Two things that happen in the pharmaceutical industry today despite the FDA.
Many drug candidates (compounds with IND status sanctioned by the FDA ) are pushed into clinical investigation prematurely by venture capital funded biotech, that more established and careful pharma companies would stay away from. These have a high rate of failure in the clinic. This is not fraud, by the way, it is usually a combination of hubris, inexperience, and a response to the necessity of rapid returns.
Marketing wins over clinical efficacy, unless the difference is large. Tagamet was the first drug for stomach ulcers released in the late ’70s.It was rapidly overtaken by Zantac, in the ’80s, through aggressive marketing, despite minimal clinical benefit. Today there is a large industry of medical writers sponsored by the pharmaceutical industry, whose job it is to present and summarise the clinical findings on a new drug in the most favourable way possible without straying into actual falsehood.
The scientists working at the sharp end of drug discovery, who fervently believe that what they do benefits mankind (this is, I believe, a gratifyingly large proportion of them) generally respect the job the FDA do. This is despite the hoops they force us to go through. Without the FDA keeping us honest, the medicines market would be swimming with highly marketed but inadequately tested products with dubious medicinal value. Investors would be less choosy about following respected well thought-out science, when placing their money. True innovation would actually be stifled because true innovation in drug discovery only shows its value once you’ve done the hard (and expensive) yards to prove medical benefit over existing treatments. Honest and well enforced regulation forces us to do the hard yards and take no short cuts.
In 2023 55 new drugs were approved by the FDA, hardly a sign that innovation is slacking. Without regulation the figure might be ten times higher but clinicians would be left swimming in a morass of claims and counter claims without good guidance (currently generally provided by the FDA) of what treatments should be applied in which situation.
Yes, but the costs are sufficiently high that it discourages researchers from trying to create new medicines which would be broadly helpful but unprofitable. Such as better treatments and preventative medicine for diseases that only afflict poor people in underdeveloped regions.
It doesn’t have to be all or nothing. We could have a scaled back paranoia around risk, and thus allow the FDA to pass medication for vastly decreased process costs.
The question then is about trade-offs. Given that there will be QUALYs lost on either side of the decision boundary, we should seek to minimize regret. Instead we are seeking to minimize Copenhagen-ethics-style culpability, and thus incurring a lot of regret. Getting rid of the FDA entirely would shift the decision boundary, but probably too far in the opposite direction. That doesn’t mean the status quo is near optimal.
It is true that most pharma companies concentrate on indications that supply returns to offset the cost of development. The FDA does have a mechanism for Orphan Drug approval, for rare diseases, where the registration requirements are significantly lowered. According to this site 41 orphan drug approvals were made in 2023. Whether this mechanism is good enough allow the promototion of rare disease in the larger pharmaceutical industry is a good question. I wonder how many of these drugs, or their precursors, originated in academic labs,, and were then spun out to a start-up or sold on?
Orphan drugs, yes. But no program for “drugs to more cheaply prevent conditions common in poor people but completely absent in rich people.” That’s the program I’d like to see.
The FDA does not provide good guidance on what treatments should be applied in what situations. They approve drugs for a limited set of uses and that’s it. Most drugs are applied “off label” which the FDA rules that drug companies specifically cannot comment on—so not only does the FDA not provide guidance on the most common use for most medications, they actually prevent that guidance from being provided.
One reason the company might not be allowed to comment on is that they lack the knowledge in that space so would only be marketing from a basis of ignorance.
However, the FDA does not prevent such guidance as a quick look at sited like WebMD or PDR will generally include information on off label use.
My understanding is that off-label often means that the potential patient is not within the bounds of the clique of patients included in the approved clinical trials. We don’t usually perform clinical trials on children or pregnant women, for instance. Alternatively, strong scientific evidence is found that a drug works on a related disease to the actual target. It may well make sense to use drugs off label where the clinician can be comfortable that the benefits out-way the possible harms. In other cases, of course, it would be extremely poor medicine. In any case, having statistically significant and validated evidence that a drug actual does something useful, is non-negotiable IMO.
