FDA Dangles Golden Ticket to Spur Drugs for Neglected Diseases(npr.org)
npr.org
FDA Dangles Golden Ticket to Spur Drugs for Neglected Diseases
http://www.npr.org/blogs/health/2014/05/16/291972744/fda-dangles-golden-ticket-to-spur-drugs-for-neglected-diseases
34 comments
This isn't the only fast track program the FDA has. While they might not be the most flexible organization, at least they are probably thinking in terms of risk/benefit to the public rather than in terms of safe/unsafe.
[deleted]
The FDA has probably caused more deaths in the past half century than all of the rest of the American state put together, wars and all, by slowing progress in medicine, making all sorts of avenues for research and development unprofitable, and making medicine that does exist far more expensive.
Regulators at the FDA are capricious and malign, and there are countless stories of petty revenge via increased demands for data and enormous imposed costs in time and money. This is the way things always go in the late stages of centralized, powerful bureaucracy with a side order of regulatory capture.
The only good thing I can find to say about the bureaucrats at the FDA is that they respond to regional regulatory arbitrage - to medical tourism - by loosening their grip and letting things through. Or at least they do when said treatments are so widely available elsewhere in the world that the risk of looking bad by continuing to block them in the US is worse than the risk of looking bad because one of the outcomes of a normal, low error rate in medicine gets picked up by the press. Look at simple stem cell transplants, now available in the US these last couple of years, for a good example of this in practice.
Regulators at the FDA are capricious and malign, and there are countless stories of petty revenge via increased demands for data and enormous imposed costs in time and money. This is the way things always go in the late stages of centralized, powerful bureaucracy with a side order of regulatory capture.
The only good thing I can find to say about the bureaucrats at the FDA is that they respond to regional regulatory arbitrage - to medical tourism - by loosening their grip and letting things through. Or at least they do when said treatments are so widely available elsewhere in the world that the risk of looking bad by continuing to block them in the US is worse than the risk of looking bad because one of the outcomes of a normal, low error rate in medicine gets picked up by the press. Look at simple stem cell transplants, now available in the US these last couple of years, for a good example of this in practice.
The FDA has more than likely directly prevented hundreds of millions deaths worldwide. It's literally one of very few safeguards you can rely on to know that you're not eating poison.
Amusingly, the top comment on a front page HN post [1] right now concerns one of the first court cases [2] that gave FDA some real power. Before this case, companies could sell a poison like emetic tartar and market it as a hangover drug. Selling stuff like this still happens today in countries without an FDA equivalent. [3] It even happens in countries with a drug regulatory body, but one that's weak. [4]
As with all regulation, there's a balance between benefit/risk. As you point out, there is a financial and time burden of regulation. But with warts and all, the work that the FDA has done and currently does far outweighs these burdens.
> The only good thing I can find to say about the bureaucrats at the FDA is that they respond to regional regulatory arbitrage - to medical tourism - by loosening their grip and letting things through. Or at least they do when said treatments are so widely available elsewhere in the world that the risk of looking bad by continuing to block them in the US is worse than the risk of looking bad because one of the outcomes of a normal, low error rate in medicine gets picked up by the press. Look at simple stem cell transplants, now available in the US these last couple of years, for a good example of this in practice.
I'm not quite sure how to respond to this rant. But I'll point out findings from a 2012 NEJM study comparing the FDA to the EU's EMA and Canada's Health Canada: [5]
"RESULTS: There were 510 applications for novel therapeutic agents approved from 2001 through 2010 — 225 by the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there were 289 unique agents. The median length of time for completion of the first review was 303 days (interquartile range, 185 to 372) for applications approved by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health Canada (P<0.001 for the comparison across the three agencies). The median total review time was also shorter at the FDA than at the EMA or Health Canada (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in both the United States and Europe (either by the EMA or through the mutual recognition process), of which 121 (63.7%) were first approved in the United States; similarly, 154 were approved in both the United States and Canada, of which 132 (85.7%) were first approved in the United States."
[1] https://news.ycombinator.com/item?id=7758508
[2] https://en.wikipedia.org/wiki/United_States_v._11_1/4_Dozen_...
[3] http://ijp-online.com/article.asp?issn=0253-7613;year=2007;v...
