Biomedical Engineering Reference
In-Depth Information
be able to review serious adverse event reports from two protocols, but
that they would not be permitted to discuss the adverse event reports in
the public meeting. Some members of RAC were clearly not comfortable
with this lack of transparency and drafted language, approved by a
majority of RAC members, that sought to clarify the existing RAC
policy—namely, that no adverse event reports were to be considered con-
fidential. Press stories about these refusals to disclose serious adverse
events also began to appear.
During 1997 and 1998, there was also a parallel development that has
not been as widely reported; a few academic researchers and companies
began recruiting subjects into novel gene transfer research protocols
before RAC review had occurred, but after the FDA had given the
researchers permission to proceed with their Investigational New Drug
Applications. To their credit, the RAC chair, RAC's staff, and the NIH
general counsel stood firm, ultimately threatening the academic institu-
tions collaborating with the private companies in these protocols with
the termination of all NIH grant and contract funding to those academic
institutions if they did not wait until after RAC review before beginning
the actual conduct of their trials.
The most dramatic event in the history of human gene transfer
research occurred in September 1999. As mentioned above, Gelsinger
died while participating in a gene transfer study. The death of this
eighteen-year-old, relatively healthy research subject and the subsequent
investigation revealed fundamental flaws in the oversight system and led
to an agonizing reappraisal of clinical research involving human gene
transfer.
As noted earlier, researchers at the University of Pennsylvania sub-
mitted an OTC deficiency protocol to the NIH and RAC in fall 1995.
The director of the university's Institute for Human Gene Therapy
(IHGT), James Wilson, took the lead in presenting the protocol to RAC.
Yet the principal investigator for the protocol was Wilson's associate,
Mark Batshaw, a pediatrician. In brief, OTC deficiency is a single-gene
disorder that causes the buildup of excessive levels of ammonia in the
liver. According to the protocol design, six cohorts, each comprised of
three subjects, were to receive increasing doses of an adenoviral vector
and an inserted gene. The protocol was designated a phase 1 study; that
is, the goal of the study was to investigate the potential toxicity of the
