CAN TREATMENT THAT IS HELPFUL ON AVERAGE BE HARMFUL TO SOME PATIENTS - A STUDY OF THE CONFLICTING INFORMATION NEEDS OF CLINICAL INQUIRY ANDDRUG REGULATION

Randomized controlled trials ate conducted with heterogeneous groups o f patients, and the trial results represent an estimate of the average difference in the responses of the treatment groups, Clinicians, howe ver, engage in a process of clinical inquiry, assembling data that wil l allow an assessment of the appropriate choice of treatment according to more narrowly defined clinical features. We describe a method of c linical inquiry within RCTs that can enhance the applicability of resu lts to clinical decision making. Our methods included the use of data from the Beta-Blocker Heart Attack Trial, which enrolled 3837 subjects in 31 clinical centers, The 31 centers were divided into 21 dominant centers (mortality rates higher for placebo than propranolol) and 10 d ivergent centers (higher mortality rates for patients randomized to pr opranolol). Overall, compared to placebo, propranolol reduced the risk of dying for the ''average'' patient from 9.8 to 7.2%. Results for pa tients in dominant centers (RR = 0.50) were significantly different fr om those in divergent centers (RR = 1.33). We identified two cotherapi es-aspirin use and coronary artery surgery-that subsequently affected the benefits of propranolol in divergent centers, For patients in dive rgent centers, propranolol reduced the risk of dying for patients trea ted with aspirin and/or coronary surgery (RR = 0.39), but not for pati ents not receiving these therapies (RR = 1.42). We conclude that diffe rences in results across centers of a multicenter RCT may reflect impo rtant distinctions in the clinical conditions of enrolled subjects. Th ese distinctions help to identify subgroups of patients in which treat ment that has an average overall benefit may be harmful for some patie nts.