Executive Summary

OSTEOPOROSIS CLINICAL EFFICACY ANALYSIS SHOULD INCLUDE FRACTURE REDUCTION frequency and "a favorable effect on bone mass," according to FDA's proposed revisions to the "Guidelines for the Clinical Evaluation of Agents Used in the Treatment or Prevention of Osteoporosis-" Fracture incidence alone may not be an appropriate endpoint for prevention studies, however, and the effectiveness of an agent fracture frequency," the guidelines state. Presented at a June 24 meeting of FDA's Endocrinologic and Metabolic Drugs Advisory Cmte., the revised guidelines point out that while an agent demonstrated to have favorable effects on bone mass would also be expected to reduce the pain and disability associated with osteoporosis, relief of pain and disability should be considered"as supportive of, and not a substitute for, bone mass and fracture frequency data." In regard to the evaluation of skeletal mass, the guidelines underscore the importance of measuring cortical bone mass in patients as well as trabecular bone mass using multiple techniques. "In addition," the document states, "it is desirable to assess bone mass at several different locations, including, if possible, locations that are prone to osteoporosis-related fractures. Two techniques for in vivo evaluation of skeletal mass that have been recently incorporated into the revised guidelines are dual-photon absorptiometry of the spine and X-ray computerized tomography. Other previously indentified methods include single photon absorptiometry, radiogrammetry, radiographic densitometry, in vivo neutron activation analysis, bone biopsy and calcium balance measurements. The guidelines maintain that each technique must be established empirically in each laboratory and that reference to similar data from other labs is "usually not acceptable." It was noted during the cmte.'s discussion that current treatment of osteoporosis consists of decreasing the rate of bone loss rather than increasing bone mass and that, therefore, the word "treatment" is perhaps misleading. "There is nothing at all that's effective for laying down new bone," commented consultant Stephen Marx, MD. "What's available right now is preventive therapy for patients who don't have the established disease and preventive therapy for patients who do have active, ongoing osteoporosis." FDAer Gloria Troendle, MD, responded that the agency views a specific indication as a "definition of a population" that should receive a drug. "In the absence of better drugs we have felt that it was alright to go ahead and treat people who already have osteoporosis with drugs which actually do not restore bones but which only prevent further loss," she stated. "We probably have not been as effective as we should be in making this distinction clearer in the package inserts and perhaps we should modify some of these package inserts to clarify that point." Added FDA Metabolism and Endocrine Div. Director Solomon Sobel, MD, "Our definition of treatment did not imply that we are laying down new bone. . . [it] really rested on what we would be directing the therapy toward."