ANTI-INFECTIVE GUIDELINES DEVELOPED OUTSIDE FDA BY SPECIALTY GROUP

ANTI-INFECTIVE GUIDELINES DEVELOPED OUTSIDE FDA BY SPECIALTY GROUP, the Infectious Diseases Society of America (IDSA), will be presented to the agency in the fall. As part of a contract initiated by FDA with the professional society in 1988, ID-SA has been developing an update of the current FDA anti-infective guidelines. The current guidelines date back to 1977. David Gilbert, MD, Providence Medical Center medical education director, has been the principal investigator in charge of rewriting the FDA guidelines. Based on submission of the guidelines to FDA this fall, Gilbert predicts that the guidelines could go into effect in early 1991, "certainly" by 1992. The final document is expected to be assembled in September by Gilbert and co-principal investigator Calvin Kunin, MD, Ohio State University. The project director is Thomas Beam, MD, Buffalo Veteran's Administration Medical Center. The guidelines will be ready in October at the time of the Interscience Antimicrobial Agents and Chemotherapy meeting and will be presented to the FDA commissioner and the Anti-Infectives Drugs Advisory Committee in November. Gilbert discussed the project on May 14 at the The 1990 NDA Pipeline Conference cosponsored by International Business Communications and F-D-C Reports. A first draft of the document has been prepared and the society is working on a second draft. The first draft covers preclinical and clinical trials, including Phase IV studies. The document also mentions international studies, Gilbert said. The draft is currently about 60 pages in length. In addition to the general guidelines being written by Gilbert, Kunin and Beam, a total of 13 subcommittees are working on supplementary guidelines in specific disease or organism areas. Anti-viral agents will not be addressed specifically in the final guidelines. The "major change" in the new guidelines, Gilbert said, is "there would be a greater role for academicians in the planning and conduct of clinical trials once the initial Phase I pharmacokinetics are achieved." For example, Gilbert noted that investigators would "help design" Phase II protocols in addition to approving them. Investigators would provide both interim and final analysis of data for safety and efficacy. "We are trying to ease" the job for corporate sponsors "with the FDA by increasing the credibility of your NDA," Gilbert explained. The IDSA proposal is a way "of providing assurance to the agency that the information presented is not the result of some bias -- not tha you would purposely bias the information, of course -- but some bias that has occurred as a result of the collected data from a variety of sites being analyzed, synthesized, prepared by the sponsor and then submitted to the agency without any in-depth involvement by the investigators." The new document requires more precise definition of infectious disease entities in study protocols, Gilbert observed. For example, he said, it would differentiate between types of respiratory infections, which are often not distinguished in protocols. The IDSA final document also calls for more precise definitions of microbiological end-points, offering "about 30 categories by which one can define microbiological outcome." Other changes in the draft include permitting study sponsors to use an unapproved dosage of an approved product for comparison studies if that dosage can be represented as standard medical practice. For example, he said, nafcillin is approved at a 6 gms per day dosage level but is routinely used at 12 gms per day. Therefore, comparison studies to nafcillin should be performed versus the higher dose. IDSA's contract with FDA will take 36 months and will cost the agency "a little" over $400,000, Gilbert said. None of the funding has been distributed as honoraria and that the majority of the funding has gone toward travel expenses. Some funding supported the relocation of the project director to Washington D.C. for six months in order to work with the agency on the project. The project is important as a potential model for other efforts to farm out some of FDA's ancillary duties in drug development regulation to outside groups.