OF RECORD

The report below was delivered by President Rodin to the Danforth Committee on May 24, 2000.

Action by the University of Pennsylvania in Response to the "Report of the Independent Panel Reviewing the Institute for Human Gene Therapy"

May 24, 2000

Click here for the Independent Panel's Report on the IHGT

Click here for the list of Penn Staff interviewed by the Independent Panel

Introduction

The University of Pennsylvania is grateful to Dr. William H. Danforth, who chaired the external committee appointed by President Rodin to review the conduct, oversight and monitoring of clinical trials at the Institute for Human Gene Therapy ("IHGT"). The University also is grateful to the members of the committee, a group of particularly distinguished scientists and researchers, who brought their collective insight and considerable experience to the task.

The committee examined a number of profoundly complex and interrelated issues fundamental to the conduct of research, not only at the University of Pennsylvania, but also throughout the academic research community at large. We believe that their work provides useful advice on issues that are of concern to other universities, scientific societies and federal agencies as well as congressional committees with oversight responsibilities.

The University also is grateful for the ongoing work of an internal committee of distinguished scientists and researchers, also appointed by President Rodin, which has been conducting a proactive review of all aspects of research using human subjects across the University. While this internal committee, chaired by Provost Robert L. Barchi, M.D., Ph.D., will continue its work through the summer, its interim findings have been useful as a guide to many of the actions the University has taken and is taking now.

Response to the Basic Findings

We fully agree with the overall finding of the Danforth Committee that cutting-edge research--like gene therapy and physician-sponsored clinical trials using human subjects--requires significant investments, if the research is to meet the standards of excellence that we expect at the University of Pennsylvania. We also believe that the Danforth Committee has raised many of the fundamental questions that the University must address as it moves forward in a new age of clinical research.

We are encouraged, though, by the Danforth Committee's findings that the University and IHGT: (i) are committed to compliance with all applicable regulations and to correct any past deficiencies; (ii) were changing processes and practices to conform to the FDA's requirements before that agency began its investigation; and (iii) have already instituted a number of important changes.

Action Taken by the University of Pennsylvania

Many of the issues facing us in the area of research using human subjects today are the subject of a broader national dialogue concerned with improving the oversight and compliance process for physician-sponsored clinical research in an academic setting. The University of Pennsylvania will continue to participate in that discussion with our colleagues, professional associations and public officials to search for new national policies. At the same time, Penn is moving forward, guided by the work of both the Danforth and Barchi committees, with a range of actions to ensure that clinical research at the University meets the highest possible standards for academic excellence and patient safety.

We have taken, and are taking, a series of steps to strengthen oversight and monitoring of our clinical trials, to enhance the professional management, organization and focus of IHGT, to address issues of ethical decision making specific to research using humans, to further reinforce the Institutional Review Board's role in oversight and patient protection and to comprehensively review our policies on conflict of interest. These include:

1. The University believes the Danforth Committee is certainly correct in suggesting that clinical trials involving human subjects at universities across the country will require increasingly stringent oversight and regulatory compliance. Consistent with the suggestions of the committee, the University has taken, or will take, the actions listed below. Our goal at Penn is to ensure the highest possible standard of continuing excellence in all clinical trials.

a. Every clinical trial proposed at Penn in the future will be assessed by the Office of Regulatory Affairs ("ORA") in concert with the Institutional Review Board ("IRB") to determine the level of monitoring it will require for strict compliance with all applicable regulations. Most clinical trials at Penn have external sponsors, such as pharmaceutical firms, that are required to professionally monitor the trials. For the remaining trials at Penn that are sponsored by a physician or an academic center, monitoring will be provided by professional staff from ORA or, for studies deemed by ORA and the IRB to involve significant risk, by a contract research organization under agreement with the University;

b. Each of the limited number of current clinical trials at Penn that have no external sponsorship and monitoring will be reviewed by a professional contract research firm to determine any additional monitoring it may require. The University is presently recruiting firms for this purpose.

c. The University is developing a set of clear standards that will guide the review and monitoring of all clinical trials; and

d. The University is developing a compendium of Standard Operating Procedures for research involving human subjects at Penn and a process for ensuring that all investigators have access to, are cognizant of and are in full compliance with these procedures.

