Book Review: Pharmaceutical Life Sentences

Image courtesy of istockphoto.

Image courtesy of istockphoto.

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.