scientific director of Perlegen Sciences in Santa Clara, CA, and a member of the NBAC.

One recommendation that is receiving broad support, however, is the recommendation that systematic changes would outline when trials would require administrative vs. full board review. (See "Summary of National Bioethics Advisory Commission Recommendations," in this issue.) The NBAC report also encourages Congress to pass legislation mandating that all research involving human participants be covered by federal regulations, regardless of the funding source.

On the heels of other criticism

The NBAC is not alone in its critical assessment of the way IRBs operate in today’s health care setting. A team of researchers from Duke University in Durham, NC, also suggest that the current system is in need of reform.1

The researchers assembled the Duke Working Group on Monitoring Clinical Trials in May 2000 to specifically address adverse event reporting and the interactions among various parties during multicenter clinical trials. Clinical trials have moved beyond single institution settings to industrywide efforts involving multiple sites, and as a result, those individual IRBs are ill-equipped to accurately evaluate the information, some of which is potentially critical, contained in adverse events reports, says Michael A. Morse, MD, professor of medical oncology and transplantation in the department of medicine at Duke.

IRBs may only have access to data from trials in which they have authority, and often lack statistical and clinical expertise of the information to assess the overall safety and benefits, notes Morse. The Duke Working Group suggests IRBs should play three major roles in a multicenter trial:

  • review and approve a plan for monitoring the study;
  • certify that the investigators understand the regulations governing patient safety;
  • review data monitoring committee reports and query investigators as needed.

So what can IRB administrators, members, and researchers expect when the final report’s recommendations reach them this spring? "How this agency would work with the existing agencies, such as OHRP, would be confusing at first," says Alan Sugar, MD, professor of medicine at Boston University School of Medicine.

Many organizations already are on record in opposition of a new, independent federal office. The Association of American Medical Colleges (AAMC) in Washington, DC, for example, opposes the creation of NOHRO. AAMC represents the medical schools, more than 400 teaching hospitals, and academic societies nationally.

In a letter to the NBAC, Jordan J. Cohen, MD, writes, "we believe it would be undesirable and unwise at this time to establish a new, independent, single federal office to lead and coordinate the oversight system for all human research."

President Clinton established the NBAC in October 1995 as a result of a previous committee’s investigation into federally funded research involving human subjects and radioactive materials. That committee’s findings in regards to protecting research participants reported "serious deficiencies in parts of the current system," including the following:

  • variability of the quality of IRBs;
  • confusion among human participants as to whether they were involved in research or therapy;
  • insufficient attention paid to the consent process for participants with diminished decision-making capacity.

The NBAC makes recommendations now to the Bush administration and will expire in October. One of its first priorities was to examine the system for protecting human research participants. The NBAC unanimously resolved in 1997 that "no person in the United States should be enrolled in research without the twin protections of informed consent by an authorized person and independent review of the risks and benefits of the research." In 1998, NBAC indicated areas of concern and preliminary findings regarding the oversight of human research in the United States. The key concerns identified were:

Federal protections for persons serving as subjects in research do not yet extend to all Americans.

Despite widespread implementation of federal regulations by those departments and agencies sponsoring substantial amounts of biomedical research, a number of departments and agencies who sponsor primarily nonbiomedical research or little research overall have failed to fully implement these federal protections.

Federal protections do not always include specific provisions for especially vulnerable populations of research subjects.

Many federal agencies find the interpretation and implementation of the Common Rule confusing and/or unnecessarily burdensome.

Federal protections are difficult to enforce and improve effectively throughout the federal government because no single authority or office oversees research protections across all government agencies and departments.

New techniques are needed to ensure implementation at the local level.

The report addresses the basic purpose, structure, and implementation of research oversight, says Meslin. "We recommend broad, strategic changes to the oversight system. This report is not intended to be a rewrite of federal regulations, but instead to provide the guidance, direction, and justification for change."

Reference

1. Morse M, Califf R, Sugarman J. Monitoring and ensuring safety during clinical research. JAMA 2001;285:1201-1205.

[Editor’s note: To download a copy of the draft report, Ethical and Policy Issues in Research Involving Human Participants, go to the NBAC Web site: bioethics.gov/human/humanpdf_toc.html. Files are downloaded in portable document files, and requires the Adobe Acrobat Reader software.]