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1151014/
[5] http://www.nejm.org/doi/full/10.1056/NEJMsa1200223
Amusingly, the top comment on a front page HN post [1] right now concerns one of the first court cases [2] that gave FDA some real power. Before this case, companies could sell a poison like emetic tartar and market it as a hangover drug. Selling stuff like this still happens today in countries without an FDA equivalent. [3] It even happens in countries with a drug regulatory body, but one that's weak. [4]
As with all regulation, there's a balance between benefit/risk. As you point out, there is a financial and time burden of regulation. But with warts and all, the work that the FDA has done and currently does far outweighs these burdens.
> The only good thing I can find to say about the bureaucrats at the FDA is that they respond to regional regulatory arbitrage - to medical tourism - by loosening their grip and letting things through. Or at least they do when said treatments are so widely available elsewhere in the world that the risk of looking bad by continuing to block them in the US is worse than the risk of looking bad because one of the outcomes of a normal, low error rate in medicine gets picked up by the press. Look at simple stem cell transplants, now available in the US these last couple of years, for a good example of this in practice.
I'm not quite sure how to respond to this rant. But I'll point out findings from a 2012 NEJM study comparing the FDA to the EU's EMA and Canada's Health Canada: [5]
"RESULTS: There were 510 applications for novel therapeutic agents approved from 2001 through 2010 — 225 by the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there were 289 unique agents. The median length of time for completion of the first review was 303 days (interquartile range, 185 to 372) for applications approved by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health Canada (P<0.001 for the comparison across the three agencies). The median total review time was also shorter at the FDA than at the EMA or Health Canada (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in both the United States and Europe (either by the EMA or through the mutual recognition process), of which 121 (63.7%) were first approved in the United States; similarly, 154 were approved in both the United States and Canada, of which 132 (85.7%) were first approved in the United States."
[1] https://news.ycombinator.com/item?id=7758508
[2] https://en.wikipedia.org/wiki/United_States_v._11_1/4_Dozen_...
[3] http://ijp-online.com/article.asp?issn=0253-7613;year=2007;v...
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1151014/
[5] http://www.nejm.org/doi/full/10.1056/NEJMsa1200223
>The FDA has probably caused more deaths in the past half century than all of the rest of the American state put together, wars and all, by slowing progress in medicine, making all sorts of avenues for research and development unprofitable, and making medicine that does exist far more expensive.
As long as we're throwing around bullshit: false hope and pseudoscience has caused more unnecessary death at the hands of tricksters and con men in the past two thousand years than all wars humans have fought or ever will fight.
Having worked in biotech I was never a fan of some (or many) of the FDA's policies but I found this insulting. You have no clue how hard it is to develop any medicine that doesn't harm the first few patients you give it to, let alone one that actually reaches the market to help thousands or millions. You have no clue what it is like to be the only gatekeeper between a $900 billion industry working on some of the hardest scientific problems of our time and 300 million people. Almost all of whom want their cake, to eat it now, and for the calories to magically disappear from their gastrointestinal tract.
The FDA is not a product of pharmaceutical companies, it is a product of a political system made of voters like you who decide their policies based on Libertarian pamphlets, Fox News, and Reddit. A political system that allows pharmaceutical companies to selectively withhold data, that has gutted the basic scientific research institutions that allows pharma to finance billion dollar ventures, and that mercilessly punishes any mistake that it itself is supposed to catch.
You get what you vote for.
As long as we're throwing around bullshit: false hope and pseudoscience has caused more unnecessary death at the hands of tricksters and con men in the past two thousand years than all wars humans have fought or ever will fight.
Having worked in biotech I was never a fan of some (or many) of the FDA's policies but I found this insulting. You have no clue how hard it is to develop any medicine that doesn't harm the first few patients you give it to, let alone one that actually reaches the market to help thousands or millions. You have no clue what it is like to be the only gatekeeper between a $900 billion industry working on some of the hardest scientific problems of our time and 300 million people. Almost all of whom want their cake, to eat it now, and for the calories to magically disappear from their gastrointestinal tract.
The FDA is not a product of pharmaceutical companies, it is a product of a political system made of voters like you who decide their policies based on Libertarian pamphlets, Fox News, and Reddit. A political system that allows pharmaceutical companies to selectively withhold data, that has gutted the basic scientific research institutions that allows pharma to finance billion dollar ventures, and that mercilessly punishes any mistake that it itself is supposed to catch.
