Optimal design for inference on the threshold of a biomarker.

Enrichment designs with a continuous biomarker require the estimation of a threshold to determine the subpopulation benefitting from the treatment. This article provides the optimal allocation for inference in a two-stage enrichment design for treatment comparisons when a continuous biomarker is suspected to affect patient response. Several design criteria, associated with different trial objectives, are optimized under balanced or Neyman allocation and under equality of the first two empirical biomarker's moments.

Design considerations for two-stage enrichment clinical trials.

When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a "phase III-like" trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1.

Optimal and ethical designs for hypothesis testing in multi-arm exponential trials.

Multi-arm clinical trials are complex experiments which involve several objectives. The demand for unequal allocations in a multi-treatment context is growing and adaptive designs are being increasingly used in several areas of medical research. For uncensored and censored exponential responses, we propose a constrained optimization approach in order to derive the design maximizing the power of the multivariate test of homogeneity, under a suitable ethical constraint.

The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine.

Background: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC).

Methods: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI).