The .Plan

I described this phenomenon in a talk I gave yesterday, but not nearly so eloquently…

[The sheer abundance of medical knowledge] crowds out an important — in fact, the only — skill that matters in treating a patient: how to critically appraise published clinical trials. Few doctors ever read them. In effect, medicine has become a priesthood of practitioners who never review or learn to interpret the Bible to minister to their flock; they instead rely on secondhand wisdom. Or, worse, on Google.

That is why, for example, the average internist can describe the branching patterns of the major coronary arteries but not the primary clinical trials assessing how much, if at all, various cholesterol-lowering agents cut heart-attack risks. Or, for that matter, whether the trials were soundly conducted… Filling the training vacuum, an unregulated, for-profit industry of information peddlers is emerging to interpret clinical trials and guide treatment.
–Darshak Sanghavi, “Training Daze”, Slate, March 12, 2008

Anjan Chatterjee, tracing out the full, and possibly eventual, implications of enhancement technologies:

People already use legal performance enhancers, he said, from high-octane cafe Americanos to the beta-blockers taken by musicians to ease stage fright, to antidepressants to improve mood. “So the question with all of these things is, Is this enhancement, or a matter of removing the cloud over our better selves?” he said.

The public backlash against brain-enhancement, if it comes, may hit home only after the practice becomes mainstream, Dr. Chatterjee suggested. “You can imagine a scenario in the future, when you’re applying for a job, and the employer says, ‘Sure, you’ve got the talent for this, but we require you to take Adderall.’ Now, maybe you do start to care about the ethical implications.”
–Benedict Carey, “Brain Enhancement Is Wrong, Right?”, New York Times, March 9, 2008

It was 65 degrees today. I looked longingly out the window.

In 1996, Patricia Huston and David Moher published an article in the Lancet entitled, “Redundancy, disaggregation, and the integrity of medical research”. In this article they describe one particularly egregious example of “salami science” in which the results of a single study of risperidone in the treatment of chronic schizophrenia was reported in six different publications and cited in several unpublished forms, and each iteration featured different numbers of patients and different co-authors.

Last year, while doing some research for a journal club presentation, I came across the “ARISe-RD” study in which the researchers attempt to widen the indications for atypical antipsychotics by featuring it in an open-label study of patients with “treatment-resistant depression”. I kept finding different references to the paper, and by the end of the day I had located 8 different abstracts, published between 2003 and 2006. At some point during the paper’s meandering journey through time and space, Charlie Nemeroff (labeled by T.E.N. magazine as “boss of bosses” in the field of psychiatry) had mysteriously become senior author. Equally mysteriously, Martin Keller (regarded by some as a bigwig) — who was, according to the authorship rosters, not involved with the study prior to 2006 — makes an appearance on the final manuscript in which he is credited with “study concept and design”.

Gawd. And we’re pushing these drugs on kids on the basis of these kinds of schlock researchers?

Rapaport MH, Canuso CM, Loescher A, Lasser R/.Gharabawi G : Preliminary results from the ARISe-RD (Risperidone Augmentation in Resistant Depression) trial 156th Annual Meeting of the American Psychiatric Association, May 17-22, San Francisco CA 2003, NR179

Rapaport M, Canuso CM, Loescher A, Lasser RA, Gharabawi G : Preliminary results from the Risperidone Augmentation in Resistant Depression) trial 156th Annual Meeting of the American Psychiatric Association, May 17-22, San Francisco CA 2003, P. 184

Rapaport MH, Canuso CM, Rouillon F, Leblanc J, Young AH, Loescher A, Bossie C, Turkoz I, Gharabawi G : Results from the augmentation with risperidone in resistant depression trial 157th Annual Meeting of the American Psychiatric Association; 2004 May 1-6; New York, NY 2004, NR799

Canuso C, Gharabawi G, Bouhours P, Leblanc J, Dunbar F, Rapaport MH. Results from open-label phase of ARISe-RD (augmentation with risperidone in resistant depression) [abstract]. Int J Psychopharmacology 2004;7(Suppl 1):S345

Gharabawi G, Canuso C, Greenspan A, Bossie C, Loescher A, Turkoz I, Alexopoulos G : Remission and maintenance effect of risperidone augmentation for older patients with resistant depression. Neuropsychopharmacology 2004, 29 Suppl 1, S87

