It doesn’t take two trials

In June, the FDA issued new draft guidance stating that drug makers no longer needed to run two trials to demonstrate the efficacy of a new drug before it could be approved; rather, “one adequate and well-controlled clinical investigation with confirmatory evidence” could satisfy the evidentiary standard. It was a controversial move, although others pushed back saying the two trial guidance isn’t commonly followed in the first place and was an unnecessary burden.

In a recent post, the biostatistician Kaspar Rufibach shared a characteristically thoughtful take. When drug developers want to maximize their chances of succeeding in the second trial, they often try to design it identically. But, for a drug that “just” showed significance in the first trial, its chance of succeeding in a second, identical trial is just a coin toss: 50%. Better, he suggests, would be to run a single, larger trial, or run a second trial that’s different and gathers evidence for the drug’s effect on another disease, in another region, or a different route of administration, for example.