ALS臨床試験デザインとアウトカムの再考

抄録

Although numerous clinical trials for investigational ALS drugs have been conducted to date, most have been unsuccessful, and a definitive strategy for achieving positive outcomes remains elusive. Reflecting on the history of ALS drug development in Japan, several challenges and future directions have been identified.

First, establishing a national framework to promote ALS clinical trials in Japan is essential, drawing on the experiences of major consortia in Europe and North America (e.g., TRICALS and NEALS). Furthermore, as demonstrated by successful Japanese trials, enrolling patients at earlier disease stages is crucial. To enhance the accuracy of ALSFRS–R assessments and facilitate the smooth execution of international multicenter trials, the development and dissemination of standardized assessment manuals must be prioritized.

Finally, long–term outcome evaluations are necessary to address the limited duration of randomized controlled trials (RCTs). This can be achieved by monitoring long–term prognoses through open–label extension studies following RCTs, or by comparing post–marketing surveillance data with patient registries. Regarding the use of real–world data to evaluate treatment efficacy, relevant guidelines are still being developed by the ICH and other regulatory bodies, warranting close monitoring of future advancements.