Nemeroff CB, Canuso CM, Mahmoud R, Loescher A, Turkoz I, Rapaport MH, Gharabawi GM : Augmentation with risperidone in chronic resistant depression:A double-blind placebo-controlled maintenance trial. Neuropsychopharmacology 2004, 29 Suppl 1, S159

McIntyre RS, Canuso CM, Bossie CA, Turkoz I, Gharabawi GM : Symptoms of anxiety and relapse in patients with resistant depression. 45th Annual NCDEU (New Clinical Drug Evaluation Unit) Meeting; 2005 June 6 - 9; Boca Raton, FL 2005, 170

Rapaport MH, Gharabawi GM, Canuso CM, Mahmoud RA, Keller MB, Bossie CA, Turkoz I, Lasser RA, Loescher A, Bouhours P, Dunbar F, Nemeroff CB : Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation. Neuropsychopharmacology 2006, 31(11), 2505-13

Tomorrow the New England Journal will publish a study that has statistically identified a genetic risk factor for periodic leg movements in sleep. Though this study is identified as being about “periodic leg movements in sleep”, clearly it has implications for reifying the syndrome known as “restless legs syndrome”.

The Restless Legs Foundation is identified as one of the study’s sponsors. GlaxoSmithKline (manufacturer of ropinirole, FDA-approved to treat moderate-to-severe primary “restless legs syndrome”) is identified in the foundation’s 2006 Annual Report as having contributed greater than $250,000 to the foundation. Likewise, Boehringer-Ingelheim Pharmaceuticals, Inc. (manufacturer of pramipexole, also FDA-approved to treat “restless legs syndrome”) is identified as having contributed greater than $150,000. The foundation’s total revenue was $1.48 million in 2006, suggesting that a minimum of 25 percent of revenue was derived from two drug companies with a clear financial motivation to improve the diagnosis and (pharmacological) management of “restless legs syndrome”. The benefits of collaboration between drug companies and the disease treatment advocacy groups they sponsor, as reflected in sales of prescription medications, have been clearly documented (1-5). Although some disease treatment advocacy groups argue that a broad funding base may shield them from undue influence by drug companies (5), readers of the study should note that the Restless Legs Foundation appears to have a narrower revenue stream.

1. Buttle F, Boldrini J. Customer relationship management in the pharmaceutical industry: The role of the patient advocacy group. Journal of Medical Marketing 2001;1:203-214.

2. Moynihan R, Heath I, Henry D. Selling sickness: the pharmaceutical industry and disease mongering. BMJ 2002;324:886-891.

3. Mintzes B. Should patient groups accept money from drug companies? No. BMJ 2007;334:935.

4. Ginsberg T. Donations tie drug firms and nonprofits. Philadelphia Inquirer, May 28, 2006, page A01.

5. Rubenstein S. Industry fights switch to generics for epilepsy. Wall Street Journal, July 13, 2007, page A1.

One of the coolest, most effective tools that a drug rep has in her — she is often a her, and she is often quite fetching — marketing toolbox is knowing exactly what you prescribe on a daily basis. The way she does this is by linking your prescribing data (available from data vendors like IMS Health) with your personal data (available from the American Medical Association) in order to construct physician-specific prescribing profiles. Clearly, this puts physicians at a disadvantage when it comes to hitting on cute drug reps. You can whisper cute nothings like “can you stop by the office later? I use Neurontin a lot for pain syndromes but really would like to hear more about off-label uses for psychiatric conditions”, but unfortunately for you, she already knows that, out of 378 physicians in her district, you are ranked 370th in terms of prescribing volume.

Because so many physicians complained about the AMA’s complicity in this scheme,

…the AMA last year began allowing doctors to “opt out” and shield their individual prescribing information from salespeople, although drug companies can still get it. So far, 7,476 doctors have opted out, AMA officials said.

“That gives the physician the choice,” said Jeremy A. Lazarus, a Denver psychiatrist and high-ranking AMA official.
–Christopher Lee, “Doctors, Legislators Resist Drugmakers’ Prying Eyes”, Washington Post, May 22, 2007

Bull honkey.

