9 ms·

Why Are So Few Blockbuster Drugs Invented Today?

58 points by forrest_t 12y ago

rayiner 12y ago
> They found that for every billion dollars spent on research and development since 1950, the number of new drugs approved has fallen by half roughly every nine years, meaning a total decline by a factor of 80. They called this Eroom’s Law, because it resembled an inversion of Moore’s Law It's not an inversion of Moore's law, it's totally consistent with it. Every time you shrink transistor size by half, you spend exponentially more capital on the new fabs: http://www.futrfab.com/wp-content/uploads/2012/04/Small-Volume-Technology-Fabrication_new.pdf http://www.futrfab.com/wp-content/uploads/2012/04/Small-Volu... (Figure 2).
- sliverstorm 12y ago
  Cost per transistor is still plummeting IIRC though, while for them cost per drug is rising.
  - rayiner 12y ago
    The cost per new drug is a capital cost, not a production cost. So the right comparison isn't cost per transistor (that's more like cost per pill), but rather cost per new die or cost per new process shrink.
  - deleted 12y ago
    [deleted]
- Alex3917 12y ago
  The idea that all the easy to discover drugs have been found isn't really accurate. What's actually happening is that the FDA has signaled that they are going to do slightly more to make sure drugs targeting the general public are reasonably safe and actually plausibly work, and so the drug manufacturers have basically just given up in trying to pass even this minimal bar. This is why they are all targeting rare diseases, not because they are inherently more profitable to treat, but because the FDA bar for safety and efficacy is lower.
  - Dwolb 12y ago
    I disagree. Traditional drug firms have proven they're unable to adequately innovate with internal R&D due to large bureaucratic overhead. Additionally, old blockbuster drug patents are rapidly expiring and these firms have nothing new to offer except for small iterations on the old drug (e.g. a small change in chemistry which offers no to very little additional benefit to the patient while securing a new patent for the firm). In short, competition is increasing and they're unable to make huge leaps forward in technology to stay ahead of the competition. Recognizing these facts, large firms have begun prospecting and betting on start-up companies who focus on rare diseases because this is a space where innovation has very little bureaucratic overhead and there is very little competition. Also, this is also a space in which the market size is small and where barriers to entry are high, reducing the threat of future competition. In fact, if big companies believe they have bought a company with a promising drug, they would prefer higher hurdles for FDA certification to reduce potential competition.
    - jonlucc 12y ago
      I think this prospecting will create a problem though. If big pharma increasingly prefer to purchase startup biotech companies that have an asset at whatever phase the pharma is looking for, then the only people developing new drugs will be small startups. It reduces the opportunity for assets built for one target to be worked up in another area (e.g. an autoimmune drug to be tried in models of ALS). It also discourages non-risky scientists, as the jobs will increasingly be in volatile companies that leave you wondering if your company card will work when you check into a hotel at a conference.
      - Dwolb 12y ago
        Agreed. It is a problem but you have to wonder if the market will be self-correcting. If there are no companies left to prospect, what will fill the gap? Maybe the major question is how long will a prospecting strategy last?
  - refurb 12y ago
    I agree entirely. There is no doubt that the FDA has become more and more rigorous over time. And yes, pharma companies have responded by moving to therapeutic areas that are easier to get FDA approval in. Cancer is another great example. It's not the only reason for the shift, but it's a big one[1] [1]http://biotechtranslated.com/2011/07/24/it%E2%80%99s-like-watching-5-year-olds-play-soccer%E2%80%A6/ http://biotechtranslated.com/2011/07/24/it%E2%80%99s-like-wa...
jmckib 12y ago
> Doing so, he knew, would require years of clinical trials in preparation for a new-drug application submission to the F.D.A. “That’s the only reason people were afraid.”
narrator 12y ago
A lot of interesting drugs are developed and marketed only overseas these days. The Russian pharmaceutical industry has come up with a lot of interesting ones lately. For example: http://pharmstd.com/page_22.html http://pharmstd.com/page_22.html
- aomurphy 12y ago
