Prescribing by Numbers: Drugs and the Definition of Disease

4. Risk and the Symptom: The Trials of Orinase

c h a p t e r f o u r Risk and the Symptom The Trials of Orinase Everyone here is claiming to be in the public interest, and when everybody is riding the horse of the public interest in a different direction, there is great controversy. —robert f. bradley , Committee on the Care of the Diabetic, 1975 Early in the afternoon of May 20, 1970, a report was leaked over the Dow Jones newswires that Orinase (tolbutamide),“a drug used to lower blood sugar in diabetic patients,” might be harmful.1 Orinase had been Upjohn’s showcase success and sales leader for nearly a decade, and news of its possible toxicity spelled disastrous things for the company and its investors. Before the New York Stock Exchange closed that afternoon, Upjohn’s stock had fallen in heavy trading.The next morning,the Washington Post reported the preliminary findings from the federally funded University Group Diabetes Program (UGDP)— the largest, longest, and most definitive study of diabetes therapy yet performed —with the implication that at least eight thousand patients a year may have already died as a result of Orinase consumption. As the story was picked up by the Associated Press, the Food and Drug Administration (FDA) hastily issued a press release that provided only the briefest abstract of the study and pronounced that the agency intended to revise the labeling of tolbutamide and other oral hypoglycemic drugs.2 In the meantime, all hell broke loose. At that time, hundreds of thousands of Americans were taking Orinase every day for mild (asymptomatic) diabetes, largely on the premise that the pill reduced their long-term risk for diabetic complications and heart disease.Over the next few days, FDA commissioner Charles Edwards received hundreds of phone calls and letters from patients concerned to find that the drugs they were taking to reduce their health risks might actually be increasing them. “C.P.,” a Virginia man, wrote:“I have a mild diabetes—the kind that shows up in blood tests only it does not show in normal urine tests. For the past two years have been taking 2 Pills daily Upjohn Orinase and using saccharin . . .Last week both were pointed out as dangerous to use as reported in the Wash Post. My Doctor thinks he should have more authoritative information before advising discontinuing or curtailment of these items. Could your office please advise on continued use of these items in view of frightening reports of Wash Post newspaper . I am 65 years old.”3 C.P. and the rest of the Washington Post’s readership were among the manyAmericans who learned of Orinase’s putative toxicity before their physicians did.4 This “premature announcement” of Orinase’s toxicity ,before the FDA had issued any warning to physicians and before the UGDP study was published in the clinical literature, unleashed a public debate over risk and asymptomatic disease that lasted more than a decade; created rancorous divides between advocates,researchers,and regulatory agencies;and left hundreds of thousands of diabetics, their families, and their physicians in a muddle of uncertain practice, contested information, and strained trust.5 If patients like C.P. were disturbed by the news of Orinase’s toxicity, the news hit their physicians twice as hard. Those who learned of the controversy through the newspaper were relatively lucky compared to the thousands of physicians who first learned of the debacle from their agitated patients. Commissioner Edwards subsequently received the following letter from a “Poor Practitioner,” who complained hotly of the difficulty he was thrown into due to the study’s untimely publicity and the regulatory and epistemological uncertainty that followed: Dear Dr. Edwards: Now that my nurse,receptionist,and bookkeeper are no longer tying up the three telephone lines to discuss with patients who are extremely worried and apprehensive about the Orinase situation, I am able to obtain a free line to dictate this letter to your attention. I sincerely believe that the “public leak” by the F.D.A. to the newspapers, and Walter Cronkite in particular, is not only a very stupid and indiscreet action on the part of your agency,but I firmly also believe this transgresses any and all med116 Orinase and Diabetes, 1960–1980 ical ethic. This is a scare tactic to the general public who are using an ethical and adequate drug program and in so doing this, you...