Letters Section Editor: Robert M. Golub, MD, Senior Editor.
To the Editor: Since alcoholic patients represent an extremely heterogeneous population, the design of the COMBINE Study1 was selective, with a goal of striving for high internal validity at the expense of generalizability. The selection process a priori favored patients for whom completing the trial was expected. Of the 4965 potential patients screened, only 1383 were enrolled. Abstinence, an inclusion requirement, was achieved by about 92% without prior inpatient detoxification. Patients were abstinent before onset of study treatment, and a large proportion remained abstinent throughout. Since both placebo response (78% days abstinent) and data completeness (94% with complete drinking data) are extraordinarily high for alcohol-dependent patients, the COMBINE Study may have targeted a subpopulation of such patients with a low need for a specific relapse prevention treatment. Consequently, even though the percent days abstinent for both naltrexone and acamprosate was in the range reported by previous studies that combined and compared both drugs,2,3 no significant benefit compared with the placebo condition was detectable.
Kiefer F, Mann K. Pharmacotherapy and Behavioral Intervention for Alcohol Dependence. JAMA. 2006;296(14):1727-1729. doi:10.1001/jama.296.14.1727-b