JAMA: The Inverse Logic of the Pharmaceutical Inverse Benefit “Law”

In today’s fast paced and rapidly changing medical environment, health care practitioners in every area—from primary care to psychiatry and anywhere from surgeons to nurses—depend on new clinical information and data to learn about breakthroughs in science and medical technology.  While some health care practitioners can learn about such breakthroughs from colleagues and others can read about them in journals, a large majority of practitioners simply do not have the time to pour over piles of journal articles and clinical studies to find the pertinent information to help them improve their skills and knowledge.

Continuing Medical Education (CME) is also another option for health care practitioners to learn about new information and updates to guidelines and best practices in specific clinical areas.

Some practitioners even chose purely commercial events, sponsored by a specific pharmaceutical or medical device company to learn about a new product, treatment, use, or indication. Other health care practitioners learn about new drugs and treatments by participating in research sponsored in part or entirely by the pharmaceutical industry.

Throughout all of these interactions, health care practitioners depend on a certain level of interaction with industry. This physician-industry relationship is essential for many reasons, and without which, many patients could potentially suffer.

Consequently, one of the types of physician-industry interactions that has been heavily criticized over the past several years is marketing. Many anti-industry critics believe that pharmaceutical and medical device companies use marketing techniques, representatives, and other mechanisms to influence the clinical decisions and prescribing behavior of health care practitioners.

While no one can dispute that in the past there were abuses by some drug representatives and companies in discussing the off-label use of products with physicians or the provision of free meals and inappropriate gifts, times have changed significantly since then, and such behaviors are almost entirely non-existent. Policies enacted by PhRMA and AdvaMed have placed strict bans on gift giving, and numerous regulations from FDA, HHS, DOJ and OIG have made the risk and penalty for any illegal behaviors severe. And the enforcement of such rules over the past several years has increased dramatically through efforts to root out fraud and abuse in government programs such as Medicare and Medicaid.

Despite the vast changes in the way companies use their marketing budgets and drug representatives, Howard Brody, MD, PhD, and Donald W. Light, PhD, recently wrote an article in the American Journal of Public Health, proposing a “pharmaceutical inverse benefit law.”

According to the authors, this “inverse benefit law” is a heuristic device to help physicians understand how pharmaceutical marketing affects their decision-making process when prescribing medications. A summary of the article, published in the Journal of the American Medical Association (JAMA) without any balance, noted that the “authors’ proposed law came about following recent highly publicized withdrawals of certain drugs from the market due to safety concerns.”

The JAMA article explained that the “law was inspired by Hart’s inverse care law, itself inspired by the inverse square law of physics. Consequently, “the law states that the benefit-to-harm ratio among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed.” JAMA asserted that, “the inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing.”

Accordingly, Drs. Brody and Light’s article “suggest 6 marketing strategies that create an environment in which prescribing certain drugs could undermine, rather than promote, patient safety and public health.” The 6 marketing strategies are:

• Reducing thresholds for diagnosing disease. For example, type II diabetes guidelines have gradually reduced the blood glucose threshold at which diabetes should be diagnosed despite a lack of evidence that tight control improves major outcomes. While early detection may provide more opportunities for diet and exercise to treat diabetes, if physicians prescribe hypoglycemics based on these thresholds, many more patients would be treated.
• Relying on surrogate end points. When physicians accept surrogate end points rather than improved clinical outcomes as goals of therapy, fewer patients need to be treated to demonstrate an improved outcome, even though that outcome does not directly benefit the patient. Surrogate endpoints also make it easier for marketers to be more persuasive about the first strategy, reducing thresholds for diagnosing disease.
• Exaggerating safety claims. By overemphasizing the safety of a new drug that has been used in relatively few patients, marketers encourage physicians to prescribe the medication 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.” For example, the invention of the “disease” categories of “prehypertension” and “prediabetes” potentially expands the patient population to be treated. But this approach requires treating much larger numbers of persons to benefit a few, while exposing all of those treated to potential adverse events.
• 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.

 

Discussion

In making these 6 claims, Dr. Brody noted he created this concept “to help physicians understand the subtle manipulation that they may face and should reject.”

If the manipulation is so subtle, then how are Brody and Light able to understand and identify it? What specialized training or expertise do they have in noticing this “subtle manipulation? Or is it that Brody and Light are making a living selling books and writing articles claiming that such “subtle manipulation” even exists?

Nevertheless, Brody noted that the main focus of their proposed “law” is on physicians and how our willingness to allow research published and promulgated by drug companies can lead us into doing things that seem quite innocent but that may have dire consequences.”

But what exactly are these things that “can” lead doctors to do things that have dire consequences?

Dr. Brody suggests the 6 examples above as ways that doctors “may” or “might” be “subtly manipulated,” however, he provides no evidence of how often this occurs. More importantly, he only describes the “potential” harm that could occur to patients, but does not include any evidence or harm to patients from this “subtle manipulation.”

While there have certainly been abuses in the past, which correspond to some of the marketing principles Dr. Brody has listed above, these abuses are extremely rare and limited to a few cases that were handled and corrected through legal and regulatory actions.

Physicians and health care practitioners are aware of these “6 marketing strategies” because they are highly trained professionals and can interpret scientific data without being influenced. Companies are not in the business of reducing thresholds for diagnosing disease. They make drugs to treat certain diseases and it is up to the scientific organizations and health agencies to set guidelines for proper diagnosis.

Moreover, companies are not exaggerating safety and efficacy claims because the FDA through DDMAC must explicitly approve such claims. If a company or drug representative made such exaggerations, it would be illegal, and companies have no reason to exaggerate such claims when the product is already approved.

Additionally, companies are not creating new “diseases” by expanding the patient populations. The reality is, Americans are becoming unhealthier by eating more and exercising less. Cancer, heart disease, diabetes, asthma, and numerous other rare and serious diseases still take the lives of millions of Americans each day. If expanding a patient population to help diagnose, prevent, and treat patients is creating a new “disease,” then we should applaud those companies who are helping to create the tests and guidelines to identify and treat these people.

Conclusion

In the end, the proposed new “law” to make doctors aware of “subtle manipulation” from marketing does more harm than it does good. It creates more unnecessary confusion about the information physicians are receiving and could harm patients when physicians refuse to look at studies or research or collaborate with industry for fear of “subtle manipulation.” 

Today, Americans are not living longer because of a better diet and exercise (clearly, just look at the obesity population). Americans are not living longer because the world is getting warmer.

Today, Americans are the living longer because there are medications and devices that prevent and treat disease. It is time to let doctors have the independence they need to evaluate sources of information. Doctors have enough to worry about with following guidelines, evaluating patients, ordering tests, and running their practices. There is no need to add another thing to their checklist, especially when looking for “subtle manipulation” would be like looking for a needle in a haystack.