4 ms·

It's absolutely true that risk aversion is not the only thing holding back drug trials. But it's definitely part of the problem. Think about insulin. In 1921 B

It's absolutely true that risk aversion is not the only thing holding back drug trials. But it's definitely part of the problem. Think about insulin. In 1921 Banting and Best had the idea. It was in a patient's arm by 1922. And they won the Nobel Prize by 1923. http://www.nobelprize.org/educational/medicine/insulin/discovery-insulin.html Early in 1921, Banting took his idea to Professor John Macleod at the University of Toronto, who was a leading figure in the study of diabetes in Canada. Macleod didn't think much of Banting's theories. Despite this, Banting managed to convince him that his idea was worth trying. Macleod gave Banting a laboratory with a minimum of equipment and ten dogs. Banting also got an assistant, a medical student by the name of Charles Best. The experiment was set to start in the summer of 1921. ... In January 1922 in Toronto, Canada, a 14-year-old boy, Leonard Thompson, was chosen as the first person with diabetes to receive insulin. The test was a success. Leonard, who before the insulin shots was near death, rapidly regained his strength and appetite. The team now expanded their testing to other volunteer diabetics, who reacted just as positively as Leonard to the insulin extract. The news of the successful treatment of diabetes with insulin rapidly spread outside of Toronto, and in 1923 the Nobel Committee decided to award Banting and Macleod the Nobel Prize in Physiology or Medicine. That was before the FDA gained the power of premarket approval, a time when pharma moved at the speed of software. Nowadays that past is characterized as a time of patent medicines and scam artists. But if you actually get into the history books you'll see that description is like characterizing the modern internet as a giant repository of spam and scams. In other words, absolutely that spam/scam stuff existed (and indeed crystals and faith healing persist to the present day), but real innovation in drugs also occurred at the same time. The fundamental point there is that Banting and Best could do empirical human trials. You can't predict what a novel drug will do without humans who are willing to risk their lives. In computers these people are called early adopters. If risk aversion was slowing pharma innovation then we'd see a lot of potentially efficacious compounds failing safety trials. Instead what we see is that the cost to discover candidate compounds before they're ever tested on humans. Yes, the thing is that drug companies face a significant penalty with the FDA if they fail a safety trial. It's not just a one off, it influences the FDA's perception of them as a "reputable" company. If the FDA thinks of you as disreputable or a cowboy, they will inspect the hell out of you and issue Form 483s [0] till the cows come home. And that's not even including the PR impact and the market sell-off should you ever actually have a TGN 1412 incident[1]. So there is a very significant economic risk to "failing fast" in pharma. Over and above the hit to brand, if the PR fallout is bad enough the FDA has a number of tools with which to criminalize failure. The Park Doctrine[2] is what they do for "off-label marketing", and they would escalate considerably if they felt public opinion demanded it. Anyway, this is why drug companies are doing all these simulations and iterating primarily around drug molecules that are known to be safe. No one ever got fired for buying IBM, and no one ever got fired for trying molecules compliant with Lipinski's rule of five[3]. Sure, that's still a pretty wide class of molecules, but "radical innovation" in compounds is just not going to fly with the FDA. After all, it took the FDA more than a decade to begin considering adaptive clinical trials[4] in lieu of the standard Phase I/II/III design. How long will it take them to agree that aging could be treated as a disease, or to allow the development of enhancing drugs? These things probably won't happen until there's some sort of major conflict in which enhancing drugs become the difference between victory and defeat. Then the floodgates will open. [0] http://blog.fdazilla.com/2011/09/fda-will-issue-10000-483s-in-2011-one-every-52-minutes/ http://blog.fdazilla.com/2011/09/fda-will-issue-10000-483s-i... [1] http://en.wikipedia.org/wiki/TGN1412 http://en.wikipedia.org/wiki/TGN1412 [2] http://www.gatewayfda.com/fda-regulations/under-park-doctrine-fda-can-prosecute-individuals-for-company-violations-of-fdca/ http://www.gatewayfda.com/fda-regulations/under-park-doctrin... [3] http://en.wikipedia.org/wiki/Druglikeness http://en.wikipedia.org/wiki/Druglikeness [4] http://jnci.oxfordjournals.org/content/102/16/1217.extract http://jnci.oxfordjournals.org/content/102/16/1217.extract

