Saturday, May 17, 2014

Era of Blockbusters Is Over? I Hope So.

1BOM posted a link to a Forbes article on the issue of blockbuster drugs.  Journalists are typically slow to pick up on this because it takes the element of scandal out of any relationship between physicians and the pharmaceutical industry.  After all, aren't physicians clueless about pharmaceutical advertising and mindless cogs in Big Pharma's attempts at hegemony?  The tone of the article is that Big Pharma is now increasing the drug prices for therapies targeting fewer conditions.  No thanks to Big Pharma for all of the innovation currently used by the generic pharmaceutical companies.  As an example, I bought a bottle of montelukast (90 tablets) a month ago for $9.  It is the Singulair product list as Merck's 2010 blockbuster drug in the Forbes article.  As far as I can tell, it is the only effective treatment for an asthma attack that has caused me to take oral prednisone, inhaled glucocorticoids of various types, nebulizer treatments, inhaled ipratropium, and various inhaled beta agonists for the past four months.  I didn't see the US government or the academic community inventing montelukast.  In fact, I don't see the US government or the academic community doing much about the fact that the average asthmatic is still wheezing and there is no effective approach to preventing the spread of respiratory viruses that are a major cause of this problem.  I guess their solution is to partner with managed care and suggest that pay-for-performance is going to save us all.  Maximum treatment with everything except montelukast has done nothing for me.  What would pay-for-performance do?

Maybe that is why doctors who I have seen always ask:  "Are you sure you NEVER have smoked?" That seems to happen after the usual: "I like to treat asthmatics because I can do so much for them!"  If that is true why are most asthmatics still wheezing?  I think it is fair to say that the only reason I am wheezing less at this point is due to Merck.  The necessary CME disclosure at this point is that I do not own any pharmaceutical company stock, but I am quite willing to admit it when I see a good product defined as one that works for me.  Since the focus of this blog is on psychiatry - I also get direct feedback from patients that the medication I prescribe has had some of the same effects.  That is even in the case of medications that I never prescribe - paroxetine and fluoxetine, in people I see for consultation.  And for all of the clinical trials obsessed out there - I suppose I could just say or think: "I guess this person is unfamiliar with the meta-analyses critical of antidepressant efficacy." or at least: "I guess this person has never been on the Internet and read about the horrendous side effects of these medications."  But being the foolish psychiatrist I am, I am likely to think that a person with severe depression requiring hospitalization, severe postpartum depressions with psychosis and suicide attempts, or severe disabling depression may have actually found an effective medication that works for them.  I am much less impressed by the work of statisticians than the experience of my patients, especially when their lives are back on track.

In terms of the cost of psychiatric medications, this is really an old issue.  It was years ago when I noticed that people could pick up citalopram for $4 a month at Wal-Mart.  I had to point the wide availability of generic antidepressants in a response to a Washington Post article.  I guess the DSM-5/Big Pharma conspiracy is not looking too good now.   Sure there are new antidepressants, but there is no reason why they should be first line drugs.  Anyone with an first time PHQ-9 elevation is going to get an inexpensive SSRI.

All of the critics of Big Pharma were naturally slow to pick up on it, especially the antipsychiatry crowd because it means that the moral high ground is lost.  They can no longer devalue everything that psychiatrists do based on the alleged Big Pharma connection with a handful of psychiatrists.  Of course they can keep the conspiracy theories going about some missing clinical trial results of a now generic drug that is over thirty years old.  They can conflate that as having something to do with psychiatry despite the fact that the major regulators like the FDA have done nothing about the drug based on post marketing surveillance.  They  can blame psychiatry for the overprescribing of primary care physicians and the institutionalized overprescribing of managed care systems.  The antipsychiatrists will certainly continue to hate psychiatry and the critics will still have an axe to grind with particular psychiatrists. But at least I won't have to tolerate a smug blogger proclaiming that they were "Keeping psychiatry honest since 2007."  I have actually done very well maintaining my honesty without the help of a self promoting blog and the psychiatrists I know have done the same.

And wait a minute - what about the real epidemic that has been actually killing more than 10,000 people per year for over a decade?  Plenty of generics there and plenty of ways to take way too much acetaminophen.

