From a variety of sources, it determined that the approvals of...

From a variety of sources, it determined that the approvals of orphan drugs do not necessarily follow the pattern for approvals of drugs for common conditions, for which FDA often asks for evidence from two phase III trials. For example, Appendix B presents an analysis of medical officer reviews for drugs approved from 2007 to 2009. (Before 2007, these reviews were not consistently public.) For the 44 drugs approved during this period, the author located full medical officer reviews for 30. (The remaining 14 drugs included 9 clotting factors or immune globulins, 4 previously approved drugs, and 1 other product.) For the 30 drugs collectively, the medical reviews reported a total of 71 trials evaluating efficacy. The trials enrolled a median of 179 participants, and treatment lasted a median of 8.5 weeks. Of the 71 trials, 55 were considered pivotal trials that provided key evidence of efficacy. They included 30 phase III studies, 17 phase II studies, 1 phase I study, and 4 phase IV studies (which were conducted following FDA approval of the drug for a different indication).

In this sample, 13 of the 30 orphan drugs were approved based on a single efficacy trial, including 8 based on a single phase III trial; 4 based on a single phase II trial; and 1 based on a single phase I trial. Among the 55 pivotal trials, 27 had a double-blind design, 5 were single-blind, and the remaining 23 did not have blinding. Twenty-six trials used placebo controls, and 11 used active comparators. Thirty-eight studies were randomized. Thirteen were single-arm studies.

Don't get surprised if it does happen.

The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy.

Source