Pharmaceutical Life Sentences
Arthur Daemmrich reviews Jeremy Greene’s Prescribing by Numbers: Drugs and the Definition of Disease.
Jeremy Greene. Prescribing by Numbers: Drugs and the Definition of Disease. Baltimore: Johns Hopkins University Press, 2007. xv + 336 pp. $49.95.
Some years ago Novartis ran an advertisement for its diabetes treatment Starlix that ended with the slogan, “Novartis—we’re with you for life.“ At one time such chronic conditions as heart disease, diabetes, and some forms of cancer were certain death sentences. Today, however, medicines developed to treat these conditions and a host of other ailments can turn death sentences into life sentences, offering a success story of advances in medicinal chemistry, drug development, and marketing. But the same pills can also produce less benign life sentences for people without symptoms who nevertheless adhere to strict dosage regimens, live with uncomfortable side effects, and pay for multiple drug prescriptions.
Until the mid-1950s medicine and industry focused their efforts on treating and preventing acutely dangerous contagious disease. Since then focus has shifted to identifying risk factors and treating chronic conditions. This shift changed dynamics among physicians, patients, government regulators, and industry marketers. Each of these groups now relates to the experience of illness and defines disease differently than in the past.
Greene tells the story of the transition of chronic disease from “a process of inevitable decay” to a routine part of medicine, with the use of pharmaceuticals in its treatment as “crucial to the definition of disease and the philosophy of health promotion” (p. xi). At the core of Greene’s book are case studies of the development of three drugs: Diuril (chlorothiazide) in the 1950s, Orinase (tolbutamide) in the 1960s, and Mevacor (lovastatin) in the 1980s. To tell his broader story and to analyze the impact of what this shift meant for doctors and patients, Greene expands each of his cases to explore the relevant drug class, the changing landscape of regulation by the Food and Drug Administration (FDA), debates concerning clinical trial methods, and industry marketing practices in each period.
Throughout, Greene focuses on the question of how public health priorities became closely aligned with the pharmaceutical industry’s marketing practices (and research foci, I would add). To this reviewer’s relief Greene avoids the easy way out often used by more muckraking authors of pitching this change as a sellout to industry. He instead offers a nuanced description of the development of “therapeutics of risk reduction” (p. 4) with multiple lines of influence, subtle power shifts, and gains and losses for patients and physicians. Greene’s approach is subtle, especially when he suggests, for example, that “relationships between drug and disease are not merely a matter of pharmacological theory, clinical trials, epidemiological change, or marketing tactics but are instead overdetermined by some combination of these elements” (p. 17). Laudably avoiding oversimplification, Greene presents multiple lines of causality and influence that occasionally leave the reader stranded in complexity.
Fortunately, the three thoroughly researched and well-documented case studies bring clarity to his narrative. Greene first tells the history of Diuril, a hypertension drug launched by Merck in 1958, by analyzing Merck’s changing strategies as the firm—and its competitors—added marketing staff and shifted from supplying pharmacists with raw medicinal chemicals to producing packaged pills for the consumer. As Greene describes, Diuril’s success as an antihypertensive resulted from a confluence of changing clinical, research, and marketing practices. After Diuril was introduced, hypertension itself underwent a transformation from being defined by patient-reported chest pain and shortness of breath to being defined almost solely in terms of blood pressure numbers. Building on the specifics of the case, he finds that clinical research in the 1950s became interwoven with drug marketing, and he describes their interfaces and co-evolution from that point forward.
Greene’s second case is the development of Orinase in the 1960s as a diabetes therapy. Upjohn sought to market its drug not as a direct competitor to insulin but as a treatment for the newly created condition of “pre-diabetes.” As in the Diuril case, drugs and disease would redefine one another, but Orinase encountered resistance from a medical community concerned about possible long-term side effects and the negative impact of diagnosing “hidden diabetics” (although early diagnosis has since become an important area of clinical and industry research). A long-running controversy concerning possible increased cardiovascular risk among Orinase users erupted in 1970, but although the controversy played out similarly to the more recent Vioxx (rofecoxib) case, the transformation of diabetes diagnosis from symptom-defined (frequent urination, etc.) to numerical (early testing of insulin levels) was well under way. Restricting the disease definition in the face of risk proved harder, Greene argues, than expanding the definition.
The book’s third case explores cholesterol and definitions of risk for coronary heart disease through the testing and marketing of Mevacor. Greene argues that treatment of high cholesterol declined over the course of the 1970s and then rose again in the 1980s in concert with a new wave of chemotherapeutic interventions. With a high-profile launch in 1987 Mevacor aligned with public health efforts by the National Cholesterol Education Program and other groups seeking to push Americans to be tested for cholesterol levels. Greene argues that Mevacor’s marketing introduced the medical community and the public to the word statins (now commonly known as a class of cholesterol-lowering drugs) and the concept of using a pill to treat high cholesterol.
In a conclusion that brings the three cases together, Greene describes various reactions to a 2003 British Medical Journal article in which two epidemiologists advocated the development of a preventative “polypill.” The hypothetical tablet would be made from a combination of commonly taken drugs: a statin, various blood pressure-lowering agents, folic acid, and aspirin. Although the pill was never marketed nor tested in a clinical trial, the authors did seek to patent the concept. Strikingly, a CNN poll revealed that 95% of viewers over 55 would take it if it were available. Physicians were more skeptical, at least to the degree that letters to the editor of the British Medical Journal cited by Greene offer a representative sample. In this example Greene elegantly brings to the fore a conundrum for contemporary medicine: the drug-consuming public has readily adopted numerical risk factors as a way to talk about disease and thus will accept drugs that treat those numerical values, even when physicians understand that in many cases they are treating probabilities, not clearly defined diseases.
Some readers may wish for more definitive policy statements, but Greene, through his focus on issues of disease diagnosis and definition, has done a greater service by raising broader relevant questions. As our pharmaceutical life sentences lengthen (which seems vastly preferable to the stark alternative of death) we need a more engaged policy discussion. For the good of the U.S. health-care system the discussion must shift from narrow questions of conflict of interest and restructuring the FDA to issues of how to balance decision-making control for defining disease and deciding on treatment, given the different stances of physicians, industry, regulators, and patients. In addition, policy debates must clarify, as Greene puts it, which forms of engagement among marketers, public health decision makers, and medical practitioners are productive and which are deceptive. If we can move the current debate in Congress and the upcoming presidential debates in this direction, there may yet be reason to hope that not all health-care issues end in stalemate.