It's a Textbook! It's an Ad! It's Nemeroff/Schatzberg!

Drs. Nemeroff and Schatzberg are back in the limelight, once again dragging the good name of psychiatry through the mud. According to today's New York Times, in 1999 SmithKline Beecham, the maker of Paxil, funded and ghost-wrote a textbook for which this ethically-challenged duo took credit.

What were they thinking?

I imagine the conversation went something like this.

N: "Let's write a textbook for primary care doctors."
S: "Sounds good. But I don't have the the time."
N: "Neither do I."
S: "Hmmm."
N: "Hmmm."
S: "So what do we do?" [N grins.] "Wait, you're not seriously considering--"
N: "Why not? What are you, suddenly Dr. Holier Than Thou?"
S: "All right, don't remind me about Corcept and your 60,000 shares. What's your plan?"
N: "Simple. We know that SmithKline Beecham's Paxil is losing market share to Pfizer's Zoloft. I'll call my friends there, ask them for an 'unrestricted educational grant.'" [S nudges N. N grins and winks. But then S frowns.]
S: "The money will be nice, but who's going to write it?"
N: "SmithKline will hire a PR firm to do it. All we have to do is review it and make some final tweaks."
S: "But isn't that a little sleazy, even for us? You know they'll play down Paxil's disadvantages--that it causes more sexual side effects, more weight gain, and more drug interactions than Zoloft."
N: "Some studies show that's true, others are more equivocal."
S: [Lightly socks N on the shoulder] "Don't BS me, you sound like you're giving one of your Paxil drug talks to naive country docs."
N: "You know me too well!"
S: "As usual you're very persuasive. I'm in."
N: "I think this is the continuation of a beautiful friendship...."

Is Your Doctor a "Return on Investment"?

Ever since ProPublica published its disturbing database called Dollars for Docs, there have been many local news stories written about hired gun physicians who take money from drug companies to promote drugs to other doctors. A particularly good one was published yesterday in the SentinelSource by the Chicago Tribune's Judith Graham.

The Tribune interviewed about a dozen physicians who make thousands per year from drug company talks, and, according to Graham, "all said they believe such ties have no effect on their medical practices."

But Graham also interviewed a former drug rep, who provided the unvarnished and rather ugly truth about how these apparently well-meaning doctors are actually being manipulated by their handlers:

"Angie Maher, a former Michigan drug sales representative turned whistle-blower, described training sessions where psychologists and coaches would brief her on how to play on doctors’ vulnerabilities — their desire to feel important, their eagerness to be on the cutting edge — while working to boost sales. Each time a physician would give a talk, Maher would fill out a “return on investment” spreadsheet tracking prescription trends for all the doctors who attended the event. If sales went up, the speaker was asked to give another presentation, she said. If not, further invitations to speak would not be extended."

That says it all. Time for these doctors to wake up and realize that have transformed themselves into ROIs for their sponsoring companies.

Two more from Dollars for Docs: Psychiatrists Rule the Hired Guns, and "Thought Leaders" are Cash Cows

Psychiatrists are at the top of the Hired Gun list

According to Medscape, psychiatrists accept more money from drug companies for promotional speaking than any other specialty listed on ProPublica's Dollars for Docs database.

"Of the 384 physicians in the $100,000 group, 116 are psychiatrists. Leading all psychiatrists was Roueen Rafeyan, MD, in Chicago, Illinois, who received $203,936 from Eli Lilly, AstraZeneca, Johnson & Johnson, and Pfizer, mostly for professional education programs."

While discouraging, this does not surprise me, since American psychiatry has fallen into a practice style that relies on medication at the expense of getting to know patients. The slogan of the modern psychiatrist has become "I prescribe, therefore I am," and drug companies are quick to approach them with offers of cash payments in return for prescriptions. While this deal is never made explicit (it would be considered an illegal kickback), in fact the expectations underlying these financial relationships are painfully clear.

NPR Shows how "Thought Leaders" are really "Prescription Writers"

NPR ran a nice piece (which can be read here) scrutinizing whether drug companies hire speakers because they are experts, or rather because they prescribe a lot of their drugs and are good at getting other docs to follow suit.

