An excerpt from The Truth About Statins.
Like all physicians, I’ve had interactions with pharmaceutical companies. Shortly after I went into private practice in Rhode Island in 1977, I received a telephone call from a drug company representative. He offered me an all-expense-paid weeklong trip to Germany to attend a medical conference. I was taken aback, knowing that the cost of such a trip would run to thousands of dollars. I replied that I was in solo private practice and was the single mother of three young children, so I was not free to attend. I also felt this was a not-so-subtle attempt to make me feel beholden, to influence me in favor of his company’s medications.
Over the years, I have met with drug company representatives in my office because they can provide free samples of whatever drugs they are promoting, and sometimes my getting free samples is the only way that some of my patients can afford their medications. I’ve also attended drug company dinners where a paid expert lectures on one drug or another. Spouses used to be welcomed at these dinners, and my husband attended a few. But with increasing attention focused upon the ethics of drug company–physician interactions, medical organizations and the pharmaceutical industry agreed that it was no longer appropriate for spouses to be included in these venues.
After many years in private practice, I was asked by the CEO of my hospital to set up and direct a Women’s Cardiac Center, so, since 2002, I have been a salaried hospital employee. Despite the fact that my office door now says Women’s Cardiac Center, many of my male patients from my former practice still come to me, and many of the women patients I see want me to take care of their male relatives. Throughout my time in Rhode Island, I have been on the clinical faculty at Brown University’s medical school. I have supervised and taught scores of medical students, interns, residents, and fellows, a part of my job that I find very rewarding. I enjoy both bedside teaching and lecturing. And being exposed to bright young physicians on a daily basis spurs me to always keep up with the latest research in my chosen field of cardiology.
About the time my first book came out in 2004 (How to Keep from Breaking Your Heart: What Every Woman Needs to Know About Cardiovascular Disease), a Pfizer representative whom I’d gotten to know over several years asked me if I would be interested in becoming a speaker for Pfizer, specifically on Lipitor, the company’s premier statin drug. I told her that I would be happy to speak about gender-specific aspects of heart disease in women, but that I wasn’t interested in just getting up in front of a bunch of doctors and plugging one or another of Pfizer’s medicines. She assured me that my chosen topic would be fine, and I went off for a two-day course in New York, where various physicians, scientists, and Pfizer officials lectured on being effective speakers, demonstrated the slide sets to use, and took us through the FDA-approved indications for Lipitor.
I then made up my own slide sets on heart disease in women and began to be invited to give Pfizer-sponsored dinner talks in restaurants and Pfizer-sponsored lectures at hospitals in New England and the surrounding states. (Most, if not all, hospitals provide opportunities for their staff physicians to keep up with continuing medical education requirements by sponsoring educational lectures, called grand rounds, on the latest advances in medicine.) Pfizer paid very well: $1,000 for a lecture that didn’t involve travel out of Rhode Island, and $1,500 plus travel expenses for lectures out of state. My talks on gender-specific aspects of heart disease seemed to be well received, and I felt I was educating doctors on an important subject that might be unfamiliar to them.
Despite the fact that Pfizer was sponsoring my talks, I never failed to point out that there was no evidence that Lipitor—or any statin for that matter—prevented cardiac events in women who did not have established cardiovascular disease. I mentioned the results of the ASCOT-LLA study, in which there were seventeen primary end points out of about 1,500 women in the placebo group and nineteen primary end points out of about 1,500 women in the Lipitor-treated group.
One night a regional manager attended one of my talks—and suddenly I was no longer invited by Pfizer to give lectures.
In 2006 the Women’s Cardiac Center at the Miriam Hospital was chosen to be one of the sites to participate in a large clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and by Kos Pharmaceuticals, the company that made Niaspan, a long-acting, high-dose version of the B vitamin niacin. (Kos was subsequently bought by Abbott Laboratories, which continued to cosponsor the trial.)
Niacin, in high doses, does all the right things to blood fat levels: it lowers triglycerides, lowers LDL cholesterol, and raises HDL cholesterol. The hypothesis proposed by the study designers, Drs. B. Greg Brown and William Boden, was that “extended-release niacin and simvastatin would prove superior to simvastatin alone at equivalent on-treatment LDL cholesterol levels in reducing clinical cardiovascular events in patients with established vascular disease, low HDL-C, and high triglycerides.”
This trial went by the catchy name AIM-HIGH, which stands for Atherothrombosis Drug Intervention for Metabolic Syndrome with Low HDL/High Triglycerides and Its Impact on Global Health Outcomes. The AIM-HIGH trial was interested in recruiting as many women as possible. It was expected that the trial would be completed in 2012. However, the study was ended in April 2011 when the Data Monitoring and Safety Board concluded that, based on the results to date, extended-release niacin offered no benefits beyond statin therapy alone in reducing clinical events.
