Bipolar, Kids, Key Opinion Leaders, and Cash

The New York Times has just run a great story about just how much doctors in Minnesota have been stumping for various atypical antipsychotic meds and how this is related to the large upswing in their usage. Though the focus of the article is on kids, the same quite likely holds true for adults as well.

The patient who gets the most coverage in the story is Anya Bailey, who, at age 12, apparently developed an eating disorder and was prescribed Risperdal. I’ve never seen a shred of evidence to support such a prescription, but the doctor was apparently thinking the side effect of weight gain would be a bonus in her case.

Anya developed a “crippling knot in her back” as a result of treatment. Her mother alleges that she was never told that the evidence base behind such a prescription was nonexistent. The authors say it nicely (highlighting added):

Just as surprising, Ms. Bailey said, was learning that the university psychiatrist who supervised Anya’s care received more than $7,000 from 2003 to 2004 from Johnson & Johnson, Risperdal’s maker, in return for lectures about one of the company’s drugs.

Doctors, including Anya Bailey’s, maintain that payments from drug companies do not influence what they prescribe for patients.

But the intersection of money and medicine, and its effect on the well-being of patients, has become one of the most contentious issues in health care. Nowhere is that more true than in psychiatry, where increasing payments to doctors have coincided with the growing use in children of a relatively new class of drugs known as atypical antipsychotics.

These best-selling drugs, including Risperdal, Seroquel, Zyprexa, Abilify and Geodon, are now being prescribed to more than half a million children in the United States to help parents deal with behavior problems despite profound risks and almost no approved uses for minors.

SNIP

From 2000 to 2005, drug maker payments to Minnesota psychiatrists rose more than sixfold, to $1.6 million. During those same years, prescriptions of antipsychotics for children in Minnesota’s Medicaid program rose more than ninefold.

Those who took the most money from makers of atypicals tended to prescribe the drugs to children the most often, the data suggest. On average, Minnesota psychiatrists who received at least $5,000 from atypical makers from 2000 to 2005 appear to have written three times as many atypical prescriptions for children as psychiatrists who received less or no money.

Key Opinion Leaders: Let's talk about folks who are quick to try out new drugs, often for uses that have little supporting evidence. They are called “high flyers” or early prescribers, as well as some other terms. These are the docs most highly targeted by drug companies because they tend to yield the highest return on investment. How do you target docs? With key opinion leaders. Find a "respected" physician to talk with the high flyers (though other docs are also targeted). Use a KOL who will be seen as "objective" -- this will help convince the doctor to start using the new drug(s). Read the following snippet from a company that contracts with Big Pharma to develop KOLs to influence prescribing habits. All emphases are mine.

The professional networks of physicians play an important role in product adoption. A decision to adopt a product can be profoundly influenced by Key Opinion Leader (KOL) peers who have already formed a positive opinion about a product.

Through our uniquely created patent pending process we target those KOL’s focused on top prescribers of treatments for a given specialty. These leaders significantly influence the opinions, and behaviors of others through their knowledge, advice and enhanced perspective, creating advocates which, then help gain the adoption of the product.

In this case our highly trained engineers delivered a solution using the latest technology and our proven process in a matter of weeks. Our Successful KOL program strategies are based on systematic and rigorous methods for identification, new research techniques, and the use of the latest technologies. We leveraged these strategies so that BMS could establish long-term relationships of mutual trust with these leaders built on integrity and continuity.

Through our user-friendly methodology we have proven that successful marketing and adoption of a product requires a minimum of four steps. We incorporate these four steps as the basis for this successful solution:

1. Awareness: The physician recognizes the product by name.
2. Agreement: The physician evaluates and agrees to the theoretical premise of the product.
3. Adoption: The physician decides to use the product on a trial basis.
4. Integration: The physician incorporates the product into his daily practice of medicine.

Ain’t that neat? I think you’ll see how this relates to the remainder of the NYT article, to which we now return.

