Prescribing by habit and evidence

A recent Rolling Stone article on the over-prescribing of Eli Lilly's anti-psychotic Zyprexa (olanzapine) started me thinking in a general way about the psychology of choosing what to prescribe.  I've written before about the effects of pharmaceutical marketing, how billions are spent to influence doctors' prescribing habits at both rational and non-rational levels.  The Zyprexa article offers more on this topic.  But it also widened the issue for me as I reflected on my own prescribing.  For today I'll let Big Pharma off the hook and look at other influences that affect prescribing.

Most doctors have "favorite" medications within a particular class that we prefer to prescribe.  Besides marketing influences, this can result from anecdotal experience:  If my last patient had a wonderful result on this drug, maybe my next will too.  Conversely, if my last patient had a terrible reaction, how can I risk giving the same drug to my next patient?  Such reasoning is unscientific yet very compelling.  First-hand outcomes are psychologically hard to discount, even when careful studies of large numbers of subjects provide far better evidence for the risks and benefits of a given treatment than anyone's limited personal experience.  Likewise, the opinion of a trusted colleague (or attending physician, if one is a trainee) tends to make an impact regardless of the popularity of, or evidence base for, that opinion.

These are the sorts of biases that the evidence-based medicine (EBM) movement tries to stamp out.  According to EBM, we should base clinical decisions on the best available evidence, ideally large randomized controlled trials.  On the one hand, the need for Western medicine to declare itself "evidence-based" is almost an embarrassment; it should go without saying.  The scientific method is the bedrock of allopathic Western medicine.  It separates physicians from faith healers and snake-oil salesmen.

On the other hand, many areas of medicine lack the EBM gold-standard of randomized controlled trials (or the trials are inconclusive, conflict with each other, etc).  Studies of certain treatments, like dynamic psychotherapy, present severe methodological challenges. Randomized studies of invasive surgical procedures can be unethical.  Some studies are funded and others are not, for reasons having nothing to do with science.  Moreover, the results of randomized controlled trials are population averages, and individual patients do not always react the way the "average" patient does.  Fully evidence-based practice is an ideal, not possible in real life.

More important, both the prescribing physician and the patient are people, and we humans have feelings and preferences that affect our choices.  Doctors often prescribe particular drugs within a class purely out of habit.  The familiarity is comforting; dosing is easier, potential side-effects and interactions with other drugs are no surprise and are handled in stride. Experience prescribing one drug increases at the expense of familiarity with equally good alternatives.  Conversely, some physicians are "early adopters" who like to prescribe the newest product out.  While this is not my style, I assume the motivation is to be on the cutting-edge of the field.  The effect of the prescriber's personality on treatment decisions sounds like a ripe area for research.  A brief PubMed search reveals a few interesting abstracts: 1, 2, 3, 4.

Patients, too, have preferences, not only for heavily advertised products, but also for medications taken by relatives and friends.  And doctors, knowing that a patient's belief in a treatment can aid its success, are inclined to prescribe what the patient asks for — if it is in the right ballpark.  Patients also weigh risks and benefits in personal ways.  One patient may disregard potential weight gain as a trivial concern, while another flatly refuses any treatment that can add pounds.  EBM can never account for such personal preferences.  (Some PubMed abstracts on patient attitudes and preferences: 1, 2, 3, 4.)

The prescribing of psychiatric medications is a combination of evidence-based medicine and the art of medicine.  The latter includes unfortunate biases — at times leading to overprescribing of medications such as Zyprexa — as well as essential sensitivity to psychological issues and patient preferences.  Until doctors are replaced by computers, and patients accept treatment without regard to individual preference, medicine will always reflect this combination.

Long hours in medical and surgical residency

The New York Times health blog "Well" today posted:

A national panel of medical experts proposed significant and costly changes for training new doctors in the nation’s hospitals, recommending mandatory sleep breaks and more structured shift changes to reduce the risk of fatigue-related errors.

 The report was issued by the Institute of Medicine (IOM).  As expected, there are hundreds of comments on the blog.  Many established doctors defend current training practices (or lament the loss of even more grueling ones in the past) as the best way to get maximal experience during training.  Some residents also defend current practice, while others recount mistakes made while sleep-deprived, and call the system senseless.  Most self-identified laypeople condemn as obviously poor patient care a system where doctors work for over 24 hours without sleep.

Sleep deprivation during medical/surgical training has been an interest of mine since I was in training myself in the 1980s.  I even wrote a paper on it as a medical student.  This is my commentary I posted to the "Well" blog.  I invite your thoughts here.

I’m a psychiatrist involved in medical education my whole career. It’s a relatively easy specialty in terms of training hours. But I was a med student and had a medical internship like other MDs, and was appalled by the hazing justified as a necessary educational experience. Like a fraternity initiation, each generation of doctors imposes it on the next to keep medicine special, to maintain a sharp in-group/out-group distinction. It is also perpetuated institutionally thanks to the unbeatable economics of paying a highly trained, intelligent workforce minimum wage.

There is no way to learn everything in training, whether residency is 3 years or 10. The conceit that the current system teaches residents “everything they need to know” leads to calls to add residency years to make up for reduced hours. But how did we determine we’re teaching residents the “right” amount now?