2. We have greatly benefited from the Danforth Committee's questions about the scope of IHGT. Created in the belief that it made practical sense to combine in one entity virtually all phases of basic science, pre-clinical and clinical work in gene therapy, IHGT and the University have now come to a different view. Experience has shown that it is very difficult to align all required areas of expertise within a single integrated institute or center. Consistent with this conclusion, Penn and IHGT have jointly determined that IHGT can best serve the important future of gene therapy by resolutely focusing on a pre-clinical mission of molecular and cellular work and animal model experimentation. IHGT will not serve as a sponsor of clinical trials in the future.

3. The University is undertaking a comprehensive review of ethical decision-making specific to research using human subjects at the University, and future ethical discussions regarding the testing of gene therapy in human subjects will be overseen by an IRB with special expertise in evaluating gene therapy. In addition, the School of Medicine will establish a new, free-standing Department of Bioethics that will take the place of the Center for Bioethics.

4. The University's internal committee chaired by Provost Barchi has begun a formal, comprehensive review of its IRB system. The review will examine how to strengthen the IRB's ability to protect the vital interests of patients as well as other relevant issues. This review will include examining the proposals being developed by Congress and others. It also will build on the significant changes recently initiated at Penn following an outside review completed in the summer of 1999 and the hiring of Joseph R. Sherwin, Ph.D., as Director of ORA. Following his appointment, IRB policies and procedures were strengthened to ensure, among other things, and include:

a. Strict adherence to all IRB regulatory requirements, including those governing when expedited review is appropriate, and who has the authority to perform that review.

b. Implementation and use of a new database tracking system that identifies primary and secondary reviewers and monitors IRB discussion of substantive issues and its recommendations for changes in protocols and consent forms. (This new database tracking system was available on Oct. 1, 1999).

c. A new 24-hour adverse event hotline that is monitored on nights and weekends by the IRB Director and Associate Director. (This new 24-hour adverse event hotline became available on Feb. 1, 2000).

d. Substantial, regular training and education for IRB members and staff.

e. Training for Medical School faculty, which ultimately will be integrated into a requirement for certification of both principal investigators and research coordinators before permitting submission of protocols for IRB review.

f. A new ORA web site, and a new brochure that has been distributed to the University's research community. (The new ORA web site was available on Dec. 15, 1999; the brochure is in its second printing).

g. Addition of new professional staff in the ORA, and additional positions are being recruited as of this writing.

h. Development of new Standard Operating Procedures for IRB members that clearly delineate the requirement for continuing review and the responsibilities of the convened IRB, the chair and the staff.

5. The University believes that perceived as well as actual conflicts make clinical trials open to criticism and suspicion, and that investments in new medical therapies are uniquely controversial.

The proposed new guidelines of the American Society of Gene Therapy, issued in April 2000, would prohibit all investigators and team members directly responsible for patient selection, the informed consent process and/or clinical management in a trial from having equity, stock options or comparable arrangements in companies sponsoring the trial. These guidelines are consistent with restrictions that Penn established five years ago.

Nevertheless, the University agrees with the Danforth Committee that a full review of its policies on conflict of interest should be undertaken at this time, and the internal review committee, chaired by Dr. Barchi, has initiated such a review.

While we have moved aggressively in a variety of areas, we recognize that we have considerable work to do to ensure that we structure the best possible climate for clinical trials, one that always ensures high standards and always puts the interests of our patients above all else. We will continue to work with our colleagues throughout the academic community, with regulators and with lawmakers to accomplish that task.

Ed Note: Please see the Independent Panel's Report on the IHGT.

Almanac, Vol. 46, No. 34, May 30, 2000

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