Stumping for Drug Companies: From the NYT piece...

In Minnesota, psychiatrists collected more money from drug makers from 2000 to 2005 than doctors in any other specialty. Total payments to individual psychiatrists ranged from $51 to more than $689,000, with a median of $1,750. Since the records are incomplete, these figures probably underestimate doctors’ actual incomes.

Anya’s doctor, George Realmuto gave several educational marketing speeches for Concerta, manufactured by Johnson & Johnson, which also makes Risperdal. He had the following to say (and I hope he was misquoted) when asked about why he gives marketing speeches for drugs.

“To the extent that a drug is useful, I want to be seen as a leader in my specialty and that I was involved in a scientific study,” he said. [i.e. I wanna be a key opinion leader???]

The money is nice, too, he said. Dr. Realmuto’s university salary is $196,310.

“Academics don’t get paid very much,” he said. “If I was an entertainer, I think I would certainly do a lot better.”

Hey, can someone fetch me the Kleenex? Making $196,310 per year is a sign that he does not “get paid very much.” Cry me a river. In-blanking-credible.

As the interview continued, Dr. Realmuto said that upon reflection his payments from drug companies had probably opened his door to useless visits from a drug salesman, and he said he would stop giving sponsored lectures in the future.

Good for him. Now I’m not saying that his Concerta gig made him prescribe Risperdal in Anya’s case. Might having a cozy relationship with J & J lead to prescribing more J & J products? Perhaps, but I don’t know. What concerns me most is that, if he was quoted correctly and in context, he really thinks that a $200k salary is not enough income. If that’s the case, and he’s willing to put his stamp of approval on a drug via marketing speeches because a $200k salary is insufficient, then that level of greed is astounding by most standards.

Moving along…

The drug industry and many doctors say that these promotional lectures provide the field with invaluable education. Critics say the payments and lectures, often at expensive restaurants, are disguised kickbacks that encourage potentially dangerous drug uses. The issue is particularly important in psychiatry, because mental problems are not well understood, treatment often involves trial and error, and off-label prescribing is common.

The analysis of Minnesota records shows that from 1997 through 2005, more than a third of Minnesota’s licensed psychiatrists took money from drug makers, including the last eight presidents of the Minnesota Psychiatric Society.

The psychiatrist receiving the most from drug companies was Dr. Annette M. Smick, who lives outside Rochester, Minn., and was paid more than $689,000 by drug makers from 1998 to 2004. At one point Dr. Smick was doing so many sponsored talks that “it was hard for me to find time to see patients in my clinical practice,” she said.

“I was providing an educational benefit, and I like teaching,” Dr. Smick said.

Giving so many speeches pimping new drugs that you can’t find time to see patients? Dr. Smick is hereby officially nominated for a Golden Goblet Award (1, 2). That’s Pimpin’ it Hard.

Even the immediate past president of the American Psychiatric Association, Dr. Steven Sharfstein, chimed in, pointing out that it’s sure odd that Lexapro is the most prescribed antidepressant in the absence of evidence that it’s better than generic antidepressants – could it be that Lexapro still has key opinion leaders talking up the drug, Forest Labs has reps pushing Lexapro in office visits, and that Lexapro is featured in quite a bit of medical journal advertising? Hey, do you think that the meteoric rise of Cymbalta might also be due to marketing rather than scientific evidence?

Child and Adolescent Bipolar: The controversy continues. From the NYT article…

The sudden popularity of pediatric bipolar diagnosis has coincided with a shift from antidepressants like Prozac to far more expensive atypicals. In 2000, Minnesota spent more than $521,000 buying antipsychotic drugs, most of it on atypicals, for children on Medicaid. In 2005, the cost was more than $7.1 million, a 14-fold increase.

SNIP

Many Minnesota doctors, including the president of the Minnesota Psychiatric Society, said drug makers and their intermediaries are now paying them almost exclusively to talk about bipolar disorder.

