In total, Thalidomide caused around 2,000 deaths and 10,000 birth defects. Compare that to the 100,000 people that the FDA killed by not approving a single beta blocker sooner. The FDA waited until 1981 to let doctors prescribe Timolol to prevent heart attacks. Stunningly, the FDA bragged that approving Timolol would save up to 17,000 lives a year.[1] That same drug had been in use in Europe since the mid-70s, meaning that the FDA tacitly admitted to killing 100,000 people by forbidding its use in the US. Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people.
The FDA is also the reason why epi-pens are so expensive[2], why Martin Shkreli was able to jack up the price of Daraprim[3], why many drugs suffer from shortages[4], and why home testing for covid was delayed for so long[5]. And don't forget that covid community spread was discovered in February of 2020 only because researchers risked jail time by violating the FDA's prohibition on testing.[6]
Yes, the FDA lets leaders avoid an occasional political snafu. But the organization kills far more people than it saves.
So, defensive language aside, I think that the FDA has a point in its white paper. The reason we don’t have cures for a lot of diseases is not so much that pesky regulations keep great drugs from getting to the market. It’s that we don’t know enough – yep, even in 2015 – to make so many great drugs.
Now, when I mentioned that we’d surely have killed off more people by doing drug research by the more direct routes, the reply is that we’ve been killing people off by moving too slowly as well. That’s a valid argument. But under the current system, we choose to have people die passively, through mechanisms of disease that are already operating, while under the full-speed-ahead approaches, we might lower that number by instead killing off some others in a more active manner. It’s typically human of us to choose the former strategy. The big questions are how many people would die in each category as we moved up and down the range between the two extremes, and what level of each casualty count we’d find “acceptable”.
So while it’s not crazy to say that we should be less risk-averse, I think it is silly to say that the FDA is the only (or even main) thing holding us back. I think that this has a tendency to bring on both unnecessary anger directed at the agency, and raise unfulfillable hopes in regards to what the industry can do in the near term. Neither of those seem useful to me.
The replies to my comment here nicely delimit the cleft stick the FDA is in. You are on the "oh, god, just let them try it already! the FDA are stick in the mud beancounters just holding everyone back" side.
A few others are on the "But this one time, they didn't pull Vioxx fast enough, and look at what it got us!!" side.
For myself, I'm glad that 1. i don't have to walk that tightrope and 2. there are enough people to make an institution old enough to have memory that _do_ walk that tightrope.
But i'm pretty sure that sanity is somewhere in the middle, case by case, agonizingly slow clinical trial by agonizingly slow clinical trial.
"So while it’s not crazy to say that we should be less risk-averse"
Surely the way around that is to expand temporary/experimental approvals. This would require the patient to be properly and adequately informed of the risks of taking any new drug after which he/she would sign consent which would indemnify pharma, researchers, FDA etc.
That said, any such approach should be very tightly controlled to ensure unethical cowboys in the pharma industry don't take advantage of it.
"You hereby acknowledge that neither the safety nor efficacy of this....procedure/substance has not been established. As a result of taking it, literally anything could happen to you and/or your future unborn children."
It is already really hard to assess costs and benefits of medical treatments; expecting an ordinary person--dealing with a scary diagnosis--to do so with even less information seems ethically...fraught.
Given your quoted text was written by hprotagonist, perhaps you should be addressing him in the first instance rather than me. But then you've also addressed me by asking 'What would that consent form look like?' and that impinges on or is inferred from what I said in reply to hprotagonist.
That said, as I've addressed the matter of the wonderful Frances Kelsey and her rigorous approach to the approval of thalidomide, I will address issue of experimental treatments more in general as well as emphasizing same issues with respect to COVID-19 and the ongoing shemozzle that surrounds them.
