5 ms·

This is a good example of a downside of regulation: regulations embed assumptions that favor certain outcomes. Those assumptions might have made sense when the

This is a good example of a downside of regulation: regulations embed assumptions that favor certain outcomes. Those assumptions might have made sense when the regulations were written, but are very slow to adapt to changes in the industry. The FDA drug approval process was basically designed for things like antibiotics: Single molecular compound, high purity, standardized dosage and application, and run trials with many many patients. Treatments that don't fall under that umbrella (like phages) are very difficult to develop and bring to market, even if they work very well, just because of the impedance mismatch. Phages are basically individually tailored to the patient, require a lot of work in administering, and difficult to test under the FDA's guidelines. Many people have unnecessarily died because treatments that could be are lifesaving aren't brought to market due to too much rigidity in the system. To be fair, the FDA has been active in coming up with ways for things like phages to be brought to market safely, but it's a very slow, uphill battle.

Retric 10y ago
To be fair, Phages are also vastly worse than antibiotics in they need to be extremely targeted. So, it's really not clear they are worth investing a lot of time or money developing until we have zero other options.
- smallnamespace 10y ago
  Antibiotics are extremely expensive to develop (on the order of billions of dollars), and patients regularly die because 1) the antibiotics were ineffective against the particular bacteria in their body or 2) the antibiotics wiped out their normal flora, and give them intractable cases of C. difficile and the like. > zero other options Those patients literally had zero other options than just dying. Phages should be another weapon in our arsenal. You're right that they might not end up working out, but right now there is chronic underinvestment in research to find out whether work, because nobody is going to heavily fund research for therapies that will never pass the regulatory hurdle. It seems like bad risk management to back ourselves into a corner -- the whole point of research is to find out whether other things work. Defense in depth isn't just for software security.
  - Retric 10y ago
    The problem is they are not free. If we trade 1 new Antibiotic and get X Phage treatments how large an X do you need to break even? Next is it cheaper to find the next Antibiotic or get those X Phage treatments adopted? Current estimates suggest Antibiotics are still a vastly better investment. I mean we have plenty of ridiculously expensive treatments out there already. It's not clear creating such things are a good investment vs. reducing traffic fatalities etc.
    - smallnamespace 10y ago
      Well, the only way to answer that question is to do some more research on phages, and I guarantee you, the funding for antibiotics research is more than 100x that for phage therapies, in large part because of regulation. Phage therapies are actually used regularly in Georgia, Russia, and other parts of the former Soviet Union, in part because they couldn't get access to antibiotics during WW2 and right afterwards. You can do the math as to whether we've passed the point of diminishing marginal returns on antibiotics.
      - Retric 10y ago
        Look for actual numbers, the USSR for example did quite a bit of Phage research and then gave it up. So, no it's not 100x in favor of Antibiotics, which get vastly less funding than you might think.
        smallnamespace 10y ago
        They didn't give it up, it's still practiced today: "Phage therapy is used in Russia, Georgia and Poland" [1]. Also [2]. [1] https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy [2] https://www.phagetherapycenter.com/pii/PatientServlet?command=static_home https://www.phagetherapycenter.com/pii/PatientServlet?comman...
        Retric 10y ago
- digikata 10y ago
  Do bacteria develop resistance to phages as quickly as they might an antibiotic? A longer usable lifetime may change the balance of costs considerably.
  - vkou 10y ago
    They do, but unlike an antibiotic, the phage is likely to evolve to be better at killing resistant bacteria.
HillaryBriss 10y ago
FWIW, Silicon Valley investor Jim O'Neill, who might well be the next head of the FDA, said this in 2014 about that: “We should reform FDA so there is approving drugs after their sponsors have demonstrated safety -- and let people start using them, at their own risk, but not much risk of safety,” O’Neill said in a speech at an August 2014 conference called Rejuvenation Biotechnology. “Let’s prove efficacy after they’ve been legalized.” http://www.bloomberg.com/politics/articles/2016-12-07/trump-team-is-said-to-consider-thiel-associate-o-neill-for-fda http://www.bloomberg.com/politics/articles/2016-12-07/trump-...
- ufmace 10y ago
  Now that's something interesting. I found it funny that the article didn't seem to even briefly question whether the drug approval process could be changed to make it simpler to get things like phages to patients. If we're getting lots of political change, this sounds like something that could benefit.
- wahern 10y ago
  That makes a ton sense, except that one wonders if any manufacturer will ever bother proving efficacy. Worse, they may instead double-down on marketing campaigns. Doctors and other professionals, working scientists or not, are susceptible to marketing like anybody else. So we'd need to see other mechanisms, regulatory or otherwise[1], that would counter that effect. FDA approval is a powerful motivator for 1) companies to find actually effective therapies and 2) as an extremely efficient signaling mechanism to the market regarding efficacy. But it's sub-optimal for many reasons, including erring too heavily on the side of safety. It's just not obvious what would replace it. Don't forget, snake oil thrives in the free market. [1] Medicare reimbursements predicated on FDA efficacy approval? I'm not sure insurance companies can be expected to do the right[2] thing. It might be cheaper to reimburse a snake oil treatment that allows the patient to die than to pay a premium for an effective treatment. And while presumably a good doctor would insist on the effective treatment, at the margins the insurance company could expect to profit from allowing their patients to choose the snake oil. [2] Where "right" means a course of action that maximizes long-term social wealth (i.e. preferring effective treatment and therefore subsidizing research), rather than simply maximizing the short-term utility of patients and profits (i.e. allowing the patients the salve of snake oil, with reimbursements, in lieu of effective treatment).

