Optimizing disease progression study designs for drug effect discrimination
2013 (English)In: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 40, no 5, 587-596 p.Article in journal (Refereed) Published
Investigate the possibility to directly optimize a clinical trial design for statistical power to detect a drug effect and compare to optimal designs that focus on parameter precision. An improved statistic derived from the general formulation of the Wald approximation was used to predict the statistical power for given trial designs of a disease progression study. The predicted value was compared, together with the classical Wald statistic, to a type I error-corrected model-based power determined via clinical trial simulations. In a second step, a study design for maximal power was determined by directly maximizing the new statistic. The resulting power-optimal designs and their corresponding performance based on empirical power calculations were compared to designs focusing on parameter precision. Comparisons of empirically determined power and the newly developed statistic, showed excellent agreement across all scenarios investigated. This was in contrast to the classical Wald statistic, which consistently over-predicted the reference power with deviations of up to 90 %. Designs maximized using the proposed metric differed from traditional optimal designs and showed equal or up to 20 % higher power in the subsequent clinical trial simulations. Furthermore, the proposed method was used to minimize the number of individuals required to achieve 80 % power through a simultaneous optimization of study size and study design. The targeted power of 80 % was confirmed in subsequent simulation study. A new statistic was developed, allowing for the explicit optimization of a clinical trial design with respect to statistical power.
Place, publisher, year, edition, pages
2013. Vol. 40, no 5, 587-596 p.
Optimal experimental design, Statistical power, Wald test, Disease progression studies
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-210213DOI: 10.1007/s10928-013-9331-3ISI: 000325263800004OAI: oai:DiVA.org:uu-210213DiVA: diva2:661440