Drugs, Marketing, You and Your Physician
Pharmaceutical manufacturing has for a long time been among the most profitable businesses activities in America and around the world. These companies develop important medications, which can help each of us at some time or another.
Combining scientific research, health care and business can be a great way to help people and make a living at the same time. Corporations exist to make profits for their shareholders. As many of you already know there are very big problems in this confluence of altruism and profit making.
When the AIDS epidemic first hit there was a great deal of excitement over AZT, the first effective anti-viral for HIV, which became available in 1987. That excitement was first tempered a bit by the precise round-the-clock dosing schedule required. When patients started looking at taking AZT (aka ZIDOVUDINE) six times a day for the rest of their lives, the $7 a pill ($10,000+ annually) cost was upsetting. As AIDS activists began to ask questions and learned that manufacturing the drug cost only a tiny fraction of the selling price, many people became very angry. This anger led to congressional investigations and price reductions by the company. The cynical attitude of many towards the drug companies heightened and spread.
Although many are skeptical about the business dealings of drug companies, it is very clear to me that we all should be more skeptical and the facts bear that out.
Drug Industry Document Archives
Many people have heard of the “Cigarette Papers.” The true story was dramatized in the film THE INSIDER. A disgruntled tobacco executive leaked internal corporate documents showing that the tobacco companies knew from their own research that cigarette smoking caused health problems that they continued to deny in public. Worse still, the documents proved that the companies were actually formulating their cigarettes to maximize additive qualities. In a humorous note, the informant sent the first box of documents to Professor Stanton Glantz at the University of California, San Francisco in May 1984 with the simple return address “Mr. Butts.” The UCSF archive now holds 80 million pages of insider documents (you can read more in the book The Cigarette Papers which is also available at no cost online http://ark.cdlib.org/ark:/13030/ft8489p25j/.
Recently, what will hopefully become the first wave of similar drug company documents were sent to UCSF by a former employee of Parke-Davis. These 8,000 pages documented Parke-Davis’ promotion of the drug Gabapentin (NEURONTIN) for unapproved uses. The company’s intent was to increase the number of prescriptions and in turn the company’s profit. The documents reveal an extensive and well-planned campaign of misinformation. If you wish, you can read the Drug Industry Document Archive online at http://dida.library.ucsf.edu/. A lawsuit against the company was settled out of court for $24,640,000 plus attorney’s fees.
One of the uses of those settlement monies was to fund a meeting I attended recently called Marketing of Medicines: Critical Skills for Clinicians, held at UCSF.
I was honored to participate as a panelist discussing what we can do to counter the effects of marketing. One step I am taking is writing this blog for you. Although my own skepticism toward drug companies runs long and deep; I learned that even I was naïve. My worst assumptions were entirely justified. Worse still, those devious practices I observed and suspected were not isolated incidents. They were methodically and systematically applied by the industry. The sophistication of pharmaceutical marketing is astonishing and even frightening. Highlights of the meeting will be broadcast on UCTV (DISH channel 9412).
Drugs and Money
Everyone knows that health care costs have been rising rapidly for many years. Very little of that rise is accounted for by health providers. Drug costs are the most dramatic part of that increase. During the most recent five year period for which we have data (1997-2002) drug costs in the U.S. rose 75 percent. Americans now spend approximately $200 billion annually on prescription drugs. In 2005, the drug companies spent $29 billion, nearly $100 for every man, woman and child in America, on marketing. That expenditure exceeded the entire budget of the National Institutes of Health (NIH) the governmental department which funds health care research in the U.S.
Marketing to Physicians
The biggest chunk of these expenses, just under two-thirds, still goes to giving away drug samples. The issue of drug samples is both extremely difficult and extremely controversial. On the one hand, the offer of free medication by the companies is very generous and provides physicians with a means of getting needed medication to impoverished patients. The other side is not quite so rosy. The drugs distributed as samples are almost invariably the newest drugs on the market. In this way the drug companies familiarize physicians and patients with their new products. Unfortunately new drugs often have serious adverse effects which are not evident until the drugs are widely used. New drugs are also expensive. Consequently, when the free samples run out, patients are faced with continuing on an unusually expensive drug or going through an often confusing and sometimes unpleasant process of changing to a different medication. Some have likened this approach, perhaps unfairly, to a pusher of street drugs offering his wares free to newbies in hopes of getting them hooked.
