Adding more muscle and nerve to clinical trials

Abstract

In this review we illustrate both the fundamentals and challenges of randomized clinical trials in neuromuscular disorders and suggest directions for prospective efforts to improve the design, conduct, rigor, and objectivity of these trials. Current research in clinical trials for neuromuscular disorders and key issues affecting these trials are reviewed. This perspective addresses the planning of clinical research, level of preclinical data needed to justify trials, patient recruitment and retention, and opportunities to access federal funding and infrastructure in support of clinical trials. The need for innovation in trial design and conduct, rigorous standards for the preclinical efficacy and safety data that support trial rationale, novel collaborative paradigms, objective interpretations of outcomes, and sharing of the lessons learned from trials in any one disorder among all neuromuscular trialists are imperative to improving the heretofore limited success in delivering novel, safe, and effective therapies to patients burdened by neuromuscular disorders.

Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC)

“…For instance, lack of natural history data negatively impacts on identification of clinically important endpoints to be used in clinical trials [1]. Other challenges include delayed diagnosis, poor subject availability for recruitment into clinical trials and a lack of standardised care [1][2][3]. As a result, the development of new pharmacological treatments for such conditions is delayed and compromised [1,2].…”

Improving translatability of preclinical studies for neuromuscular disorders: lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT)

“…Researchers increasingly recognize that most preclinical experiments do not represent a true preclinical efficacy study. In the past decades, discussions on the value of mouse models in predicting a therapy's efficacy for humans concluded that preclinical efficacy studies for therapies that aim at transition to clinical trials should be conducted with the same rigor as the clinical trials themselves (Conwit et al, 2011;Knopp et al, 2015). To help achieve high-quality preclinical studies, primary and secondary outcomes should be defined in advance and assessed according to standardized protocols, adequate control groups need to be chosen, and power analysis should be used to determine sample size; randomization and blinding need to be implemented, and a careful statistical analysis should be applied.…”