Retric 10y ago

To be fair, Phages are also vastly worse than antibiotics in they need to be extremely targeted. So, it's really not clear they are worth investing a lot of time or money developing until we have zero other options.

smallnamespace 10y ago
Antibiotics are extremely expensive to develop (on the order of billions of dollars), and patients regularly die because 1) the antibiotics were ineffective against the particular bacteria in their body or 2) the antibiotics wiped out their normal flora, and give them intractable cases of C. difficile and the like. > zero other options Those patients literally had zero other options than just dying. Phages should be another weapon in our arsenal. You're right that they might not end up working out, but right now there is chronic underinvestment in research to find out whether work, because nobody is going to heavily fund research for therapies that will never pass the regulatory hurdle. It seems like bad risk management to back ourselves into a corner -- the whole point of research is to find out whether other things work. Defense in depth isn't just for software security.
- Retric 10y ago
  The problem is they are not free. If we trade 1 new Antibiotic and get X Phage treatments how large an X do you need to break even? Next is it cheaper to find the next Antibiotic or get those X Phage treatments adopted? Current estimates suggest Antibiotics are still a vastly better investment. I mean we have plenty of ridiculously expensive treatments out there already. It's not clear creating such things are a good investment vs. reducing traffic fatalities etc.
  - smallnamespace 10y ago
    Well, the only way to answer that question is to do some more research on phages, and I guarantee you, the funding for antibiotics research is more than 100x that for phage therapies, in large part because of regulation. Phage therapies are actually used regularly in Georgia, Russia, and other parts of the former Soviet Union, in part because they couldn't get access to antibiotics during WW2 and right afterwards. You can do the math as to whether we've passed the point of diminishing marginal returns on antibiotics.
    - Retric 10y ago
      Look for actual numbers, the USSR for example did quite a bit of Phage research and then gave it up. So, no it's not 100x in favor of Antibiotics, which get vastly less funding than you might think.
      - smallnamespace 10y ago
        They didn't give it up, it's still practiced today: "Phage therapy is used in Russia, Georgia and Poland" [1]. Also [2]. [1] https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy [2] https://www.phagetherapycenter.com/pii/PatientServlet?command=static_home https://www.phagetherapycenter.com/pii/PatientServlet?comman...
        Retric 10y ago
digikata 10y ago
Do bacteria develop resistance to phages as quickly as they might an antibiotic? A longer usable lifetime may change the balance of costs considerably.
- vkou 10y ago
  They do, but unlike an antibiotic, the phage is likely to evolve to be better at killing resistant bacteria.

HillaryBriss 10y ago

FWIW, Silicon Valley investor Jim O'Neill, who might well be the next head of the FDA, said this in 2014 about that: “We should reform FDA so there is approving drugs after their sponsors have demonstrated safety -- and let people start using them, at their own risk, but not much risk of safety,” O’Neill said in a speech at an August 2014 conference called Rejuvenation Biotechnology. “Let’s prove efficacy after they’ve been legalized.” http://www.bloomberg.com/politics/articles/2016-12-07/trump-team-is-said-to-consider-thiel-associate-o-neill-for-fda http://www.bloomberg.com/politics/articles/2016-12-07/trump-...

ufmace 10y ago
Now that's something interesting. I found it funny that the article didn't seem to even briefly question whether the drug approval process could be changed to make it simpler to get things like phages to patients. If we're getting lots of political change, this sounds like something that could benefit.
wahern 10y ago
That makes a ton sense, except that one wonders if any manufacturer will ever bother proving efficacy. Worse, they may instead double-down on marketing campaigns. Doctors and other professionals, working scientists or not, are susceptible to marketing like anybody else. So we'd need to see other mechanisms, regulatory or otherwise[1], that would counter that effect. FDA approval is a powerful motivator for 1) companies to find actually effective therapies and 2) as an extremely efficient signaling mechanism to the market regarding efficacy. But it's sub-optimal for many reasons, including erring too heavily on the side of safety. It's just not obvious what would replace it. Don't forget, snake oil thrives in the free market. [1] Medicare reimbursements predicated on FDA efficacy approval? I'm not sure insurance companies can be expected to do the right[2] thing. It might be cheaper to reimburse a snake oil treatment that allows the patient to die than to pay a premium for an effective treatment. And while presumably a good doctor would insist on the effective treatment, at the margins the insurance company could expect to profit from allowing their patients to choose the snake oil. [2] Where "right" means a course of action that maximizes long-term social wealth (i.e. preferring effective treatment and therefore subsidizing research), rather than simply maximizing the short-term utility of patients and profits (i.e. allowing the patients the salve of snake oil, with reimbursements, in lieu of effective treatment).