First, they interview child psychiatrist Lance Clawson. According to this entry on the Dollars for Docs website, Dr. Clawson has spoken for Eli Lilly, which paid him $56,800 in 2009 and $7,661 in the first three months of 2010. Clawson tells NPR that he feels no guilt about these talks: "I'm going out there and trying to educate other doctors about how to treat ADHD appropriately and safely," he explains. Since Clawson said he is talking about ADHD I assume he is promoting Strattera, which is Lilly's only FDA approved ADHD medication. Strattera is, indeed, effective for ADHD, but is significantly less effective than stimulants. During Dr. Clawson's talks, I therefore wonder how much time he devotes to educating his audience about this study, which showed that Strattera is significantly less effective than Concerta, or this study, showing that Strattera is much less effective than Adderall XR. Since hired guns are forced to use only the company's slides, I suspect that Dr. Clawson educates doctors the Lilly Way, rather than the Evidence-Based Medicine Way

NPR then interviews a current drug rep who knows exactly why doctors such as Clawson are chosen as "thought leaders"--because they have lots of patients to whom they will prescribe lots of the company's drug.

According to the rep: "I think nowadays a thought leader is defined as a physician with a large patient population who can write a lot of pharmaceutical drugs. Period." Furthermore, according to NPR's sources, reps very closely monitor the prescriptions of speakers after they are paid to give talks, and, according to one rep, paying a speaker $1500 to give a talk may well yield $100,000 or more in extra prescriptions.

I'd be curious to get the prescription reports for Dr. Clawson's practice after he gives his talks! I'm sure his rep has the data squirreled away in the company laptop.

ProPublica's Dollars for Docs Website

The non-profit media organization ProPublica just announced a new website/database called Dollars for Docs. It lists cash payments made to 17,000 U.S. doctors by seven large drug companies.

I’ve been browsing through the database and I have some thoughts about its strengths and weaknesses—and how it might be useful for patients.

First, here’s what these journalists did. Rather than waiting for the provisions of the Physician’s Payments Sunshine Act to take effect in 2013 (this will be a public website listing all payments to doctors from all drug companies), they decided to take matters into their own hands. Seven companies currently post physician payment data, in most cases because they were forced to as part of legal settlements. The problems is that these websites vary in quality and usability, and of course the data is split up among seven different sites.

ProPublica assigned their journalists the daunting task of combining all the data into a single spreadsheet, which is titled “Dollars for Docs”. There are two ways you can use it: either by searching for a specific doctor, or by browsing the entire database.

For example, suppose you were interested in Dr. Lawrence Dubuske, the asthma expert who famously resigned from Harvard rather than having to abide by its new prohibition on promotional speaking. You would simply type in his name, click “search”, and you would find following entries. He received $25,500 from AstraZeneca in Q1-Q2 of 2010 for “speaker compensation;” $121,875 from GSK in Q2-Q4 2009 and another $72,400 in Q1-Q2 of 2010 for “speaking.”

Missing from the data, however, is any indication of what he was speaking about, who he was speaking to, or how many talks he had to give to make that kind of serious money. That’s not ProPublica’s fault, but rather the fault of the companies for not being specific enough. It would be crucial for me to know, for example, that my doctor made $100,000 for promoting the drug that I was just prescribed. The drug may be the best choice, or it may not be, but either way, I would feel deceived if I knew nothing about the doctor’s glaring conflict of interest. If I did know about this, and if I had enough chutzpah, I might then ask my doctor whether the money influenced his or her prescribing decision. (The inevitable answer: “Of course not, this money has absolutely no influence on my medical decisions.”)

There’s another way to use the Dollars for Docs database, although this is not spelled out on the website. If you want to browse for all the doctors in your city or state who are “on the take,” simply leave the “name” field blank, choose a state from the drop down menu, and click search. You’ll get a huge spreadsheet which is arranged alphabetically by last names of the doctors. By clicking on the various columns, you can sort the data by city, drug company, amount of money, or time period of the payments. This is a nice feature that is absent from most of the drug company databases.

I sorted all Massachusetts docs by “amount” and found that one doctor received only $17 from Eli Lilly in the first quarter of 2010. This payment was described as “Advising/Consulting and International Education Programs.” I’m not sure what that means, but I can’t imagine that Lilly got too much “advising” work out of this particular doctor.

