Saturday, December 21, 2013

GSK Eliminates Appearance of Conflict of Interest - Who Is Next?

Glaxo Smith Kline came out with a major announcement a few days ago.   It will no longer pay doctors to promote its drugs and it will no longer tie the compensation of its sales force to the number of prescriptions written by doctors who have been detailed about those drugs.  These are both standard practices in the pharmaceutical industry and this is the first announcement of its kind within the industry.  GSK will continue to to provide "unsolicited independent educational grants" to educational institutions or medical societies.  Pharmaceutical reps will be paid on the basis of technical knowledge and customer service rather than sales.  GSK has been fined heavily lately about promoting off label use of its products and is currently under investigation in China.

My immediate reaction to the piece was "good riddance".  For the past decade there has been no bigger issue in psychiatry than the appearance of conflict of interest with the pharmaceutical industry.  Psychiatry has been targeted more than any other medical specialty by prominent politicians, the news media, and even by psychiatrists themselves.  There are endless blogs and opinion pieces about how the practice of psychiatry has been defined by this appearance of conflict of interest.  There are several blogs out there that have gained prominence by endlessly reviewing all of these details. It has affected the way the APA does business.  It has affected the way local district branches do business.  In the end the politicians are grandstanding on it, because the PPACA (Obamacare) will apparently list any physician receiving money from a pharmaceutical company.  That was suggested as a motivating factor in the NY Times article.  Those public lists have existed in some states like the one I have practiced in for years.

To me the arguments have always come down to advertising and ethics.  From an advertising perspective would we expect people to be affected by product advertising?  Of course we would.  The buying habits of the American population are shaped by advertising.  Selling products is more of a science than people think.  The American public can easily change its buying habits and can purchase products that are unnecessary and will be discarded after a brief period of time.  They can also be sold on products like junk food that are unhealthy but designed to be sold in large quantities.  Advertising would not seem to be the ideal basis for marketing drugs to physicians, but with many new products  physicians are now bypassed and the drug is sold directly to the consumer.  If the epidemiology  of a particular problem like "low-T" is known, direct-to-consumer marketing probably leads to many, many more physician visits than a physician suggesting to their patient that they probably have primary or hypogonadotropic hypogonadism.  All a patient has to do is go to the web site and take a non-specific checklist quiz on the features of "low-T" and be in their doctor's office to get the levels done within a week.  Things will probably go a lot smoother without a physician intermediary in the loop and I am sure that much physician behavior will be shaped by the onslaught of men coming in to be tested for "low-T".  I know for a fact that psychiatrists are approached for this problem because of the overlap between the syndrome and depression.

Part of the advertising argument has always been that there are unconscious factors in play.  Really?  That is the basis for all advertising in general.  The main difference has been that pharmaceutical representatives have been schooled on the relationship aspects of the sale.  They have been taught that basically if a physician likes them or feels indebted to them for free food, trinkets like poor quality pens that never seem to write very well, a round of golf, or tickets to the Lakers game that they may be more likely to prescribe their product.  Most physicians were apparently naive enough to not realize that there was a huge marketing database out there that tracked their prescription writing to see if they were writing the required number of prescriptions for that product.  In the real heyday of marketing bonuses to physicians, companies would pay for travel to important meetings.

While the people focused on the advertising influence kept chipping away mostly at psychiatrists, they seemed to ignore two important developments that made detailing or selling to individual physicians much less relevant.  The first was restricted formularies.  I was on the Pharmacy and Therapeutics Committee (P&T) of one of the largest health plans in the state and an affiliated hospital for a total of 10 years.  During that time, the predominant factor in the decision about whether to put a drug on a formulary that would make it available to prescribing physicians was the cost.  There were very few instances where a drug was so unique that it was made available even if it was very expensive.  In those cases a drug might be available for an incurable illness that had a negligible benefit but it was included basically for public relations.  One of the other overriding themes of the P & T Committee was that all drugs in a particular class (like antidepressants) were equivalent and therefore the least expensive drug in the class could be substituted for anything else.  This potentially led to a lot of unnecessary chaos when medications fell out of favor due to pricing and patients needed to be shifted en masse to the least expensive drug.  It gave hospitals and health plans leverage in dealing with pharmaceutical companies, but in some cases the deals were complex.  As an example, in order to get a new blockbuster drug at a good price, the health plan would need to accept the same company's generic in a different class that had been removed because it was considered too expensive.  Over a decade ago, business entrepreneurs decided that there was money to be made rationing medications to health plan enrollees and now a lot of that is done by pharmaceutical benefit managers (PBMs).  PBMs are currently a multibillion dollar industry.

