Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
INTRODUCTION, BACKGROUND, AND DEFINITIONS 29 cell research (NBAC, 1999b), all of which address issues of research oversight and IRB function. Forthcoming reports will address ethical principles for U.S. interests conducting clinical trials abroad (NBAC, forthcoming-a) and describe a 5-year review of the adequacy of the system of human subjects protection in the United States (NBAC, forthcoming-b). Reports from DHHS Office of the Inspector General In June 1998, the Office of the Inspector General (OIG) of DHHS issued a report, Institutional Review Boards: A Time for Reform (DHHS OIG, 1998b). The report's foremost finding was that âthe effectiveness of IRBs is in jeopardyâ (p. ii) and that IRBs are facing overwhelming demands. A system that was originally devised as a volunteer effort to oversee a much smaller research effort in the 1970s was characterized as contending with its growing burden with scant resources. Recommendations included better training of IRB members and investigators, recasting of federal requirements to give IRBs more flexibility yet require more accountability, reduction of potential conflicts of interest among IRBs to enhance independence, and improvement of feedback to IRBs about developments in multisite trials and prior reviews of research plans. Echoing one of the charges to the present committee, the DHHS OIG report called for greater attention to the development and reading of indicators of how well IRBs were doing their job. A Time for Reform was the flagship in a convoy of DHHS OIG reports on the protection of human research subjects. Three other DHHS OIG reports came out at the same time: (1) promising approaches to improving protections, (2) a description of the IRB process, and (3) a description of the emergence of independent boards, that is, IRBs that mainly review drug, device, and biologics trials sponsored by private industry under FDA regulations (DHHS OIG, 1998c,d,e). In April 2000, the DHHS OIG issued an update on A Time for Reform. It noted the increased enforcement efforts of both OPRR and FDA but little overall progress on its other recommendations (DHHS OIG, 2000b). DHHS OIG staff testified at hearings in both the U.S. House and U.S. Senate as Congress turned its attention to human subject protections in the year 2000 (Grob, 2000). The April 2000 DHHS OIG update specifically lauded the efforts of PRIM&R to develop standards for accreditation of IRBs and research institutions. A pair of reports published in June 2000 focused on recruiting human subjects, with one describing pressures in industry-sponsored clinical research and the other listing sample guidelines for practice (DHHS OIG, 2000c,d). Shutdowns of Clinical Research at Academic and VA Medical Centers In May 1999, OPRR halted human research studies at Duke University Medical Center, sending shock waves throughout the research community. Within a year, FDA and OPRR proceeded to halt all or some clinical research
INTRODUCTION, BACKGROUND, AND DEFINITIONS 30 projects at seven other research centers.5 These events focused the attention of research administrators on IRB operations and human subject protections with an intensity not seen in two decades. In November and December 2000, the newly established DHHS Office for Human Research Protections (OHRP)6 issued âcompliance determinationâ letters that found that studies in the intramural program at NIH were out of compliance with federal regulations. OPRR/OHRP has restricted or suspended multiple project assurances and required corrective actions at nearly a dozen academic institutions, and FDA has suspended clinical research at others.7 OPRR/OHRP sanctions were imposed when numerous deficiencies and concerns regarding systemic protections for human subjects were found. Deficiencies occurred in such areas as IRB membership, education of IRB members and investigators, institutional commitment, initial and continuing review of protocols by IRBs, review of protocols involving vulnerable persons, and procedures for obtaining voluntary, informed consent. Also in 1999 it was discovered that researchers with the U.S. Department of Veterans Affairs (VA) in West Los Angeles were performing risky research without obtaining 5 OHRP maintains a list of âcompliance determinationâ letters, indexed by month, on its website at http://ohrp.osophs.dhhs.gov/detrm_letrs/lindex.htm; FDA lists clinical researchers who have been sanctioned at http://www.fda.gov/ora/ compliance_ref/bimo/dis_res_assur.htm; and the Office of Research Integrity lists debarred investigators at http://www.fda.gov/ora/compliance_ref/debar/default.htm. 6 In June 1999, the Secretary of HHS created a new office, the Office for Human Research Protection (OHRP), to replace the Office for Protection from Research Risks (OPRR), which had been responsible for oversight of research involving human participants at institutions receiving federal funds and implementing the 18-agency federal Common Rule. The location of OPRR had been debated for years. Three background papers prepared for NBAC pointed to difficulties in having the office responsible for ethical conduct housed under the director for extramural research at National Institutes of Health (NIH), effectively subordinate to the funding office for extramural research, and poorly positioned to exert influence over the NIH intramural research program (Fletcher, forthcoming; Gunsalus, forthcoming; McCarthy, forthcoming). The NBAC papers all cited a need to elevate the administrative hub for protecting human research participants up and out of NIH, but differed in whether the location should be within DHHS or in an independent executive agency. A committee convened by then NIH Director Harold Varmus recommended in June 1999 that OPRR be moved to the level of the HHS Secretary and, among other things, that the Secretary create an external advisory committee for the office and that resources be increased for monitoring and enforcement (Office for Protection from Research Risks Review Panel, 1999). Less than six months after its creation, OHRP began a streamlined IRB registration and assurance process. 7 Multiple project assurances are agreements between institutions and the federal government that pledge compliance with human subject regulations under 45 CFR 46. Suspension of these assurances effectively ceases research requiring IRB review. FDA actions include âclinical holdsâ on all or part of an institution's research under FDA human subject regulations (21 CFR 50, 21 CFR 56, and 21 CFR 312.120).
