The Food and Drug Administration (FDA) guidance for industry, “Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment,” aims to assist drug developers with specific clinical drug development and trial design issues when creating therapies particularly for the treatment of amyotrophic lateral sclerosis (ALS), a progressive neuromuscular disease that can either be sporadic or inherited in nature.
To aid industry in designing drug development programs and clinical trials, the FDA presents:
- General considerations;
- Specific effectiveness trial considerations; and
- Other considerations, such as nonclinical safety and pharmacological considerations.
General considerations involve drug development issues, criteria for selecting patients for effectiveness trials, demonstrations of therapy effectiveness, effects on mortality, and guidelines for a data monitoring committee (DMC), an independent FDA group that periodically looks for safety signals and ensures patients are not at unreasonable risk.
For the specific effectiveness trial considerations, the FDA recommends a randomized, placebo-controlled, double-blind study. The FDA also suggests that drug developers include assessments of efficacy outcomes in trials and design. The guidance also emphasizes the importance of statistical considerations in designing clinical drug development programs. Of particular importance is a design involving appropriate clinical prognostic measures (e.g., a joint rank test), accelerated approval, and risk-benefit analysis.