The second important development was generic drugs.  Practically all of the blockbuster psychiatric medications of the past two decades are now generic drugs.  Many generic drugs are easily affordable even as direct out of pocket purchases.  At that point they are no longer actively marketed by the pharmaceutical company that held the exclusive patents.  They are more likely to be the preferred drugs of PBMs and health plan formularies.  They are in that role because of a scientific approximation.  That approximation is that all drugs in a certain class, like antidepressants that have the same purported mechanism of action are equivalent and one can be substituted for another.  That is clearly false but it allows the health plan to to provide you with the least expensive medication or charge you a hefty copay for one that is not.  It also seems to not consider after market information that can even affect generic drugs.  The best example I can think of there is the FDA warnings on citalopram.  I would guess that despite the warnings, it remains a preferred drug by most health plans.  Health plans in general seem to be geared up to prescribe antidepressants at higher and higher rates.  I would take it a step further and venture a guess that most health plans have not taken a look at the data in their systems on whether or not they have observed problems related to the FDA warning on citalopram.

The ethical argument goes something like this.  Physicians should have the best interests of their patients in mind and an advertising based conflict-of-interest to prescribe a certain drug creates an ethical concern.  On the face of it, it seems like a straightforward argument.  But there are several problems with it.  For example, what is the direct evidence that this occurs - if any?  Is it really believable that a physician would prescribe a decidedly suboptimal medication to a patient based on schmoozing with a pharmaceutical representative?  There are often other factors in play.  It is common to treat people with chronic illnesses who have suboptimal response to the current therapy and who are looking for the "next biggest thing" to try.  A physician who has been detailed on the "next biggest thing" is likely to prescribe it if asked.  There is a similar dynamic with the issue of overprescribing in general.  If a patient persists in their request for an opioid, an antibiotic, a stimulant or any other drug are they likely to get it?  The recent declaration that the CDC initiative to decrease antibiotic prescribing has failed would suggest that they will.  Finally there is the dynamic of "see the doctor and leave with a pill."  There are any number of scenarios where medications are used in medical practice and other options are not even discussed.  The psychiatric cases are highlighted but it happens as frequently in cases of mild diabetes mellitus, back pain, chronic pain of various causes, hypercholesterolemia, mild hypertension and others.  Many people have described this as "the doctor was poised over his prescription pad" but the healthcare industry is set up to see people in brief medication focused visits and physician reimbursement is tied to it.   There are also patient related factors and a recent Tom Hanks interview is illustrative.  He was on a late night talk show discussing his recent diagnosis of diabetes mellitus and he said his physician told him that if he could get back to his high school body weight he probably would not have it.  His reply was: "Well I'm going to have Type II diabetes."

The ethical arguments, especially the ones I have seen constructed by physicians also ignore the general case of conflicts of interest at the professional level.  Practically every major university department allows its faculty to supplement their salaries by consulting in private industry.  In many cases that is a major source of additional income.  In some cases those professionals are involved in setting standards and their approach is much different than the wall that is currently being constructed between the medical profession and the pharmaceutical industry.  As an example, academic and industry professionals within the engineering profession are often on committees responsible for setting standards that govern all of the products within that industry.  Their approach is to include as many industry professionals as necessary rather than suggesting the academics can set the standards themselves.  Considering that pharmaceutical companies employ some of the top scientists in the world it would seem that medicine has a lot to lose if it goes along with the prevailing assumption.  The prevailing assumption is that physicians are powerless to stop prescribing expensive medications that are of questionable benefit for their patients based solely on advertising and no scientific merit.

