Comment by tripletao

That's an unrealistically idealized view of drug development. The human use of drugs long predates anything resembling a modern concept of a biochemical mechanism. Nobody knew how morphine relieved pain, but they knew that it worked and they used it.

Today we'll generally have a proposed mechanism, but it's not necessarily correct. Acetaminophen is among the oldest and most commonly used synthetic drugs, and its mechanism is still debated. This isn't usually cause for any special concern, since our confidence in the drug's efficacy and safety comes more from animal or human trials than from mechanistic understanding. Serendipitous discoveries during human trials are still common; the first inkling that Viagra might treat ED came not from any "first seminal paper" but from the volunteers who were testing it for angina.

Clinical trials are regulatory matters. Your suggestion that it could be "unclear who conducted the phase 3" is very strange--the FDA knows who filed the application. Of course that filer could have committed fraud, but I see nothing in the slides to suggest that was the concern here. If it was, then the solution would be a non-fraudulent phase 3, not anything related to mechanistic insight.