One quarter of drug advertising expense ($7 billion in 2005) goes to drug company representatives marketing directly to doctors. Drug reps are notoriously beautiful and friendly people who set up a table near the doctors’ entrance to the hospital and visit our offices regularly pitching their latest medication. They bring with them food, samples, small gifts (a pen is the archetype) and informational materials about the products they are marketing most heavily that month. As I will discuss more later on, the “information” they provide tends to be more biased and misleading than educational. In 2004, the average income for a drug rep in the US was $81,700. Over the 10-year period from 1995 to 2005 the number of drug reps in the US nearly tripled to roughly 100,000.
Another problem is that physicians do not believe that drug marketing affects our prescribing patterns when the evidence is clear that it does. A study published in the Journal of the American Medical Association in 2000 reported that physician contact with drug reps led to higher prescribing costs, less use of generic medication, increased requests for the drugs sold by the drug reps and more rapid acceptance of new drugs.
The Tactics Of Marketing to Physicians
One element of pharmaceutical marketing is to influence key physicians in academic centers who are opinion leaders. They accomplish this by several different means of varying subtlety.
On the less subtle side, drug companies have taken key physicians on free trips to tourist spots for “educational” meetings. Research shows that pharmaceutically supported travel has an impact on physician medication prescribing, lasting at least two years after the travel. Many companies are now ending this practice.
Research As An Artful Deceit
Research is a vitally important element of efforts to improve health care. It is also a tremendous opportunity for pharmaceutical companies
Consistent with their need to make a profit, drug companies selectively pursue research of medications likely to make a lot of money. Why should a company spend money to prove that adequate water consumption reduces the risk of respiratory illness when water is free? Why should a company continue to fund research proving that an old drug is as good or better than a new drug when they will make lots more money from the new one?
An important and insidious consequence of this trend is that it shifts the basic expectations of physicians, and their patients. Physicians disregard the potential effects of many therapeutic interventions because there is little if any research showing whether these interventions work. The lack of study leads to a presumption of ineffectiveness. The NIH helps to balance this funding inequity. However, the underlying assumptions that inexpensive = cheap/ineffective can still have a profound effect on what studies are proposed and funded.
The following is a very loose outline of pharmaceutically funded research. A company develops a new drug for disease A. They conduct their own animal trials to ensure a certain level of safety. Then they start looking outside the company for a university-based researcher interested in the same disease. The company provides funding for the research, which pays for the study materials and supports the researcher and her/his university. These drug company funds flowing into academic institutions are considerable and raise concerns about conflicts of interest. Universities themselves can develop medications or devices which in turn then raise these conflict of interest questions. How can any entity, including academic ones, ethically and without bias, study products that could make them a great deal of money? The FDA is involved all along the line. When human testing is involved, human subjects committee/institutional review boards provide a certain level of oversight.
Corporate relationships with academic researchers are often highly lucrative and at best, an ethical minefield. After establishing a relationship with a researcher, drug companies usually extend that relationship into the investigation of other medications.
Years ago one of the most prominent US academic physicians studying children’s ear infections hired a promising young statistician to help him in his research. Several committees at their university, three NIH panels, the US Congress and in the federal courts have investigated what followed. The two men designed a major clinical trial of amoxicillin in the treatment of acute ear infections in children, funded by a grant of over $17 million from the NIH. The statistician determined that amoxicillin was ineffective. As the statistician’s role is to determine whether there is mathematical proof of effectiveness, it was surprising when the physician disagreed and submitted the study for publication. including both of their names. When it came out that the physician had received over $260, 000 in gifts and honoraria from the drug companies whose products they were testing in this and other studies, further investigation was clearly in order. Meanwhile the statistician had submitted the same study, with his alternative interpretation of the data, to the same medical journal.
