Policy/Position Statement

Adopted December 14, 1999
Reporting of Patient Adverse Events in Gene Therapy Trials: Statement from the American Society of Gene Therapy
Presented by: Savio L.C. Woo

Dr. Mickelson, Members of the RAC, Ladies and Gentlemen,

My name is Savio L.C. Woo from the Mount Sinai School of Medicine in New York City, and I am currently serving as President of the American Society of Gene Therapy (ASGT), which is a non-profit, voluntary and professional organization. The ASGT was founded in 1996, and it has grown to approximately 2,000 members at present. According to our Bylaws, the purposes of our society are: "to engage exclusively in scientific and educational activities, including specifically but not limited to, promoting and fostering exchange and dissemination of information and ideas related to gene therapy, to encourage the general field of research involving gene therapy and to promote professional and public education in all areas of gene therapy."

In the aftermath of the patient death that occurred at the University of Pennsylvania as well as those reportedly occurred elsewhere, it has become apparent that there are a number of salient issues surrounding the public reporting of patient adverse events in gene therapy trials that merit further discussion. The American Society of Gene Therapy supports the refinement of a system of public reporting because it provides the opportunity to produce a useful outcome for human gene therapy clinical studies, and because it will sustain credibility for this particular type of biomedical research.

There are several issues that require clarification and these deserve emphasis during the discussion that will occur at the RAC meeting on December 8th, 9th, and 10th. Some of the important points in question are as follows:

1. Complete Harmonization of Reporting Requirements Between the NIH and the FDA:

   The intent of the existing NIH Guidelines in reporting serious adverse events is clear and unequivocal. What is less clear is the definition of serious adverse events, which is addressed in Section I-E-7 of the Proposed Amendments to the NIH Guidelines. The FDA has the legal authority for regulating gene therapy trials, and it has enunciated precise definitions about classes of adverse events. This would appear to be an ideal time for the NIH and the FDA to jointly establish a completely harmonized set of requirements, so that investigators can interpret a single set of definitions and follow a single standard. The harmonized requirements will need to satisfy the legal and regulatory aspects of the FDA, and provide the public with useful and relevant information regarding gene therapy trials.

2. Maintenance of Patient Confidentiality:

   Committing information to a public database necessarily raises the need to be vigilant about the protection of patient confidentiality. In Appendix M-IV-A and M-IV-B of the existing NIH Guidelines, investigators are asked to indicate what measures will be taken to protect the privacy of patients and their families, and more particularly, what provisions will be made to maintain the confidentiality of research data. While the ASGT supports in principal the provision in Appendix M-VII-C-2 of the Proposed Amendments to the NIH Guidelines that addresses this issue, tracking reported data back to a specific time and a specific hospital location may be all that is necessary to begin to identify a patient. Additional attention needs to be given to provisions that will protect patient privacy.

3. Processing of Reported Data at the RAC/ORDA:

   A process needs to be developed that will permit the RAC/ORDA to efficiently manage the data submitted by the investigators. The inherent value in any information-gathering system lies in its relevance. Patients engaged in various gene therapy trials are often very ill with terminal diseases, and many will succumb to their underlying diseases over time. In order not to mislead the public about the actual safety or risk of gene therapy, it is important to segregate natural outcome from those serious adverse events that are related to gene therapy itself under clearly defined headings in the records maintained and updated regularly by the RAC/ORDA.

4. Appropriate Resources for the RAC/ORDA to carry out its mandate:

   The current ORDA web site shows that this office has taken on additional responsibilities. As the Office of Biotechnology Activities (OBA), there is now the mandate to administer three separate advisory committees that address disparate topics. To fulfill the challenges inherent in administering pertinent data, entering them into the system and keeping the system updated, the OBA will need to be given appropriate resources so that the objectives of reporting serious adverse events in gene therapy trials can be met. The NIH has a continuing obligation to both maintain and improve public access to human gene transfer information.

In conclusion, the Society expects its members to adhere to the tenets of all the regulatory schema that are in place, as well as those provisions in the Proposed Amendments of the NIH Guidelines that are adopted in the future. Adherence to oversight principles is important in maintaining public credibility about a newer form of biotechnology that still seeks hard evidence of success, but that has tremendous potential in shaping future therapies for a wide variety of diseases. In that context, the ASGT fully supports the NIH in its efforts to establish clear directives about serious adverse events reporting so that tragic incidences can be reduced to the lowest possible level and so that the field can move forward in the most efficient and responsible manner.

Thank you for your attention.