Re: Propecia is very, very dangerous!
I wonder if Dr. Shapiro and Dr. Cohen are anything like Dr. Daniel Carlat, basically a very accessible easily bought and assuaged dime-a-dozen pharmaceutical conduit.
Dr. Drug Rep
By DANIEL CARLAT
I. Faculty Development
On a blustery fall New England day in 2001, a friendly representative from Wyeth Pharmaceuticals came into my office in Newburyport, Mass., and made me an offer I found hard to refuse. He asked me if I’d like to give talks to other doctors about using Effexor XR for treating depression. He told me that I would go around to doctors’ offices during lunchtime and talk about some of the features of Effexor. It would be pretty easy. Wyeth would provide a set of slides and even pay for me to attend a speaker’s training session, and he quickly floated some numbers. I would be paid $500 for one-hour “Lunch and Learn†talks at local doctors’ offices, or $750 if I had to drive an hour. I would be flown to New York for a “faculty-development program,†where I would be pampered in a Midtown hotel for two nights and would be paid an additional “honorarium.â€
I thought about his proposition. I had a busy private practice in psychiatry, specializing in psychopharmacology. I was quite familiar with Effexor, since I had read recent studies showing that it might be slightly more effective than S.S.R.I.’s, the most commonly prescribed antidepressants: the Prozacs, Paxils and Zolofts of the world. S.S.R.I. stands for selective serotonin reuptake inhibitor, referring to the fact that these drugs increase levels of the neurotransmitter serotonin, a chemical in the brain involved in regulating moods. Effexor, on the other hand, was being marketed as a dual reuptake inhibitor, meaning that it increases both serotonin and norepinephrine, another neurotransmitter. The theory promoted by Wyeth was that two neurotransmitters are better than one, and that Effexor was more powerful and effective than S.S.R.I.’s.
I had already prescribed Effexor to several patients, and it seemed to work as well as the S.S.R.I.’s. If I gave talks to primary-care doctors about Effexor, I reasoned, I would be doing nothing unethical. It was a perfectly effective treatment option, with some data to suggest advantages over its competitors. The Wyeth rep was simply suggesting that I discuss some of the data with other doctors. Sure, Wyeth would benefit, but so would other doctors, who would become more educated about a good medication.
A few weeks later, my wife and I walked through the luxurious lobby of the Millennium Hotel in Midtown Manhattan. At the reception desk, when I gave my name, the attendant keyed it into the computer and said, with a dazzling smile: “Hello, Dr. Carlat, I see that you are with the Wyeth conference. Here are your materials.â€
She handed me a folder containing the schedule of talks, an invitation to various dinners and receptions and two tickets to a Broadway musical. “Enjoy your stay, doctor.†I had no doubt that I would, though I felt a gnawing at the edge of my conscience. This seemed like a lot of money to lavish on me just so that I could provide some education to primary-care doctors in a small town north of Boston.
The next morning, the conference began. There were a hundred or so other psychiatrists from different parts of the U.S. I recognized a couple of the attendees, including an acquaintance I hadn’t seen in a while. I’d heard that he moved to another state and was making a bundle of money, but nobody seemed to know exactly how.
I joined him at his table and asked him what he had been up to. He said he had a busy private practice and had given a lot of talks for Warner-Lambert, a company that had since been acquired by Pfizer. His talks were on Neurontin, a drug that was approved for epilepsy but that my friend had found helpful for bipolar disorder in his practice. (In 2004, Warner-Lambert pleaded guilty to illegally marketing Neurontin for unapproved uses. It is illegal for companies to pay doctors to promote so-called off-label uses.)
I knew about Neurontin and had prescribed it occasionally for bipolar disorder in my practice, though I had never found it very helpful. A recent study found that it worked no better than a placebo for this condition. I asked him if he really thought Neurontin worked for bipolar, and he said that he felt it was “great for some patients†and that he used it “all the time.†Given my clinical experiences with the drug, I wondered whether his positive opinion had been influenced by the money he was paid to give talks.
But I put those questions aside as we gulped down our coffees and took seats in a large lecture room. On the agenda were talks from some of the most esteemed academics in the field, authors of hundreds of articles in the major psychiatric journals. They included Michael Thase, of the University of Pittsburgh and the researcher who single-handedly put Effexor on the map with a meta-analysis, and Norman Sussman, a professor of psychiatry at New York University, who was master of ceremonies.
Thase strode to the lectern first in order to describe his groundbreaking work synthesizing data from more than 2,000 patients who had been enrolled in studies comparing Effexor with S.S.R.I.’s. At this time, with his Effexor study a topic of conversation in the mental-health world, Thase was one of the most well known and well respected psychiatrists in the United States. He cut a captivating figure onstage: tall and slim, dynamic, incredibly articulate and a master of the research craft.
