Overdosed America (19 page)

In another study, researchers in the United States obtained data under the Freedom of Information Act from
all of the studies (both published and unpublished) that the FDA had reviewed
in the process of approving seven new antidepressants (Prozac, Zoloft, Paxil, Effexor, Serzone, Remeron, and Wellbutrin SR) between 1987 and 1997—a total of 5200 pages of documents. The results of all of the “pivotal” studies (those deemed to be of high enough quality to be used in the FDA’s determinations) for these seven antidepressants were then put together to assess the overall effect of the new drugs. By looking at all the studies, the researchers avoided the distortion of “publication bias” and were able to determine whether or not the scientific evidence really showed that the new antidepressants are more effective and safer than the older ones.

When all the evidence is considered, it turns out that the new antidepressant drugs are no more effective than the older tricyclic antidepressants (the classic being amitriptyline, brand name Elavil). More important, the new antidepressants were found to be not even 10 percent more effective than the placebos: Symptoms of depression improved by 30.9 percent in the people who took the placebos; by 40.7 percent in the people who took the newer antidepressants; and by 41.7 percent in the people who took the older antidepressants. Most doctors will be surprised to know that,
for people with less severe depression
(in my experience, the majority of patients treated with the new antidepressants by primary care doctors), nine out of 10 studies showed that the new drugs are no more effective than placebos.

One of the disadvantages of the older tricyclic antidepressants is that they are much more dangerous when taken as an overdose. But a very well-kept secret, revealed by considering all the research, is that the actual rate of death from suicide is higher in patients who take the new antidepressants than in those who take the older tricyclics. Even more important, twice as many people taking the new antidepressants successfully committed suicide than did the people who took placebos. The results of all the studies—published
and
unpublished—showed that of every 1000 people with depression treated with one of the new antidepressant drugs,
4.6 more committed suicide
each year than would have if they had been treated with a placebo.

Another, more specific example of bias in the research results available to doctors is the “evidence” showing that Paxil is safe and effective for depressed adolescents. A study published in 2001 showed that
depressed adolescents were significantly more likely
to improve when treated with Paxil than when treated with a placebo. But in May 2003, when the
British drug authorities reviewed all nine studies
that had been done on Paxil for the treatment of adolescents under the age of 18—only one of which had been published—a very different picture emerged. The patients were no less depressed after taking Paxil than after taking placebos, and the incidence of emotional lability (including suicidal thoughts) was twice as high (3.2 percent versus 1.5 percent). The United Kingdom Medicines and Healthcare Products Regulatory Agency promptly advised that Paxil no longer be prescribed for patients under the age of 18.

When all of the evidence is considered, “breakthrough” is not exactly the first word that comes to mind to describe the effectiveness and safety of the new antidepressant drugs. The one advantage of the new drugs is that they cause about 12 percent fewer side effects, but that hardly justifies using them routinely for all depressed patients, considering the possibility of increased suicide risk and the increased cost.

With only selective reporting of commercially sponsored clinical trials, doctors reading their journals are led to believe that newer drugs are more effective and less dangerous than older drugs, even when the actual scientific evidence points in the other direction. Based on the best information available,
antidepressants (almost exclusively the newer ones)
were the best selling class of drugs in the United States between 1999 and 2001, and
ranked number three behind
cholesterol-lowering statins and acid-suppressing drugs in 2002 and 2003. All told, in 2001, Americans spent a total of $12.5 billion on antidepressants. That amounts to $43.85 for every man, woman, child, and infant.

Virtually all doctors keep abreast of developments in their field by regularly attending educational lectures and courses. For most doctors this is mandatory; participation in continuing medical education (CME) is required to maintain their state medical licenses. Lectures and conferences about the latest breakthroughs and state-of-the-art care are presented by experts with impressive academic credentials and are often held at prestigious academic medical centers.

Drs. Arnold Relman and Marcia Angell have publicly lamented the changes in
doctors’ continuing education meetings
over the years: “To many senior physicians who have watched the atmosphere at these meetings decline in quality from the sober professionalism of a few decades ago to the trade-show hucksterism of today, it is a dispiriting spectacle.”

I am a little younger. By the time I entered private practice, the drug industry was already playing a significant role in “educating” doctors about new drugs. I had been in practice two years when I attended grand rounds at the local hospital, which was a lecture on pain control given by a faculty member from one of the Boston medical schools. I knew that his talk was drug company–supported, but given his academic position, I didn’t think this would influence the content of his presentation. Toward the end of his informative talk he turned his attention to the benefits of a relatively new drug called Zomax, a non-narcotic pain reliever that purportedly provided as much pain relief as codeine, a claim my patients were telling me was really true. The only problem was that Zomax had a propensity to cause serious allergic reactions, some of which had been fatal. The FDA had taken the drug off the market the week before the professor’s talk. My recollection is that the manufacturer of Zomax had sponsored the talk, and evidently the terms of the professor’s contract had not been updated.

I was well aware of the problems Zomax could cause, because one of my patients, with whom I had enjoyed a particularly good relationship, was at the time suffering from a severe and unrelenting allergic reaction to Zomax. She left my practice because of this drug reaction and threatened to sue me as well. (Fortunately she did not.) Had the FDA not withdrawn this dangerous drug from the market the week before, the professor’s talk would have persuaded many doctors in the audience to prescribe Zomax for their patients as well, if they weren’t doing so already.

