Fellow progress blogger Alex Telford and I have had a friendly back-and-forth going over FDA reform. Alex suggests incremental reforms to the FDA, which I strongly support, but these don’t go far enough. The FDA’s failures merit a complete overhaul: Remove efficacy requirements and keep only basic safety testing and ingredient verification. Any drug that doesn’t go through efficacy trials gets a big red warning label, but is otherwise legal.
This was better than the surgery post 😉 I'm not going to write another detailed response because, as you point out, the crux of our disagreement boils down to different (subjective) risk tolerances.
I do think nuance in how regulation is adapted to unmet need is important however. So I'll leave this closing thought (from a response to a comment on my last piece):
"Broadly, you can put new treatments into one of two classes that exist on a spectrum between two extremes:
1. Minimizing downside is preferable (vaccines for healthy people, cosmetic surgery)
2. Maximizing upside is preferable (deadly diseases with no good treatments, transplants)
The FDA grew up during the era of mass-market blockbusters so was designed to deal with class #1-adjacent treatments. We shouldn't have the same approach for both classes, but (in my view) that doesn't mean we scrap the FDA - it has an important function. Accelerated approval etc. tries to deal with the dichotomy of risk-preference but probably doesn't go far enough. I think there are conditions (e.g. n-of-1 rare disease) where there are convincing arguments that you should be able to bring a drug to market based on the judgement of reasonable experts and some preclinical tests."
"Remove efficacy requirements and keep only basic safety testing and ingredient verification"
What does "basic safety testing" mean in the context of cancer drugs? They aren't safe at all! Chemotherapy was literally first discovered when doctors noticed what happened to soldiers attacked by mustard gas. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325736/ If you look at the side effects of any common cancer drug (let's take doxirubicin), it typically looks like this: "May cause infections, sepsis, heart attacks, breathlessness, bruising, extreme fatigue, hair loss, sore mouth, loss of appetite, diarrhea, and more."
In fact, my wife was administered that drug when she had an episode of breast cancer, and it came in an IV bag labeled with a skull and crossbones, with all kinds of warnings for the nurse to "NEVER LET THIS TOUCH YOUR SKIN" and that kind of thing. It's incredibly toxic.
All of which is to say that no cancer drug like this would ever pass a review for "safety." These drugs are not safe whatsoever. They can easily kill you. The only reason to take them is that they (hopefully) kill more cancer cells than healthy cells. Which is about efficacy.
Why doesn't the same argument favor barring off-label prescribing?
I think a key consideration here is what the alternative might be. For instance, I can imagine a system where in exchange for dropping efficacy requirements a tax on pharmaceutical profits is imposed and the FDA then directly funds efficacy studies. This would be alot better than just checking if each medicine gets over a minimum hurdle as you could revisit results and compare treatments.
In the spirit of Chesterton's fence: what happened in 1962 that caused efficacy requirements to be added? Was it just Great Society era trust-the-experts-ism, or were there real problems with useless-but-popular drugs that proponents identified at the time to justify the new requirements? If the latter, is your claim that there were better ways of addressing those problems, or that we should have just let those problems happen as a cost of the freedom to innovate?
"There is no denying that medicine has improved massively over the past 150 years alongside expanding regulatory oversight, but this relationship is not causal." Exactly. Thank you. I'm so tired of this lazy argument for the FDA.
Safety is relative to the problem that a drug is intended to treat - there are side effects that people will accept from a cancer treatment that they won't accept from, say, an acne treatment.
I'd like to propose a slightly different system:
1) If you can establish a drug as meeting a certain safety standard, you can sell it and doctors can prescribe it, but you can't claim it's good for anything, and insurers won't be required by law to cover it.
2) If you can prove efficacy for a drug, you can get a *new* patent on it - even if it's been patented before for a different condition - and insurers can be required to cover it. Otherwise, nobody would actually go to the trouble of proving effectiveness to the FDA's standards if they can just sell the drug without doing that. You can also sell a drug that doesn't meet the "unproven chemical" safety standard if the benefits outweigh the risks. (Figuring out the proper scope of such a patent is a matter for someone who knows more about the economics than I do.)
