Assessing the Value of Time Series Real-World and Clinical Trial Data vs. Baseline-Only Data in Predicting Responses to Pregabalin Therapy for Patients with Painful Diabetic Peripheral Neuropathy.

Background And Objective: Treatment challenges necessitate new approaches to customize care to individual patient needs. Integrating data from randomized controlled trials and observational studies may reduce potential covariate biases, yielding information to improve treatment outcomes. The objective of this study was to predict pregabalin responses, in individuals with painful diabetic peripheral neuropathy, by examining time series data (lagged inputs) collected after treatment initiation vs. baseline using microsimulation.

Methods: The platform simulated pregabalin-treated patients to estimate hypothetical future pain responses over 6 weeks based on six distinct time series regressions with lagged variables as inputs (hereafter termed "time series regressions"). Data were from three randomized controlled trials (N = 398) and an observational study (N = 3159). Regressions were derived after performing a hierarchical cluster analysis with a matched patient dataset from coarsened exact matching. Regressions were validated using unmatched (observational study vs. randomized controlled trial) patients. Predictive implications (of 6-week outcomes) were compared using only baseline vs. 1- to 2-week prior data.

Results: Time series regressions for pain performed well (adjusted R 0.85-0.91; root mean square error 0.53-0.57); those with only baseline data performed less well (adjusted R 0.13-0.44; root mean square error 1.11-1.40). Simulated patient distributions yielded positive predictive values for > 50% pain score improvements from baseline for the six clusters (287-777 patients each; range 0.87-0.98).

Conclusions: Effective prediction of pregabalin response for painful diabetic peripheral neuropathy was accomplished through combining cluster analyses, coarsened exact matching, and time series regressions, reflecting distinct patterns of baseline and "on-treatment" variables. These results advance the understanding of microsimulation to predict patient treatment responses through integration and inter-relationships of multiple, complex, and time-dependent characteristics.