TEST FOR TREATMENT EFFECT BASED ON BINARY DATA WITH RANDOM SAMPLE SIZES

The problem of testing for treatment effect based on binary response data is considered, assuming that the sample size for each experimental unit and treatment combination is random. It is assumed that the sample size follows a distribution that belongs to a parametric family. The uniformly most powerful unbiased tests, which are equivalent to the likelihood ratio tests, are obtained when the probability of the sample size being zero is positive. For the situation where the sample sizes are always positive, the likelihood ratio tests are derived. These test procedures, which are unconditional on the random sample sizes, are useful even when the random sample sizes are not observed. Some examples are presented as illustration.     

Incorporating historical two‐arm data in clinical trials with binary outcome: A practical approach

The feasibility of a new clinical trial may be increased by incorporating historical data of previous trials. In the particular case where only data from a single historical trial are available, there exists no clear recommendation in the literature regarding the most favorable approach. A main problem of the incorporation of historical data is the possible inflation of the type I error rate. A way to control this type of error is the so‐called power prior approach. This Bayesian method does not “borrow” the full historical information but uses a parameter 0 ≤ δ ≤ 1 to determine the amount of borrowed data. Based on the methodology of the power prior, we propose a frequentist framework that allows incorporation of historical data from both arms of two‐armed trials with binary outcome, while simultaneously controlling the type I error rate. It is shown that for any specific trial scenario a value δ > 0 can be determined such that the type I error rate falls below the prespecified significance level. The magnitude of this value of δ depends on the characteristics of the data observed in the historical trial. Conditionally on these characteristics, an increase in power as compared to a trial without borrowing may result. Similarly, we propose methods how the required sample size can be reduced. The results are discussed and compared to those obtained in a Bayesian framework. Application is illustrated by a clinical trial example.