Summary
Background: In the planning of clinical trials with count outcomes such as the number of exacerbations
in chronic obstructive pulmonary disease (COPD) often considerable uncertainty exists
with regard to the overall event rate and the level of overdispersion which are both
crucial for sample size calculations.
Objectives: To develop a sample size reestimation strategy that maintains the blinding of the
trial, controls the type I error rate and is robust against misspecification of the
nuisance parameters in the planning phase in that the actual power is close to the
target.
Methods: The operation characteristics of the developed sample size reestimation procedure
are investigated in a Monte Carlo simulation study.
Results: Estimators of the overall event rate and the overdispersion parameter that do not
require unblinding can be used to effectively adjust the sample size without inflating
the type I error rate while providing power values close to the target.
Conclusions: If only little information is available regarding the size of the overall event rate
and the overdispersion parameter in the design phase of a trial, we recommend the
use of a design with sample size reestimation as the one suggested here. Trials in
COPD are expected to benefit from the proposed sample size reestimation strategy.
Keywords
Internal pilot study - sample size - clinical trial - chronic obstructive pulmonary
disease - COPD