  I've seen this cited several time on HN recently, is there a better source for this? Sorry, I imagine a lot of this stuff is in Russian only, but I would love if you could give an article/book/post about this sort of thing.
  - narrator 12y ago
    This is their best selling drug: http://en.wikipedia.org/wiki/Arbidol http://en.wikipedia.org/wiki/Arbidol It's marketed as an over the counter cure for Influenza and only sold in Russia and China. I guess the proof is in the pudding. Death rates for influenza are low by world standards in Russian and China: http://www.worldlifeexpectancy.com/cause-of-death/influenza-pneumonia/by-country/ http://www.worldlifeexpectancy.com/cause-of-death/influenza-... Of course that could be a fluke and this drug is just a sugar pill because all medicine not approved by the FDA is fake, right? We have the most expensive medicine in the world, by far, so it must be the best!
cdoxsey 12y ago
Worth a listen: http://www.econtalk.org/archives/2012/11/angell_on_big_p.html http://www.econtalk.org/archives/2012/11/angell_on_big_p.htm...
cnp 12y ago
Silly that they need to invent new drugs when there are so many "blockbusters" right here to be grown from the ground and used
harvestmoon 12y ago
Interestingly, a quite high amount of breakthrough treatments were discovered by accident. Antibiotics, the original antidepressants, antipsychotics, lithium, viagra and others were all found initially that way. Which may imply that our discovery approach has benefited from happy accidents which are hard to replicate and where the basics have been found already.
- jonlucc 12y ago
  I think Viagra was discovered during clinical trials for hypertension. It (and it's fellow PDE5 inhibitors) is used in cardiac care, but the market is larger for "erectile dysfunction". There are certainly programs in big pharma to screen known drugs (that are already deemed safe for humans) in assays aimed at new targets.
pessimizer 12y ago
Because medicine has only recently become a science. 150 years ago, medicine was far more likely to hasten your death or kill you than improve your situation, and the only medical intervention that actually sometimes delivered results was surgery. At some point, the claims that it made started to be tested rather than simply taken on authority, basic knowledge was accumulated, and the low hanging fruit was plucked. The rest of the fruit is harder to get to, or may even be largely exhausted IMO, because the field is still operating as if all sicknesses have the possibility to be cured by a magic potion (taken orally or injected.) Now, most announced discoveries are simply false, and the largest selling drugs either useless or intoxicants (statins, SSRIs, Xanax, Adderall, etc.) I'm pleased about research on parasites and gut flora, though. It's being reduced to poop pills in its media coverage, but it's not the standard magic potion bit.
- jeffreyrogers 12y ago
  I'm not fully sure why you've been downvoted, but I think your comment on SSRIs is a bit misguided. I don't know enough about the others you've mentioned (statins, Xanax, Adderall, etc.) but the evidence for the efficacy of SSRIs is very strong and they certainly aren't intoxicating.
  - smaccoun 12y ago
    Got a link for that? Several publications have been making the news lately showing antidepressants are really no better than placebo in general http://www.scientificamerican.com/article/antidepressants-do-they-work-or-dont-they/ http://www.scientificamerican.com/article/antidepressants-do...
    - glenra 12y ago
      Try this: http://slatestarcodex.com/2014/07/07/ssris-much-more-than-you-wanted-to-know/ http://slatestarcodex.com/2014/07/07/ssris-much-more-than-yo... ...which also sort of goes along with this overview of depression treatment in general: http://slatestarcodex.com/2014/06/16/things-that-sometimes-help-if-youre-depressed/ http://slatestarcodex.com/2014/06/16/things-that-sometimes-h... The relevant upshot of that first link includes: (1) Everybody agrees SSRIs are at least somewhat better than placebo (2) Placebos really are unreasonably effective compared to non-treatment, so even merely being as effective as placebo is a huge benefit, not to mention being somewhat better than that. (3) What constitutes a "clinically significant" improvement (even relative to placebo) turns out to be kind of arbitrary. As in, a drug that misses that arbitrary goal might still be hugely beneficial to people. (especially if you compare it to non-treatment) (4) Glomming all SSRIs together into one big lump to reach conclusions about the group combines some that work pretty well with some that are known to not work well at all, which can bring down the average effectiveness of the group to below that arbitrary "clinically significant relative to placebo" mark even though individual SSRIs might on their own be more likely to make the cut.
