Flogging a dead horse

I’ve written about the subject before, I’ll do it again even if it doesn’t really make any difference. Here’s a great piece Maryn McKenna (via Ed Yong). A quote from Hughes’ op-ed which she links to in her article:

“From 1983 to 1987, 16 new antibiotics were approved by the US Food and Drug Administration (FDA); from 2003 to 2007, just 5 were approved.[5] Since 2008, only 2 have been approved”

Here’s a quote from McKenna’s piece:

“Drug resistance is a biologic inevitability — but in the 83-year history of the antibiotic miracle, starting from Fleming’s first recognition of natural penicillin, whenever resistance made one drug useless, another drug came along to save us. Those days are over.

Think for a moment like a pharma company. It’s generally accepted that it takes 10 years and about $1 billion to get a new drug from concept to marketplace. At the end of that investment of time and money, you’re left with a drug that is only taken for weeks at a time, that bacteria will develop some resistance to within a year, that doctors will cease to prescribe once approximately 20 percent of infections demonstrate resistance — and which, if it’s a very, very promising drug, doctors may not prescribe at all, because they want to preserve it for the most dire cases.

if you were a shareholder in that hypothetical company, wouldn’t you want them to make Viagra instead?”

One might ask if that hasn’t always been the case, ie. that there’s always been a trifecta of short time of treatment, risk of low sales even if drug is effective and high fixed costs related to treatment of infectious disease, and if so why did pharma-companies keep developing new drugs before? One reason things have changed is that the alternative potential profits from developing drugs treating life-style related diseases have increased dramatically. Another reason is that the development costs have increased over time, in part because the demands related to obtaining FDA-approval of a drug have increased over time. No matter why things have changed though, there’s no doubt they have; the number of new drugs which were approved in 2003-2007 was less than one third the number of drugs which were approved 20 years earlier in a similar amount of time.

Do remember that this problem is not just related to the fact that, well, bacterial infections kill people. Lots of people. Some infections don’t but that doesn’t mean they can’t be pretty damn bad anyway because of quality of life-issues; ask the deaf kid who went through an untreated ear infection causing hearing loss. But a major problem is also that a lot of medical advances made over the years depend crucially on the ability of doctor’s to deal with infections. Hughes gives the examples of “cancer treatment, surgery, transplantation, and neonatal care” in his piece; that list is not exhaustive, for instance the most common treatment of autoimmune diseases, which are caused by an overactive immune system (roughly speaking), is immunosuppression – which increases the risk of bacterial infection. And yes, there are a lot of autoimmune diseases out there.

Btw, according to McKenna antibiotics aren’t the only drugs we are running out of.


March 2, 2011 - Posted by | Cancer/oncology, Economics, Health Economics, Infectious disease, Medicine, Pharmacology


  1. Wouldn’t a rise in antibiotic demanding treatments as immunosupression and such raise revenues of providing good antibioticals? I’m quite aware, that the increased use of antibiotics make the timespan of their use shorter, but at least there must be countereffects considering the commercial possibilities.

    (Nitpicking: I see that ulcerative colitis is listed as a autoimmune disease with a status of “accepted” as such with an official looking reference, I can’t figure out how to read. Yet I believe it is more accurate to say it is strongly suspected to be so, yet there is not yet concensus about it – as Wikipedia actually says in their UC-article.)

    Comment by info | March 2, 2011 | Reply

  2. “Wouldn’t a rise in antibiotic demanding treatments as immunosupression and such raise revenues of providing good antibioticals?”

    Yes, but only if the doctors actually dare subscribe the immunosuppressants. For some diseases, there’d be no alternative to treatment of the primary disease, for others there would be a relevant tradeoff for the doctor. The point is that in a world with very little to fall back on in case of bacterial infection, the doctor who’s considering prescribing the immunosuppressant will be less likely to treat the primary disease if he by doing that might end up killing his patient by increasing infection risk significantly.

    Yes, prescribing immunosuppressants increases demand for antibiotics. So does doing major surgery. But few surgeons would dare to operate if they had no way of treating a potential post-operative wound infection. A similar mechanism is at work when it comes to the (now) standard steroid treatment regimes of many autoimmune diseases. When the number of multi-resistant strains of bacteria increases, doctors will probably be less likely to employ treatment regimes which significantly increase infection risk and this in turn leads to lower demand for antibiotics, which again decreases the profitability of developing new drugs to counteract the problem with resistance.