Anyway, I scrolled down the chart looking for the more well-funded docs, and in doing so I quickly comprehended what is probably the most striking aspect of this database—the sheer enormity of it. Sure, I already knew from published surveys that well over 100,000 doctors receive cash from drug companies. But that number becomes much more tangible as you scroll through an endless list of doctors’ names, each associated with a specific dollar amount. The thought that runs through your mind is: “How have we allowed this to happen to our once proud profession?”

But occasionally I came across the name of a colleague who I knew was ethically scrupulous. In one case, for example, a friend was listed as having received $20,000 from a company for “consulting.” He is a former medical school classmate of mine, and I know he does serious epidemiological research, and that he is uninterested in working with drug companies. The point, again, is that without getting more specific information it’s hard to know what to make of these numbers.

Nonetheless, this database focuses on explicitly “promotional” activities, such as speaking and marketing consultation, and does not include payment for research studies. The vast majority of payments are for doctors who give “educational” talks to other doctors, presumably focusing on one of the drugs made by the funding company.

Is it ethically “bad” for your doctor to give these talks? That’s controversial. Clearly, there are some good apples who will express their honest opinions about which drugs are best without being influenced by the allure of money.

Nonetheless, doctors aren’t dumb, and they are acutely aware that they are serving two masters: the stockholders of the company and the doctors they are teaching. If they say bad things about the company’s drug, they’ll watch as the speaking invitations magically evaporate.

The true malfeasance here is in the aggregated effect. The companies are using these legions of doctors to artificially manipulate medical discourse. Any doctor who participates in the enterprise knows exactly how they are being used. You decide whether this is “immoral” or not.

Seeking Editor for “The Carlat Medical Report”

Yes, I know this is a piece of rank commercialism. But it’s for a good cause.

I plan to launch a new CME newsletter called The Carlat Medical Report. It will be similar in format to my two existing newsletters (The Carlat Psychiatry Report and The Carlat Child Psychiatry Report), but it will cover topics in general medicine. Think of it as The Medical Letter with an attitude.

I’ve been casting about for an editor-in-chief through the usual channels of contacting friends and colleagues but I've had no luck so far, so I thought I’d post the job description here.

I plan to publish the newsletter monthly or so, depending on the energy of the editor. It will be available in both print and online versions. My company, Clearview Publishing, is ACCME accredited, so readers of the newsletter can get plenty of AMA PRA Category 1 credit. There will, of course, be no pharmaceutical industry funding of any sort, directly or indirectly—no sponsorship, no ads, no inserts. Furthermore neither the editor nor any of the writers can have any financial relationships with pharma.

A word about my no pharma policy. I am philosophically and politically opposed to industry sponsorship of medical education (no duh!), but I am not opposed to industry sponsorship of clinical research. In fact, I value the opinions and expertise of my colleagues who work with industry, either as researchers or as research consultants. In The Carlat Psychiatry Report I sometimes interview experts with hefty industry disclosures. I rationalize it because I feel that in an interview format I have more control over the content and can steer the conversation in a non-promotional direction. This allows readers to reap the benefit of industry know-how without being subject to the subtle (or not so subtle) commercial biases that sometimes appear in the articles and talks of academics with industry ties.

Anyway, to get back to The Carlat Medical Report, below is the formal job description along with compensation. At $1000 per month, you will not get rich being the editor of this newsletter (it will take a few hours a week of your time). But you’ll get your name out there, you will meet a lot of interesting people, and you’ll be part of what is clearly a growing trend in medical education—great practical CME without the industry hype.

If you’re interested, email me directly at drcarlat@comcast.net.

Newsletter and Job Description:

The Carlat Medical Report will be published monthly, and each issue will focus on a specific therapeutic area in medicine. There will be one or two in depth articles, one interview with a national expert on that month's topic, and 3 or 4 short "research updates" summarizing the most important articles (on any medical topic) published during the prior month. The writing will be informal, mirroring the way a doctor would discuss recommendations verbally with another doctor. Problems with excessive pharmaceutical company influence in medical practice will be discussed explicitly when relevant.

Editor-in-chief compensation and responsibilities.