mrbill 12y ago
Maybe they are, but there are hurdles in getting them to market. Here's an example about Merck's suvorexant. http://www.newyorker.com/magazine/2013/12/09/the-big-sleep-2 http://www.newyorker.com/magazine/2013/12/09/the-big-sleep-2
WalterBright 12y ago
Sam Peltzman's book "Regulation of Pharmaceutical Innovation" shows, with statistics, that the 1962 FDA requirements that drugs be proved to be effective has resulted in a dramatic slowdown of new and effective drugs, caused by the high cost of proving effectiveness. He also shows that the ineffective drugs prevented from coming to the market are far outweighed by the effective ones that are delayed or never developed at all.
- jseliger 12y ago
  Great comment. Alex Tabarrok's book Launching the Innovation Renaissance makes a similar point. That neither Peltzman nor Tabarrok are even name checked in the article is distressing.
- rayiner 12y ago
  Approaching the question from an analytical perspective, there's a very concrete, market-economic based reason for putting the brakes on such development: 1) The information asymmetry between the public and drug developers is absolutely astronomical. This undermines any free-market attempt to keep bad drugs out of the market. Moreover, nobody with the resources to prove drugs ineffective has the incentive to do so. 2) The predicative power of the science is pitiful. 90% of drugs that make it to Phase I trials do not make it through Phase III.[1] In other words, companies have no idea whether drugs will work until they actually test them on people. Indeed, there is a decent amount of evidence showing that many drugs that pass Phase III trials don't work. The cost of proving efficacy through human trials is unavoidable. The question isn't whether or not to conduct trials, the question is whether you do those trials as part of the approval process, or by selling drugs that don't work to the public at large. The inherent information asymmetry involved makes the latter a less than compelling proposition. [1] http://pipeline.corante.com/archives/2014/01/10/a_new_look_at_clinical_attrition.php http://pipeline.corante.com/archives/2014/01/10/a_new_look_a...
  - refurb 12y ago
    As for your first point, I think there are two factors that run counter to it. 1) The FDA already regulates what companies can say about their drugs. If there is no evidence your drug is effective, the FDA could certainly stop you from saying there is. 2) Without efficacy data, insurance companies won't pay much. To be honest, I would bet insurance companies wouldn't cover such drugs at all. It would be entirely on the patient to cover the costs. Taking my second point further, if you can't charge a premium for your drug, I doubt pharma companies would even develop drugs they can't prove are efficacious. Gathering efficacy data takes a lot of money, but so does safety data. If you can save 50% on clinical trial costs, but only charge 10% the price, it's a losing proposition.
Balgair 12y ago
Ok, so I work with a lot of immunologists and micro-bio people. The short answer is that science is hard. The slightly longer answer is that science is a lot about luck and sweat. Penicillin was mostly discovered by accident, as with Viagra and many other blockbusters. This is the more observational side of science, not the predictive side. The smart-insulin that was described is firmly in the predictive side, the sweat side. Luck is a factor of having a lot of scientists looking at a lot of things. Sweat is one scientist looking at one thing. Both are valid, but one takes a lot less time. And that is the issue, time. Why not so many recently? The time involved is much higher. The low hanging fruit of the tree of science has mostly been picked at this point (At least I hope so). The blockbusters are then higher up and take considerably more effort to reach. Smart insulin needs nuclear magnetic resonance imaging, a lot of modeling and p-chem, trial after trial to verify results, a lot of post-doc and grad students, data processing and computer scientists, and the resources of a lab and a half. Penicillin was a petri dish that wasn't properly sterilized. Science takes time, and as humans, we go for the easiest science first. We should not sacrifice safety for speed.
- jonlucc 12y ago
