Clinical trial design for Friedreich ataxia - Where are we now and what do we need?

Introduction: Since the discovery of the mutation in Friedreich ataxia, a series of clinical trials have been conducted to provide symptomatic or disease-modifying therapy. At this point none have reached regulatory approval. This review examines several aspects of the design of FRDA clinical trials to understand better their shortcomings.Areas covered: The mechanisms for performing clinical trials have been well developed in FRDA, including the presence of two ongoing longterm natural history studies and a patient registry that captures more than 3000 potential subjects. Still, trials to this point have not utilized this information in many situations. Studies have been smaller and shorter than predicted based on natural history studies. In addition, studies have not always matched outcome measures to specific sub cohorts or chosen subjects in the most responsive phases of the disease.Expert opinion: The optimization of clinical trials in FRDA should lead to a greater likelihood of success. Such improvements should include longer studies with more subjects, and directing of studies to optimal populations. Along with more extensive preclinical development, improved design will facilitate future success in clinical trials in FRDA.