Commercial support for doctors’ continuing education courses has been increasing at a rapid clip, doubling between 1996 and 2000. The medical industry (and in particular the drug companies)
funded more than three-fifths
of doctors’ continuing education in 2001. Industry spending on doctors’ continuing education then
increased by another 30 percent
in 2002. By 2003, the drug companies were spending more than $1500 per year on CME for every doctor in the United States, funding 70 percent of all continuing education for doctors. At first glance, this may not appear to be a bad arrangement: Drug companies do busy doctors the service of providing easy access to up-to-date research findings, distilling the information down to concise operational points, all usually within one or two hours. But it’s not so simple.

The drug companies understand precisely what it takes to persuade doctors to change their prescribing habits. They know that we have been taught in medical school and during our residencies to accept information that modifies our practice only after it has been “blessed” by doctors farther up the chain of command. In training, these authority figures are the residents, fellows, and attending physicians, depending on where you are in the hierarchy. Practicing physicians in turn look to recognized experts, usually with prestigious academic affiliations.

Marketing mavens call these doctors “thought leaders” or “key opinion leaders” (KOLs)—whether local or national—because they command enough respect to influence the medical decisions made by other doctors. These are the experts chosen to make CME presentations. The medical industry goes to great lengths to
cultivate relationships with these experts
, in the same way that athletes are recruited for product endorsements. For example, Pfizer, the manufacturer of the best-selling cholesterol-lowering statin drug Lipitor, sponsored a special meeting of leaders in the field of cardiology—doctors who could influence other doctors’ prescribing patterns. The meeting was held in Sydney, Australia, and happened to coincide with the 2000 Olympic games. With tactics like this, it is hardly surprising that companies manage to gain the allegiance of influential doctors.

Besides the talks and formal lectures, drug companies also work hard to draw doctors into an environment where they are predisposed to be agreeable—be it a convenient lunch or a luxury resort. In an article published in the
American Journal of Bioethics
titled “All Gifts Large and Small: Toward an Understanding of the Ethics of Pharmaceutical Industry Gift Giving,” the authors point out that
“food, flattery, and friendship
are all powerful tools of persuasion, particularly when combined.” It is very difficult to maintain an objective perspective about a particular drug—much less take an opposing point of view—while eating a delicious salmon and wild rice lunch provided by attractive and friendly marketing folks.

I’ve turned down more offers than I can count for “educational” dinners, sporting events, golf and ski outings, and even weekends in the best hotels plus $500. And I must confess to having given in to temptation on several occasions.

A couple of months after the Boston Celtics were defeated by the Los Angeles Lakers in the historic 1987 NBA world championship series (the last great Larry Bird–versus–Magic Johnson showdown), the manufacturer of the latest anti-inflammatory drug sponsored a weekend outing. The educational courses consisted of the Celtics’ team doctors and therapists reviewing the team’s injuries: viewing the x-ray of Kevin McHale’s heel fracture after game four and seeing how much farther the fracture had extended two games later; learning that another star’s back would go out many times each game and needed to be manipulated into place. The conference, I must admit, was fascinating.

The quid pro quo, of course, ranges from subtle pressure to prescribe the company’s product to the threat of withdrawing any future funding for research and, of course, to being cut off from future freebies. The expensive new NSAID touted at the conference did not seem to offer any real advantage, and I cannot recall writing many prescriptions for it. The manufacturer offered me no further invitations.

Does it work? The evidence is quite clear. Notwithstanding doctors’ steadfast belief in their resistance to commercial pressure, the drug companies know better: doctors who attend sponsored lectures significantly increase their prescribing of the sponsor’s drug. A study followed the
prescribing habits of 20 doctors
who attended CME seminars sponsored by the manufacturers of two different drugs. Though all but one doctor denied that attendance at the seminars had affected their prescribing habits, all but one of the doctors increased their use of the two drugs in comparison with other doctors at their institutions and in comparison with the national average. Clearly, the doctors had been influenced by education sponsored by drug companies, and it was all the more effective because they naively believed themselves impervious to such influence.

There seems to be no end to the medical industry’s influence over CME.
Nearly half of the members of the task force
that establishes the guidelines for drug industry involvement with CME are directly employed by the drug companies or are their paid consultants. Some drug and medical-device companies actually
own their own educational subsidiaries
to ensure that the right “educational” message gets communicated.

A report written by the health research group of Public Citizen describes the new industry that has emerged, called medical education and communication companies (MECCs). What are the guiding principles of these MECCs? One of the largest of these companies, Concepts in Professional Education and Communications, representing 14 drug companies, states its purpose succinctly in its marketing materials: “Medical education is a powerful tool that can deliver your message to key audiences, and get those audiences to take action that benefits your product. Whatever combination of audiences you need to motivate in order to exert maximum leverage on the marketplace, we can help you identify them, reach them, and influence their behavior.” (What’s health got to do with it?)

Purdue Pharma, the maker of the expensive painkiller OxyContin, went one step further. The company gave
$3 million to the prestigious Massachusetts General Hospital
in return for, among other things, the hospital’s renaming its current pain center the MGH Purdue Pharma Pain Center. According to a news release from Massachusetts General, the money will be used to support educational activities, including continuing medical education courses. Part of the agreement, according to the
Boston Globe,
includes MGH pain specialists conducting continuing education seminars on pain control “using Purdue-designed curriculum written, in part, to encourage wary doctors and pharmacists to prescribe pain-killers such as OxyContin.” A medical ethicist from Boston University,
George Annas, commented
: “You don’t let outside people write your curriculum. You don’t put your name on their curriculum. There’s the potential for that being a curriculum run by the drug companies.” Doctors coming to the prestigious Massachusetts General Hospital for continuing education have every reason to believe that the content of the lectures will be guided by the sole mission of improving patient care. Most will be unaware of the underlying commercial agenda of the program.