I applaud the GSK decision even though the above cited factors would suggest that for most physicians it has only historical relevance.  I would encourage all of Big Pharma to adopt the same policies toward physicians.  But this doesn't really go far enough and it is basically a token gesture at this point.  To really make a difference I would suggest that they stop giving money to politicians.  GSK spent $1.9 million on candidates and $4.9 million in lobbying last year.  All of that money was directed at a few politicians.  It is a part of a massive industry wide contribution to politicians.  What do you think buys more influence, giving free pizza and pens to doctors or giving thousands to tens of thousands of dollars to politicians?

George Dawson, MD, DFAPA

Katie Thomas.  Glaxo Says It Will Stop Paying Doctors To Promote Drugs.  New York Times December 16, 2013.


  1. I'm glad you mentioned the academic acting as consultants, but it's far worse than that. The universities now often share in the profiteering involved in research funded by the drug companies, so they have a direct financial intererst in the sales of new and more expensive drugs. This situation resulted from a changes that date back to the ultra-pro business Reagan administration. Professors are often pretty much forced to participate so that they can bring in enough money to support their salaries,(for which direct state funding has plummeted and NIMH funding dropping to about 15% of submitted research proposals), before they can get tenure - and then these same people turn around and "teach" the medical students and residents. This process seemed to escalate under Bush, and it shouldn't be surprising that Donald Rumsfeld had direct financial interests with, and worked for, Pfizer and Gilead Sciences.

  2. There's another area of COI that I think is serious.

    GSK was found guilty of promoting and disseminating fraudulent 'scientific' research, used to corrupt the medical knowledge of physicians to change their prescribing habits, in the case of Paxil study 329.

    How can one properly prescribe medication when they are bombarded with fraudulent research, ghost written articles, and bad information? This is how sales reps actually close their deal, they're the ones that disseminate this bad information. Whether or not a physician feels a need for reciprocation, enough exposure corrupts their knowledge in general.

    The relationship between this type of COI and prescription habits can be demonstrated fairly easily in court. Patients are prescribed drugs for non-FDA approved conditions, and records are recorded for all prescriptions filled. From this record, the bizarre prescriptions can be correlated with a specific illegal marketing campaign, to the date of prescription, and indication for use.

    It's truly disturbing how powerful these illegal marketing and fraud campaigns can be.

    For example, "Low-T" does not exist. The conditions symptoms are normal physiological activity (aging) and/or normal human variation. There is no agreement what level constitutes "low-T", as it not recognized as a medical illness outside illegal marketing. The FDA has not approved any product for "Low-T". The off-label promotion of testosterone products by their own manufacturers for this invented condition are an ongoing Felony offense (illegal marketing and fraud) - one which they conduct in broad public view of the authorities here in the US.

    This offense is driven by fraudulent scientific papers and ghost written articles, much like the sale of Paxil to children was.

    As far as ignoring the warnings in the FDA prescribing information goes, I think many psychiatrists seem to get the idea (maybe they've been brainwashed?) that the FDA prescribing information is not accurate, or is irrelevant.

    None the less, corruption of medical knowledge is the worst outcome of COI, and I think you're correct that what GSK announced will not really change anything.

  3. Clark,

    A couple of issues. I think it is possible to release flawed drugs (let's face it most of them are - see for example my piece on flecainide versus citalopram) and they can be successfully used in medical practice. I have not prescribed paroxetine in over 20 years because I considered it to be more flawed than most (based on enzyme inhibition and withdrawal/discontinuation symptoms and no superior therapeutic effects). I can say the same thing about fluoxetine. The research no matter how good, bad or flawed never talks very much about side effects and adverse events and in clinical practice that is the priority.