Since then, the two men’s lives have followed dramatically different courses. The statistician is now looked upon as a martyr by some because his version of the study, had it been published, would have helped reduce the overuse of antibiotics for ear infections. Unfortunately, that was not the result, and since he was labeled as a “whistle-blower”, he has been unable to conduct research. The physician continues to publish and receive awards for his work.
Unpublished Research
Manufacturers can choose whether or not to submit their research for publication. This allows them to hide results unfavorable to their product.
Over a four year period there were 56 randomized controlled clinical trials funded by drug companies comparing NSAIDs (nonsteroidal anti-inflammatory drugs like Vioxx) published in the medical literature. Not one of the studies published found that a competitor’s drug worked better! Sixteen found that their drug worked better and the other 40 found that the competitor’s drug worked as well as their own.
A researcher at the University of California San Francisco compared the most widely prescribed thyroid medication to the generic version. She found there was no difference. The manufacturer of the popular medication provided some of the funding for her research. The manufacturer banned her from submitting it for publication. As the federal government also funded the study, she notified the government. Many years later she was allowed to publish the study. Meanwhile, the company continued to make ¼ billion dollars annually on the drug, so the money they earned during the delay very much more than their legal costs.
Skewed Data
The popular caution, “There are three kinds of lies: lies, damned lies and statistics” is well appreciated by pharmaceutical companies. In every study there is a lot of data collected. It is often quite easy to select data (cherry picking) in order to demonstrate a desired outcome. Reporting the outcome at a certain time, say 3 days after beginning treatment, can look entirely different than at the end of treatment. The use of certain statistical values can be so misleading that doing so is a very common technique in medical advertising. It can even get past reviewers for medical journals. A statically significant difference is worthless if it not clinically meaningful to a patient, or is outweighed by the adverse effects or expense of the medication.
One study of an asthma drug included over 500 patients. The study was conducted at nearly 100 different institutions scattered over five continents. The study showed no significant benefit of the medication. I had a number of strong reactions to this study. First, was the realization that each study site had far too small a number of subjects to even get comfortable with the study procedures. If the average was around 6, that meant that many centers probably only had one or two patients and few had more than 20. That will limit the meaning of the data. Asthma is a disease markedly affected by the seasons. In a worldwide study involving such small numbers at each site, this was impossible to address.
Thinking more deeply about this study I reflected on drug company motivations. Many countries require drug companies to conduct clinical research in their country before they will approve a drug for sale. Drug companies do not usually publish trials showing that their drugs don’t work. Clearly the point of this trial had nothing to do with determining if the medication was effective. The only purpose of this study was to conduct research all over the world, so that the drug could be sold all over the world.
What about the larger ethical responsibilities of academic institutions? How did reviewers for a major medical journal approve publication of such a poorly designed study? Institutional review boards and human subjects committees are charged with protecting research subjects from harm. The consensus is that a study, involving human subjects which cannot obtain a meaningful result, is by definition unethical. How could so many IRB/HSC pass such a woefully designed study?
As far as the medical journal, I am reminded of comments from editors of three of the four most important medical journals in the world. Richard Horton of THE LANCET wrote: “Journals have devolved into information laundering operations for the pharmaceutical industry”. The former editor of the BRITISH MEDICAL JOURNAL said that medical journals are an extension of the marketing arm of pharmaceutical companies. Finally the title of the new book by Marcia Angell, former editor of THE ENGLAND JOURNAL OF MEDICINE, says it all: THE TRUTH ABOUT THE DRUG COMPANIES: How They Deceive Us and What To Do About It.
Diseasification
The confluence of enthusiastic researchers, often highly concerned about the health impacts of their studied disease, and a company eager to profit from selling the medication for this disease can easily fuel a crisis of anxiety about the disease. Decades ago the president of one of the world’s largest drug companies told FORTUNE magazine that he had long dreamed of making his company like a company that sells gum, so that they could sell their drugs to everyone, even healthy people.