A thorough literature review would have revealed that opt-out programs are designed to maximize participation while preserving a patina of choice. Implementation of opt-out mechanisms in various contexts has resulted in increased participation in prenatal HIV testing, medical journal reviewing, clinical research studies, and 401(k) plan saving. Clearly, default options have an enormous effect on decisions. Implicit in the AMA’s decision to implement an opt-out policy is a value judgment that the default choice option is socially preferable. Thus, the AMA can pay lip service to the value of “choice” while indirectly pocketing payments from the pharmaceutical industry on the side. The opt-out mechanism is working: although 66% of AMA members disapprove of the sale of physician-specific prescribing data to drug companies, fewer than 1% of AMA members have opted out, and only 25% of surveyed members are aware of the program’s existence.

If the AMA really is genuinely interested in “choice” yet is unwilling to publicly support the value judgment inherent in an opt-in policy, maybe they should switch to a regime of active decisions.

Steinberg is among a growing number of diabetics — including celebrity endorsers, magazine publishers and an investment advisor — who are finding business opportunities in marketing to others with the chronic disease.

“From a business perspective, diabetes is the perfect disease,” said David Kliff, a diabetic and investment analyst who specializes in diabetes-related ventures. Diabetics “consume tons of disposable products, and there is no cure. It is a license to print money.”
–Daniel Yi, “Diabetics: One Sweet Market”, Los Angeles Times, January 21, 2007

Today I declined a $100 textbook from an AstraZeneca drug rep. It was kind of hard to say no. Actually, I am still thinking about that textbook and about how much it will cost me to order it from Amazon.com.

I am very thankful that none of the residency programs at this institution allow drug reps to sponsor noon conferences (and lunches) for the residents. Not because I think that is a good policy — there are some reasons why I think banning contact with drug reps is not a great idea — but because I think I would find the food hard to resist.

“Excuse me, doctor, do you have a moment?”

I looked up briefly from my work, and –

“Hi, I’m Angelina [*] and I work with Pfizer [*]. Just wanted to introduce myself and say hi. Is now a good time to talk, or should I come back later?”

She had a nice smile. Toast of New York lipstick? Good posture. Late 20s, probably. Hands weren’t clammy, had the feel of non-greasy moisturizing lotion — Keri, perhaps. She was trying too hard to make eye contact.

Have to admit I felt a bit flustered.

“It’s kind of busy actually,” I mumbled. “No time right now, sorry.”

Why does Pfizer [*] have to send a physically attractive Chinese female drug rep after me?

T. Lynn Williamson, Ms. Napier’s cheering adviser at Kentucky, says he regularly gets calls from recruiters looking for talent, mainly from pharmaceutical companies. “They watch to see who’s graduating,” he said.

“They don’t ask what the major is,” Mr. Williamson said. Proven cheerleading skills suffice. “Exaggerated motions, exaggerated smiles, exaggerated enthusiasm - they learn those things, and they can get people to do what they want.”

Approximately two dozen Kentucky cheerleaders, mostly women but a few men, have become drug reps in recent years. While there are no statistics on how many drug representatives are former or current cheerleaders, demand for them led to the formation of an employment firm, Spirited Sales Leaders, in Memphis. It maintains a database of thousands of potential candidates.
–Stephanie Saul, “Gimme an Rx! Cheerleaders Pep Up Drug Sales”, New York Times, November 28, 2005

For more reading, go to the No Free Lunch Web site.

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[*] All names, dates, and other HIPAA non-compliant details have been confabulated.

From a paper just published in the Australia-based Internal Medicine Journal, results of a survey of a random sample of Australian physicians (39% response rate):

Of the 104 (13%) who answered ‘Yes’ to the question ‘have you sought funds from pharmaceutical industry for items or activities other than research?’, the highest-value requests were for salaries for nursing positions (one of A$80 000; US$60 000), donations to departmental funds (including one of A$60 000; US$45 000, ‘in return for time seeing reps’), support for conducting meetings or conferences and travel, including both international and domestic travel. Other requests were for assistance with education or educational materials, food for meetings, dinners, equipment, journals or textbooks, assistance to attend conferences and a request for funds for a Christmas party. Most requests were made on behalf of a conference organizing group, department or clinic, other than requests for travel and assistance to attend conferences, which were made by individuals themselves (with the exception of one request for travel assistance on behalf of members of a department). The range of the value of requests was from A$50 to A$100 000 (US$38–77 000).
–McNeill et al., “Giving and receiving of gifts between pharmaceutical companies and medical specialists in Australia”, Internal Medicine Journal, September 2006