COMMENTS AND RESPONSES TO QUESTIONS

Name: American Society of Gene Therapy (ASGT)
611 East Wells Street
Milwaukee, WI 53202
414/278-1341 phone
414/276-3349 fax
Elizabeth Dooley, Executive Director
Joseph Glorioso, PhD, President

General Impression
The document is a great educational tool, however, the Society questions whether this document is appropriate for inclusion in Appendix M. The document is over 40 pages in length and the vast majority of the information is not specific to gene therapy. There is concern regarding timely revisions if the information is added to the Appendix M. Given the evolving nature of informed consent, such revisions would be important to maximize compliance with the relevant regulations. The information provided is a good general overview provided in a user friendly format.

Educational Value

• provides an understanding of the expectations of the NIH
• useful in keeping us aware of innovative ideas to improve our consent process
• layout provides a useful tool in introducing and teaching professionals new to Gene Transfer Research and a good review for current professionals
• the discussion, the tools and background materials, the sample language, and the list of references will be helpful as an educational tool

Preferred Method of Access

• have available both as internet web pages with links and as a downloadable pdf file

Suggestions for Improvement
The Society would suggest limiting the additions to Appendix M to areas specific to gene transfer studies. Even with the disclaimer at the beginning of the document, addition of samples to the Appendix M would give the impression of directive. Examples of areas noted that would be helpful to include in Appendix M include: adding a line referring to financial conflicts of interest to M-III-A-1, adding a statement indicating that the gene transfer aspects of the study should be clearly designated in the consent form to M-III-B, adding a sentence related to study discontinuation and withdrawal consequences to M-III-B-1-c, and adding risk of cancer language to M-III-B-1-e.

• have review by FDA: that information provided meets their requirements; provide links to their specific site that addresses the issue being discussed
• provide a link of up-dated risks for the various vectors that are being used and have been reviewed with acceptable/required language for the ICF at this site under discussion of Appendix M-III-B-1-e or provide a link such as provided in Sample 2
• under discussion of a Phase I/II Study, pg17, suggestion of using 2 consent forms - may cause problems if a participant consents to one and not the other. The development of the phase II consent form if separate would be very difficult without the results of the phase I portion of the trial.
• discussion of long-term follow-up, who determines the specific follow-up activities, what activities meet the requirement?

Sidebar Boxes

• appreciate their being available alongside the discussion
• encourage addition of more tools to increase the educational value of the document

Sample Language
There is concern that all samples provided would meet the requirements of understandability and will be acceptable to the FDA, IBCs and IRBs. IRBs and IBCs have an ongoing struggle with improving the informed consent documents. Placing suggested wording in a document like Appendix M could stifle ongoing attempts to improve the informed consent process.

• appreciate samples, readily available, well worded, 8th grade level, developed by experts in communication
• helpful and important to have sample language accessible to new researchers and staff looking for additional resources.

How do you believe your organization's members will receive this guidance?
Well received as an educational tool

What aspects do you think your members will find particularly helpful?
We think the discussion is helpful in providing understanding of what is expected to investigators as an educational tool.

Would you recommend this guidance to your members?
Yes, as an educational tool

Additional Comments
The Society believes that OBA would provide a more useful and relevant addition to Appendix M by limiting the scope of the information to gene therapy specific issues. This will have the most impact for all individuals seeking advice on the important issues of clinical gene transfer.

Clearly, OBA and the RAC subcommittee have been thoughtful and thorough by drafting a document which could serve as a general resource. Providing the document on the OBA website would allow this document to be used as an educational tool.

One very disturbing statement in the current document reads "All too often, consent is viewed as only obtaining a participant's signature on a consent form". The Society must disagree most strongly with this statement. Our members, especially our clinical investigators, and the IRBs and IBCs which help formulate these documents, take the informed consent process extremely seriously. Significant efforts and resources are placed in the development and administration of the informed consent process. In fact, most investigators appropriately see the verbal process as the major critical component of the informed consent process.

In summary, the document dilutes the impact a concise summary of gene therapy related informed consent issues would have on improving the consent process. The document as written is worth providing as an educational tool on the OBA website but its attempt to define the complex nature of the informed consent process falls short and therefore inappropriate for Appendix M. For the general information about informed consent issues that make up the bulk of this document, referral to the organizations with jurisdiction will improve compliance and provide more up-to-date information.

ASGT thanks you for the opportunity to comment on the proposed addition to Appendix M. WE hope our comments will be useful in improving the informed consent process for gene transfer subjects.

The American Society of Gene Therapy is a professional, non-profit medical and scientific organization dedicated to the understanding of gene therapy and to promoting professional and public education in this field.