In an era of evidence-based medicine it is medical training itself that resists the application of empirical science. Plenty of studies show cognitive and interpersonal deficits with sleep deprivation. There are none I’m aware of that show these effects can be trained out of people, nor that long call hours “teach” residents to make hard decisions in the middle of the night. If we rely on personal anecdotes, my experience says that sleep deprivation teaches trainees that working half-awake is acceptable as long as you survive the ordeal, that procedures are more important than talking with patients — there goes prevention and lifestyle changes — and that anyone who criticizes this heroic undertaking is a wimp who “just doesn’t get it.”

Certain rote practices like CPR or running a code improve with mindless repetition, but sensitive interpersonal skills (eg, discussing a patient’s cancer diagnosis) do not improve by “practicing” them over and over when you can’t think straight. The human qualities of great doctors — caring, sensitivity, interpersonal nuance — are profound gifts. It is a cruel and misguided system that devalues these gifts in order to to maximize the repetition of protocols and procedures.

Where to go from here?

1) Obviously, the IOM’s changes will cost money. Other countries with excellent health care systems have found a way, and we can too.

2) Medicine is already too complicated to sign-out (ie, hand off) patients in the informal way we do now. Electronic medical records with built-in error checking is inevitable in the near future. It’s a good thing, particularly at this error-prone step.

3) The “ownership” of patients is a real issue, and may be made worse by a shift-work mentality. The solution is not to avoid shifts — they are inevitable in any business that is open 24/7 — but to (re-)instill a cultural norm that caring about *people* is expected, and frankly more important than memorizing the last 5 days of electrolyte values. I’d rather be treated by a well-rested doctor who cares about me but has to look up the labs.

http://www.stevenreidbordmd.com/blog.html

— Steven Reidbord MD

Does your doctor attend biased professional talks?

On October 3rd the New York Times reported that several prominent research psychiatrists are under Congressional investigation for failing to report income derived from consulting and speaking for pharmaceutical companies.  One of the field's most renowned and prolific researchers, Charles B. Nemeroff MD of Emory University, stands accused of concealing over $1 million since 2000, thereby violating federal rules aimed at avoiding conflicts of interest in medical research.  Senator Charles E. Grassley (R-Iowa), leader of the Congressional inquiry, has also sponsored the "Physician Payment Sunshine Act," which would require industry to publicly list payments to doctors.  Several states already require this, and two drug companies recently announced they will voluntarily list payments to doctors starting next year, even without legislation. Senate allegations of million-dollar malfeasance are, unfortunately, just the tip of the iceberg.  While professional journal articles, newspaper op-ed contributors, and bloggers (e.g., here, here, and here) have documented the problem for years, the public still has little grasp that over half of all continuing medical education (CME) in the US is paid for, legally, by commercial interests.  This often takes the form of sponsored talks:  Prominent physicians like Dr. Nemeroff are paid to speak to medical audiences about a specific disorder and its various treatments — one of which is nearly always a product of the sponsoring company.

To address the clear potential for bias, CME speakers are required to disclose to the audience any financial ties to industry.  However, it is unclear to what extent disclosure matters if the talk is subtly biased anyway.  After all, television commercials clearly disclose the company behind an overtly biased sales pitch, yet this form of advertising remains effective.  Corporate sponsors also argue that competition among products leads to the necessary scrutiny to arrive at the truth — speakers for Company A will critique drug B, and vice versa.  Meanwhile, the sponsored speakers themselves declare their own neutrality ("Money can't buy me!"), sometimes pointing out that, like Dr. Nemeroff, they are sponsored by so many different companies that they favor no particular product.

Since regular attendance at CME activities is required to maintain a medical license, the mere possibility that this information is slanted ought to raise alarms in the medical community and in the public at large.  Yet only a few studies have been done to find out.  A recent review of ten empirical studies concluded that "there is no empirical evidence to support or refute the hypothesis that CME activities are biased."  This conclusion has been systematically critiqued by psychiatrist Daniel Carlat MD here and here.

While conflicts of interest during presentations are worrisome enough, the biomedical research being discussed at CME talks is itself heavily funded by industry, leading to concerns (and some troubling data) about bias at even this most basic level of medical knowledge.

The ethical issues here are almost too obvious to point out.  Physicians are duty-bound to recommend the best treatment for a given patient, not the treatment presented most persuasively by an industry-paid speaker.  Willing receptivity to a possibly biased talk is little better than prescribing possibly tainted medication.  Sponsored speakers themselves ought to reflect on the ethics of giving talks they may subtly slant despite their own best intentions.  It may be sheer hubris to imagine that one can avoid any hint of favoritism when one's speaking fee is paid by the manufacturer of a product under discussion.  Stepping further back, educational institutions such as medical centers that review and approve CME ought to consider whether the industry money coming in justifies the potential bias coming out.  And stepping back again, the medical community as a whole should assess the price paid in professionalism and public trust when it accepts industry largesse.

I'm sorry to report that psychiatry is one of the medical specialties most accepting of Big Pharma money.  As a matter of principle, I avoid nearly all industry-sponsored CME (occasionally it is virtually unavoidable), as well as all direct marketing contact with sales representatives.  In my next post, I will tell how I nearly became an industry speaker myself without realizing it.