leoc 15y ago
> Nowadays that past is characterized as a time of patent medicines and scam artists. What is more pertinent is that it was the time of the Tuskeegee syphilis trials.
WildUtah 15y ago
I want to upvote your comment ten times, but there's only one of me. Thanks for the point of view, history, and references. Why, do you think, are the pharma researchers not shifting cutting edge research to places where regulation is more pliable and inventing new treatments there. Surely Latin America or China (maybe even India, depending on bureaucracy) could provide the kind of market and test bed for new treatments that fast innovation would thrive in.
- ramanujan 15y ago
  Good question. In theory this is possible, and there are a number of biotechs and medical device companies that are looking overseas. Europe is the preferred place right now for traditional biotechs & medical device companies, as getting a CE Mark is a lot less onerous and much more predictable[0] than the increasingly random FDA process. As for China (and India), they are very promising but will require entirely new business models, for a few reasons. First, the current biotech industry is based around an artificial barrier to entry (namely FDA approval) and artificial scarcity (namely drug patents). Remove the former and you remove the rationale for the latter. This is their whole business model. Second and more fundamentally, most existing pharma companies have now gone through almost 50 years with the FDA. The "fail fast" model was 2-3 human generations ago, and even really good scientists like Derek Lowe have a bit of Stockholm Syndrome. In the worldview of (most) modern pharma scientists, the FDA process is considered a law of nature, something on par with s and p orbitals. Removing FDA approval and patents from the situation would suddenly make two of the most important departments in any pharma company (regulatory affairs and IP) completely useless. A world without the FDA, where doctor, patient, and chemist made their own decisions without third party regulation would be painted as strange and worrisome. Like the TSA, the FDA has dozens of full time PR professionals[1,2] dedicated to convincing you that "your safety is their priority". Unlike the TSA, most people (even most in the industry) don't question whether the FDA is actually protecting people. Without going into detail, then, successful business models for pharma/biotech/device companies in China/India would be based on validating products in a highly empirical fashion, getting them to market rapidly and protecting them from competitors via execution without any IP enforcement. Think something more like the supplements market, where creatine, omega 3, and energy drinks rose to the fore over the last few decades...except with even smarter people doing the formulations. No traditional pharma is culturally capable of doing this. Moreover, even if they were, the FDA would frown on this threat to their review authority. If this hypothetical rogue pharma had any desires of ever selling into the US market or not having their reputation destroyed by the FDA with a few press releases, they wouldn't try setting up this sort of low-regulation phenomenological branch overseas. So, to really exploit the potential of true drug legalization, it'd have to be new companies. [0] http://www.eurekalert.org/pub_releases/2011-05/iti-fpa052311.php http://www.eurekalert.org/pub_releases/2011-05/iti-fpa052311... [1] http://www.fda.gov/NewsEvents/Newsroom/MediaContacts/default.htm http://www.fda.gov/NewsEvents/Newsroom/MediaContacts/default... [2] http://www.fda.gov/AboutFDA/ContactFDA/FindanOfficeorStaffMember/FDAPublicAffairsSpecialists/default.htm http://www.fda.gov/AboutFDA/ContactFDA/FindanOfficeorStaffMe...

leoc 15y ago

> Nowadays that past is characterized as a time of patent medicines and scam artists. What is more pertinent is that it was the time of the Tuskeegee syphilis trials.

WildUtah 15y ago

I want to upvote your comment ten times, but there's only one of me. Thanks for the point of view, history, and references. Why, do you think, are the pharma researchers not shifting cutting edge research to places where regulation is more pliable and inventing new treatments there. Surely Latin America or China (maybe even India, depending on bureaucracy) could provide the kind of market and test bed for new treatments that fast innovation would thrive in.

ramanujan 15y ago
Good question. In theory this is possible, and there are a number of biotechs and medical device companies that are looking overseas. Europe is the preferred place right now for traditional biotechs & medical device companies, as getting a CE Mark is a lot less onerous and much more predictable[0] than the increasingly random FDA process. As for China (and India), they are very promising but will require entirely new business models, for a few reasons. First, the current biotech industry is based around an artificial barrier to entry (namely FDA approval) and artificial scarcity (namely drug patents). Remove the former and you remove the rationale for the latter. This is their whole business model. Second and more fundamentally, most existing pharma companies have now gone through almost 50 years with the FDA. The "fail fast" model was 2-3 human generations ago, and even really good scientists like Derek Lowe have a bit of Stockholm Syndrome. In the worldview of (most) modern pharma scientists, the FDA process is considered a law of nature, something on par with s and p orbitals. Removing FDA approval and patents from the situation would suddenly make two of the most important departments in any pharma company (regulatory affairs and IP) completely useless. A world without the FDA, where doctor, patient, and chemist made their own decisions without third party regulation would be painted as strange and worrisome. Like the TSA, the FDA has dozens of full time PR professionals[1,2] dedicated to convincing you that "your safety is their priority". Unlike the TSA, most people (even most in the industry) don't question whether the FDA is actually protecting people. Without going into detail, then, successful business models for pharma/biotech/device companies in China/India would be based on validating products in a highly empirical fashion, getting them to market rapidly and protecting them from competitors via execution without any IP enforcement. Think something more like the supplements market, where creatine, omega 3, and energy drinks rose to the fore over the last few decades...except with even smarter people doing the formulations. No traditional pharma is culturally capable of doing this. Moreover, even if they were, the FDA would frown on this threat to their review authority. If this hypothetical rogue pharma had any desires of ever selling into the US market or not having their reputation destroyed by the FDA with a few press releases, they wouldn't try setting up this sort of low-regulation phenomenological branch overseas. So, to really exploit the potential of true drug legalization, it'd have to be new companies. [0] http://www.eurekalert.org/pub_releases/2011-05/iti-fpa052311.php http://www.eurekalert.org/pub_releases/2011-05/iti-fpa052311... [1] http://www.fda.gov/NewsEvents/Newsroom/MediaContacts/default.htm http://www.fda.gov/NewsEvents/Newsroom/MediaContacts/default... [2] http://www.fda.gov/AboutFDA/ContactFDA/FindanOfficeorStaffMember/FDAPublicAffairsSpecialists/default.htm http://www.fda.gov/AboutFDA/ContactFDA/FindanOfficeorStaffMe...