You get what you vote for.
This was written by people who are much closer to your viewpoints on economic freedom than mine. They are very mild and conservative in their estimations of cost in lives. I suggest you read it:
http://fdareview.org/harm.shtml
The delay and large reduction in the total number of new drugs has had terrible consequences. It is difficult to estimate how many lives the post-1962 FDA controls have cost, but the number is likely to be substantial; Gieringer (1985) estimates the loss of life from delay alone to be in the hundreds of thousands (not to mention millions of patients who endured unnecessary morbidity). When we look back to the pre-1962 period, do we find anything like this tragedy? The historical record—decades of a relatively free market up to 1962—shows that voluntary institutions, the tort system, and the pre-1962 FDA succeeded in keeping unsafe drugs to a low level. The Elixir Sulfanilamide tragedy, in which 107 people died, was the worst of those decades. Every life lost is important, but the grisly comparison is necessary. The number of victims of Elixir Sulfanilamide tragedy and of all other drug tragedies prior to 1962 is very small compared to the death toll of the post-1962 FDA.
http://fdareview.org/harm.shtml
The delay and large reduction in the total number of new drugs has had terrible consequences. It is difficult to estimate how many lives the post-1962 FDA controls have cost, but the number is likely to be substantial; Gieringer (1985) estimates the loss of life from delay alone to be in the hundreds of thousands (not to mention millions of patients who endured unnecessary morbidity). When we look back to the pre-1962 period, do we find anything like this tragedy? The historical record—decades of a relatively free market up to 1962—shows that voluntary institutions, the tort system, and the pre-1962 FDA succeeded in keeping unsafe drugs to a low level. The Elixir Sulfanilamide tragedy, in which 107 people died, was the worst of those decades. Every life lost is important, but the grisly comparison is necessary. The number of victims of Elixir Sulfanilamide tragedy and of all other drug tragedies prior to 1962 is very small compared to the death toll of the post-1962 FDA.
I watched someone die of cancer possibly years too soon because it took Genentech an extra two years to get approval for Avastin for his condition, volunteered for a patients rights NGO, and worked in several companies heavily regulated by the FDA. I know all too well about the cost in human lives of not just the FDA but the companies who gouge customers on the cost of insurance, medical equipment, and even the basic technology needed to look closely at a cell in an academic lab.
You can talk about the economics of human lives but the reality is simple: removing the FDA won't bring on a Golden Age of medicine that will bring back the dead. Instead, the companies developing the medicine that can actually save people, companies that are now "delayed" and overburdened by regulation, will be beaten down by a market of charlatans with big marketing budgets and limited liability.
Thanks to Facebook, I know of half a dozen former classmates who have close relatives that lost years of their lives because they chose to listen to some neo naturalist instead of their oncologist. That is the alternative. It already exists and destroying the FDA would unleash the flood of crazy that it has tried, with so little actual support, to hold back for all these years.
You can talk about the economics of human lives but the reality is simple: removing the FDA won't bring on a Golden Age of medicine that will bring back the dead. Instead, the companies developing the medicine that can actually save people, companies that are now "delayed" and overburdened by regulation, will be beaten down by a market of charlatans with big marketing budgets and limited liability.
Thanks to Facebook, I know of half a dozen former classmates who have close relatives that lost years of their lives because they chose to listen to some neo naturalist instead of their oncologist. That is the alternative. It already exists and destroying the FDA would unleash the flood of crazy that it has tried, with so little actual support, to hold back for all these years.
This is not a binary issue. I don't see why we can ban alternative medicine and have some regulations, but make them more reasonable.
I wasn't arguing against constantly reviewing effectiveness and reassessing regulation, I was responding to the vilification of a consumer protection agency by someone who does not have the credentials to be deciding what "reasonable" is in this context.
The pharmaceutical industry was doing extremely well until the 1990s - that's 35 years of success despite the FDA. Now what it is that caused the pharma crisis that started in 2003 I do not know.
