Issues in clinical trial design I

The health care community is actively debating the ethics of placebo-controlled trials in diseases with uniform or high mortality. This debate, which has been particularly active for AIDS and breast cancer, now involves ALS trials. Patients are increasingly reluctant to enter randomized placebo-controlled trials (RPCTs), particularly when the drug being tested is safe and available through other sources. The ramifications of what appears to be a significant shift in societal attitudes is more than an academic debate and poses a serious threat to successful evaluation of promising therapeutic agents. We believe that a careful reassessment of current clinical trial design in ALS is necessary, and it is appropriate to explore the role of alternatives to randomized placebo control subjects, alternatives that could meet both scientific and humanitarian needs. In this report, we extend our studies on the natural history of ALS and suggest ways in which a natural history database can be used in phase II trials. Over the years, an inordinate number of drugs have been reported to be effective in ALS, only to …