Considerations for development of an evidence dossier to support the use of mobile sensor technology for clinical outcome assessments in clinical trials.

BACKGROUND: Mobile sensors offer enormous potential for the collection of informative clinical endpoints in clinical trials to support regulatory decision making and product labelling. There are currently no specific guidelines on the information needed to enable regulators to review and accept proposed endpoints derived from mobile sensors for use in drug development trials. OBJECTIVE: The purpose of this working group report is to recommend the structure and content of an evidence dossier intended to support whether a clinical endpoint derived from mobile sensor data is fit-for-purpose for use in regulatory submissions for drug approvals. EVIDENCE DOSSIER: The structure and content of a dossier to provide evidence supporting the use of a sensor-derived clinical endpoint is described. Sections include clinical endpoint definition and positioning, the concept of interest, the context of use, clinical validation and interpretation, study implementation, and analytical validity with sensor performance verification in support of the selected sensor. CONCLUSIONS: In the absence of definitive regulatory guidance, this report provides a considered approach to compiling a comprehensive body of evidence to justify acceptance of mobile sensors for support of new drug applications.

Assessing disability progression with the Multiple Sclerosis Functional Composite.

BACKGROUND: The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event. OBJECTIVE: Evaluate a new method for analyzing disability progression using the MSFC. METHODS: MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for >or=3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects. RESULTS: Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL. CONCLUSION: MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies.