May 10, 2019 by Scott H. Podolsky, MD et al | New England Journal of Medicine
Preying on Prescribers (and Their Patients) — Pharmaceutical Marketing, Iatrogenic Epidemics, and the Sackler Legacy
(New England Journal of Medicine) – In 2018, Massachusetts joined more than two dozen other states in suing Purdue Pharma, the makers of OxyContin, for “the harm they inflicted in our state” by helping to drive the current opioid crisis. Drawing particular attention to the actions of the family that controls the company, the Sacklers, the case against Purdue has been framed in terms of unconscionable corporate (and individual) profit at the expense of the public’s health — chiefly through the manipulation of prescribing practices and of the approach to pain recommended in clinical journals, medical curricula, and professional guidelines. As a Boston Globe writer mused, “Physicians are persuaded by marketing, just like everybody else. Now there’s a discomfiting thought.”1
Discomfiting as the thought may be, it is not new: marketing’s role in physician education has long been evident to pharmaceutical companies, journal editors, and therapeutic reformers alike.2 And though the Sackler family did not invent the practice of selling drugs to physicians, they were pioneers whose story illustrates the ways marketers developed, naturalized, and monetized the interface between the pharmaceutical industry and prescribing physicians. This history stretches back to a moment of both medical and marketing innovation at the founding of modern pharmaceutical practice: the advent of antibiotics and the marketing strategies that made them America’s first blockbuster drugs.
In the years after penicillin entered the civilian marketplace in the mid-1940s, antibiotics promised boom times for American pharmaceutical firms. By 1950, Lederle, Parke-Davis, and Pfizer had brought to market Aureomycin (chlortetracycline), Chloromycetin (chloramphenicol), and Terramycin (oxytetracycline), respectively — the first “broad-spectrum” antibiotics, all subjects of patents and new branding and marketing techniques. Before Terramycin, Pfizer had chiefly been known as a supplier of chemicals to other companies and had never marketed its own patented, branded drug. So to sell Terramycin, it turned to a public relations firm — the William Douglas McAdams company, led by psychiatrist Arthur Sackler — and in the process helped to revolutionize drug marketing.
Pfizer Drug-Detailing Memo, October 1954.
Under Sackler’s guidance, Pfizer increased its drug sales force from 8 “detail men” in 1950 to 2000 by 1957 (including, at one point, 70 medical students). Internal memos reveal that the marketing campaigns for Terramycin and, soon, Tetracyn (tetracycline) were conducted like military campaigns and described in the language of combat. Doctors in nearly every specialty were persuaded to consider conditions ranging from upper respiratory infections to urinary tract infections as necessitating antibiotics. The “prey” described in an internal Pfizer sales document from 1954 entitled “Easy Prey for Terramycin” referred not to the microbes Terramycin killed, but the prescribing physicians whose behavior could easily be swayed by marketing tactics3(see photo). Pfizer President John McKeen estimated in 1950 that antibiotics could be considered warranted in 30 to 50% of cases seen by physicians, and between 1950 and 1956, that estimate became a self-fulfilling prophecy, as U.S. antibiotic consumption nearly quintupled, setting in motion patterns of antibiotic overprescribing (and overexpectation) that contribute to antibiotic resistance and preventable adverse effects.
Many of the promotional techniques now commonplace in prescription-drug marketing — detailing, free samples, free food and drink, flashy journal advertising and mailings — were perfected by Pfizer and its competitors in the crucible of the broad-spectrum antibiotic marketing wars. Though not alone, Pfizer was at the vanguard, thanks largely to Arthur Sackler. As the Medical Advertising Hall of Fame declared in 1998, “No single individual did more to shape the character of medical advertising than the multi-talented Dr. Arthur Sackler. His seminal contribution was bringing the full power of advertising and promotion to pharmaceutical marketing.”3
Though it may seem inevitable now, the decision to allow marketers such wide scope to shape the circulation of potent and potentially dangerous drugs was just that — a decision. Other approaches were available. Pharmaceutical opioids, for example, were regulated by the Federal Bureau of Narcotics (FBN) from 1929 to 1968. When Winthrop Chemical Company introduced the first fully synthetic opioid, Demerol (meperidine), in 1944, they launched it with an array of marketing measures: they solicited the support of influential physicians, made extravagant claims (including low addiction risk), and developed a campaign to advertise to physicians and market to the public. But the FBN considered many of these strategies illegitimate. The bureau litigated advertisements line by line, discouraged use of colorful imagery, disallowed free samples, followed up aggressively on complaints about detailing hype, and even launched its own cautionary public relations campaign. Combined with strict prescribing limits enforced by medical authorities, the FBN response allowed a genuinely innovative drug to be incorporated into the medical armamentarium without dramatically increasing overall opioid prescribing or use.
