Biomedical Engineering Reference
In-Depth Information
vector and the transgene rather than to provide a treatment for the sub-
jects' underlying disease.
The OTC deficiency protocol disappeared from public view after the
December 1995 RAC review, during which RAC voted to recommend
several changes in the study design. The protocol did not become visible
again until the June 1999 meeting of the American Society for Gene
Therapy, for which Wilson and his colleagues prepared an abstract
reporting results from their first four cohorts of subjects. Most members
of the public and most RAC members did not attend this meeting,
however, and were thus unaware of the study's progress. From the public
record of the study compiled in late 1999 and 2000, we now know that
this clinical trial proceeded through several stages between early 1996
and September 1999, the month during which a study participant died.
From February through December 1996, the FDA reviewed the OTC
deficiency protocol. In December, the agency permitted the study to
proceed. Recruitment of subjects began early in 1997, and in April the
first subject in the first cohort completed her participation in the proto-
col. During the remainder of 1997, 1998, and the first nine months of
1999 the trial continued; three subjects were recruited into each of the
first three cohorts, four were recruited into the fourth cohort, three into
the fifth, and two into the sixth. The second subject in the sixth cohort,
Gelsinger, died as a result of his participation in the trial.
There are contextual factors related to this trial that deserve more
detailed review. The first set of factors concerns the local level—that is,
actions taken and policies adopted by the researchers and the University
of Pennsylvania. In June or July 1995, a funding arrangement was
entered into by the IHGT, the University of Pennsylvania, and Genovo,
a company that had been founded by IHGT's Wilson in 1992. Accord-
ing to the terms of the five-year agreement, Genovo would provide
funding for IHGT's research in exchange for the exclusive right to license
patents resulting from Wilson's human gene therapy research. This finan-
cial arrangement supplied approximately $4.7 million per year to IHGT,
or approximately 20 percent of the institute's budget. The arrangement
was approved by the University of Pennsylvania's Conflict of Interest
Standing Committee.
9
During late 1996 and the following year, there were two instances of
miscommunication between the Penn researchers and the FDA. As both
