BENCHMARKS

The following letter by President Judith Rodin was sent on January 31, 2000 to Senator William Frist , the chairman of the Senate Subcommittee on Public Health which held hearings last week in Washington on the human gene therapy trials.

President Judith Rodin's Letter to U.S. Senate on Gene Therapy

 

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 these issues.

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:

  1. 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.
  2. 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.
  3. 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.

 

Respectfully,

Almanac, Vol. 46, No. 20, February 8, 2000

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