    Research in general is false and that is why Ioannides article with that title was so widely accepted. As a regular reader of Nature and Science, I have read countless articles that seemed like they were groundbreaking that never panned out. In fact - hardly any have whether they were written in pure think tanks with no corporate sponsorship or by the employees of a business. The tools to recognize good from bad research needs to be available to any physician as well as he ability to analyze the data they are seeing develop in front of them. At some point every prescribing physicians is pouring over the FDA approved package insert for a drug to determine if a rare reaction is the result of their prescription of if one of their patient's numerous medical problems is a contraindication to a prescription. In a situation I will post soon, you may need to figure it out yourself.

    My point on the FDA warning is that they are ignored by corporations and generally not physicians. In fact, my guess is that psychiatrists alone have probably done hundreds of thousands if not millions of excess ECGs in search of the prolonged QTc interval that the FDA has been focused on for the past 15 years. The yield on that testing is extremely low and as far as I am concerned the analysis of the data at the FDA is questionable. But with the level of concern if you are a corporation with a large electronic health record and you potentially have tens of thousands of patients in your database on the drug and getting ECGs - there should be somebody in your IT department who can pull that data and some group of physicians who can analyze it. This would happen in some departments before business interests took over the practice of medicine and turned psychiatry into prescribing antidepressants for the masses in the shortest period of time.

    As far as COI goes that in my opinion is the greatest conflict of interest is the financial priority of businesses that run it. The financial intermediaries (HMOs, MCOs, PBMs, insurance companies) rationing both the quantity and quality of care in order to maximize profits from their patient/subscriber base. Psychiatric services by far are the most rationed and the best examples are often getting people on the least expensive drug in the shortest period of time and calling that quality care. That drug is frequently citalopram. Physicians who disagree with that model are often shown the door.

  4. Thank you for the thoughtful response,

    COI is such a large and convoluted topic it's easy to get lost in, especially as pharmaceutical companies are so regularly convicted of felonies, and in the case of Pfizer, organized crime (RICO conviction). They tend to take much attention away from other issues.

    It's easy to forget the many other factors often.
    Thanks for pointing those out.

  5. Are we really going to go down the rabbit hole of more regulation as an answer to everything? When very clearly, deregulation and streamlining of the FDA process was a Godsend in treating HIV? No, it's not the fault of the thought leaders who sold themselves out, it's the fault of Ronald Reagan. When it costs over a billion dollars and fifteen years to get down the pipeline. Really?

    Aspirin would never get approved today yet it is incredibly useful. So is off label prescribing, and any psychiatrist that doesn't prescribe off label for some cases is cheating their patients out of fear.

    Physicians blaming pharma for everything are like carpenters blaming Craftsman Corporation for lousy construction. Drugs are tools, and barring outright fraud by pharma, it is the role of the physician to evaluate their merit and utility. Particularly those overrated thought leaders in medicine who are largely responsible for the opioid epidemic.

    I always tell my colleagues who revel in pharma bashing, be careful, without them you're no different from a psychologist, except they've done more therapy.

    1. I agree with your description of medications as tools (and used that at the end of my next post). Another aspect here is that Big Pharma usually doesn't get bashed without psychiatry being bashed. Both of us are generally blamed for exposing people to side effects. There are certainly many monied interests that want to use the rhetoric in a blaming manner. The reality here is that we treat serious conditions and that is the only way you can justify using potentially toxic medications to treat them. Most people who decide to take a medication go into it with their eyes open. They realize there is a potential upside, but even watching TV ads for what is in some cases cosmetic treatment ends with disclaimers about activation of TB, cancer and death.

      Also agree with your about the negative impact of thought leaders. In many cases there is a government or IOM initiative that is strictly politics as usual. These initiatives can be wide ranging and I hope to post a big conflict of interest piece the first of the year on how all of this flows down onto the backs of physicians.

      In that scheme of things Big Pharma COI is trivial and it gets more trivial as the generics accumulate and we get more name brand drugs that aren't much better. I am hoping that Big Pharma can come up with some antibiotics before we slip more deeply into the post antibiotic era.