Defining responders to therapies by a statistical modeling approach applied to randomized clinical trial data

作者：Francesca Bovis, Luca Carmisciano, Alessio Signori, Matteo Pardini, Joshua R. Steinerman, Thomas Li, Aaron Tansy, Maria Pia Sormani · 发表于：BMC Medicine · 年份：2019 · DOI：10.1186/s12916-019-1345-2 · 被引用次数：20 · 研究领域：Multiple Sclerosis Research Studies、vaccines and immunoinformatics approaches、Bacterial Infections and Vaccines

BACKGROUND: Personalized medicine is the tailoring of treatment to the individual characteristics of patients. Once a treatment has been tested in a clinical trial and its effect overall quantified, it would be of great value to be able to use the baseline patients' characteristics to identify patients with larger/lower benefits from treatment, for a more personalized approach to therapy. METHODS: We show here a previously published statistical method, aimed at identifying patients' profiles associated to larger treatment benefits applied to three identical randomized clinical trials in multiple sclerosis, testing laquinimod vs placebo (ALLEGRO, BRAVO, and CONCERTO). We identified on the ALLEGRO patients' specific linear combinations of baseline variables, predicting heterogeneous response to treatment on disability progression. We choose the best score on the BRAVO, based on its ability to identify responders to treatment in this dataset. We finally got an external validation on the CONCERTO, testing on this new dataset the performance of the score in defining responders and non-responders. RESULTS: The best response score defined on the ALLEGRO and the BRAVO was a linear combination of age, sex, previous relapses, brain volume, and MRI lesion activity. Splitting patients into responders and non-responders according to the score distribution, in the ALLEGRO, the hazard ratio (HR) for disability progression of laquinimod vs placebo was 0.38 for responders, HR = 1.31 for non-r...