I’m genuinely floored by this piece. It’s not just well-researched - it’s elegantly reasoned, historically grounded, and quietly powerful in how it pulls you from anecdote to insight. You’ve taken something as complex (and often polarizing) as drug regulation and made it human, urgent, and impossible to look away from. I've never given this topic much thought, but the clarity, depth, and care in every line of your writing has made me sit up, gasp, wonder, and as with most things these, hope that reason prevails.
Thanks for a wonderful read shedding light on an important topic. Very well-crafted essay that is appealing to the biotech professionals as well as readable for a layman!
Great read. I agree with most this, but to play the devil's advocate, does FDA have no adverse effects as well overall? e.g. delaying life saving medications, etc. I'm fairly ignorant, but I suspect some smart economists must have calculated numbers on both sides of the scale: lives saved vs cut short due to FDA's lengthy approvals..
I imagine the level of scrutiny new medications get, like a massive dial knob. You don't want to be too liberal and approve drugs too early, nor too conservative / safety minded and trap innovation in forever bureaucracy cycles. You want FDA to be in a happy medium. I have a huge suspicion that our govt. apparatus is on the conservative side of this scale. The larger optimization function is not taken into account, I feel like. No government bureaucrat would want to approve the next Thalidomide, therefore tremendously incentivized to be conservative :/
Thanks, Onur! And that is such an insightful observation. I completely agree with you about the strong incentives to err on the side of safety and how that can cause missed opportunities in the window during which large trials are conducted. Two things come to mind. First, even if there was a slight bias towards safety rather than efficacy, how would that pan out on average? The clinical trial success rate in the very last stage (Phase 3) of trials still hovers around 50%. So, half of those drugs don't end up showing efficacy. But nearly all drugs have side effects. Hence, the FDA tries to play the numbers game, I believe. Their policies are probably utilitarian on average, although many individual cases will be exceptions. Also, many common diseases already have drugs that work reasonably well as a first-line option (like statins etc.). So, it keeps getting harder for new drugs to show an added benefit.
Secondly, for the more severe cases like genetic diseases and cancers, the FDA actually routinely approves drugs through something called "accelerated approval." That lets them allow marketing of drugs after smaller Phase 2 trials, conditional on a Ph3 study showing success. It's worked quite well in many cases. But unfortunately, companies have started gaming that system. Once they get approval from a small study, they keep dragging their feet and take years to run a Ph3 study because the company has no incentive to risk getting their approval repealed. And in many cases even if their Ph3 fails, they start a second study to "assure" the FDA that their new study design will find something meaningful. Meanwhile, they make billions from a drug with questionable efficacy and certain side effects.
I know it may seem like I am just only defending the FDA, which I didn't plan to do. I actually think there is a need for a lot of reform at the FDA, and more transparency especially. Many times (like with Biogen's recent Alzheimer's drug) the FDA has made some very questionable decisions that do make one wonder about bias and hidden motives. But here, my goal was to mostly highlight how complex the whole thing is. And hopefully this rambling comment reply helps reinforce at least the point that when the FDA messes up, it may be because they are struggling with the inherent complexity instead of the assumption of corruption.
I’m genuinely floored by this piece. It’s not just well-researched - it’s elegantly reasoned, historically grounded, and quietly powerful in how it pulls you from anecdote to insight. You’ve taken something as complex (and often polarizing) as drug regulation and made it human, urgent, and impossible to look away from. I've never given this topic much thought, but the clarity, depth, and care in every line of your writing has made me sit up, gasp, wonder, and as with most things these, hope that reason prevails.
Thanks so much for such a generous reading of the piece, Shradha! And for such kindness always.
Thanks for a wonderful read shedding light on an important topic. Very well-crafted essay that is appealing to the biotech professionals as well as readable for a layman!
Thank you for reading it and sharing this comment!
Great read. I agree with most this, but to play the devil's advocate, does FDA have no adverse effects as well overall? e.g. delaying life saving medications, etc. I'm fairly ignorant, but I suspect some smart economists must have calculated numbers on both sides of the scale: lives saved vs cut short due to FDA's lengthy approvals..
I imagine the level of scrutiny new medications get, like a massive dial knob. You don't want to be too liberal and approve drugs too early, nor too conservative / safety minded and trap innovation in forever bureaucracy cycles. You want FDA to be in a happy medium. I have a huge suspicion that our govt. apparatus is on the conservative side of this scale. The larger optimization function is not taken into account, I feel like. No government bureaucrat would want to approve the next Thalidomide, therefore tremendously incentivized to be conservative :/
Anyway, I know very little. Maybe FDA is great :P
Thanks, Onur! And that is such an insightful observation. I completely agree with you about the strong incentives to err on the side of safety and how that can cause missed opportunities in the window during which large trials are conducted. Two things come to mind. First, even if there was a slight bias towards safety rather than efficacy, how would that pan out on average? The clinical trial success rate in the very last stage (Phase 3) of trials still hovers around 50%. So, half of those drugs don't end up showing efficacy. But nearly all drugs have side effects. Hence, the FDA tries to play the numbers game, I believe. Their policies are probably utilitarian on average, although many individual cases will be exceptions. Also, many common diseases already have drugs that work reasonably well as a first-line option (like statins etc.). So, it keeps getting harder for new drugs to show an added benefit.
Secondly, for the more severe cases like genetic diseases and cancers, the FDA actually routinely approves drugs through something called "accelerated approval." That lets them allow marketing of drugs after smaller Phase 2 trials, conditional on a Ph3 study showing success. It's worked quite well in many cases. But unfortunately, companies have started gaming that system. Once they get approval from a small study, they keep dragging their feet and take years to run a Ph3 study because the company has no incentive to risk getting their approval repealed. And in many cases even if their Ph3 fails, they start a second study to "assure" the FDA that their new study design will find something meaningful. Meanwhile, they make billions from a drug with questionable efficacy and certain side effects.
I know it may seem like I am just only defending the FDA, which I didn't plan to do. I actually think there is a need for a lot of reform at the FDA, and more transparency especially. Many times (like with Biogen's recent Alzheimer's drug) the FDA has made some very questionable decisions that do make one wonder about bias and hidden motives. But here, my goal was to mostly highlight how complex the whole thing is. And hopefully this rambling comment reply helps reinforce at least the point that when the FDA messes up, it may be because they are struggling with the inherent complexity instead of the assumption of corruption.
Thanks again for commenting, buddy!
This is very enlightening. Thanks Gairik!
I see. I think to me this addendum makes me understand and appreciate the post better.