[random78965]

I think all your criticisms of randomized controlled trials (apart from the ethical one) apply to your suggested approach, no?

RCTs are the gold standard for demonstrating efficacy precisely because of the controls. I agree that they're not going to give you enough info about potential side-effects - a thorough monitoring program is definitely necessary for that.

But without RCTs, showing that a drug works would be much harder. How would you weed out the snake oil?

[A_D_E_P_T]

RCTs were not required and were rarely performed prior to 1962, and yet that period from roughly 1940 to 1960 is still today widely known as "the Golden Age of drug development." How did they know, back then, that new drugs work? Simple: They have sufficiently powerful (in a statistical sense) effects in a patient population. Very powerful effects require a very small population -- this applies to ALL drugs that are curative -- whereas moderate effects would require a large population. Reasonably sized safety trials and extensive postmarketing surveillance are entirely sufficient.

> How would you weed out the snake oil?

The current paradigm is "better 10,000 people die of neglect than 1 person die of snake oil or quackery." I'm okay with a little bit of snake oil if it means that more drugs are being introduced more quickly, and I trust practitioners and patients to, more often than not, determine the therapeutic regimens that are right for them.

[random78965]

I see! My intuition was that it would be hard to evaluate efficacy without RCTs - I assumed low effect sizes, which I guess is not necessarily true for many drugs.

Agreed that there should be a faster way to trial drugs and get them to market. Though I've heard that the "slowness" of the FDA is actually overstated; not sure how true that claim is.

[youainti]

Those were also small molecule drugs which are relatively simple to produce compared to modern large molecule drugs (biologics such as modern insulin, mrna vaccines, humira, many cancer drugs, etc.)