Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

Background: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in , which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering .

Methods: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa.

DIA's Adaptive Design Scientific Working Group (ADSWG): Best Practices Case Studies for "Less Well-understood" Adaptive Designs.

Adaptive design (AD) clinical trials use accumulating subject data to modify the parameters of the design of an ongoing study, without compromising the validity and integrity of the study. The 2010 US Food and Drug Administration (FDA) Draft Guidance on Adaptive Design Clinical Trials described a subset of 7 primary design types as "less well-understood." FDA defined these designs as those with limited regulatory experience.

Statistical challenges in drug approval trials that use patient-reported outcomes.

This article describes challenging aspects of the use of patient-reported outcome instruments in clinical trials for drug approval, in our perspective as statistical reviewers at the US Food and Drug Administration. We discuss aspects of planning and interpreting results in clinical trials (1) adapting an existing patient-reported outcome instrument for use in clinical trials, (2) using multi-item patient-reported outcomes and (3) missing patient-reported outcome values from many subjects over time. These challenges are illustrated with multiple examples from different clinical trials for different indications.