In a perfect world, doctors would not prescribe – and patients would not take – drugs that do more harm than good. But it’s complicated. The benefits and harms of drugs are determined in randomized, controlled clinical trials. For many reasons, the outcomes of such trials may not provide doctors with the information they need to decide who should take what.
For example, harmful effects (like death) may not show up during the limited time span of a trial. Data from trials may be selected – and other data ignored — to produce positive results. This is apt to happen when clinical trials are conducted by the pharmaceutical industry, rather than by economically disinterested parties, such as the NIH or independent academic institutions. Also, the participants in the trial may differ significantly (in age, gender, and health, e.g.) from patients who end up taking the drugs. As a recent article in JAMA put it, “most clinical trials fail to provide the evidence needed to inform medical decision making.”
The Inverse Benefit Law
If you follow pharma news, you will have noticed that many high profile, aggressively marketed drugs turn out to be either ineffective or positively dangerous (think Vioxx, widely prescribed for arthritis, which turned out to cause heart attacks and stroke). Howard Brody, MD, and Donald Light, PhD, have proposed an explanation for this phenomenon. They call it the Inverse Benefit Law: “The ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed.” Or (for those who feel fuzzy about inversion): The more aggressively a drug is marketed, the more likely the drug will cause harm, be ineffective, or deliver little by way of benefit.
Brody and Light have published an article on their “law” in the American Journal of Public Health. The article, unfortunately, is behind a pay wall, but Dr. Brody explains the idea at length in a post on his blog. Brody, btw, is the author of Hooked: Ethics, the Medical Profession, and the Pharmaceutical Industry, plus books on the placebo response and bioethics. Donald Light is the editor of The Risks of Prescription Drugs.
As Brody points out in his blog post, the Inverse Benefit Law seems counterintuitive for a number of reasons. Why would the marketing of a drug have anything to do with its benefit or harm? That should depend entirely on the properties of the drug. Why would the pharmaceutical industry want to market ineffective drugs? It can only hurt their already tarnished reputation. (I just read somewhere that the public regards those in the pharmaceutical industry as worse than lawyers, but better than real estate agents.) And what about the FDA? They’re presumably protecting us from drugs that are ineffective or harmful.
How pharma gets doctors to overprescribe
In addition to Dr. Brody’s easy to understand explanation, Mike Mitka has a summary of the Inverse Benefit Law in a recent issue of JAMA (also, unfortunately, behind a pay wall).
Basically, the answer to the question “Are the most heavily marketed drugs the least beneficial?” is: “It depends of who’s taking them.” A drug may be very beneficial for patients who have quite severe symptoms – very high blood pressure or very high levels of blood sugar, e.g. But because those patients are only a small percentage of the total patient population, drug companies want to market their drug to patients whose symptoms are less severe. (Makes sense, no? More prescriptions, more revenue.) But for patients who have less severe symptoms, the harm is more likely to exceed the benefit. You need to treat many more of those people (number needed to treat or NNT) to get beneficial results. And all those people who don’t benefit – and who may not even need the drug – are subjected to the drug’s harmful side-effects.
Doctors need to be aware of how pharmaceutical companies convince them to prescribe drugs for people who won’t benefit. Brody and Light discuss six pharma strategies. (I quote from both Brody and Mitka in what follows.)
- Reducing the threshold for diagnosing disease. “The magic cutoff for diabetes used to be blood sugar of 140, then 126, and finally 110, with the guidelines suggesting these changes often being written by docs with financial ties to drugmakers.”
- Using surrogate end points. Using “blood pressure, blood sugar, etc. to sell drugs that don’t change the outcomes really important to patients like preventing stroke, heart attacks, and deaths.”
- Exaggerating safety claims. “By overemphasizing the safety of a new drug that had been used in relatively few patients, marketers encourage physicians to prescribe the medications to an expanded population of patients with milder symptoms, thereby exposing larger numbers of individuals to the drug, and therefore to the potential for adverse events.”
- Exaggerating efficacy claims. “When an expensive new drug performs no better than established lower-cost therapies but may have an advantage for a small subset of a patient population, marketers emphasize the latter to imply that the new drug is better than an established therapy, with the goal of its widespread use beyond the patient subset.”
- Creating new “diseases.” Diseases “like ‘social phobia’ or making previous non-disease states into diseases (like osteopenia).”
- Encouraging unapproved uses. “Because promoting unapproved uses of a drug is illegal, some marketers have used tactics such as manipulating the content of continuing medical education programs, hiring leading physicians to give presentations recommending off-label use, and sponsoring ghostwritten articles on off-label indications.”
Mitka goes on to solicit a number of medical opinions on the Brody/Light law. One doctor he consulted was H. Gilbert Welch, author of the recent book Overdiagnosed: Making People Sick in the Pursuit of Health. The Brody/Light explanation is consistent with the arguments Welch makes in his book. Welch comments:
Aggressive marketing expands the market for drugs to be used on patients with milder diseases, patients who cannot really benefit from such medications. … I am a believer in medical care for sick patients, but not when you make those with mild or no complaints into “sick” patients.
Welch’s latest book explains the disadvantages of being diagnosed “at risk” — and subsequently accepting treatment — when there are no signs or symptoms of disease. The book expands on the explanations offered in his previous book, Should I Be Tested for Cancer?: Maybe Not and Here’s Why. The argument – directed at patients — can be subtle and is up against heavily publicized fear-of-disease campaigns: “The early warning signs of colon cancer: You feel great. You have a healthy appetite. You’re only 50.” He does an excellent job of explaining sophisticated concepts. Convincing physicians not to overdiagnose is hindered, unfortunately, by the fear of lawsuits for malpractice, but the Brody/Light Inverse Benefit law offers support for what Welch is preaching.
In addition to the Welch books, which I recommend highly, an excellent book that speaks directly to many of the pharmaceutical industry issues in question here is Carl Elliott’s White Coat, Black Hat: Adventures on the Dark Side of Medicine. It’s not only insightful and informative, but fascinating and a pleasure to read.
Screening for cancer and overdiagnosis
The downside of overly aggressive cancer screening
Creating an epidemic of cancer among the healthy
Mental illness in college students: Overdiagnosed
Should grief be labeled and treated as depression?
How the pharmas make us sick
The last well person
David L. DeMets, PhD and Robert M. Califf, MD, A Historical Perspective on Clinical Trials Innovation and Leadership. Where Have the Academics Gone?, The Journal of the American Medical Association, February 16, 2011, 305(7), pp 713-714
Howard Brody, The Inverse Benefit Law: Making Sense of How Marketing Turns (Maybe) Good Drugs into Bad, Hooked: Ethics, Medicine, and Pharma, January 14, 2011
Howard Brody, MD, PhD and Donald W. Light, PhD, The Inverse Benefit Law: How Drug Marketing Undermines Patient Safety and Public Health, American Journal of Public Health, January 13, 2011
Make Mitka, New “Law” Attempts to Explain Strategies Drug Marketers Use to Sway Prescribing, The Journal of the American Medical Association, March 16, 2011, 305(11), pp 1083-1084
Donald W. Light, The Risks of Prescription Drugs
H. Gilbert Welch, Overdiagnosed: Making People Sick in the Pursuit of Health