  > Science takes time, and as humans, we go for the easiest science first. We should not sacrifice safety for speed. I agree, but it is also a function of money. Pharmaceutical companies often rely on basic research from academia to get pointed in the right direction. As that decreases, there are fewer academics discovering fewer new pathways that pharma can target drugs for. Additionally, funding is aimed at investigators who are likely to succeed. It is common for a lab to essentially work one grant ahead of funding in order to be sure to deliver.
  - Balgair 12y ago
    > Funding is aimed at investigators who are likely to succeed. You have no idea. Friends at other universities have a very high end microscope 'core' that can be used all that apply as a shared cost and time device. Orientation went great, 'yeah, its awesome to use, you get great data, blah blah blah'. When she came to the lab however, she found that only 2 professors' labs could use the core, as they had outbid all the other professors for the time, for then next 15 years. Its a small thing, but it speaks to the incredible gains that go to the 'winners' and the scraps that are given to 'losers.'
HarryHirsch 12y ago
Derek Lowe has another theory: http://pipeline.corante.com/archives/2014/11/06/what_happens_after_your_first_drug_approval.php http://pipeline.corante.com/archives/2014/11/06/what_happens... Your average startup brings exactly one drug to market, and then is aquired and broken up. The current system does not encourage building institutional experience in the field, in fact it destroys it.
colordrops 12y ago
D.R.A.C.O. is a broad spectrum antiviral developed at MIT, but currently languishing without almost any funding. It theoretically can cure almost any virus, and has been successful in vitro and in mice. The mechanism should work in humans, and yet no one wants to fund it. It's completely baffling to me that no one is aware of this, and that it's not being fast-tracked and funded by governments around the world: http://en.wikipedia.org/wiki/DRACO_(antiviral) http://en.wikipedia.org/wiki/DRACO_(antiviral)
- stuaxo 12y ago
  Could Kickstarter be an option?
  - jeffreyrogers 12y ago
    I don't know the legal issues involved with Kickstarting a drug, but I do know of at least one medical technique (Vasalgel) that has been/is being crowdfunded, so it is possible.
- refurb 12y ago
  I don't know enough about DRACO, but I would argue that pharma companies have already kicked the tires and passed on it. I know a few people that work in pharma business development and they scour academic labs for anything of value. For whatever reason, they don't believe that DRACO as value, at least right now. In the meantime, if it's as promising as you say, academic labs shouldn't have trouble getting funding to further develop it.
  - colordrops 12y ago
    > I don't know enough about DRACO So what are you saying besides laying out your untested assumptions about how the world works? There are endless reasons why research doesn't get funded, and many of those aren't because the research is bad. > In the meantime, if it's as promising as you say, academic labs shouldn't have trouble getting funding to further develop it. What evidence do you have to back this up? Do you have any idea on how much money is made in treatments for viral disease? Do you know how much would be lost if all viral disease was cured?
notastartup 12y ago
I believe the biggest reason is the lack of embracing software in the process. You still have people standing around in front of beakers and petridish. You are using the same darn rigid rules from 18th century. This is why progress is so slow. Imagine if you opened up the vast knowledge of drugs and creating new drug and testing it was as easy as writing a program, it would do wonders. Software is not eating up the world in this slice of the market.
mkempe 12y ago
Because of government controls and bureaucratic incentives: on the one hand, the FDA is by its nature and rules inclined to block new drugs and medical devices; on the other hand, potential inventors are either turned off or handicapped by the FDA rules and controls. I've developed internal software tools for healthcare companies -- having had to study and learn the FDA rules, and having seen what these companies go through, I'd rather give up on engineering than work in the development of medical devices. A sane, creative mind cannot work and flourish under compulsion.
georgewfraser 12y ago
Great review article on this topic in nature: http://diyhpl.us/~bryan/papers2/bio/Diagnosing%20the%20decline%20in%20pharmaceutical%20research%20and%20development%20efficiency.pdf http://diyhpl.us/~bryan/papers2/bio/Diagnosing%20the%20decli...

