Pre-registration would not hinder them doing that discovery, but they would have had to do another registration and study to get it to the market with the new use. They would likely still be able to use the outcome of the original study to assess the safety of the drug.

Which actually makes an important but subtle point: just because the rate of positive effects identified went down doesn't mean the effects that would otherwise have been identified were all false. It just means we don't know. There may be extremely strong evidence of effects that would overcome any amount of multiple testing correction, but they still aren't allowed to use it. It might take years or even decades for them to do a follow up study to validate the result, which means a significant number of people are harmed by not having access to the drug in the interim. Just playing devil's advocate to make the point that it's not a given that we're getting an better overall outcome by being this stringent.

> [...], which means a significant number of people are harmed by not having access to the drug in the interim.

Yes, that might happen. The more likely outcome though is that we are saved from a lot of drugs that don't work any better than chance (or even worse).

Fair enough... but the issue here is about findings of an effect versus no effect. It's about statistical significance. In order for single-comparison p-values and the like to be valid, there has to be a (one) single comparison. There is a way to do 'any-of-k' testing, but the required effect sizes get larger.