This was better than the surgery post 😉 I'm not going to write another detailed response because, as you point out, the crux of our disagreement boils down to different (subjective) risk tolerances.
I do think nuance in how regulation is adapted to unmet need is important however. So I'll leave this closing thought (from a response to a comment on my last piece):
"Broadly, you can put new treatments into one of two classes that exist on a spectrum between two extremes:
1. Minimizing downside is preferable (vaccines for healthy people, cosmetic surgery)
2. Maximizing upside is preferable (deadly diseases with no good treatments, transplants)
The FDA grew up during the era of mass-market blockbusters so was designed to deal with class #1-adjacent treatments. We shouldn't have the same approach for both classes, but (in my view) that doesn't mean we scrap the FDA - it has an important function. Accelerated approval etc. tries to deal with the dichotomy of risk-preference but probably doesn't go far enough. I think there are conditions (e.g. n-of-1 rare disease) where there are convincing arguments that you should be able to bring a drug to market based on the judgement of reasonable experts and some preclinical tests."
"Remove efficacy requirements and keep only basic safety testing and ingredient verification"
What does "basic safety testing" mean in the context of cancer drugs? They aren't safe at all! Chemotherapy was literally first discovered when doctors noticed what happened to soldiers attacked by mustard gas. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325736/ If you look at the side effects of any common cancer drug (let's take doxirubicin), it typically looks like this: "May cause infections, sepsis, heart attacks, breathlessness, bruising, extreme fatigue, hair loss, sore mouth, loss of appetite, diarrhea, and more."
In fact, my wife was administered that drug when she had an episode of breast cancer, and it came in an IV bag labeled with a skull and crossbones, with all kinds of warnings for the nurse to "NEVER LET THIS TOUCH YOUR SKIN" and that kind of thing. It's incredibly toxic.
All of which is to say that no cancer drug like this would ever pass a review for "safety." These drugs are not safe whatsoever. They can easily kill you. The only reason to take them is that they (hopefully) kill more cancer cells than healthy cells. Which is about efficacy.
Why doesn't the same argument favor barring off-label prescribing?
I think a key consideration here is what the alternative might be. For instance, I can imagine a system where in exchange for dropping efficacy requirements a tax on pharmaceutical profits is imposed and the FDA then directly funds efficacy studies. This would be alot better than just checking if each medicine gets over a minimum hurdle as you could revisit results and compare treatments.
In the spirit of Chesterton's fence: what happened in 1962 that caused efficacy requirements to be added? Was it just Great Society era trust-the-experts-ism, or were there real problems with useless-but-popular drugs that proponents identified at the time to justify the new requirements? If the latter, is your claim that there were better ways of addressing those problems, or that we should have just let those problems happen as a cost of the freedom to innovate?
"There is no denying that medicine has improved massively over the past 150 years alongside expanding regulatory oversight, but this relationship is not causal." Exactly. Thank you. I'm so tired of this lazy argument for the FDA.
Safety is relative to the problem that a drug is intended to treat - there are side effects that people will accept from a cancer treatment that they won't accept from, say, an acne treatment.
I'd like to propose a slightly different system:
1) If you can establish a drug as meeting a certain safety standard, you can sell it and doctors can prescribe it, but you can't claim it's good for anything, and insurers won't be required by law to cover it.
2) If you can prove efficacy for a drug, you can get a *new* patent on it - even if it's been patented before for a different condition - and insurers can be required to cover it. Otherwise, nobody would actually go to the trouble of proving effectiveness to the FDA's standards if they can just sell the drug without doing that. You can also sell a drug that doesn't meet the "unproven chemical" safety standard if the benefits outweigh the risks. (Figuring out the proper scope of such a patent is a matter for someone who knows more about the economics than I do.)