58 points by forrest_t 12y ago

> They found that for every billion dollars spent on research and development since 1950, the number of new drugs approved has fallen by half roughly every nine years, meaning a total decline by a factor of 80. They called this Eroom’s Law, because it resembled an inversion of Moore’s Law It's not an inversion of Moore's law, it's totally consistent with it. Every time you shrink transistor size by half, you spend exponentially more capital on the new fabs: http://www.futrfab.com/wp-content/uploads/2012/04/Small-Volume-Technology-Fabrication_new.pdf http://www.futrfab.com/wp-content/uploads/2012/04/Small-Volu... (Figure 2).

sliverstorm 12y ago
Cost per transistor is still plummeting IIRC though, while for them cost per drug is rising.
- rayiner 12y ago
  The cost per new drug is a capital cost, not a production cost. So the right comparison isn't cost per transistor (that's more like cost per pill), but rather cost per new die or cost per new process shrink.
- deleted 12y ago
  [deleted]
Alex3917 12y ago
The idea that all the easy to discover drugs have been found isn't really accurate. What's actually happening is that the FDA has signaled that they are going to do slightly more to make sure drugs targeting the general public are reasonably safe and actually plausibly work, and so the drug manufacturers have basically just given up in trying to pass even this minimal bar. This is why they are all targeting rare diseases, not because they are inherently more profitable to treat, but because the FDA bar for safety and efficacy is lower.
- Dwolb 12y ago
  I disagree. Traditional drug firms have proven they're unable to adequately innovate with internal R&D due to large bureaucratic overhead. Additionally, old blockbuster drug patents are rapidly expiring and these firms have nothing new to offer except for small iterations on the old drug (e.g. a small change in chemistry which offers no to very little additional benefit to the patient while securing a new patent for the firm). In short, competition is increasing and they're unable to make huge leaps forward in technology to stay ahead of the competition. Recognizing these facts, large firms have begun prospecting and betting on start-up companies who focus on rare diseases because this is a space where innovation has very little bureaucratic overhead and there is very little competition. Also, this is also a space in which the market size is small and where barriers to entry are high, reducing the threat of future competition. In fact, if big companies believe they have bought a company with a promising drug, they would prefer higher hurdles for FDA certification to reduce potential competition.
  - jonlucc 12y ago
    I think this prospecting will create a problem though. If big pharma increasingly prefer to purchase startup biotech companies that have an asset at whatever phase the pharma is looking for, then the only people developing new drugs will be small startups. It reduces the opportunity for assets built for one target to be worked up in another area (e.g. an autoimmune drug to be tried in models of ALS). It also discourages non-risky scientists, as the jobs will increasingly be in volatile companies that leave you wondering if your company card will work when you check into a hotel at a conference.
    - Dwolb 12y ago
      Agreed. It is a problem but you have to wonder if the market will be self-correcting. If there are no companies left to prospect, what will fill the gap? Maybe the major question is how long will a prospecting strategy last?
- refurb 12y ago
  I agree entirely. There is no doubt that the FDA has become more and more rigorous over time. And yes, pharma companies have responded by moving to therapeutic areas that are easier to get FDA approval in. Cancer is another great example. It's not the only reason for the shift, but it's a big one[1] [1]http://biotechtranslated.com/2011/07/24/it%E2%80%99s-like-watching-5-year-olds-play-soccer%E2%80%A6/ http://biotechtranslated.com/2011/07/24/it%E2%80%99s-like-wa...

jmckib 12y ago

> Doing so, he knew, would require years of clinical trials in preparation for a new-drug application submission to the F.D.A. “That’s the only reason people were afraid.”

