For how we live.
Analgesic trials keep failing, and one reason is that the comparison arm keeps improving. Where a trial recruits, how long it runs and how big it is all move the placebo response — and none of that is about the drug.
The FDA's approval bar requires no clinically meaningful difference from the original, and a large switching trial found no loss of control. The savings gap is a market problem, not a safety one.
Pain medicine added a third mechanistic category in 2017 and has been arguing about it since. There is no test for it, the criteria work by exclusion, and the experts who wrote them say that is a problem.