Simulating effects of biomarker enrichment on Alzheimer's disease prevention trials: Conceptual framework and example

Background: We present a conceptual framework for simulations to determine the utility of biomarker enrichment to increase statistical power to detect a treatment effect in future Alzheimer's disease prevention trials. We include a limited set of simulation results to illustrate aspects of this framework. Methods: We simulated data based on the Alzheimer's Disease Anti-Inflammatory Prevention Trial, and a range of sample sizes, biomarker positive predictive values, and treatment effects. We also investigated the consequences of assuming homogeneity of parameter estimates as a function of dementia outcome. Results: Use of biomarkers to increase the sample fraction that would develop Alzheimer's disease in the absence of intervention from 0.5 to 0.8 would increase power from 0.35 to 0.69 with n = 200. Ignoring sample heterogeneity resulted in overestimation of power. Conclusion: Biomarker enrichment can increase statistical power, but estimates of the expected increase are sensitive to a variety of assumptions outlined in the framework. (C) 2014 The Alzheimer's Association. All rights reserved.