narrator 12y ago

A lot of interesting drugs are developed and marketed only overseas these days. The Russian pharmaceutical industry has come up with a lot of interesting ones lately. For example: http://pharmstd.com/page_22.html http://pharmstd.com/page_22.html

aomurphy 12y ago
I've seen this cited several time on HN recently, is there a better source for this? Sorry, I imagine a lot of this stuff is in Russian only, but I would love if you could give an article/book/post about this sort of thing.
- narrator 12y ago
  This is their best selling drug: http://en.wikipedia.org/wiki/Arbidol http://en.wikipedia.org/wiki/Arbidol It's marketed as an over the counter cure for Influenza and only sold in Russia and China. I guess the proof is in the pudding. Death rates for influenza are low by world standards in Russian and China: http://www.worldlifeexpectancy.com/cause-of-death/influenza-pneumonia/by-country/ http://www.worldlifeexpectancy.com/cause-of-death/influenza-... Of course that could be a fluke and this drug is just a sugar pill because all medicine not approved by the FDA is fake, right? We have the most expensive medicine in the world, by far, so it must be the best!

cdoxsey 12y ago

Worth a listen: http://www.econtalk.org/archives/2012/11/angell_on_big_p.html http://www.econtalk.org/archives/2012/11/angell_on_big_p.htm...

cnp 12y ago

Silly that they need to invent new drugs when there are so many "blockbusters" right here to be grown from the ground and used

harvestmoon 12y ago

Interestingly, a quite high amount of breakthrough treatments were discovered by accident. Antibiotics, the original antidepressants, antipsychotics, lithium, viagra and others were all found initially that way. Which may imply that our discovery approach has benefited from happy accidents which are hard to replicate and where the basics have been found already.

jonlucc 12y ago
I think Viagra was discovered during clinical trials for hypertension. It (and it's fellow PDE5 inhibitors) is used in cardiac care, but the market is larger for "erectile dysfunction". There are certainly programs in big pharma to screen known drugs (that are already deemed safe for humans) in assays aimed at new targets.

pessimizer 12y ago

Because medicine has only recently become a science. 150 years ago, medicine was far more likely to hasten your death or kill you than improve your situation, and the only medical intervention that actually sometimes delivered results was surgery. At some point, the claims that it made started to be tested rather than simply taken on authority, basic knowledge was accumulated, and the low hanging fruit was plucked. The rest of the fruit is harder to get to, or may even be largely exhausted IMO, because the field is still operating as if all sicknesses have the possibility to be cured by a magic potion (taken orally or injected.) Now, most announced discoveries are simply false, and the largest selling drugs either useless or intoxicants (statins, SSRIs, Xanax, Adderall, etc.) I'm pleased about research on parasites and gut flora, though. It's being reduced to poop pills in its media coverage, but it's not the standard magic potion bit.

jeffreyrogers 12y ago
I'm not fully sure why you've been downvoted, but I think your comment on SSRIs is a bit misguided. I don't know enough about the others you've mentioned (statins, Xanax, Adderall, etc.) but the evidence for the efficacy of SSRIs is very strong and they certainly aren't intoxicating.
- smaccoun 12y ago
  Got a link for that? Several publications have been making the news lately showing antidepressants are really no better than placebo in general http://www.scientificamerican.com/article/antidepressants-do-they-work-or-dont-they/ http://www.scientificamerican.com/article/antidepressants-do...
  - glenra 12y ago
    Try this: http://slatestarcodex.com/2014/07/07/ssris-much-more-than-you-wanted-to-know/ http://slatestarcodex.com/2014/07/07/ssris-much-more-than-yo... ...which also sort of goes along with this overview of depression treatment in general: http://slatestarcodex.com/2014/06/16/things-that-sometimes-help-if-youre-depressed/ http://slatestarcodex.com/2014/06/16/things-that-sometimes-h... The relevant upshot of that first link includes: (1) Everybody agrees SSRIs are at least somewhat better than placebo (2) Placebos really are unreasonably effective compared to non-treatment, so even merely being as effective as placebo is a huge benefit, not to mention being somewhat better than that. (3) What constitutes a "clinically significant" improvement (even relative to placebo) turns out to be kind of arbitrary. As in, a drug that misses that arbitrary goal might still be hugely beneficial to people. (especially if you compare it to non-treatment) (4) Glomming all SSRIs together into one big lump to reach conclusions about the group combines some that work pretty well with some that are known to not work well at all, which can bring down the average effectiveness of the group to below that arbitrary "clinically significant relative to placebo" mark even though individual SSRIs might on their own be more likely to make the cut.

