Phase 2 submissions are evaluated based upon the following judging criteria. When evaluating submissions, judges assign each submission 1 to 5 (5 being the highest; 1 being the lowest) points for each of the judging criteria.
Phase 2 interim criteria
Off-Target Characterization
Extent to which the data and results demonstrate the ability to characterize (monitor, measure, and evaluate) relevant off-target effects outside of the intended autonomic function. Characterization of off-target effects should include appropriate and sufficient controls and statistical analyses.
Interim Targeting Performance
Extent to which the data and results demonstrate the necessary requirements for selectively modulating an autonomic function with a high degree of tunability, accuracy, and precision. Controls and statistical analysis of autonomic function modulation should be appropriate and sufficient for determining effect.
Phase 2 final criteria
Off-Target Characterization
Extent to which the data and results demonstrate the ability to characterize (monitor, measure, and evaluate) relevant off-target effects outside of the intended autonomic functions. Characterization of off-target effects should include appropriate and sufficient controls and statistical analyses.
Final Targeting Performance
Extent to which the data and results demonstrate the necessary requirements for selectively modulating two or more autonomic functions each with a high degree of tunability, accuracy, and precision. Controls and statistical analysis of autonomic function modulation should be appropriate and sufficient for determining effect.
Plans for how to address FDA feedback
Extent and feasibility to which FDA concerns are addressed if applicable (if determined to be non-significant risk, this criterion will not be utilized).
Clinical Relevance
Extent to which the results are likely to provide clinically relevant improvement in target function (not just statistical significance) as well as potential comparisons to currently available prescribed treatment for target indication if applicable.
Technology Readiness
Do in vivo studies demonstrate the efficacy of the proposed technology in accordance with its intended use? Have biomarker(s), assays, and endpoint(s) been used that can be further used in clinical studies? What is the feasibility of submitting for an FDA IDE within 1-2 years (i.e., by the end of a potential phase 3)?
Phase 2 judging considerations
Judges will be asked to consider the following in their evaluations of the above criteria:
Neuro-modulation control
Demonstrated ability to control each autonomic function independently, and for any and all target functions identified, how the approach resulted in:
- Precision of stimulation outcomes within a generally accepted range of variability. How consistently does a given neuromodulation parameter result in similar change in the intended autonomic function (as indicated by biomarker measurement)?
- Accuracy of stimulation outcomes to a generally accepted standard of error for the target indication(s). How close is the measured result to the intended change in autonomic function (as indicated by biomarker measurement)?
- Tunability of both the stimulation parameters (e.g., amplitude, pulse width) and resultant change in autonomic function. How finely adjustable is the functional response (as indicated by biomarker measurement) in regard to a change in the stimulation parameter?
Biomarker Characteriza-tion
A quantitative assessment of both on-target and off-target events that occur in response to neuromodulation. Identified biomarkers must include those which are regulated by the same nerve being modulated and be correlated with outcome.
A biomarker is a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic interventions. Biomarkers may include molecular, histologic, radiographic, or physiologic characteristics. Source: FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK326791/ Co-published by National Institutes of Health (US), Bethesda (MD).