Thursday, April 26, 2007

More on the Techniques Used by Reps

In HOOKED, I was able to use testimony from former drug reps to illustrate the various techniques that are used to influence physicians--almost always without the physicians ever having a clue as to how they are being manipulated. A recent paper that takes advantage of another former rep--the second author--is:

The article includes a long table that classifies physicians by type--"friendly and outgoing," "aloof and skeptical," "mercenary," etc.--and explains how the rep would effectively get each type to prescribe more of the company's drugs.

This paper has some of the most direct and unambiguous statements about how the rep system operates. As the former rep, Shahram Ahari, says, "During training, I was told, when you're out to dinner with a doctor, 'The physician is eating with a friend. You are eating with a client.'" The article covers the power of gifts, how the rep scopes out the doc looking for what buttons to push, how the reps use prescribing data to customize their detailing to each physician, and the use of samples.

Anari again: "[To constantly sway the doctors] is a job I'm paid and trained to do. Doctors are neither trained nor paid to negotiate. Most of the time they don't even realize that's what they're doing..."

An Inside Peek: How Much the Drug Industry Supports Samples for Indigent Patients

Every time I have heard anyone representing the pharmaceutical industry's point of view defend physicians' cozy relationships with detail people, the case is argued that these relationships yield free samples for the docs, who then can give some of these samples to their indigent patients. In HOOKED, I discuss several reasons why this system is a flawed way of getting drugs for the indigent.

Whether or not this is a good way to provide drugs for those otherwise unable to pay, I found it interesting to compare the standard industry rhetoric with an insider's view of what the average drug company may think of this practice.

Thanks to Adriane Fugh-Berman and Shahran Ahari (see next post), I had my attention directed to an October, 2004 article in Pharmaceutical Executive:

The article, which is mostly about how to package sales reports so that the data make sense to the reps in the field, has a sidebar story, "Customization Case Study." (You have to click separately on that part of the story to read it.)

The sidebar tells how one drug company increased its market share by 86% using several techniques. Included in what they achieved were "reduc[ing] cannibalized prescriptions from oversampling," "reduc[ing] rep calls on low potential subscribers by 27 percent," "decreas[ing] sampling costs by 24 percent," "reallocat[ing] samples to high-opportunity prescribers most receptive to sampling as a promotional vehicle," "identify[ing] prescribers who were oversampled and take corrective action immediately."

If I translate all this into plain English, it seems to be saying: the reps were beat up by their managers to pick out the docs who actually gave a lot of samples to indigent patients, and who accordingly wrote fewer prescriptions for the drugs; those docs were given many fewer samples. Instead, the docs who used the samples "properly"--that is, as a prelude to actually writing prescriptions for well-insured patients who could afford the drugs--got more samples.

The report went on to conclude triumphantly, "No longer oversampled by reps, low prescribers cut back on giving patients free samples and began writing more prescriptions."

So much for the industry making it possible for docs to give free samples to the needy.

New England Journal Study Shows Widespread Relationships of Physicians with Industry

The Institute on Medicine as a Profession at Columbia University is rapidly establishing itself as the 800-pound gorilla of the forces in medicine concerned about pharmaceutical industry influence. Their latest salvo comes in the form of a survey of about 3100 physicians in six different medical specialties, published in this week's New England Journal of Medicine, and available on line: For press coverage, see:,1,3419565.story (cannot guarantee how long this latter will remain up on the web).

The main take home message is that this is the first large-scale national survey of physicians conducted since the much touted PhRMA code of ethics went into effect in 2002, and supposedly put the kibosh on some of the more generous and outrageous forms of gift-giving. The authors of the study are appropriately cautious in drawing conclusions--after all, they did not do a before-and-after comparison survey--but imply that the "code of ethics" has not been very effective in altering the landscape of massive influence of the drug companies.

The major findings of interest: 94% of physicians surveyed took one form of benefit or another from industry; the most common were food in the workplace (83%) and "free" drug samples (78%). Twenty-eight percent received some form of payment, mostly for consulting or serving on a speaker's bureau. Among the specialties, monthly contacts with industry representatives ranged from a high of 16 by family docs to a low of 2 among anesthesiologists. Docs in solo or private group practices reported more contacts with industry than docs in hospital or staff-HMO settings.

My fellow family physicians had more contacts with the industry per month than any other specialty but were paid considerably less often than cardiologists. (Maybe we should up our rates.)

One message that I think comes through loud and clear from this survey, despite its various limitations (the response rate, for example, was 52%, which is about par for the course in trying to get harried physicians these days to fill out surveys), is the factoid of 28% being paid as consultants or speakers. Could it really be the case that fully a quarter of all physicians have so much specialized knowledge, and stand out so much from their peers, that they are appropriate recipients of company fees for these services? Or are such fees really a disguised way of giving company cash gifts to physicians who are both high prescribers, and willing to do the company's bidding by trying to persuade their peers to do likewise?

Saturday, April 14, 2007

Grisham's King of Torts: Fictional Depiction of Evil Drug Industry

I am grateful to a colleague for calling my attention to John Grisham's novel, The King of Torts, originally published in 2003. I admit to not being a devotee of Grisham's novels and so wasn't sure what to expect. The novel depicts the rise and --well, maybe I had better not give away the ending--of the career of one Clay Carter, who enjoys a rapid rise from a poor public defender to one of a select group of mass tort (or class-action lawsuit) plaintiffs, a tribe for which Grisham apparently has little sympathy.

