> They've already been proven in the other countries -- higher numbers of patients than you have in normal clinical trials -- but because the approval rules are excessively rigid and unreasonable, that doesn't count.

You are wrong. You absolutely can get drugs approved in the US based on real-world studies or observational data. The reason this happens so infrequently is actually because it's virtually impossible to prove a drug is safe and effective using real-world studies or observational data.

We don't rely on (super expensive) RCTs because FDA says you need RCTs. We rely on them because FDA says you need to prove your drugs are safe and effective, and no one knows a better/cheaper/faster way to do that than RCTs.

You can absolutely bundle up a bunch of observational data and file for approval. You likely won't get it, not because observational data isn't allowed, but that observational data almost certainly cannot prove the claims you're making. Drug makers know this, so they don't even try. But you're welcome to!

> The reason this happens so infrequently is actually because it's virtually impossible to prove a drug is safe and effective using real-world studies or observational data.

This is back to the thing where you define the requirement in terms of the regulations.

If you have 10,000 people taking a drug for years and it's "unsafe" then it would be conspicuous. A third of them would be dead or their children would have a significantly higher proportion of birth defects than the overall population and the people with the same condition who took a different drug, etc.

Whereas if it has some minor side effects, it might not be able to pick that up, but that's because they're minor, so why should that be a reason to prohibit it by law?

The thing that really makes the point is how different the process is for food. Their hands are tied there, because food is full of chemistry and biology. You're cooking a plant. Heat triggers chemical reactions. If you use a different temperature for a different amount of time, you get different chemical reactions. The same thing if you store it for a different period of time under different conditions. If you grow the same plant in a different place or use a different variety. If you change the proportions of different ingredients.

It would be totally infeasible to require RCTs every time a restaurant wanted to add a new item to their menu or change their supplier of tomatoes. We don't even do that with drugs -- different brands of the same drug have "inactive ingredients" and the requirement is essentially that they themselves be on the safe list but not that anybody has done a comprehensive study to prove that they're inert and unable to affect e.g. the metabolism of the active ingredient. "Sugar is a drug" but the patient doesn't even get a choice about whether it's that or something else they have to ingest along with their prescription.

So every time you bite into a sandwich you're putting a million unknown chemical compounds into your body. We're not even talking about herbicides or preservatives here. The chicken feed was fish meal from the Pacific rather than the Atlantic and that affects what's in the chicken, which results in a different chemical reaction when you cook it in the sauce. And for the most part that doesn't matter. The food is more likely to be bad for you because it's full of sodium and high fructose corn syrup on purpose than because it contains <enigmatic organic compound> unintentionally. We have more problems when something contains e.g. heavy metals (which we already know are bad for you) than when it contains something novel.

So we're running the scenario where you don't require RCTs for everything in parallel because we have to, and it seems to be fine. What does that say about the claim that not de facto requiring RCTs is "unsafe"?