Is it ethical to conduct placebo-controlled clinical trials in the development of new agents for XXXX ? An industry perspective.

@entity1 @entity170 @entity174 @entity3604
To represent industry on the topic of this conference, position papers were obtained from six pharmaceutical and biotechnology companies. Despite their holding a wide range of positions in the market with regard to prevention and treatment of @entity170 , all companies were unanimous in their concerns about the ability to conduct randomized placebo-controlled clinical trials (PCTs) in the future. The clinical research environment contains conflicting directives. Regulatory agencies strongly prefer (even insist on) PCTs as a requirement for drug approval, while many physicians, @entity1 studies institutional review boards, and informed @entity1 believe that it is no longer ethical to place @entity3604 @entity1 on placebo because effective therapies are now available. PCTs offer the best means of calibrating the absolute efficacy of a new agent and identifying its side effects against a "neutral" background. Are comparison-controlled clinical trials (CCTs) using an approved drug the answer? No. Examples are given that illustrate that such trials require very large numbers of @entity1 to show "non-inferiority" (approximately 15,000-20,000) or "superiority" (approximately 30,000) compared with an existing approved therapy. Such studies are not only impractical, but also accumulate a greater number of @entity174 during the course of clinical research in both the new treatment and control (active comparator) groups than would occur in PCTs. Total adverse experiences and exposure of @entity1 to investigational agents is considerably greater when CCTs rather than PCTs are used. Based on this analysis, industry recommends that regulatory approval of new agents for @entity170 be based on (1) conduct of PCTs in @entity1 at low risk for @entity174 (e.g., T-score < -2.5 and no previous @entity3604 ); (2) use of bone mineral density as an end-point for the indication "to preserve or improve bone mass"; (3) a 2-year, rather than 3-year, trial period; (4) demonstration of no adverse effect on bone quality preclinically; (5) extrapolation of clinical trial results to higher risk @entity1 ; (6) an option for the sponsor to perform additional @entity174 end-point studies postapproval to obtain an indication for "treatment to reduce the risk of @entity174 specifically in the spine, hip, or both"; and (7) the option to file for a "prevention" claim before a "treatment" claim.
