NRx Pharmaceuticals has announced the publication of a paper in the American Journal of Clinical Psychopharmacology detailing a novel methodology for improving the reliability of psychometric ratings in clinical trials for depression. The approach, used in a Phase 2b/3 trial of NRX-101, achieved a 94.5% rating accuracy, potentially reducing the cost and risk of failure in future trials.
Enhanced Rater Reliability
The study, led by Sapko et al., focused on enhancing interrater reliability (IRR) on the Montgomery-Åsberg Depression Rating Scale (MADRS), a primary endpoint in depression trials. NRx Pharmaceuticals developed a comprehensive program for training and monitoring study site raters, addressing a common issue of statistical variability across different sites.
Impact on Clinical Trial Efficiency
According to Dr. Jonathan Javitt, Chairman, CEO, and Chief Scientist of NRx Pharmaceuticals, the improved methodology allowed the team to identify statistically significant improvements in recovery from suicidality and reduction in akathisia in a study with only 90 patients. Typically, such studies require several hundred participants to achieve statistical significance. The trial concordance, defined as no more than 3 points of disagreement between site raters and central raters on a 60-point scale, was observed in 94.5% of ratings. Standard industry practice often accepts variance up to 6 points.
Future Implications
NRx Pharmaceuticals plans to implement this improved methodology in future drug development and clinical trials within its network of HOPE clinics. The company is currently developing NRX-101, an FDA-designated investigational Breakthrough Therapy for suicidal treatment-resistant bipolar depression and chronic pain. They also plan to file an NDA for Accelerated Approval for NRX-101 in patients with bipolar depression and suicidality or akathisia. Additionally, NRx has announced plans to submit a New Drug Application for NRX-100 (IV ketamine) for the treatment of suicidal depression.
