The Nonlinear Library LW - We Need Major, But Not Radical, FDA Reform by Maxwell Tabarrok
Feb 25, 2024
12:03
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: We Need Major, But Not Radical, FDA Reform, published by Maxwell Tabarrok on February 25, 2024 on LessWrong.
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.
Before getting into Alex's points let me quickly make the positive case for my position.
The FDA is punished for errors of commission: drugs they approve which turn out not to work or to be harmful. They don't take responsibility for errors of omission: drugs they could have approved earlier but delayed, or drugs that would have been developed but were abandoned due to the cost of approval. This asymmetry predictably leads to overcaution.
Every week the Covid-19 vaccines were delayed, for example,
cost
at least
four thousand lives. Pfizer
sent their final Phase 3 data to the FDA on November 20th but was not approved until 3 weeks later on December 11th. There were successful Phase I/II human trials and successful primate-challenge trials 5 months earlier in July. Billions of doses of the vaccine were ordered by September. Every week, thousands of people died while the FDA waited for more information even after we were confident that the vaccine would not hurt anybody and was likely to prevent death.
The extra information that the FDA waited months to get was not worth the tens of thousands of lives it cost. Scaling back the FDA's mandatory authority to safety and ingredient testing would correct for this deadly bias.
This isn't as radical as it may sound. The FDA didn't have efficacy requirements until 1962. Today, off-label prescriptions already operate without efficacy requirements. Doctors can prescribe a drug even if it has not gone through FDA-approved efficacy trials for the malady they are trying to cure. These off-label prescriptions
are effective, and already make up
~20% of all prescriptions written in the US. Removing mandatory efficacy trials for all drugs is equivalent to expanding this already common practice.
Now, let's get to Alex's objections. Most of
his post was focused on
my analogy between pharmaceuticals and surgery. There are compelling data and arguments on both sides and his post shifted my confidence in the validity and conclusions of the analogy downwards, but in the interest of not overinvesting in one particular analogy I'll leave that debate where it stands and focus more on Alex's general arguments in favor of the FDA.
Patent medicines and snake oil
Alex notes that we can look to the past, before the FDA was created, to get an idea of what the pharmaceutical market might look like with less FDA oversight.
Maxwell argues that in the absence of government oversight, market forces would prevent companies from pushing ineffective or harmful drugs simply to make a profit. Except that there are precedents for exactly this scenario occurring. Until they were stamped out by regulators in the early 20th century,
patent medicine hucksters sold ineffective, and sometimes literally poisonous, nostrums to desperate patients. We still use "
snake oil" today as shorthand from a scam product.
There is no denying that medicine has improved massively over the past 150 years alongside expanding regulatory oversight, but this relationship is not causal. The vast majority of gains in the quality of medical care are due to innovations like antibiotics, genome sequencing, and robotic surgery.
A tough and discerning FDA in the 1870s which allows only the best available treatments to be marketed would not have improv...
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.
Before getting into Alex's points let me quickly make the positive case for my position.
The FDA is punished for errors of commission: drugs they approve which turn out not to work or to be harmful. They don't take responsibility for errors of omission: drugs they could have approved earlier but delayed, or drugs that would have been developed but were abandoned due to the cost of approval. This asymmetry predictably leads to overcaution.
Every week the Covid-19 vaccines were delayed, for example,
cost
at least
four thousand lives. Pfizer
sent their final Phase 3 data to the FDA on November 20th but was not approved until 3 weeks later on December 11th. There were successful Phase I/II human trials and successful primate-challenge trials 5 months earlier in July. Billions of doses of the vaccine were ordered by September. Every week, thousands of people died while the FDA waited for more information even after we were confident that the vaccine would not hurt anybody and was likely to prevent death.
The extra information that the FDA waited months to get was not worth the tens of thousands of lives it cost. Scaling back the FDA's mandatory authority to safety and ingredient testing would correct for this deadly bias.
This isn't as radical as it may sound. The FDA didn't have efficacy requirements until 1962. Today, off-label prescriptions already operate without efficacy requirements. Doctors can prescribe a drug even if it has not gone through FDA-approved efficacy trials for the malady they are trying to cure. These off-label prescriptions
are effective, and already make up
~20% of all prescriptions written in the US. Removing mandatory efficacy trials for all drugs is equivalent to expanding this already common practice.
Now, let's get to Alex's objections. Most of
his post was focused on
my analogy between pharmaceuticals and surgery. There are compelling data and arguments on both sides and his post shifted my confidence in the validity and conclusions of the analogy downwards, but in the interest of not overinvesting in one particular analogy I'll leave that debate where it stands and focus more on Alex's general arguments in favor of the FDA.
Patent medicines and snake oil
Alex notes that we can look to the past, before the FDA was created, to get an idea of what the pharmaceutical market might look like with less FDA oversight.
Maxwell argues that in the absence of government oversight, market forces would prevent companies from pushing ineffective or harmful drugs simply to make a profit. Except that there are precedents for exactly this scenario occurring. Until they were stamped out by regulators in the early 20th century,
patent medicine hucksters sold ineffective, and sometimes literally poisonous, nostrums to desperate patients. We still use "
snake oil" today as shorthand from a scam product.
There is no denying that medicine has improved massively over the past 150 years alongside expanding regulatory oversight, but this relationship is not causal. The vast majority of gains in the quality of medical care are due to innovations like antibiotics, genome sequencing, and robotic surgery.
A tough and discerning FDA in the 1870s which allows only the best available treatments to be marketed would not have improv...