The other problem with the Big Pharma conspiracy theories has been a general naivete about capitalism and marketing.  Advertising is good for the New York Times, but not a medical journal or meeting.  Physicians need to be cloistered from market influences.  They could be corrupted in a way that is inimical to the interests of patients.  Direct advertising of toxic medication to consumers is a much preferred route.  As far as the "me too drug" argument goes, let me illustrate the problem with that argument by my trip to the convenience store today.  I ran out of grape juice today.  I only drink Welch's 100% grape juice, diluted at a ratio of about 5:1 with carbonated water.  I drink about 576 fluid ounces of the stuff per month.  Rather than go to a supermarket, I went to a convenience store because it was closer.  On the shelf were a vast array of chemical drinks and sodas of no nutritional value, small bottles priced at what I could buy 64 ounces of pure unsweetened grape juice for.  The comparisons were overwhelming.  Self proclaimed nutritional drinks that had no calories, no protein, and plenty of artificial sweeteners.  Natural juice "beverages" or "cocktails" that had vanishingly low amounts of actual juice.  All of these products basically knock offs of fruit juice, but, heavily marketed, neatly packaged, much more expensive, and having the occasional nutrient value of added vitamins.   Does a "me too" pharmaceutical have less value than a "me too" soft drink?  There is no comparison.

I also had the association to my Peace Corps experience.  In the country where I served in Africa, there was a place called the Northern Frontier Zone.  There was a police outpost there and you had to sign a register acknowledging that the local government was not responsible for your safety once you crossed into that territory.  One of the best ways to get there was to hitchhike on large trucks carrying Coca-Cola.  You just had to get comfortable laying on cases of Coke.  Over the years,  I have drank as much Coke as anybody - but for the purposes of this post and the focus on advertising and marketing consider what I am saying here.  In 1975, Coke was widely available in remote African villages and the Northern Frontier zone.  For most people it was more widely available than clean water.  Since then. they have sold increasing amounts of the product.  The world is dominated by American cola manufacturers.  Are "me too" pharmaceutical products less valuable than Coca-Cola?  I would suggest that they are probably not and they are marketed a lot less vigorously.  Unless I have missed it there has been no complaint about Coke's world domination, although I sincerely hope that a psychiatrist is never photographed drinking a can.

I might be biased by a good four months of decreased wheezing, but I hope the general message on the Forbes article gets out and clears some of the air.  In psychiatry, there are many more important things to focus on than conspiracy theories that really don't apply to the vast majority of psychiatrists.  You can't take physicians out of their historical mandarin role and instead blame them for colluding with Big Pharma.  It may have been a political strategy to get them out of that role and suggest that politicians (of all people) should assume that role.

The work psychiatrists do is tough and demanding.  No psychiatrist who I have ever talked with expects a pat on the back.

Getting out of our face is a pretty modest wish.

George Dawson, MD, DFAPA

Supplementary 1:  I also have no financial interest in any of the other products mentioned here including Welch's grape juice or Coca-Cola.  I used the real names because they are historically accurate.


  1. You've covered a lot of ground in this article. The only confusing part was about the me-too drugs.

    Me-too drugs are a drug companies business, yet I don't think they move science forward. The pharmacists I knew really disliked them. I suppose it is on how they were marketed. They didn't just market that there is a population their medication may work for where others failed, they actively had to bash the competition by making up stuff about better side effect profiles.

    There was one pharmacist that spent much time fighting them off of formularies, yet if a medication was working for an inpatient prior there wasn't an issue with them bringing in their own meds if they insisted, and if a physician really wanted it, it wasn't unusual for me to go to a retail pharmacy to pick some up and repack for their stay in the hospital.

    The soda and juice example is lost on me. Why would it be a good thing to have soda in an area before clean water? And, all the grape juice examples are just evidence of the garbage companies will sell us.

  2. That's my point RB.

    The only reason why you have Coke before clean water and "garbage" of limited value being sold to us is marketing. And yet - the only complaining about this occurs in the context of Big Pharma. Sure the pharmacists dislike marketing because (like physicians) they are not the consumers. They just have to deal with it.

    On the other hand - the Golden Age of Big Pharma began with H-2 blockers. I know some pharmacists who invested at that point and did quite well. On the other hand there is not doubt that the "me too" drugs ranitidine and famotidine were much better.

    These days PBMs are much more relevant and can package various generics with their flagship name brand drug and make money off health plans.

  3. I think my definition of a "me too" drug may be be more limited than yours. In my mind, they are no better than each other; they may just work differently in different people, perhaps a Godsend for some.

