gms | German Medical Science

In a paired confirmatory diagnostic accuracy study, a new experimental test is compared within the same patients to an already existing comparator test. The gold standard defines the true disease status. Hence, each patient undergoes three diagnostic procedures. If feasible and ethical, regulatory agencies prefer this study design to an unpaired design [1]. The initial sample size calculation is based on assumptions about, among others, the prevalence of the disease and the proportion of discordant test results between the experimental and the comparator test [2].

To adjust these assumptions during the study period, an adaptive design for a paired confirmatory diagnostic accuracy study is introduced. This adaptive design is used to re-estimate the prevalence and the proportion of discordant test results to finally re-calculate the sample size. It is a blinded adaptive design as the sensitivity and the specificity of the experimental and comparator test are not re-estimated. Due to the blinding, the type I error rates are not inflated.

An example and a simulation study illustrate the adaptive design. The type I error rate, the power and the sample size of the adaptive design are compared to those of a fixed design. Both designs hold the type I error rate. The adaptive design reaches the advertised power. The fixed design can either be over-or underpowered depending on a possibly wrong assumption regarding the sample size calculation.

The adaptive design compensates inefficiencies of the sample size calculation and therefore it supports to reach the desired study aim.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.