As with the Frances Kelsey/thalidomide matter where the outcome could have been truly disastrous for thousands of unborn kids if Kelsey had not dealt with it as a matter of urgency and that she had done so with rigor and tenacity, a similar situation exists with the various therapies for COVID-19, especially those that are truly experimental and or have not yet demonstrated their medical effectiveness. As you rightly acknowledge when you quote hprotagonist where he says "that neither the safety nor efficacy of this....procedure/substance has not been established. As a result of taking it, literally anything could happen to you and/or your future unborn children."
As with just about any vexing matter, I'd assert that the key issues always involve both its magnitude and our perceived urgency to rectify it, thus it's the product of both that will determine how soon and how proactively we will act. As COVID-19 is an out-of-control pandemic that continues to kill people on mass, we are forced to act urgently in order to stem its spread. This call to urgent action alters everything, as it has now forces us to undertake risks that are not normally associated with responsible prudent behaviour.
As I mentioned in an earlier post on a different issue, 'desperate times call for desperate measures'—and with desperate measures come very considerable risks. Moreover, with COVID-19, when it comes to weighing up options, the luxury of time is not on our side. And as we've seen everywhere, that has had a considerable and often very detrimental bearing on the ways we've responded to the pandemic not to mention the many decisions we've already made in our attempts to combat it.
Such experiences are not new to human beings, as we've faced many similar situations in the past. The problem here however is that we've not learned much from the fact. For instance, we could have drawn valuable knowledge from well-established protocols that have evolved from battlefield triage experience. Here, ambulance personnel, stretcher-bearers and medicos charged with aiding the wounded and dying face terrible extremes that they would never experience in normal life. As an experience, it's as bad as it ever gets, and that's why it's such a worthwhile and relevant example in our ongoing battle with COVID-19. Moreover, tragically, such experience is all too commonplace (thus it's a realistic one): as the history of warfare shows, battlefield triage situations have occurred many hundreds and hundreds—if not thousands—of times in the past, and no doubt, they will continue to occur repeatedly into the future. Not learning from the experience of history is a form collective madness.
There is any number of instances where with enormous courage and often without previous experience, rescuers have had to make decisive life-changing decisions in an instant—an instant that encompasses anything and everything that's truly relevant at this point, from triage decisions and concomitant actions thereof, to considerations of one's own safety and the safety of others around one, to one's own ethical behaviour and related humanitarian considerations. Moreover, rescuers not only have to remain self-composed to adequately manage the enormous stress they are under but also they must remain capable of performing their appalling and arduous task without fail, and for that, they call heavily on their training.
As a medico in a war triage situation, you will be surrounded with dozens of wounded and dying soldiers and you'll only have split seconds to decide between those who may likely live and thus be rescued and those who you will have to leave out on the battlefield to die—and you'll have to do all that almost automatically as you'll have precious little time to think through your actions. Right, you will find yourself in an ethically fraught situation—one that's as ghastly and truly horrible as it's ever possible to be in.
This is where training is crucial—vitally important. You will have been trained to be decisive, objective and as unemotional as it's possible to be in these circumstances in order that you will not only save as many lives as is humanly possible but also later to stop you going mad from PTSD—or at least ameliorating its effect (as you can comfort yourself from knowing that you've performed your duty to the extent of doing everything humanly possible in extremely difficult circumstances).
The logistics of introducing new and untested procures into the treatment of COVID-19 are similar to the triage scenario mentioned above. As a professional involved in the decision-making process, one would have to quickly weigh up the potential benefits that any new procedure would likely bring for the patient against possible unforeseen and potentially life threatening risks—and then be honest and as forthright as is possible with the patient by explaining everything.
One's decisions will involve risks and sometimes they will be wrong and will result in disastrous consequences, at other times one's decisions will be correct but force majeure—an act of God will intervene and things will go horribly wrong. One may even make correct decisions based on the best advice available but ultimately in the light of further experience, this advice may also prove to be wrong.
What one cannot do is to procrastinate or vacillate around making hard decisions, or failing to make them at all, or by watering them down because of nonsensical political reasons. For as we have all too often seen in the recent past, these dubious and hesitant actions have cost many, many lives. As all us know by now, this deadly virus waits for no one.