--Must be an MD or DO
--Compensation: $1000 per issue honorarium
--Will be the identified "face" of the newsletter--"Mary Smith, MD, Editor-in-Chief" would be prominently displayed below the masthead and the editor's photo and email contact would be on the home page of the website. Reader and press inquiries would go directly to editor.
--In conjunction with publisher, will put together a stellar, non-industry affiliated editorial board for the newsletter.
--Will decide on content for each issue
--Will write one of the in depth articles (about 1000 words) for each issue
--Will assign other articles and research updates to other writers
--Will be responsible for interviewing the Expert of the Month (or may assign this to someone else)
--Agrees to no financial relationships with pharmaceutical or device companies within the last year and during editorship tenure
--Estimated time commitment required: about one day per week.

Menopause: The Scandal (Part Two)

In part one of this post, I introduced some of the admittedly controversial issues surrounding the use of hormone replacement therapy in menopausal women, and I pointed out that the proper forum for scientific debate and medical education is in journals and medical meetings. Furthermore, in order for us to trust the integrity of this education, it should not be funded by the pharmaceutical industry. Let drug companies fund research and advertising all they want--but scientific debate among doctors should be completely independent of a promotional agenda.

This sounds obvious but the current system of CME all too often turns a blind eye to what has become a constant stream of artful transgressions of this principal. Journal supplements have become a key promotional strategy for drug companies seeking to influence prescribing behavior. This fact is hardly news, and such corrupted supplements are a dime a dozen to this day. What is unusual about Dr. Fugh-Berman's recent article about the marketing of Premarin is that she reveals a smoking gun--that is, documentation from Wyeth and DesignWrite showing that the CME was planned with an explicitly promotional intent.

The trail of evidence begins with a proposal for Wyeth submitted by DesignWrite, entitled "Premarin Publication Program" (yes, the pdf is available from the Drug Industry Document Archive at UCSF, and it makes for pretty creepy bedtime reading). On page 3 of the proposal, DesignWrite tells Wyeth exactly what it plans to do in order to get more doctors to prescribe Premarin:

"The specific objective of this program is to 1) increase physician awareness on the multitude of benefits that hormone replacement therapy provides for postmenopausal patients, 2) diminish the negative perceptions associated with estrogens and cancer, and 3) blunt the competitive threat of raloxifene, a selective estrogen receptor modulator, expected to be approved early next year for osteoporosis."

Ghost-writing is big business. Wyeth paid DesignWrite $25,000 per Premarin-boosting article and ended up paying the company several million dollars between 1997 and 2003. They paid a particularly big chunk of cash, $413,140, for a CME meeting and journal supplement. DesignWrite apparently loves producing CME supplements for companies, because, as they say in their publication plan,

"The value of journal supplements is that it allows you to better tailor your marketing message since it is a manufacturer-sponsored publication form. Additionally, reprints of supplements may be purchased and distributed widely among health care professionals via sales representatives and direct mail."

DesignWrite put on a 2001 meeting of Wyeth's hired guns in order to provide content for the supplement. They helpfully produced this outline of what each article should say--basically, they all minimized concerns that HRT causes breast cancer.

Eventually, the supplement was published in 2001 by the journal Women's Health in Primary Care and Wyeth mailed it to 128,000 physician, bought 1,500 additional copies for its sales force, and distributed the supplement to media and “select thought leaders”. In her article, Fugh-Berman publishes a pretty damning table comparing each carefully crafted marketing message with a corresponding sentence as it was published in a CME article. And of course, each article has an identified academic "author," with the actual writer having been an employee of DesignWrite in each case.

All in all, this is a nauseating example of the use of accredited CME to manipulate doctors.

Menopause: The Scandal (Part One)

Are rooms too hot for you? Are you sweating when everyone else is staying cool? Is sex not what it once was? If so, you may be entering menopause, and Wyeth, along with several other pharmaceutical companies, may have just the drug for you. The trouble is that the side effects, such as breast cancer and heart disease, may not be worth the cure.

Hormone replacement therapy (HRT) used to be tremendously popular, and Wyeth's Prempro (a combination of estrogen and progesterone) was at the top of the heap. That is, until preliminary results of the Women's Health Initiative were announced in 2002. Thus began the long saga of re-evaluating the science behind HRT, the latest installment of which is a fascinating and rather disquieting article just published in PLOS: The Haunting of Medical Journals: How Ghostwriting Sold “HRT," by Dr. Adriane Fugh-Berman.

