<< Previous Section | < Previous Page | Next Page > | Next Section >> Case: Appropriateness of Placebo Controls Matrix Pharmaceuticals developed a new drug that increased bone density in mice by facilitatinging osteoblast function without stimulating osteoclasts nearly as much, thus increasing bone density. Phase I and II trials were conducted with no significant morbidity at an effective dose. A number of international experts in the field were asked to consult on the design of the hopefully definitive Phase III clinical trial that was going to be carried out at 100 sites in 15 countries. Matrix's vice president for research proposed a placebo-controlled trial of 8,000 women over one year, with a direct measure of bone density, DEXA scanning, as the principal end point. A European investigator indicated that they follow the latest version of the Helsinki Accord that indicated that placebo controls should not be used if there are effective standard therapies. In the case of osteoporosis, bisphosphonate were effective and relatively safe standard therapies. An American representative pointed out that the FDA prefers placebo-controlled trials if there is no serious safety issue. Furthermore, he pointed out, comparison with an effective agent to demonstrate "non inferiority" or "superiority" would require a study of 30,000 women rather than 8,000, would take much longer, by vastly more expensive, and would require a greater number of adverse endpoints in both treatment categories to reach a conclusion, thus making it less safe over all for the research participants. Company representatives agreed whole heartedly and suggested that the study be designed so that it focused on early findings, diminished bone density by DEXA and appropriate chemistries. The key to a successful outcome and limited fracture morbidity would lie in the selection criteria for participants. Another team member argued that an intermediate end-point like change in bone density by DEXA scan will not answer the question about preventing fractures. Bisphosphonates have been shown to reduce fractures already so that a new agent will have to be equal to or superior to them in protecting against fractures. In that case they will have to recruit women at high risk for osteoporotic fractures, for whom a placebo control is not benign at all. Another team member added that with the availability of bisphosphonates, very few women with osteoporosis will be found in developed countries that are not taking an effective agent. Therefore most of the study will have to be done in developing countries. There are plenty of untreated Americans if you look to underserved populations, stated one of the team. Questions: Put yourself in the position of an ethics consultant to this meeting. What would you recommend as the most appropriate ethical randomized clinical trial for this new agent and give your reasons for the choice? << Previous Section | < Previous Page | Next Page > | Next Section >> Chapter 3 Quick Links Ethics and Study Design Introductory Ethics Design Appropriate Risk to Benefit Ratio Selection of Subject Populations Cases Bibliography Chapter 3 Download (PDF)