As someone who used to work in pharmaceutical R&D, the important thing to remember is the hurdle to get over hasn’t remained constant.

The FDA has gotten significantly more strict in its review than it was in the 1960s.

A good example is hERG inhibition as an off-target effect. It’s a receptor on heart muscles and will result in QT prolongation and potential arrhythmias.

It wasn’t discovered until the 1990s. Now every molecule is screened and many are dumped. The impact can vary but there are tons of drugs on the market now that are hERG inhibitors (many discovered after the fact).

It’s a good example of the increased rigor that the FDA applies to everything they review that past trials never had to face.

It's interesting that you frame it as the FDA increasing regulation and not that science has increased its foreknowledge of problems.