mrbill 12y ago

Maybe they are, but there are hurdles in getting them to market. Here's an example about Merck's suvorexant. http://www.newyorker.com/magazine/2013/12/09/the-big-sleep-2 http://www.newyorker.com/magazine/2013/12/09/the-big-sleep-2

WalterBright 12y ago

Sam Peltzman's book "Regulation of Pharmaceutical Innovation" shows, with statistics, that the 1962 FDA requirements that drugs be proved to be effective has resulted in a dramatic slowdown of new and effective drugs, caused by the high cost of proving effectiveness. He also shows that the ineffective drugs prevented from coming to the market are far outweighed by the effective ones that are delayed or never developed at all.

jseliger 12y ago
Great comment. Alex Tabarrok's book Launching the Innovation Renaissance makes a similar point. That neither Peltzman nor Tabarrok are even name checked in the article is distressing.
rayiner 12y ago
Approaching the question from an analytical perspective, there's a very concrete, market-economic based reason for putting the brakes on such development: 1) The information asymmetry between the public and drug developers is absolutely astronomical. This undermines any free-market attempt to keep bad drugs out of the market. Moreover, nobody with the resources to prove drugs ineffective has the incentive to do so. 2) The predicative power of the science is pitiful. 90% of drugs that make it to Phase I trials do not make it through Phase III.[1] In other words, companies have no idea whether drugs will work until they actually test them on people. Indeed, there is a decent amount of evidence showing that many drugs that pass Phase III trials don't work. The cost of proving efficacy through human trials is unavoidable. The question isn't whether or not to conduct trials, the question is whether you do those trials as part of the approval process, or by selling drugs that don't work to the public at large. The inherent information asymmetry involved makes the latter a less than compelling proposition. [1] http://pipeline.corante.com/archives/2014/01/10/a_new_look_at_clinical_attrition.php http://pipeline.corante.com/archives/2014/01/10/a_new_look_a...
- refurb 12y ago
  As for your first point, I think there are two factors that run counter to it. 1) The FDA already regulates what companies can say about their drugs. If there is no evidence your drug is effective, the FDA could certainly stop you from saying there is. 2) Without efficacy data, insurance companies won't pay much. To be honest, I would bet insurance companies wouldn't cover such drugs at all. It would be entirely on the patient to cover the costs. Taking my second point further, if you can't charge a premium for your drug, I doubt pharma companies would even develop drugs they can't prove are efficacious. Gathering efficacy data takes a lot of money, but so does safety data. If you can save 50% on clinical trial costs, but only charge 10% the price, it's a losing proposition.

Balgair 12y ago

Ok, so I work with a lot of immunologists and micro-bio people. The short answer is that science is hard. The slightly longer answer is that science is a lot about luck and sweat. Penicillin was mostly discovered by accident, as with Viagra and many other blockbusters. This is the more observational side of science, not the predictive side. The smart-insulin that was described is firmly in the predictive side, the sweat side. Luck is a factor of having a lot of scientists looking at a lot of things. Sweat is one scientist looking at one thing. Both are valid, but one takes a lot less time. And that is the issue, time. Why not so many recently? The time involved is much higher. The low hanging fruit of the tree of science has mostly been picked at this point (At least I hope so). The blockbusters are then higher up and take considerably more effort to reach. Smart insulin needs nuclear magnetic resonance imaging, a lot of modeling and p-chem, trial after trial to verify results, a lot of post-doc and grad students, data processing and computer scientists, and the resources of a lab and a half. Penicillin was a petri dish that wasn't properly sterilized. Science takes time, and as humans, we go for the easiest science first. We should not sacrifice safety for speed.