For readers of this blog, the interesting aspect of the novel is its depiction of the behavior of the large drug companies, analogous to John Le Carre's novel, The Constant Gardener. The novel depicts in turn three drugs. The first, "Tarvan," is a wonder drug that has unprecedented powers to kill the craving in drug addicts and to keep them clean. The bad news is that for a small percentage, it unleashes unpredictable homicidal tendencies. The company is depicted as having to cover up this terrible side effect because it had set out to evade FDA regulations by launching a secret set of trials, without research board approval or informed consent. The closest analogy in real life seems to be the suicidal and occasionally homicidal urges caused by the serotonin-reuptake-inhibitor class of antidepressant drugs.

The next bad drug in the novel is "Dyloft," a heavily marketed arthritis drug that turns out at first to have the unanticipated side effect of causing bladder tumors, again in a relatively low percentage of patients. Initially these tumors are for the most part benign, so the actual harm done by the drug is limited--though as the novel unfolds, Dyloft turns out to have another trick up its sleeve. The company is depicted as aware of this side effect and engaged in covering it up so as not to damage sales. The closest analogy to "Dyloft" seems to be Vioxx and its cousins, though the risk they created was the more serious one of heart attacks.

Finally we encounter the drug "Maxatil," a female hormone that ends up causing excess cases of breast cancer and some other diseases. This drug turns out to be a booby trap for the unwary mass tort lawyer; it is difficult to prove that the drug was the actual cause of any given case of cancer, so the company is able to dig in its heels and fight off the legal threat. "Maxatil" obviously seems to have been suggested by the unexpected findings in the Women's Health Study that post-menopausal estrogens increase the risk of cancer and heart disease. (Wyeth's track record in defending lawsuits against its hormone drug, Prempro, appear so far to be mixed.) The fictional company that makes "Maxatil" is depicted as less evil than the makers of the other two drugs; it is not so clear that they hid any evidence of risks.

If these parallels are correct, then Grisham gets credit for a fair amount of prescience; his book was published in 2003, but it was not till 2004 that most people knew about the serious risks associated with SSRI antidepressants and with Vioxx.

All this is clearly fiction, so what does it matter? I take up space here simply to note indirect evidence of a feature of popular culture--the notion that a big drug company would market a drug with clear dangers, and hide the evidence so as to maximize its profits, apparently seems today to be a sufficiently plausible scenario to the average member of the American public, that best-selling authors have no qualms about basing a novel on such a premise.

Friday, April 13, 2007

FDA Funding and Drug Safety: New Report from GWU

When I first downloaded this report from the Rapid Public Health Policy Response Project at George Washington University in DC, I was taken aback to see the Pfizer logo on the first page; but the content, though partly supported by Pfizer's "Public Health and Policy Group," seems reasonably balanced.

The report summarizes existing law on the Prescription Drug User Fee Act (PDUFA) and the current debate over whether this law promotes adequate attention to drug safety, as opposed merely to speedier approval reviews to keep the industry happy.

In HOOKED, I argue that PDUFA should be repealed and the FDA supported fully from congressional appropriations, not industry user fees. So I was pleased to read in the report the line-up of those who argue that this is the case:

Four former FDA commissioners
The Institute of Medicine report on the FDA
Consumer groups
Twenty-two experts in drug safety and regulation, including 3 former editors of the New England Journal

The report can be obtained at:

Wednesday, April 4, 2007

Evergreening Redux: Meet the "New" Drug, Invega

HOOKED describes several stories of the process that pharma insiders call "evergreening"--finding a way to extend the effective patient life of a drug that is about to go generic (off-patent) and so lose the higher prices that brand-name drugs command. Sometimes this involves legal maneuvering to keep generic competitors at bay. Other times this requires chemical manipulation of the drug itself. Chemically, two strategies are popular:
  • The Prilosec-Nexium scenario: Many drugs are racemic mixtures of two isomers, mirror-image molecules, of which only one is biologically active. The "new" drug is simply the active isomer of the old drug. (For some reason, when a drug is just being released to the market, it never seems worth the company's while to go to the trouble of separating out the active isomer. This only seems to suddenly appear to be an advantage when the parent drug is about to go off-patent.)
  • The Claritin-Clarinex scenario: The "new" drug is the active metabolite of the old drug--what the body turns the old drug into after it is ingested.
I'm informed by the March 12 issue of The Medical Letter that the FDA has recently approved Invega, manufactured by Janssen, for treatment of schizophrenia. By the merest coincidence, Invega happens to be the active metabolite of Janssen's blockbuster second-generation antipsychotic, Risperdal. Also by the merest coincidence, the patent on Risperdal is set to expire in December 2007. Clarinex rides again...

If the company proceeds true to form, the Janssen reps that last week were telling all my fellow physicians that Risperdal was the greatest drug ever invented for psychosis, and for calming down the disturbed, demented elderly patient, will now be telling the docs that Risperdal is chopped liver, but that this wonderful new, breakthrough drug, Invega-- now, that's what's really best.

The Medical Letter offers its opinion: "[Invega] is likely to be similar to risperidone [Risperdal] in effectiveness and adverse effects. No specific madvantages of the new formulation have been demonstrated. ... Whether risperidone or [Invega] is a better choice than a first-generation drug that vosts much less is unclear." That last sentence is key. Research is now accumulating that suggests that the expensive second-generation antipsychotics like Risperdal probably have few of the advantages over the cheaper, older drugs that were originally attributed to them--another victory for pharmaceutical marketing over science.