On to the “research” regarding treating bipolar in children and adolescents. As discussed in the NYT article, there was a study done, in which 30 adolescents took either Depakote + placebo or Depakote + Seroquel. The combined treatment group did better at the end, but about half of the adolescents in the Depakote + Seroquel group dropped out of the study. So basically the study was a wash. Yet, in the published paper, it was stated that Depakote + Seroquel “is more effective for the treatment of adolescent bipolar mania” than just Depakote + placebo. Nice.

Melissa DelBello (author of aforementioned study) and Robert Kowatch (both of the University of Cincinatti), conducted another study on treatment of adolescent bipolar, in which Seroquel showed about equal results (perhaps a slight advantage) to Depakote. Both DelBello and Kowatch also give marketing talks for Seroquel – no doubt they are both considered “key opinion leaders.”

There have been a few other studies done, but it is safe to say the evidence base is pretty weak for treatment of child and adolescent bipolar disorder. Data on longer-term (like longer than a month or two) treatment is sorely lacking.

Here’s what one Minnesota psychiatrist had to say regarding the meager evidence base on child/adolescent bipolar:

“We don’t have time to wait for them to prove us right,” said Dr. Kent G. Brockmann, a psychiatrist from the Twin Cities who made more than $16,000 from 2003 to 2005 doing drug talks and one-on-one sales meetings, and last year was a leading prescriber of atypicals to Medicaid children.

Wait a minute, Kent Brockmann – take away one ‘n’ on his name and you’ve got this guy. HA! Anyway, Dr. Brockman needs to give kids atypicals because it is urgent – maybe he buys into the 75% of “bipolar” children become suicidal line. This line of "prescribe new meds because it's an urgent, urgent emergency" makes me wonder if the docs who are all over the atypicals now are the same ones who were prescribing Neurontin for everything as well because they "couldn't wait" for the data to vindicate their prescribing practices. As it turns out, Neurontin for psych disorders turned out to be a flop, but that didn't stop it being prescribed like candy by many docs. Maybe I'm wrong -- the Neurontin crowd could be entirely different than the atypicals for everything (and bipolar is everywhere) crowd -- I'm just taking a guess.

Oh, and as for safety…

In 2006, the Food and Drug Administration received reports of at least 29 children dying and at least 165 more suffering serious side effects in which an antipsychotic was listed as the “primary suspect.” That was a substantial jump from 2000, when there were at least 10 deaths and 85 serious side effects among children linked to the drugs. Since reporting of bad drug effects is mostly voluntary, these numbers likely represent a fraction of the toll.

Summary: The bipolar diagnosis in kids is highly controversial (1, 2, 3, 4, 5, 6) and there is pert-near no evidence favoring treatment using atypical antipsychotics to manage their “bipolar” symptoms. Key opinion leaders have done a nice job of pimping atypicals – the $170 - $250k many of these folks earn in academia just ain’t enough – they have to provide “education” to their colleagues regarding these “life-saving” medications. Drug companies decide to push a diagnosis and recruit KOLs (as well as utilizing other tricks) to persuade doctors to prescribe the new meds, regardless of supporting evidence.

Thank whomever designed the law in Minnesota requiring disclosure of industry funding. This set of data regarding industry funding could just keep giving... And thank the good folks at the New York Times, specifically Gardiner Harris, Benedict Carey and Janet Roberts, for their insightful piece of work.

Note that I'm not saying everyone who does drug-sponsored speaking gigs is a gold-chain wearing, cane-toting pimp. What I am suggesting is that conflicts of interest often influence people, even when they think they are not being influenced. I'm all about the openness. Patients should probably be aware if their doctors are receiving income on the side through promotion of a certain medication or medications. Is that too much to ask?

Also, what world do people live in when they think that a $200k salary is insufficient? Is this a sign of entitlement, poor money management, really rich tastes, or what? How many McKinnells do people think they're worth, anyway?

Hat Tip: Furious Seasons.