jonlucc 12y ago
> Science takes time, and as humans, we go for the easiest science first. We should not sacrifice safety for speed. I agree, but it is also a function of money. Pharmaceutical companies often rely on basic research from academia to get pointed in the right direction. As that decreases, there are fewer academics discovering fewer new pathways that pharma can target drugs for. Additionally, funding is aimed at investigators who are likely to succeed. It is common for a lab to essentially work one grant ahead of funding in order to be sure to deliver.
- Balgair 12y ago
  > Funding is aimed at investigators who are likely to succeed. You have no idea. Friends at other universities have a very high end microscope 'core' that can be used all that apply as a shared cost and time device. Orientation went great, 'yeah, its awesome to use, you get great data, blah blah blah'. When she came to the lab however, she found that only 2 professors' labs could use the core, as they had outbid all the other professors for the time, for then next 15 years. Its a small thing, but it speaks to the incredible gains that go to the 'winners' and the scraps that are given to 'losers.'

HarryHirsch 12y ago

Derek Lowe has another theory: http://pipeline.corante.com/archives/2014/11/06/what_happens_after_your_first_drug_approval.php http://pipeline.corante.com/archives/2014/11/06/what_happens... Your average startup brings exactly one drug to market, and then is aquired and broken up. The current system does not encourage building institutional experience in the field, in fact it destroys it.

colordrops 12y ago

D.R.A.C.O. is a broad spectrum antiviral developed at MIT, but currently languishing without almost any funding. It theoretically can cure almost any virus, and has been successful in vitro and in mice. The mechanism should work in humans, and yet no one wants to fund it. It's completely baffling to me that no one is aware of this, and that it's not being fast-tracked and funded by governments around the world: http://en.wikipedia.org/wiki/DRACO_(antiviral) http://en.wikipedia.org/wiki/DRACO_(antiviral)

stuaxo 12y ago
Could Kickstarter be an option?
- jeffreyrogers 12y ago
  I don't know the legal issues involved with Kickstarting a drug, but I do know of at least one medical technique (Vasalgel) that has been/is being crowdfunded, so it is possible.
refurb 12y ago
I don't know enough about DRACO, but I would argue that pharma companies have already kicked the tires and passed on it. I know a few people that work in pharma business development and they scour academic labs for anything of value. For whatever reason, they don't believe that DRACO as value, at least right now. In the meantime, if it's as promising as you say, academic labs shouldn't have trouble getting funding to further develop it.
- colordrops 12y ago
  > I don't know enough about DRACO So what are you saying besides laying out your untested assumptions about how the world works? There are endless reasons why research doesn't get funded, and many of those aren't because the research is bad. > In the meantime, if it's as promising as you say, academic labs shouldn't have trouble getting funding to further develop it. What evidence do you have to back this up? Do you have any idea on how much money is made in treatments for viral disease? Do you know how much would be lost if all viral disease was cured?

notastartup 12y ago

I believe the biggest reason is the lack of embracing software in the process. You still have people standing around in front of beakers and petridish. You are using the same darn rigid rules from 18th century. This is why progress is so slow. Imagine if you opened up the vast knowledge of drugs and creating new drug and testing it was as easy as writing a program, it would do wonders. Software is not eating up the world in this slice of the market.

mkempe 12y ago

Because of government controls and bureaucratic incentives: on the one hand, the FDA is by its nature and rules inclined to block new drugs and medical devices; on the other hand, potential inventors are either turned off or handicapped by the FDA rules and controls. I've developed internal software tools for healthcare companies -- having had to study and learn the FDA rules, and having seen what these companies go through, I'd rather give up on engineering than work in the development of medical devices. A sane, creative mind cannot work and flourish under compulsion.

georgewfraser 12y ago

Great review article on this topic in nature: http://diyhpl.us/~bryan/papers2/bio/Diagnosing%20the%20decline%20in%20pharmaceutical%20research%20and%20development%20efficiency.pdf http://diyhpl.us/~bryan/papers2/bio/Diagnosing%20the%20decli...