107th Congress

Human Subjects Legislation

H.R. 4697 and S. 3060

Background

In 1991, the core U.S. Department of Health and Human Services (DHHS) regulations (45 CFR Part 46, Subpart A) were formally adopted by more than a dozen other departments and agencies that conduct or fund research involving human subjects. Known as the Federal Policy for the Protection of Human Subjects, or "Common Rule," these regulations require initial and continuing review by Institutional Review Boards (IRBs), which review both the scientific design of research protocols and informed consent documents and procedures. This system of protections has been reviewed by several governmental bodies, which have examined whether the current system is functioning adequately and whether gaps in the system need to be closed. In June 1998, the DHHS Inspector General (IG) issued four related reports that concluded that IRBs were reviewing too much, too quickly, and with too little expertise. The reports suggested that the system was so stressed that it was no longer able to function adequately. After a research subject died in a clinical trial involving gene transfer research in September 1999, additional attention was focused on the need to bolster current policies to protect human subjects in research.

These events culminated in June 2000 with the creation of a new office within the Office of the Secretary to oversee the protection of human subjects in research funded by DHHS. The Office of Human Research Protections (OHRP) replaced the former Office for Protection from Research Risks, which had been housed within the National Institutes of Health (NIH). Subsequent to this action, on May 23, 2001, the General Accounting Office (GAO) issued a statement (in lieu of a formal report) suggesting that although DHHS had made considerable progress in implementing changes, the changes were not comprehensive enough, and the pace was not quick enough. In August 2001, the Clinton Administration's National Bioethics Advisory Commission (NBAC) issued a report recommending numerous improvements and reforms to the IRB system. The recommendations included the following: 1) creation of a new independent office that would oversee all human subjects research, 2) extension of current protections to all federally and privately funded human subjects research, 3) implementation of an accreditation process for IRBs, and 4) development of policies for reporting investigator conflicts of interest in research.

On May 9, 2002, Representatives Diana L. DeGette (D-CO) and Jim Greenwood (R-PA) introduced H.R. 4697 in an effort to revamp the Federal human subjects protection system to incorporate recommendations by GAO, DHHS IG, and NBAC. Most notably, the bill would have extended Federal protections to all research involving human subjects, including research that is not federally funded.

On May 23, 2002, the Senate Health, Education, Labor and Pensions Committee (Senator Edward M. Kennedy [D-MA], Chairman) held a hearing to explore these issues. On October 4, Senator Kennedy introduced S. 3060, which, like H.R. 4697, would have extended Federal protections to all research involving human subjects, regardless of funding source.

There were, however, a few key differences between the bills. First, although both set up a system for accrediting IRBs, H.R. 4697 would have made such accreditation voluntary, while S. 3060 would have imposed mandatory accreditation. Second, only the Senate bill would have regulated the scientific conduct of clinical research by prohibiting clinical trials using placebos in certain situations. Third, S. 3060 would have imposed civil monetary penalties for violations, whereas a similar enforcement mechanism was not included in H.R. 4697.

Provisions of the Legislation/Impact on NIH

H.R. 4697—Human Research Subject Protection Act of 2002

H.R. 4697 contains the following significant provisions of interest to NIH:

• The bill would have codified OHRP as an entity within the Office of the Secretary.
• The bill would have extended Federal protections contained in 45 CFR Part 46 (including those that pertain specifically to certain vulnerable populations) to all human subjects research, regardless of funding source. This would have required review by an IRB and specified informed consent requirements.
• The bill would have required the Secretary of Health and Human Services (HHS) to review the requirements of 45 CFR Part 46 and corresponding requirements of the Food and Drug Administration 21 CFR Parts 50 and 56 to determine the extent to which such requirements can be harmonized.
• The bill would have required specific informed consent elements that differ in some cases from those included in current regulations.
• The bill would have expanded IRB membership to require that "not fewer than two members, or 20 percent of all members," shall be nonscientific members and "not fewer than two members, or 20 percent of all members," shall be individuals who are not affiliated with the institution. In addition, not fewer than 2 members or 25 percent of all members shall have scientific expertise. If a proposal is to include a member of a vulnerable population as a subject, an IRB would have been required to include at least one member who is an expert in issues involving those populations. Current regulations require simply that each IRB include at least one scientific member, one nonscientific member, and one member who is not affiliated with the institution.
• The bill would have required that all IRBs register with the Secretary of HHS. It would also have provided for a system of voluntary accreditation of IRBs by an entity recognized by the Secretary.
• The bill would have required investigators to disclose to the IRB if a particular proposal has been reviewed by a different IRB. This provision was intended to minimize "IRB shopping."
• The bill would have required investigators to disclose to the IRB any conflicts of interest, or interests that create the appearance of a conflict of interest. Current regulations do not include this requirement.
• The bill would have permitted institutions to recover costs associated with compliance with human subjects protections as direct costs.
• The bill would have required that adverse events be reported to the IRB, the sponsor of the trial, and OHRP.
• The bill would have given authority to OHRP to suspend any research protocol (regardless of funding source) if the entity involved is not in compliance with applicable requirements; however, the bill would not have provided authority to OHRP to impose civil monetary penalties for such violations.
• The bill would have authorized $20 million for fiscal year 2003 for the purpose of carrying out this Act.

S. 3060—Research Revitalization Act of 2002

• The bill would have extended Federal protections contained in 45 CFR Part 46 (including those that pertain specifically to certain vulnerable populations) to all human subjects research, regardless of funding source. This would have required review by an IRB and specified informed consent requirements.
• The Director of OHRP would have been a political appointee with a 6-year term.
• The bill would have required mandatory accreditation of IRBs.
• The bill would have permitted institutions to recover costs associated with compliance with human subjects protections as direct costs.
• The bill would have authorized the creation of Cooperative Review Boards for reviewing multisite clinical research.
• For research conducted in foreign countries, the bill would have required that the Director of OHRP publish a list of foreign countries with human subjects protections comparable to those of the United States. For research intended to be conducted in a country on the list, the bill would have required that the research be reviewed by an ethics review board, without specified standards. For research intended to be conducted in a country not on the list, the research would have to be reviewed by both a local ethics committee and an IRB.
• The Director of OHRP would have been required to develop regulations requiring appropriate compensation for participants in research.
• The bill would have prohibited placebo-controlled clinical trials if an "available...effective treatment" exists, and "there is risk of significant harm."
• The bill would have prohibited investigators from conducting research if 1) the research was deemed "greater than minimal risk," and 2) the investigator had a significant financial interest, unless an IRB granted a waiver.
• The bill would have required investigators to disclose any significant financial interest in the research to both the IRB and the research participant.
• In addition to permitting the Director of OHRP to suspend an IRB's registration, the bill would have permitted the imposition of civil monetary penalties up to $250,000 for violation of the provisions in the bill.

Status and Outlook

H.R. 4697 was introduced by Representatives DeGette and Greenwood on May 9, 2002, and referred to the House Energy and Commerce Committee. S. 3060 was introduced by Senator Kennedy on October 4. Although there was no further action on this legislation during the 107th Congress, both bills are expected to be introduced again when the 108th Congress convenes.