    My gripe is the massive effort spend on creating a medication because another company is making a windfall profit it, and not spending it on creating something better, Again, not my call for how a company or a hospital spends their money, but I am glad I did a stint in pharmacy. I think I have a better perspective as a patient. Maybe to the chagrin of my physicians, yet they don't have to live in this body of mine. For H-2 blockers, I'd take a PPI over them any day. Yet, you know what I would take over either. A fundoplication, even with all of its risks.

    What you say about H-2 blockers and the rise of Big Pharma matches what the pharmacists told me, although I never heard them use the term Big Pharma, and I don't either. They are just companies to me. They do some good things like their charity plans, and quite a few bad things like every other company I have ever dealt with.

    I am glad you have a med that works for you now. The vast majority of medications aren't evil incarnate. They are like everything else in world; all in how you use them.

  4. I only use the term Big Pharma so the antipsychiatrists, critics and detractors know I am referring to the same entity. It is a rhetorical term like psychiatry in the monolithic sense - as if there was such an entity.

    I real life and in talking with pharmacists in many capacities we use the specific company name.

    Even the PPIs have been problematic - the first one has more interactions even though it is generic.

    Fundoplication - really?

    I am reminded of the definition of minor surgery = surgery on someone else. Everyone has their preferences.


  5. I understand why you use the term Big Pharma and I didn't mean to imply anything different. I felt I had to call it out in the context of my conversations with pharmacists though; that they didn't think in those terms, nor did I, even though we both could hate on drug companies sometimes.

    The other thing I didn't state which you so plainly do, is how much medications have helped people to include saving their lives. I take this as a given (that you have to spell it out says a lot about what people take for granted). And for the awesome benefits from meds, I give credit to the scientists and physicians who worked on them. However, I do wonder what we could have had better instead of as patients being content with good enough, and what decisions in the boardrooms have had on us all. But, these are things I'll never know.

    For surgery, one and done, is how I look at it. I made a decision for surgery to correct sleep apnea because I had an indication for it (hypertrophic tonsils), the 50/50 odds were good enough for me, and I didn't like the thought of being tied to a machine for the rest of my life even though I preferred using it to not. It worked out ok. Actually, all of my surgeries have been good. Of course, I've had awesome surgeons. Perhaps, I shouldn't press my luck :)

  6. Thought experiment: I give you 1.5 billion dollars and 15 years to get a new drug to market. If it fails at any one of the three levels, you lose all your money, if it succeeds, then you make 10 billion dollars. Which strategy do you employ?

    A. Develop a novel drug with a completely new mechanism of action never before tried.

    B. Take another company's drug that is working and selling big, change a H to a CH3 in the molecule, or find the working enantionmer and isolate it, then sell it as another drug.

    I think the question answers itself...

  7. Well, if every drug company exec thought like this, then we'd never have a novel drug. Of course we are fast approaching this or that they will all switch to creating biomedical devices because developing meds is just too expensive.

    I'd rather give the 1.5 billion dollars to some scientists that have some business sense and let them see what they could do with it. I live in Kodak, Xerox and IBM land and I've seen how companies with zero vision, no novel ideas or worse, novel ideas that they don't develop, with a pursuit of only short-term profits end up. I've been surprised at how long a company can run on fumes from the enterprise built decades ago.

    I don't know how to have competition in an area so expensive, yet I hope for more. Then the old companies with no ideas can just go to their graves. I was really excited about the kid that "discovered" a marker in blood to identify pancreatic cancer until the skeptics blew me out of the water with the fact that he hasn't published any data yet. Maybe it is a legal thing. Still sad regardless. Those kind of events bring me hope and having them end badly is very disappointing.

  8. What's the solution? We do need blockbusters, particularly for infectious disease.

    We also need them to be affordable.

    Maybe set up a 2 billion dollar prize (kind of like the book "Longitude" for an antibiotic that can fight MRSA better than vancomycin...but with the caveat that its sold for 1 dollar a pill....phase 1 and phase 2 only for approval...

    1. I like your idea. It is a novel idea to us, but centuries old; kind of cool.

      Anyway, I don't expect to see the government supporting anything like this for infectious diseases until we have another plague. In the meantime, I can still hope for some rogue scientists working somewhere to find the next penicillin.

  9. Here's a timely article on the subject. One I came across just now.