Institutional Review Boards: A Time for Reform (1998a). Its foremost finding was that “the effectiveness of IRBs is in jeopardy,” and it found that IRBs are facing overwhelming demands (1998a, p. ii). OIG concluded that the system originally devised as a volunteer effort to oversee a much smaller research effort in the 1970s was having difficulty contending with its growing and broadening workload with scant resources.
But the focus of national attention has not been exclusively on IRBs; the institutions in which research is conducted have also been in the spotlight. In May 1999, the federal office charged with overseeing federally funded research, the Office for Protection from Research Risks (OPRR), halted human research studies at Duke University Medical Center. This was shocking to the research community and the public, for if a highly respected institution such as Duke could be noncompliant, then problems were likely to be more widespread than previously imagined. From October 1998 through December 2001, OPRR and its successor, the DHHS Office for Human Research Protections (OHRP), restricted or suspended a number of multiple project assurances and cited 113 research organizations for non-compliance (OHRP, 2001); the Food and Drug Administration (FDA) has also suspended clinical research at other organizations. In addition, issues concerning conflicts of interest at the investigator and institutional levels have forced professional groups and academic institutions to revisit or create policies to ensure that research participants are not placed in harm’s way because the financial interests of those funding or conducting the research conflict with the need to assure participant protection.
Attention was already focused on the protection of human research participants in 1999 when 18-year-old Jesse Gelsinger died in a Phase 1 gene transfer study at the University of Pennsylvania. He was a relatively healthy (i.e., medically stable) young adult with a genetic condition—ornithine transcarbamylase deficiency—who had suffered intermittent health crises throughout his life but was responding relatively well to medications when he entered the gene transfer trial (Gelsinger, 2000; Lehrman, 2000a,b). The details of the case are complex and to some extent contested. Although Gelsinger was aware that he was participating in a gene transfer study, FDA found that the consent form had been altered from the original approved document and that data relevant to safety had not been reported. Questions were raised about whether some participants in the trial, including Gelsinger, fit the revised inclusion criteria and whether the IRB and relevant federal agencies were notified of adverse events that had occurred in studies with animals and in previous participants (Weiss and Nelson, 1999).
The Gelsinger case was heavily reported in the national media and drew the attention of clinical investigators and research administrators throughout the world. It also became the focus of a Senate hearing and commanded direct attention from the Secretary of DHHS, who subsequently