Two things that happen in the pharmaceutical industry today despite the FDA.
Many drug candidates (compounds with IND status sanctioned by the FDA ) are pushed into clinical investigation prematurely by venture capital funded biotech, that more established and careful pharma companies would stay away from. These have a high rate of failure in the clinic. This is not fraud, by the way, it is usually a combination of hubris, inexperience, and a response to the necessity of rapid returns.
Marketing wins over clinical efficacy, unless the difference is large. Tagamet was the first drug for stomach ulcers released in the late ’70s.It was rapidly overtaken by Zantac, in the ’80s, through aggressive marketing, despite minimal clinical benefit. Today there is a large industry of medical writers sponsored by the pharmaceutical industry, whose job it is to present and summarise the clinical findings on a new drug in the most favourable way possible without straying into actual falsehood.
The scientists working at the sharp end of drug discovery, who fervently believe that what they do benefits mankind (this is, I believe, a gratifyingly large proportion of them) generally respect the job the FDA do. This is despite the hoops they force us to go through. Without the FDA keeping us honest, the medicines market would be swimming with highly marketed but inadequately tested products with dubious medicinal value. Investors would be less choosy about following respected well thought-out science, when placing their money. True innovation would actually be stifled because true innovation in drug discovery only shows its value once you’ve done the hard (and expensive) yards to prove medical benefit over existing treatments. Honest and well enforced regulation forces us to do the hard yards and take no short cuts.
In 2023 55 new drugs were approved by the FDA, hardly a sign that innovation is slacking. Without regulation the figure might be ten times higher but clinicians would be left swimming in a morass of claims and counter claims without good guidance (currently generally provided by the FDA) of what treatments should be applied in which situation.
Yes, but the costs are sufficiently high that it discourages researchers from trying to create new medicines which would be broadly helpful but unprofitable. Such as better treatments and preventative medicine for diseases that only afflict poor people in underdeveloped regions. It doesn’t have to be all or nothing. We could have a scaled back paranoia around risk, and thus allow the FDA to pass medication for vastly decreased process costs. The question then is about trade-offs. Given that there will be QUALYs lost on either side of the decision boundary, we should seek to minimize regret. Instead we are seeking to minimize Copenhagen-ethics-style culpability, and thus incurring a lot of regret. Getting rid of the FDA entirely would shift the decision boundary, but probably too far in the opposite direction. That doesn’t mean the status quo is near optimal.
It is true that most pharma companies concentrate on indications that supply returns to offset the cost of development. The FDA does have a mechanism for Orphan Drug approval, for rare diseases, where the registration requirements are significantly lowered. According to this site 41 orphan drug approvals were made in 2023. Whether this mechanism is good enough allow the promototion of rare disease in the larger pharmaceutical industry is a good question. I wonder how many of these drugs, or their precursors, originated in academic labs,, and were then spun out to a start-up or sold on?
Orphan drugs, yes. But no program for “drugs to more cheaply prevent conditions common in poor people but completely absent in rich people.” That’s the program I’d like to see.
The FDA does not provide good guidance on what treatments should be applied in what situations. They approve drugs for a limited set of uses and that’s it. Most drugs are applied “off label” which the FDA rules that drug companies specifically cannot comment on—so not only does the FDA not provide guidance on the most common use for most medications, they actually prevent that guidance from being provided.
One reason the company might not be allowed to comment on is that they lack the knowledge in that space so would only be marketing from a basis of ignorance.
However, the FDA does not prevent such guidance as a quick look at sited like WebMD or PDR will generally include information on off label use.
My understanding is that off-label often means that the potential patient is not within the bounds of the clique of patients included in the approved clinical trials. We don’t usually perform clinical trials on children or pregnant women, for instance. Alternatively, strong scientific evidence is found that a drug works on a related disease to the actual target. It may well make sense to use drugs off label where the clinician can be comfortable that the benefits out-way the possible harms. In other cases, of course, it would be extremely poor medicine. In any case, having statistically significant and validated evidence that a drug actual does something useful, is non-negotiable IMO.