No abstract

Desmopressin (orally disintegrating tablet) is an effective and well tolerated treatment for men with nocturia. Treatment with 50 μg desmopressin, the minimum effective dose, provided sustained improvement of nocturia throughout the study and meaningful benefits to patients with an improved safety profile.

At a dose of 25 μg, desmopressin orally disintegrating tablet is an effective and well tolerated treatment for women with nocturia. Treatment provides rapid and sustained improvement in nocturia and quality of life.

A new guideline on the clinical investigation of steroid contraceptives in women, which has been released by the European Agency for the Evaluation of Medicinal Products (EMEA), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the effectiveness of a contraceptive method. However, the interpretation of the Pearl Index as a statistical parameter, for which a confidence interval can be calculated, needs further clarification. The guideline does not provide the necessary definitions. In this paper, two statistical models, the Bernoulli model and the Poisson model, are compared; both can be used for the calculation of the Pearl Index and its upper confidence limit. The Poisson model proved to be more suitable, because it can accommodate incomplete treatment cycles. Unambiguous definitions and statistical formulae for the calculation of overall Pearl Index and the Method Failure Pearl Index are given. Finally, the sample sizes required to fulfill the EMEA's guideline are given.

In double-blind randomized clinical trials, it is common practice to randomize patients using randomly permuted blocks. In this article, it is demonstrated that before unblinding statistical inference of the treatment effects can be conducted, yielding consistent and rather precise estimates even in the presence of an additive block effect. With an even greater precision, the within-group standard deviation on which power calculation are usually based can be inferred from blinded data. The use of blocks of random lengths as suggested by ICH-E9 in the (unlikely) case that previous treatment allocation can be guessed by strong pharmacological effects, merely complicates the analysis but blinded inference can still be conducted without much extra loss of information. On the one hand, one might argue that this possibility of blinded inference takes away the need of conducting interim analyses for administrative or business reasons or for sample size reestimation. On the other hand, however, it most probably will have a disputable, positive or negative effect on the conduct of the remainder of the trial. If regulators and the pharmaceutical world at large want to avoid this possibility, then other unrestricted, biased coin, or more general dynamic allocation randomization procedures may be less controversial alternatives. It at least provides another strong argument in favor of using large blocks as the precision of blinded inference decreases with increasing block lengths. If blinded inferences are deemed a useful replacement of interim analyses in nonpivotal trials, then further guidelines will be needed on consequent decision-making aspects.