Yesterday I got a marketing email from an often-helpful educational entity. Blurring the line between education and marketing, it is sponsored by a consortium of pharmaceutical manufacturers. This email asked if my patients were in the “BP Success Zone”. What the is that supposed to mean? BP means blood pressure. High blood pressure causes health problems, especially in the long term. This email was asking if I have medicated my patients’ blood pressures down below 120/80. Building on a statistical house of cards plus anxiety, pharmaceutical companies, with help from some elements of the medical community have slapped healthy normal people with unwarranted disease labels. Cholesterol, blood pressure, ADHD, depression, osteoporosis and irritable bowel are among the disease which can be very hurtful to many people but easy categories in which to nudge millions more people who should not be concerned and certainly not taking medication.
Pharmaceutically sponsored educational meetings are an excellent example of wolves in sheeps clothing. The ostensible purpose of such meetings is to educate physicians about a disease. One or more highly regarded university-based physicians provide very inexpensive (company sponsored) fully accredited education to physicians. The company or companies that sponsor such conferences make certain that their products are highlighted in every way possible. Sometimes such meetings are like any other big CME conference in some hotel somewhere. Other times they will hold the session at the best restaurant in town. There might even be a trip involved to some beautiful destination far away from the physician’s home at company expense.
Teleconferences are increasingly popular in this age of electronic connectedness and high gasoline costs. Sometimes physicians who decide to accept an offer to listen in on one of these teleconferences are paid substantially (up to $500) for participating. One of the documents in the Drug Industry Document Archives explains “The key goal of the teleconferences was to increase NEURONTIN new prescriptions by convincing non-prescribers to begin prescribing and current prescribers to increase their new prescription behavior.” To learn how to better market the medications and to ensure that the teaching physicians did their jobs, drug company employees listen in on these teleconferences “Instruct the teleconference operator that should be in LISTEN ONLY mode and your name should NOT be announced during introductions”.
Sponsorship of University CME meetings
All physicians must accumulate a certain number of Continuing Medical Education (CME) hours each year. CME conferences cost a good deal of money. Despite our grumbles about how expensive CME meetings are to physicians ($2-300 a day is common) the real cost is quite a bit more than we pay. Commercial sponsorship, almost entirely from pharmaceutical companies, contributes substantially more than admission fees. These sponsorships provide nearly two-thirds of medical school income from CME.
Twenty years ago Marjorie Bowman investigated the impact of two different CME courses on calcium channel blocking drugs. Each course was sponsored by a different pharmaceutical company making a different calcium channel blocking drug. She found that speakers were nearly three times as likely to mention positive effects of the sponsoring companies drug, and negative or equivocal effects of a competitor’s drug.
Drug companies have created an environment where physician acceptance of gifts is the norm. When I entered medical school 30 years ago we were each given a stethoscope from a drug company. Urged on by an informational flyer written by a classmate, who was to become my closest friend, I refused mine. The director of my residency program was a wise and extremely socially conscious physician who I deeply respected. When he traveled to the huge annual meeting of the American Academy of Family Physicians 25 years ago, he told me he was bringing an empty suitcase to carry home all of the drug company gifts he knew he would receive. A study of physicians in their residency training, published in 2001, found that 97% of them were carrying some item (pen, reference book, etc) with a drug company brand.
Only recently are academic institutions responding to the ethical issues created by these gifts, and establishing policies. At this point only five of the nearly 200 US medical schools prohibit drug company representative contacts with their students. Earlier this year the Accreditation Council for Continuing Medical Education issued updated guidelines for commercial support of continuing medical education, which will hopefully help.
Advertising to Physicians
Discussing my daughter’s homework with her and sorting out the meaning of “pseudoscience” and “propanagnda”, it struck me that these terms can reasonably be applied to the advertisements in medical journals and the intentionally selective data drug reps present to the physicians they market to.
In the UCSF meeting, we had two small group sessions. In one of them we looked carefully at common drug advertisements from medical journals. It was fun because many years ago I learned never to look at the ads. They were simply too misleading. It was interesting to check in on the current state. In the old days, the disinformation in the ads was easy to spot. It was usually something like showing a graph of the difference between the product and something else (placebo or a competing medication). Although the difference was visually dramatic, if you looked carefully you could see that the graph started at the point some difference appeared deleting the rest of the data. Consequently this representation hugely magnified the trivial difference. Now the ads more skillfully deflect attention towards meaningless images or facts, present unimportant but favorable statistics, while concealing the important data or information about adverse effects. None of them, of course, mention the relative cost of the latest drug (always HIGH). Clearly pharmaceutical company efforts to manipulate physicians’ opinions are becoming increasingly sophisticated.
