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Joshua Durso-finley

Alumni

Publications

Deep Learning Prediction of Response to Disease Modifying Therapy in Primary Progressive Multiple Sclerosis (P1-1.Virtual)
Jean-Pierre René Falet
Joshua Durso-finley
Brennan Nichyporuk
Julien Schroeter
Francesca Bovis
Maria-Pia Sormani
Doina Precup
Tal Arbel
Douglas Arnold
2022-05-02
Neurology (unknown)
doi.org
Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning
Jean-Pierre R. Falet
Joshua Durso-finley
Brennan Nichyporuk
Julien Schroeter
Francesca Bovis
Maria-Pia Sormani
Doina Precup
Tal Arbel
Douglas Lorne Arnold
Disability progression in multiple sclerosis remains resistant to treatment. The absence of a suitable biomarker to allow for phase 2 clinic… (see more)al trials presents a high barrier for drug development. We propose to enable short proof-of-concept trials by increasing statistical power using a deep-learning predictive enrichment strategy. Specifically, a multi-headed multilayer perceptron is used to estimate the conditional average treatment effect (CATE) using baseline clinical and imaging features, and patients predicted to be most responsive are preferentially randomized into a trial. Leveraging data from six randomized clinical trials ( n  = 3,830), we first pre-trained the model on the subset of relapsing-remitting MS patients ( n  = 2,520), then fine-tuned it on a subset of primary progressive MS (PPMS) patients ( n  = 695). In a separate held-out test set of PPMS patients randomized to anti-CD20 antibodies or placebo ( n  = 297), the average treatment effect was larger for the 50% (HR, 0.492; 95% CI, 0.266-0.912; p  = 0.0218) and 30% (HR, 0.361; 95% CI, 0.165-0.79; p  = 0.008) predicted to be most responsive, compared to 0.743 (95% CI, 0.482-1.15; p  = 0.179) for the entire group. The same model could also identify responders to laquinimod in another held-out test set of PPMS patients ( n  = 318). Finally, we show that using this model for predictive enrichment results in important increases in power.
2021-10-31
medRxiv (preprint)
doi.org