Is it the fact that the easy fruits have all been picked, there is nothing left to be discovered because everything at market already does a good job at a much better price point than any new drug? Or is it the fact that Pharma doesn't produce on a timescale that Wall Street likes, or both? Hell, Facebook is valued like Pfizer, but Facebook gives faster returns on capital.
Your argument is completely at odds with observable facts.
Is it the fact that the easy fruits have all been picked, there is nothing left to be discovered because everything at market already does a good job at a much better price point than any new drug? Or is it the fact that Pharma doesn't produce on a timescale that Wall Street likes, or both? Hell, Facebook is valued like Pfizer, but Facebook gives faster returns on capital.
Your argument is completely at odds with observable facts.
Consider that direct-to-consumer marketing of pharmaceuticals was allowed in the US in 1997. Is it so surprising that the new drug pipeline started drying up a few years later?
Currently, marketing budgets dwarf R&D budgets at the large pharma companies, so I don't expect the situation to improve any time soon.
Currently, marketing budgets dwarf R&D budgets at the large pharma companies, so I don't expect the situation to improve any time soon.
After all the red tape, prescription Drugs still Kill Over 100,000 People Each Year which is vastly higher than your estimate.
Sure, looser regulations might save some lives but so does not using a seat belt. The only sane way to do such comparisons is by looking at both lives saved and lost. And if your looking at the Cost/befit of something you can't use a baseline of other countries without including their costs as well.
Edit: To be clear it's a huge but subtle point. If the FDA saves 10k more lives than X, and costs a total of 20k lives you have no idea if it's better than nothing without knowing X.
Sure, looser regulations might save some lives but so does not using a seat belt. The only sane way to do such comparisons is by looking at both lives saved and lost. And if your looking at the Cost/befit of something you can't use a baseline of other countries without including their costs as well.
Edit: To be clear it's a huge but subtle point. If the FDA saves 10k more lives than X, and costs a total of 20k lives you have no idea if it's better than nothing without knowing X.
The FDA is not elected, or even indirectly elected. They are career bureaucrats with career tenure who cannot be fired. How would you even know that they are doing a good job? Last I looked, Americans have terrible health care relative to other countries; the FDA has no responsibilit for that?
You must be kidding, right? The for the last 20-30 years the head of the FDA has been a very volatile position covered with public scandals and the agency has an insane turn over rate due to the structure, workload, and public pressure [1].
Actually it looks like the developed countries with more, better treated bureaucrats are doing far better.
[1] http://www.washingtonpost.com/r/2010-2019/WashingtonPost/201...
Actually it looks like the developed countries with more, better treated bureaucrats are doing far better.
[1] http://www.washingtonpost.com/r/2010-2019/WashingtonPost/201...
Access to healthcare is firmly in the bailiwick of Congress. Hell, the rest of the First World has similar authorities that determine what drug gets to market, their criteria are similar, and their healthcare metrics aren't nearly as awful as the United States.
And for the "career bureaucrats", if you want a modicum of stability you need them, you can't have elections or change the rules every other year - what you need is institutional memory and predictability.
And for the "career bureaucrats", if you want a modicum of stability you need them, you can't have elections or change the rules every other year - what you need is institutional memory and predictability.
To be honest, I doubt drugs make sense for all diseases. Autism may not have one single cure for example.
I appreciate people not being crippled or killed by poisonous patent medicines, myself. Or by untested procedures, or harmful implants and cosmetic surgeries, etc.
It would be better if the FDA had more power over largely fraudulent markets like homeopathy, naturopathy, herbal medicine, etc. But for the time being those scams are largely unrestricted.
It would be better if the FDA had more power over largely fraudulent markets like homeopathy, naturopathy, herbal medicine, etc. But for the time being those scams are largely unrestricted.
But do it carefully. Has probiotics ever harmed anyone for example?
It's not regulated so we haven't studied it enough but yes, it's called probiotic sepsis [1].
[1] http://ajcn.nutrition.org/content/83/6/1256.long
[1] http://ajcn.nutrition.org/content/83/6/1256.long
I'm intensely grateful for the FDA.
I'm alive because of experimental treatments (bone marrow transplant), monitored by the FDA and others. At the time, patients with my profile had 90% mortality.
I will tell you firsthand, and watching my hospital friends die, that in most cases, the cure is at least as bad as the disease. Which is why doctors, who would know best, often choose to go out with grace (no heroic measures).