    As to the nitpick, if you think the article is incorrect, why not leave a comment on the talk page of the wikipedia article and/or a tag/correction in the main article? That’s how wikipedia improves over time.

    Comment by US | March 2, 2011 | Reply

  3. My undereducated wild guess is that in the medium-to-long run, antibiotics as a way to fight bacterial infections will go the way of abacuses (abaci?). Rather than trying to make molecules that kill bacteria, humans will build entities – nanomachines, manufactured viruses, or whatever – that go after them. Creating a temporary homeostasis within the human body that is inhospitable to bacteria is akin to fumigating a room to kill mice, the alternative being releasing cats – ideally cats that do not also tear up the furniture.

    To go back to the issue at hand though: I am not sure I understand the “… doctors will cease to prescribe once approximately 20 percent of infections demonstrate resistance” bit. Will the doctors really not prescribe it if the best alternative is a drug with 50% of bacteria strains resistant to it? Sure, especially in the USA’s litigious culture, they may require you to sign waivers for liability if they do surgery on you, and you get killed by a bacterial infection afterwards, which turned out resistant to their best antibiotics, but… yes, it will affect treatment decisions, but I do not see why necessarily in the direction of “the drug will never be prescribed”. If it’s the best (i.e.with least resistance to) drug, it seems to me it will still be a blockbuster, especially given the explosion of “optional” surgeries – cosmetic, joint replacements, etc.

    To sum up, I definitely see a problem for patients, but not so much for pharma companies. They have other big problems – I have friends relatively high up the food chain in marketing research in Bristol-Myers Squibb – and most of those come from the gov’t getting in the way. Insider tip: in the next 10-20 years, expect major consolidation of Big Pharma companies, with drug development mostly outsourced to start-ups which are to be acquired as soon as they have anything remotely viable in the pipeline.

    Comment by Plamus | March 3, 2011 | Reply

  4. @Plamus:

    ‘Rather than trying to make molecules that kill bacteria, humans will build entities […] that go after them.’

    Human’s have, just like most other living species today, spent more than 500 million years developing our own highly complex natural system for just these kinds of purposes. We have 20 cats in our living room already. We can improve upon that system on the margin, but to think that we can engineer a solution system which is far superior to one that has already been shown to be able to handle hundreds of millions’ of years worth of selective pressures – I don’t think that’s realistic.

    Regarding prescriptions, the main point is that resistance increases in consumption. The more you use the stuff, the more strains will become resistant over time. It will be 20 percent for a while, then it will become 50 percent. Maybe it will never get there; at some point the cost/benefit-ratio tips and the drug will no longer be prescribed or be prescribed at a volume that makes the expected future revenue streams very small.

    “If it’s the best (i.e.with least resistance to) drug, it seems to me it will still be a blockbuster” – but the expected payoffs from a drug which in 30 percent of cases is ineffective is different from the expected payoffs from a drug which works in 95 percent of the cases. The higher the difference in effectiveness rates, all else equal the faster the convergence in effectiveness (/resistance) rates. Unless doctors systematically decide to limit the use of the effective drug and only use it as a last resort, in which case the convergence speed might be slowed down somewhat. This is what is happening now and this is why even new and highly effective drugs aren’t used as much as it might be optimal to do in the short run; the doctors already take into account that there might not be a new superdrug coming around anytime soon to replace the existing one if they don’t limit use of the effective drug significantly. This behaviour limits future supply but it also decreases the likelihood that mrs. Faber in bed 4 dies of pneumonia.

    Maybe nano-stuff makes a big breakthrough, what do I know, but right now we’re getting fewer new treatment options every year and the ones we have get obsolete at a faster and faster rate. That doesn’t sound like progress to me.

    Btw., my big brother currently works in pharma as well (I don’t want to say any more than that at this point). I never said pharma companies were in trouble, I (/and McKenna) just made the case that their current incentives do not give much cause for optimism regarding the future of patients. FDA’s restrictive approval procedures of new drugs (and similar national systems in Europe) is part of the problem, I have no problem agreeing with that – we know that it’s one of the reasons why the fixed costs are so high.

    Comment by US | March 3, 2011 | Reply

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