Application of improved statistical methodologies for clinical trials in Progressive Supranuclear Palsy

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease with a prevalence of 1-9/100,000 and an average disease duration of approximately 8 years. Effective symptomatic treatments and disease-modifying therapies are not available. Therefore, development of innovative therapies to slow down or halt disease progression are urgently required. Numerous investigational new drugs are entering the clinical trial pipeline for evaluation of their safety and efficacy. The experience and data generated by the consortium coordinator with the past clinical trials in PSP has demonstrated limitations of previously used methodologies, including heterogeneity in disease progression rates, limitations of the primary endpoint, limitations resulting from the short observation period and reluctance to be randomized to placebo. Identification of these limitations opened up ways forward to improve methodologies for future trials.

Aim: The applicants therefore aim to optimize clinical trial methodology for PSP.

Methods: The consortium will develop more sensitive and more relevant endpoints (modified outcome measures, composite endpoints), develop prediction models, more efficient trial designs (adaptive designs, delayed-start designs, longer duration trials, platform trials, basket trials), and use historical longitudinal data for multiple outcome measures to improve statistical power.

Perspective: Applying the statistical methods developed by the applicants will help to improve the trial design and the statistical analysis methods for future trials in PSP.