- The Honorable William Frist
- U.S. Senate
- 416 Russell Office Building
- Washington, DC 20510-3802
Dear Senator Frist:
I want to take this opportunity to provide you with some background
on our activities in support of the current investigation of clinical trials
at the Institute
for Human Gene Therapy ("IHGT") at the University of Pennsylvania.
First and foremost, I want you to know how seriously the University
is approaching this matter. The death of Jesse Gelsinger was a terrible
tragedy, and we are determined to learn everything we can about it to understand
precisely what happened and what might be done to improve clinical trials
throughout the University and at all institutions affiliated with us. We
intend for our research programs, particularly those involving human subjects,
to meet the highest standards. Nothing less is acceptable.
We have several, extensive efforts underway to achieve this goal and
to respond to the important concerns raised by federal regulators. We
have launched two independent reviews, led by eminent scientists, and we
have been and will continue to be strongly committed to cooperating fully
with the FDA, NIH, Congress and any other appropriate body as they review
The key facts to date are these: On Sept. 17, 1999, Jesse Gelsinger,
an 18-year-old with a rare metabolic disease known as ornithine transcarbamylase
deficiency ("OTC"), who was participating in an experimental
gene therapy trial at the Institute for Human Gene Therapy at the University
of Pennsylvania, died at the Hospital of the University of Pennsylvania
four days after being injected with corrective genetic material for the
disease. OTC is an inherited disorder that in its most common form causes
death in affected newborn males because of their inability to properly
process nitrogen in food proteins due to a genetic defect in the liver.
The clinical trial was voluntarily halted pending review. All appropriate
regulatory agencies, including the Food and Drug Administration, which
approved the trial, were notified promptly; we pledged to cooperate, fully
and completely, with any agency reviews undertaken. Thereafter, the FDA
began a review of the clinical trial. On Jan. 19, 2000, the FDA completed
its on-site review and issued a Form 483 raising important questions about
IHGT's monitoring and oversight of this and other clinical trials. Two
days after issuing the Form 483, the FDA placed a hold on all clinical
trials at IHGT. On Jan. 18, 2000, the Office for Protection from Research
Risk ("OPRR") forwarded to us a citizen complaint with regard
to the review of the OTC clinical trial by Penn's Institutional Review
Board and commenced an investigation.
The University takes the FDA's action and OPRR's letter--and the questions
raised about IHGT's monitoring and oversight of clinical trials--extremely
seriously. A team of scientists and administrators is working around-the-clock
to ensure that the IHGT provides a comprehensive, detailed and accelerated
response to the FDA and the OPRR as soon as possible.
Additionally, I have initiated two separate reviews related to this
matter--an independent review by outside experts and an internal review
by Penn faculty--both of which will involve distinguished research scientists
with a wealth of academic expertise and relevant experience.
The independent panel will be made up of senior academic leadership
and renowned research scientists who are unaffiliated with the University
of Pennsylvania. It will be chaired by William H. Danforth, M.D., Chancellor
Emeritus and Vice Chair of the Board of Trustees of Washington University
in St. Louis, and it will include Joseph B. Martin, M.D., Ph.D., Dean of
the Faculty of Medicine, Harvard Medical School; Edward J. Benz, Jr., M.D.,
Sir William Osler Professor and Director of the Department of Medicine,
Johns Hopkins University School of Medicine; Inder Verma, Ph.D., American
Cancer Society Professor of Molecular Biology, The Salk Institute, La Jolla,
Calif.; Rochelle Hirschhorn, M.D., Professor of Medicine and Cell Biology
and Chief of the Division of Medical Genetics, Department of Medicine,
New York University School of Medicine; and Daniel Callahan, Ph.D., Director
of International Programs, The Hastings Center, Garrison, N.Y. They will
have a broad mandate to conduct a comprehensive review of every aspect
of IHGT's procedures for oversight and monitoring of clinical trials.
This committee will report directly to me; its charge follows below:
- To conduct a thorough, independent review in order to carefully evaluate
and assess IHGT's oversight and monitoring of clinical trial programs,
with particular emphasis on the FDA's findings about the OTC Therapy Trial
and IHGT's response to those findings.
- To recommend any additional actions necessary to ensure the highest
standards are set and met in the conduct, oversight and monitoring of future
IHGT clinical trials, including a framework for University monitoring of
compliance with these recommendations.
- To report findings of review to the President of University of Pennsylvania
and recommend issues to be referred to the University's faculty committee
charged with reviewing human subject research.
Additionally, I have formed a committee of Penn faculty, chaired by
Provost Robert L. Barchi, himself a distinguished scientist and scholar,
and comprised of research scientists with a wealth of talent and relevant
experience, who will conduct a proactive review of all aspects of research
involving human subjects anywhere at Penn. They will examine everything
we do, from the mechanics of the approval process, to oversight and the
functions of our Institutional Review Board, to ultimate accountability
for this research.
Again, we deeply regret Jesse Gelsinger's death, and we want to learn
everything we can about how and why he died. We also want to consider
everything and anything we can do to improve our oversight and monitoring
procedures for essential clinical research. As I said, nothing less than
the highest possible standards are acceptable. And, Penn is deeply committed
to cooperating fully with the appropriate regulatory agencies and public
officials examining these complex issues.
We welcome any suggestions you may have on how we are approaching this
matter, and, of course, we will keep you informed of all significant developments.