—Our tacrine study was designed to support preliminary results from a preceding enrichment trial1 and to define dose-response characteristics using doses from 20 to 80 mg/d. The a priori hypothesis (as indicated on page 2525) addressed whether tacrine improves patient response on the Alzheimer's Disease Assessment Scale (ADAS) cognitive and the clinician-rated Clinical Global Impression of Change (CGIC). The ADAS cognitive has been validated in Alzheimer's disease and demonstrated sensitivity to modest drug effects and cognitive deterioration over time.2 However, the clinician-rated CGIC had not been validated in this patient population.3 Therefore, our primary focus on ADAS cognitive reflected uncertainty in use of the CGIC when the study was designed. The sample size was set to provide sufficient power to detect ADAS cognitive effects based on previous studies of tacrine.1Primary analyses based on "evaluable completers" were most appropriately presented in the original publication.
Farlow M, Hershey LA, Sadowsky CH, Gracon SI, Lewis KW, Dolan-Ureno J. Tacrine in Alzheimer's Disease-Reply. JAMA. 1993;269(22):2849-2850. doi:10.1001/jama.1993.03500220034020