A little background first. HRT came into vogue over the last couple of decades as a way of decreasing some of the nuisance symptoms of menopause (such as hot flashes and vaginal dryness) as well as potentially preventing more serious diseases of older age, such as heart disease, cancer, osteoporosis, and dementia. In the 1990s, the NIH funded placebo controlled clinical trials of HRT in order to determine once and for all whether HRT actually did improve outcomes for post-menopausal women. The largest part of the Women's Health Initiative study enrolled 16,000 postmenopausal women between the ages of 50 and 79 (average age was 63). These women were randomized to either Prempro or placebo, and were followed for an average of about five years.

But in 2002 the study was halted. Why? Because a preliminary analysis of the data showed that women in the Prempro group had increased risks of breast cancer, heart disease, stroke, and pulmonary embolism. But this group also showed a decreased risk of colon cancer and hip fracture (Rossouw J et al., JAMA 2002;288:321-333). And for those women who were less than five years postmenopausal, Prempro actually reduced the heart disease risk.

The WHI results were therefore somewhat mixed, but they nevertheless led to significant decline in prescriptions of HRT to all women, particularly those who are post-menopausal. Many reasonable doctors have been skeptical of the results of the WHI, and there is plenty of room for debate.

While Dr. Fugh-Berman clearly believes that the dangers of HRT usually outweigh the benefits, her recent article is not really about the scientific merits of either argument. It is about something that I think anybody would regard as scandalous--the fact that marketing executives have become central participants in medical debates. Fugh-Berman shows convincingly that Wyeth used marketers and ghost-writers to manipulate medical opinion, with the result that doctors are making critical prescribing decisions based on the "medical" opinions of business school graduates.

Because of her legal consultation in a suit against Wyeth, Fugh-Berman had early access to thousands of documents implicating the company in deceptive marketing techniques. These documents are now public.

Her article is a guided tour of the worst of worst.

Most of the documents relate to Wyeth's work with DesignWrite, a medical education and communications company (MECC) that specializes in using medical education to help companies market their drugs. The documents showed that DesignWrite told Wyeth that it would “position the product [Prempro] appropriately to influence prescribers.” The strategy was to make sure that plenty of Prempro-friendly papers were published in medical journals.

Let's take a little step back here. The nature of science is skepticism and debate. Prempro is presumably neither "good" nor "bad." Well-informed physicians differ on the significance of the risks and on which women are reasonable candidates for the drug. Medical journals and scientific meetings are the appropriate forums for airing these opinions. If a physician wanted to write a paper defending Prempro because she truly believed that the concerns have been overblown, nobody would have a problem with it. Even if she didn't have time to write it herself, and paid a medical writer to write the first draft, that would be legitimate, as long as the medical writer were acknowledged.

But this is not the process of medical discourse that we are talking about here. Wyeth decided that it simply didn't have the time to wait for physicians to decide on their own that Prempro was such a valuable drug that it needed defending. It's not that there weren't plenty of doctors who sincerely believed in Prempro. It's just that they didn't see the issue as being so scientifically important that they would devote their time to writing papers about the issue. Clearly, they needed some nudging.

This was exactly DesignWrite's job. Their medical writers would write a paper that emphasized Prempro's advantages while minimizing its side effects. DesignWrite would then search for key opinion leaders who they believed were already concerned that HRT was getting a bad rap. To such KOLs, they would say, essentially, "Doctor, we know you are concerned about the underuse of HRT. We have written a first draft of a paper outlining these issues. Would you like to review it? In return for your help, we will make you the sole author of the paper, and we will make sure it gets into a prestigious journal. Whadaya say?"

There is no evidence that DesignWrite offered these doctors any money for their services. There was no need to. The payoff was much greater than a couple of G's. They were offering a guaranteed publication in a prestigious journal, along with the many perks that flow from that, such as academic promotion, media interviews, invitations to speak at top medical conferences, paid consultancies and speaking gigs from pharmaceutical companies, and lucrative invitations from MECCs to write and teach industry-supported CME programs.

Basically, these papers are career rocket fuel for KOLs. Who could refuse such an offer?

In Part Two: Fugh-Berman names names, and calls out some sleazy CME.