He began by reviewing the results of the meta-analysis that had the psychiatric world abuzz. After carefully pooling and processing data from eight separate clinical trials, Thase published a truly significant finding: Effexor caused a 45 percent remission rate in patients in contrast to the S.S.R.I. rate of 35 percent and the placebo rate of 25 percent. It was the first time one antidepressant was shown to be more effective than any other. Previously, psychiatrists chose antidepressants based on a combination of guesswork, gut feeling and tailoring a drug’s side effects to a patient’s symptom profile. If Effexor was truly more effective than S.S.R.I.’s, it would amount to a revolution in psychiatric practice and a potential windfall for Wyeth.
One impressive aspect of Thase’s presentation was that he was not content to rest on his laurels; rather he raised a series of potential criticisms of his results and then rebutted them convincingly. For example, skeptics had pointed out that Thase was a paid consultant to Wyeth and that both of his co-authors were employees of the company. Thase responded that he had requested and had received all of the company’s data and had not cherry-picked from those studies most favorable for Effexor. This was a significant point, because companies sometimes withhold negative data from publication in medical journals. For example, in 2004, GlaxoSmithKline was sued by Eliot Spitzer, who was then the New York attorney general, for suppressing data hinting that Paxil causes suicidal thoughts in children. The company settled the case and agreed to make clinical-trial results public.
Another objection was that while the study was billed as comparing Effexor with S.S.R.I.’s in general, in fact most of the data compared Effexor with one specific S.S.R.I.: Prozac. Perhaps Effexor was, indeed, more effective than Prozac; this did not necessarily mean that it was more effective than the other S.S.R.I.’s in common use. But Thase announced that since the original study, he had analyzed data on Paxil and other meds and also found differences in remission rates.
For his study, Thase chose what was at that time an unusual measure of antidepressant improvement: “remission,†rather than the more standard measure, “response.†In clinical antidepressant trials, a “response†is defined as a 50 percent improvement in depressive symptoms, as measured by the Hamilton depression scale. Thus, if a patient enters a study scoring a 24 on the Hamilton (which would be a moderate degree of depression), he or she would have “responded†if the final score, after treatment, was 12 or less.
Remission, on the other hand, is defined as “complete†recovery. While you might think that a patient would have to score a 0 on the Hamilton to be in remission, in fact very few people score that low, no matter how deliriously happy they are. Instead, researchers come up with various cutoff scores for remission. Thase chose a cutoff score of 7 or below.
In his study, he emphasized the remission rates and not the response rates. As I listened to his presentation, I wondered why. Was it because he felt that remission was the only really meaningful outcome by which to compare drugs? Or was it because using remission made Effexor look more impressive than response did? Thase indirectly addressed this issue in his paper by pointing out that even when remission was defined in different ways, with different cutoff points, Effexor beat the S.S.R.I.’s every time. That struck me as a pretty convincing endorsement of Wyeth’s antidepressant.
The next speaker, Norm Sussman, took the baton from Thase and explored the concept of remission in more detail. Sussman’s job was to systematically go through the officially sanctioned “slide deck†— slides provided to us by Wyeth, which we were expected to use during our own presentations.
If Thase was the riveting academic, Sussman was the engaging populist, translating some of the drier research concepts into terms that our primary-care-physician audiences would understand. Sussman exhorted us not to be satisfied with response and encouraged us to set the bar higher. “Is the patient doing everything they were doing before they got depressed?†he asked. “Are they doing it even better? That’s remission.†To further persuade us, he highlighted a slide showing that patients who made it all the way to remission are less likely to relapse to another depressive episode than patients who merely responded. And for all its methodological limitations, it was a slide that I would become well acquainted with, as I would use it over and over again in my own talks.
When it came to side effects, Effexor’s greatest liability was that it could cause hypertension, a side effect not shared by S.S.R.I.’s. Sussman showed us some data from the clinical trials, indicating that at lower doses, about 3 percent of patients taking Effexor had hypertension as compared with about 2 percent of patients assigned to a placebo. There was only a 1 percent difference between Effexor and placebo, he commented, and pointed out that treating high blood pressure might be a small price to pay for relief from depression.
It was an accurate reading of the data, and I remember finding it a convincing defense of Effexor’s safety. As I look back at my notes now, however, I notice that another way of describing the same numbers would have been to say that Effexor leads to a 50 percent greater rate of hypertension than a placebo. Framed this way, Effexor looks more hazardous.
And so it went for the rest of the afternoon.
Was I swallowing the message whole? Certainly not. I knew that this was hardly impartial medical education, and that we were being fed a marketing line. But when you are treated like the anointed, wined and dined in Manhattan and placed among the leaders of the field, you inevitably put some of your critical faculties on hold. I was truly impressed with Effexor’s remission numbers, and like any physician, I was hopeful that something new and different had been introduced to my quiver of therapeutic options.
At the end of the last lecture, we were all handed envelopes as we left the conference room. Inside were checks for $750. It was time to enjoy ourselves in the city.
You can read the rest of this very common behind-the-scenes scenario here. Right this very minute your patient's rights are being actively sold to the highest bidder in some swanky hotel or ski resort.
http://www.nytimes.com/2007/11/25/magaz ... ref=slogin