Direct to Consumer Advertising (DTC)
Expenses on DTC from 1997-2005 tripled to $4.5 billion. This represents 14% of all drug company marketing expenses. In 2000 Merck spent more money marketing one drug (Vioxx which has since been recalled due to safety concerns) than the entire marketing budget of Dell Computer, Nike, Pepsi or Budweiser.
I looked through a recent issue of Reader’s Digest and found that over 1/3 of the first 100 pages were ads for prescription drugs. They were all misleading to one degree or another, but actually less cleverly so than in medical journals. They mostly used appealing images spiced with a dose of fear to manipulate readers towards their products. Most commonly the fear spiced sales pitch is that YOU have a problem, that problem is worse than you think and fortunately they have a product which can help. The drugs advertised are often relatively new and highly toxic, but the ads very effectively mask that reality. Familiar faces are there to help you with your problems, such as Sally Field for your osteoporosis and Abraham Lincoln for your insomnia. Although Sally says she can take one pill a month, she does not say that she actually does take the drug or even that she has osteoporosis. I somehow doubt that Abraham Lincoln and his friend (is that a beaver in those ads?) really need you there to play chess or hang out in the kitchen with them for a snack.
The ad about poor leg circulation, loudly proclaiming its dire consequential risks, was among the worst. It was stealth-funded by the pharmaceutical industry, which you can only learn by reading the microprint at the bottom of the page, where the phrase “Pharmaceuticals Partnership” is nearly visible along with the names of some drug companies. The ad directs readers to a toll-free number, a website and an enclosed postcard you can send in to receive FREE information.
Effects On The Patient-Physician Relationship
During our panel discussion, a physician in the audience asked us how she could quickly and effectively respond to a patient carrying a discount coupon for a prescription drug, that she believes not to be a good choice for this patient. This physician was concerned that the time she could spend with the patient was already limited and addressing this patient’s request would impair her ability to provide attentive care. In addition, patients understandably want to save money. Refusing a patient’s money saving request often will not sit well with the patient.
My response was that all she could do was to honestly express her concern for the patient’s well-being, and express her professional opinion against this medication choice. This approach works fairly well in my office because I spend much more time than the average physician with my patients. Physicians who are working in a situation where they are punished for spending “too much” time with their patients can not do this. As I said in the meeting, even I feel pressured in this situation, as if “the drug rep from hell had taken over my patient’s body”. The drug companies have learned that they can most effectively alter our prescribing patterns by marketing through our patients’ mouths. In 2002 53 million Americans asked their physicians about a medication they had seen advertised somewhere.
False Advertising
One example of my own naiveté was that, like most Americans, I assumed that the FDA approved the drug ads we see on television and in the popular press. That is not the case. Knowing how misleading drug ads have always been in medical journals, I should have been more suspicious. The FDA can demand the correction of false or misleading drug advertisements. However, FDA citations usually take 6 months, and because the marketing life of an advertisement is shorter than that, the ads are already gone. In 1997 the FDA issued 142 notices of advertising violations to drug companies. In 2006, despite a three-fold rise in drug advertising to consumers, the FDA only issued 21 violation notices. The FDA can also issue fines and pursue court actions. In the present lax regulatory climate the FDA has not been imposing any fines or legal actions.
Summary
I should apologize for how long this article has been. I will not. It could have been a whole lot longer and maybe should have been. This is an extremely important matter impacting your health and that of your family so I hope you take seriously. Recognize that you and your physicians must be wary to avoid being mislead by marketing misinformation.
Further reading
OVERDOSED AMERICA by John Abramson, clinical faculty Harvard Medical School <www.overdosedamerica.com
THE TRUTH ABOUT THE DRUG COMPANIES: How They Deceive Us And What To Do About It by Marica Angell, former editor of the New England Journal of Medicin
SELLING SICKNESS by Ray Moynihan and Alan Cassels