OIG issues follow-up report on human subjects: More work needed

Legislative change is most likely catalyst, OIG says

Recent deaths of gene therapy patients have brought human subject research under greater public scrutiny. Now the government wants to know why its recommended reforms issued in June 1998 largely have been ignored by the research community.

In April, the Department of Health and Human Services (HHS) Office of the Inspector General (OIG) issued a follow-up report to its June 1998 report, "Institutional Review Boards: A Time for Reform." Last month, HHS Secretary Donna Shalala warned researchers that while the Clinton administration still supports biomedical research, more protections need to be in place for the use of human subjects. Shalala said she soon will announce who will oversee the recently moved Office for Protection from Research Risks (OPRR). "I will select the person personally with the advice of Surgeon General and Assistant Secretary for Health, David Satcher," she said in a statement.

(For more on moving the OPRR out of National Institutes of Health [NIH], see Medical Ethics Advisor, February 2000, pp. 13-17. To see how each agency affects institutional review boards [IRBs], see chart, p. 64.)

The OIG report, "Protecting Human Research Subjects: Status of Recommendations" (OEI-01-97-00197, April 2000), concludes that overall, few of the office’s previous recommendations have been enacted.

The follow-up report was published on the heels of an open letter sent to the health care community in March urging providers to self-disclose improper conduct. Inspector General June Gibbs Brown stated that providers who promptly self-disclose improper conduct may be eligible for "favorable treatment in the resolution of their case, including less rigorous corporate integrity agreements."

"We want to encourage providers to come forward and disclose conduct that threatens the federal health care programs, including Medicare and Medicaid," Brown wrote. "A provider’s good-faith self-disclosure and continued cooperation go a long way in convincing the Office of Inspector General that less rigorous integrity requirements are needed to protect the federal programs."

Events contribute to controversy

Since the OIG’s original report was published in June 1998, the following actions and events have received attention from the HHS and national media:

• Congress held two hearings addressing improving the effectiveness of IRBs.

• The National Bioethics Advisory Commission continued deliberations on what reforms should be undertaken.

• Shalala relocated the OPRR from the NIH to the Office of the Secretary and established an advisory committee to provide scientific and ethical guidance to OPRR.

• A participant died in a gene therapy study conducted at the University of Pennsylvania in September 1999, the first death directly linked to an experimental gene therapy procedure.

• A joint project between the FDA and NIH to enhance human subject protections resulted in a new government clinical trial Web site: www.clinicaltrials.gov.

The OIG reports that while there’s been an increase in enforcement of requirements such as on-site investigations and suspension of funding at seven institutions, there’s room for improvement. In fact, the report lists six areas where reforms have not been enacted. (For a list of recommendations and actions taken, see p. 63.) Here is a summary of the six areas and an explanation of the deficiencies:

1. Flexibility and accountability: Minimal progress has been made in recasting federal IRB requirements so they grant IRBs greater flexibility and hold them more accountable for results. Too much IRB attention now focuses on review responsibilities of questionable protective value.

2. Oversight and protections: Minimal progress has been made in strengthening continuing protections for human subjects participating in research. Continuing IRB review of research after it initially has been reviewed is a low priority at many IRBs. IRBs know little of what actually occurs during the consent and research processes.

3. Education: No educational requirements have been enacted for investigators or IRB members. The most important continuing protection for human subjects is the presence of well-trained and sensitized investigators and IRB members.

4. Conflicts of interest: There has been no progress in insulating IRBs from conflicts that can compromise their mission in protecting human subjects. The increased commercialization of research and the growing importance of research revenues for institutions heighten the potential for conflicts of interest in clinical research.

5. Workload: Minimal progress has been made in moderating workload pressures of IRBs. IRBs are inundated with protocols and adverse event reports. With limited personnel and few resources, many IRBs are hard-pressed to give each review sufficient attention.

6. Federal oversight: Minimal progress has been made in re-engineering the federal oversight process. Federal oversight of IRBs is not equipped to respond effectively to the changing pressures and needs of the current system of protections.

The NIH cannot implement many of the recommendations, the OIG says, because of a 1991 policy known as the Common Rule. Core HHS regulations concerning IRBs and human subject protections were incorporated into a federal policy for HHS and 16 other federal agencies.

Changes to the rule must concur at all 17 agencies. The OIG agrees with the NIH’s claims that changing its policy would require a lengthy complex process of obtaining consent from other agencies. The OIG concludes in its report the likely catalyst for a timely change in policy would come from legislative changes.

One health provider isn’t waiting for legislative changes to improve protections for its research participants. The twist is that the provider is a government entity that was stripped of federal research funds for violating protections last year.

The Department of Veterans Affairs announced that starting this past May, the National Committee for Quality Assurance will implement an accreditation program for biomedical research at 150 VA medical centers nationwide. The $5.8 million contract will last five years.

Independent survey teams will conduct accreditation visits every three years at medical centers conducting human research. The teams will certify that the medical center is effectively managing research risk and identify improvements needed.