With COVID-19, we are in new territory. Only later after the results of our present decisions and actions have been properly assessed, and after the statisticians have analyzed the data contained within their integrands, that a new best practice will be established for this current COVID-19 scenario.
In the interim, we have to act as professionally as is possible by not only taking the best advice available but also by making informed decisions based actual evidence gathered from procedures and things that have already been demonstrated to work.
By acting in as truly professional manner as is humanly possible, it is unlikely that your worst dreamt scenario that 'literally anything could happen' will, in fact, actually happen.
Taking the median of public opinion does not result in an accurate understanding of reality. The FDA optimizes for minimizing scandals, not for helping people. That’s why they kill 100x more people by not approving good things than they do by approving bad things.
"Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people."
I was unaware that propranolol was approved as late as that in the US. This seems very strange as Sir James Black's work on propranolol was widely known and he was widely respected before he was knighted and awarded the Nobel Prize for his work with both propranolol and cimetidine.
Why on earth did the FDA take so long to approve it given that there was no other beta blocker available at the time? (Thus, the hypertension issue could easily have been perceived as a crisis even allowing propranolol to be, say, approved on a temporary basis much earlier on.)
Looking at the FDA's record of approvals, it's hard to see any consistent granularity in its approach. I'm curious as to why this may be the case.
The article you reference mentions a major Norwegian study showing that it prevents death had just concluded. So the FDA was acting on fresh data.
In addition, timolol is one of many molecules in the beta-blocker class and propranolol, another beta-blocker, was already approved in the US since 1973. And from a quick cursory google search, it appears there is no difference between the two when it comes to reducing hypertension and future risk of heart attacks.
The FDA approved propranolol in 1973, but not for treatment of hypertension or angina. It wasn't until 1978 that they allowed beta blockers to treat those diseases (which are the bulk of lives saved by beta blockers).
The WaPo article does talk about a study that had just concluded, but Timolol had been studied for over a decade previously, and had been used in Europe for years. I didn't have to look hard to find a US study done in 1976 that praised Timolol's effectiveness in protecting cardiac muscle after a heart attack.[1]
If you doubt that Timolol is far more effective at preventing heart attacks than propranolol, then why believe the rest of the WaPo article? It references a study that you can't find on the Internet because it was published over 40 years ago.
The bottom line is this: Despite the drug being considered safe by the relevant European authorities, the FDA forbade US doctors from prescribing it. Had the FDA simply allowed doctors to prescribe compounds approved by their European counterparts, they would have avoided tens of thousands of deaths.
But the FDA does not dictate how drugs can be used, only whether they can be marketed and sold. There is nothing stopping a physician in the US from using propranolol for preventing heart attacks before the FDA gives its blessing for that use.
If you look at cancer treatments today most uses (not drugs, uses) are not formally approved by the FDA. It all based on research, publications and guidelines.
Sure, but that kind of makes sense for why the FDA acts like they do, if you want more risky off-label treatments without the large studies the FDA requires, your doctor (and you) can take the risk at your (and their) option.
The FDA is also the reason why epi-pens are so expensive[2], why Martin Shkreli was able to jack up the price of Daraprim[3], why many drugs suffer from shortages[4], and why home testing for covid was delayed for so long[5]. And don't forget that covid community spread was discovered in February of 2020 only because researchers risked jail time by violating the FDA's prohibition on testing.[6]
Yes, the FDA lets leaders avoid an occasional political snafu. But the organization kills far more people than it saves.
1. https://www.washingtonpost.com/archive/politics/1981/11/26/d...
2. https://slatestarcodex.com/2016/08/29/reverse-voxsplaining-d...
3. https://slatestarcodex.com/2015/09/24/the-problems-with-gene...
4. https://slatestarcodex.com/2019/04/30/buspirone-shortage-in-...
5. https://www.nytimes.com/2020/05/15/us/coronavirus-testing-se...
6. https://www.nytimes.com/2020/03/10/us/coronavirus-testing-de...