And yet science marches on.
Today BMTs are routine and in some cases are practically outpatient treatments.
The development and approval of new drugs and therapies are exactly as fast as they should be. Want something faster, then work towards it.
In other words: less talk, more walk.
I'm alive because of experimental treatments (bone marrow transplant), monitored by the FDA and others. At the time, patients with my profile had 90% mortality.
I will tell you firsthand, and watching my hospital friends die, that in most cases, the cure is at least as bad as the disease. Which is why doctors, who would know best, often choose to go out with grace (no heroic measures).
And yet science marches on.
Today BMTs are routine and in some cases are practically outpatient treatments.
The development and approval of new drugs and therapies are exactly as fast as they should be. Want something faster, then work towards it.
In other words: less talk, more walk.
We'd probably be better off if every drug got a priority review. The FDA's incentives are warped: they get blamed for releasing a drug that causes harm, but receive little blame if a drug that would have prevented harm is delayed or not released.
To be fair, those kinds of stories usually play out in the financial news around drug companies, many of which have lobbyists and a team whose job it is to make sure they can get their drugs through.
Why don't we spend $10M to bolster the review team and clear the queue instead of creating $150M worth of perverted incentives that the companies will inevitably recoup from the health care system? Medicaid alone will probably pay more than it would take in salaries for qualified people to process applications.
> Why don't we spend $10M to bolster the review team and clear the queue instead of creating $150M worth of perverted incentives that the companies will inevitably recoup from the health care system?
Because:
1. the $10 million would come out of the FDA's budget while the $150 million doesn't; and
2. spending $10 million to clear the queue would do nothing to incentivise drug development for neglected diseases, such as leishmaniasis.
Because:
1. the $10 million would come out of the FDA's budget while the $150 million doesn't; and
2. spending $10 million to clear the queue would do nothing to incentivise drug development for neglected diseases, such as leishmaniasis.
These are both good points, but it is also important to note that it is not very easy to hire people to review drugs at the FDA. They have to be pretty aware of the state-of-the-art in their field in order to be able to effectively provide guidance to the drug companies.
The tremendous time and money requirement to navigate the FDA process for approval of a drug meanwhile does a lot to disincentivize the drug development for neglected diseases.
It's biting its own tail.
It's biting its own tail.
Now this is the type of thing that's fun to see, I feel like this story's gonna be mentioned in the next freakonomics or Gladwell book. Good for the FDA, they should be congratulated for doing something good. And this is good.
Maybe they can create an incentive to create new antibiotics? I've heard there are few if any in the pipeline since they are not profitable to pharma companies and resistance is increasing alarmingly fast!
The GAIN Act was passed last year which provides incentives for new anti-infectives. The DISARM Act is another one being looked at that would make it easier for hospitals to use the latest and greatest antibiotics.
Ah! Good to hear they are legislating towards a bit more progress. Do you know if any pharma companies have re-entered antibiotic research since GAIN passed? I believe there's only a small handful of them left.
Not to mention creating new drugs without implementing any rational controls over their use in humans and livestock is like pouring more gas on the fire.
But I digress about leaving science to legislators....
Not to mention creating new drugs without implementing any rational controls over their use in humans and livestock is like pouring more gas on the fire.
But I digress about leaving science to legislators....
Roche just in-licensed a new compound to restart their antibiotic franchise.
http://www.roche.com/media/media_releases/med-cor-2013-11-04...
http://www.roche.com/media/media_releases/med-cor-2013-11-04...
In other words, it's a lever that the FDA can (will they?) use to solve an important problem: the discrepancy between drugs that bring the greatest profit and drugs that bring the greatest societal benefit. Potentially a loss of efficiency in the strictest economic sense, but also potentially a very good thing in terms of benefit to society.
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It seems insane that drug approvals could be safely expedited by four months, at the suggested value to companies of $150-$300 MM, and this isn't done routinely. That revenue could easily pay for the extra eyeballs at FDA -- which are certainly much cheaper than the clinical trials themselves. I think if Congress were to question the FDA's workings, this could be prima facie evidence that the pace of drug reviews isn't set by hard constraints of public safety: it's slower than it could be, and agency leaders know it.