In Arthur Sackler’s view, such moderation deprived the country of the benefits of aggressive marketing. “Pharmaceutical advertising has made one of the major contributions in the rapid dissemination of new therapeutic information,” he claimed in 1957. “There are fascinating case histories of wonderful medications inadequately used and only applied to a small percentage of those patients who require them.”2 But by the time Senator Estes Kefauver (D-TN) began his investigation of the pharmaceutical industry in 1959 (leading to the passage of the 1962 Kefauver–Harris amendments and a more muscular process of Food and Drug Administration approval), the costs of overprescribing were beginning to add up. As Kefauver and his staff, who had become famous for investigating organized crime, began to investigate Arthur Sackler’s web of influence and its impact on clinician behavior, the sketches they made of Sackler’s apparently vertically integrated empire — of drug companies, advertising staff, and medical journals — looked like components of a Mafia investigation.3,4
By mid-1960, Kefauver’s staff had dropped their pursuit of Sackler. But included within their diagrams was the 1952 purchase of the small company Purdue Frederick by Sackler and his two psychiatrist brothers, Raymond and Mortimer (who would later purchase Arthur’s shares in the firm). In 1995 — 2 years before Arthur Sackler was posthumously inducted into the Medical Advertising Hall of Fame — Purdue launched its long-acting opioid OxyContin. The company pioneered aggressive approaches to educating physicians about the use of opioids for noncancer pain, including (according to the Massachusetts lawsuit) the ongoing reformulation of pain as the “fifth vital sign” and the ascribing of OxyContin addiction to specific problem patients, rather than to the drug itself. Critically, Purdue saw physicians as easy prey for OxyContin, just as prescribers had been prey for Terramycin. The human toll of opioid overprescription now represents one of the largest iatrogenic epidemics in history.
The recent Globe article concludes that “we need better firewalls. It’s up to doctors to protect themselves — and their patients — from the dark arts practiced by Purdue and other drug companies.”1 Yet neither the problem nor the solution is new. From the 1950s onward, therapeutic reformers have asked the medical profession to create barriers between pharmaceutical marketing and physician education, whether in journals, grand rounds, or formal continuing medical education. Meanwhile, pharmaceutical marketing to clinicians marches on: from 1997 to 2016, spending increased from $15.6 billion to $20.3 billion, including $5.6 billion for drug detailing, $13.5 billion for drug samples, $979 million for direct physician payments, and $59 million for disease education.5 In the case of OxyContin and its competitors, “education” programs also included public relations campaigns that exploited and repurposed an existing reform effort to increase physicians’ responsiveness to people suffering from pain.
Given these numbers, it is worth asking: Can a firewall ever truly be enough? The parade of boom–bust cycles in pharmaceuticals (so inevitable that some see it as a kind of natural phenomenon, a “life cycle”) points to a more fundamental problem: the marriage of medical and marketing innovation that has become the defining feature of “modern” pharmaceuticals. Perhaps it is time to rethink our approach to medical innovation itself and ask whether a marketing model is even the right means for promoting the value of new therapeutic products.
From the Department of Global Health and Social Medicine, Harvard Medical School, and the Center for the History of Medicine, Countway Medical Library — both in Boston (S.H.P.); the Department of History, State University of New York, Buffalo, Buffalo (D.H.); and the Department of History of Medicine and the Center for Medical Humanities and Social Medicine, Johns Hopkins University School of Medicine, Baltimore (J.A.G.).