(2021-08-04) Alexander Adumbrations Of Aducanumab
Given that the FDA fast-track approved a sketchy drug which might not work, it’s fair to wonder if their standards have gotten too lax - or at least if they should stop fast-tracking things. The Atlantic article dutifully makes this case via a somewhat labored global warming metaphor.
While I acknowledge that aducanumab probably sucks, I think the Atlantic article and its global warming metaphor are totally off base. Nobody in the “FDA is too strict” camp has written a rebuttal yet, so I want to try my hand at this.
The Atlantic article says that “The FDA’s standards began to slide in the late 1980s and early ’90s” with the fast-track approval of AIDS drugs:
The article acknowledges that the AIDS drugs actually worked out great - they in fact cured AIDS effectively and saved lots of lives. “But”, it concludes, "that level of success is not at all the norm."
Here’s another good example: coronavirus vaccines. The FDA still has not fully approved any coronavirus vaccine. The only reason you’re allowed to get vaccinated anyway is because of a fast-track provisional approval somewhat like the one used for aducanumab. Coronavirus vaccines have probably also averted a few hundred thousand deaths.
It’s just something that happens sometimes and doesn’t happen sometimes. So how often do you have to save hundreds of thousands of lives before it’s worth the risk of occasionally also permitting a dud medication that “offers false hope”? How is this even a question?
How many lives would have been saved if good drugs had been released a few years earlier, versus how many lives would have been lost by missing dangerous side effects or approving duds?
And these kinds of analyses, while good, can only count the drugs we know about. The real cost is the thousands of life-saving medications that are stillborn because nobody wants to go through the literally-one-billion-dollars-per-drug FDA approval process.
Could the US have done equally well?
when the US declared that the coronavirus was a “public health emergency”, the FDA announced that the emergency was so grave that they were banning all coronavirus testing, so that nobody could take advantage of the emergency to peddle shoddy tests. Perhaps you might feel like this is exactly the opposite of what you should do during an emergency? This is a sure sign that you will never work for the FDA.
By March 1, China was testing millions of people a week, South Korea had tested 65,000 people, and the USA had done a grand total of 459 coronavirus tests
NYT did a great article on Dr. Helen Chu, a doctor in Seattle who was running a study on flu prevalence back in February 2020, when nobody thought the coronavirus was in the US. She realized that she could test her flu samples for coronavirus, did it, and sure enough discovered that COVID had reached the US. The FDA sprung into action, awarded her a medal for her initiative, and - haha, no, they shut her down because they hadn’t approved her lab for coronavirus testing.
I worry that people are going to come away from this with some conclusion like “wow, the FDA seemed really unprepared to handle COVID.” No. It’s not that specific. Every single thing the FDA does is like this
A while back I learned about Infant Short Bowel Syndrome
The FDA approved an early draft of the nutrient fluid, but it didn’t have enough fish oil
Around the late 90s/early 00s, researchers figured out what was going on and recommended adding fish oil to the IV fluid. The FDA responded that they had only approved the non-fish-oil version
Around 2010, Boston Children’s Hospital found some loophole that let them add fish oil to their nutrient fluid on site
Around 2015 the FDA said that if your doctor applied for a special exemption, they would let you import the correct nutritional fluid from Europe
Finally in 2018 the FDA got around to approving the corrected nutritional fluid and now babies with short bowel syndrome do fine, after twenty years of easily preventable state-mandated deaths
But How Can The FDA Be Too Strict And Not Strict Enough At The Same Time? Very easily! Lots of things are too strict and not strict enough at the same time! I wrote a whole article on this! 2014-09-17-AlexanderJointOverAndUnderdiagnosis
Consider the police.
Are the police too strict, or not strict enough? I don’t think there’s a good answer to this question. I would rather say the police are bad at their job.
My own profession is little better, as I’ve discussed before. Many people get diagnosed with psychiatric diseases and pumped full of medication when they shouldn’t be. Other people don’t get diagnosed with psychiatric diseases or treated with medication even when they desperately need it.
if anyone ever gives you control of the FDA Lever, you should definitely absolutely for the love of God push it as far toward LESS as it is possible for it to go
But I have to admit that this isn’t costless
Is there some better solution?
I think that given their mandate - approve drugs that definitely work, reject ones that are unsafe/ineffective, expect people to freak out and demand your head if any unsafe/ineffective drug gets through, nobody will care no matter how many lifesaving treatments you delay or stifle outright - they’re doing the best they can
And it’s hard to even blame the people who set the FDA’s mandate. They’re also doing the best they can given what kind of country / what kind of people we are.
The FDA mandate is set the same way (as the Global War On Terror) - we’re open to paying limitless costs, as long as it lets us avoid a very specific kind of scandal which the media will turn into 24-7 humiliation of whoever let it happen
So the long-term solution is to become a different kind of country and different sorts of people - eg raise the sanity waterline.
But until then, are there any small changes that would help around the edges?
The most plausible small change I can think of is to unbundle FDA approval.
why exactly are we expecting lots of people to spend $50,000/year on this drug?
The answer is: to a first approximation, health insurance companies have to cover anything the FDA approves. I don’t understand the exact legalities of this, but it seems basically literally true for Medicare and Medicaid, and de facto approximates being true for private insurers
Once an insurance company agrees to cover a drug, neither the patient nor the doctor has any incentive to avoid it just because it costs $50,000.
So when I talk about unbundling FDA approval, I mean that instead of the FDA approving the following bundle of things… It’s legal for doctors to prescribe a drug; It is mandatory for insurances to cover a drug.
…the FDA can say one of those two things, but not the other.
There’s a third thing it might be helpful to unbundle, one we’re already secretly unbundling.
people might stop trusting the FDA... They feel like if they ever allow even one bad drug through, then in the eyes of the public all kinds of anti-vax hysteria and vaccines-cause-autism bullshit will be retroactively justified, and public health officials will never have any authority ever again. If you model all FDA/CDC/etc policy as an attempt to avert this outcome, your predictions will be right more often than not.
means that public policy will forever be held hostage to the whims of the stupidest person around.
So maybe a third thing we could unbundle is: The FDA is staking its entire reputation on this drug.
I think that unbundling is what the FDA is trying to do right now with COVID-19 vaccines. They approve them for emergency use. If future evidence proves the vaccines safe, then good, we got them. If future evidence proves the vaccines unsafe, then the FDA can say “yeah, well, technically we never said they were safe, so this doesn’t mean we’re ever wrong”.
Maybe it’s expecting too much of the American people, but I wish the FDA could lean into this strategy.
Grant drugs one-star, two-star, etc approvals
Then you could attach different legal rights and requirements to each of those.
People are really scared of this solution, because it introduces choice into this system. If you say that insurance companies are allowed to cover a certain drug, but not forced to do so, then different insurances will cover different drugs, and you’ll have the usual capitalism / free market thing. Patients will have to choose which insurance to get without necessarily knowing very much about medicine, and maybe companies will try to trick or exploit them, and maybe the patients will make the wrong choice.
This is the nightmare scenario that the existing US health system exists to avoid. I know you can think of lots of different ways that changing things could go wrong, and so can I. But I can’t stress enough how often the current system results in things going wrong that nobody thought of because they are too stupid to even imagine possible.