The AIM-HIGH trial recruited over three thousand people at ninety-eight centers around the United States and Canada. I was the principal investigator at the Women’s Cardiac Center site. Every time we randomized someone into the study, and every time we saw someone for a study visit, my hospital got paid by the sponsors. None of that money came to me, nor was my salary based on the number of patients that we recruited into the trial.
Abbott Laboratories expressed interest in adding me to its speaker’s bureau, and I told the company the same thing that I had told Pfizer: I would be happy to lecture about gender-specific aspects of cardiovascular disease, but not just about its products. (Abbott also sells fenofibrate, or Tricor, another lipid-lowering medicine, though not a statin. It has actions similar to niacin but works by a different mechanism.) This was satisfactory for a few years, but then Abbott decided that its speakers could use only Abbott-provided slides, at which point I told the company that I was not interested in doing this and stopped speaking at Abbott-sponsored events.
I have also on occasion been paid by the medical device companies Medtronic and Guidant Corporation to speak on gender-specific aspects of heart disease, but I neither insert medical devices myself nor teach cardiology fellows how to do these procedures. So, all in all, my interactions with the pharmaceutical/medical device companies have complied with ethical guidelines. Does this mean that I have not been influenced by these interactions? It certainly does not.
As Dana Katz, a bioethicist, and his colleagues wrote in the American Journal of Bioethics in 2003: “When a gift or a gesture of any size is bestowed, it imposes on the recipient a sense of indebtedness. The obligation to directly reciprocate, whether or not the recipient is directly conscious of it, tends to influence behavior.”
Indeed, there is an increasing body of knowledge on the ways that seemingly rational decisions can be influenced by such mundane things as receiving inexpensive gifts. Try to find a doctor’s office that doesn’t contain pads and pens imprinted with a pharmaceutical company’s logo and the name of one of its drugs, thoughtfully provided by company representatives. Doctors bristle at the accusation that these trifles, or even the occasional free dinner-cum-lecture, can influence their prescribing habits. And on a conscious level, no doubt they are correct in saying that they are not being swayed in their prescribing decisions. But the story is not that simple. And we’ve known for many decades now, thanks to Sigmund Freud and others, that our subconscious plays a role in determining how we act and react. But in Freud’s time, we didn’t have the tools to actually investigate what aspects of brain metabolism might underlie the workings of the unconscious mind. Nowadays we do.
In 2007 the Association of American Medical Colleges held a symposium at Houston’s Baylor College of Medicine entitled “The Scientific Basis of Influence and Reciprocity.” The seminar was designed to explore how objectivity was affected by gifts, favors, and influence. It sought to impart information about the “underlying neurobiological substrates” involved in the “process of influence and reciprocity,” so that the academic community could “evaluate and manage its relationship with industry.”
“Neurobiological substrates” is a fancy way of referring to changes in brain function that occur without our conscious knowledge or control. One of the participants in the symposium presented the findings of an experiment using functional MRIs (fMRIs) of the brain in people playing a “two-person trust game.” Specific areas of the brain react when one receives a favor or gift from another. This research demonstrated that biologic changes occur in the brain when gifts are exchanged and that there exists “the human tendency to expect . . . that favors given will be paid back. In fact, the experiment suggests, but does not prove, that this process has strong automatic components that covertly influence one’s decision to trust someone else.”
In other words, accepting even a pen, pad, or coffee mug may generate an unconscious bias toward trusting that what a drug company representative says about his or her product is true. Big Pharma spends an estimated $30 billion a year on marketing. It is naive to believe that drug companies shell out that kind of money without proof that it works to increase sales.
But far more dangerous to our health and safety than low-cost gifts to practicing physicians is the influence that Big Pharma and medical device companies exert over academic medical centers, the supposed bastions of ethical scientific research and advanced medical care. A 2003 article in the Journal of the American Medical Association reported on a survey of academic medical centers and found that almost two-thirds of them owned stock in companies that sponsored research within the same institution. The authors also found a significant correlation between industry sponsorship of research and pro-industry outcomes. In other words when a drug company was sponsoring research on one of its drugs, the study was more likely to find that the drug was beneficial than when a study was not sponsored by the company that made the drug being investigated. Industry sponsorship was also associated with restrictions on publication and data sharing.
As Marcia Angell wrote in the Boston Review in 2010: “The boundaries between academic medicine . . . and the pharmaceutical industry have been dissolving since the 1980s, and the important differences between their missions are becoming blurred. Medical research, education, and clinical practice have suffered as a result.”
-Barbara H. Roberts is Director, The Women’s Cardiac Center at The Miriam Hospital and Associate Clinical Professor of Medicine, Alpert Medical School of Brown University. She is the author of The Truth About Statins.