Treatment selection using prototyping in latent-space with application to depression treatment

PLoS One. 2021 Nov 12;16(11):e0258400. doi: 10.1371/journal.pone.0258400. eCollection 2021.

Abstract

Machine-assisted treatment selection commonly follows one of two paradigms: a fully personalized paradigm which ignores any possible clustering of patients; or a sub-grouping paradigm which ignores personal differences within the identified groups. While both paradigms have shown promising results, each of them suffers from important limitations. In this article, we propose a novel deep learning-based treatment selection approach that is shown to strike a balance between the two paradigms using latent-space prototyping. Our approach is specifically tailored for domains in which effective prototypes and sub-groups of patients are assumed to exist, but groupings relevant to the training objective are not observable in the non-latent space. In an extensive evaluation, using both synthetic and Major Depressive Disorder (MDD) real-world clinical data describing 4754 MDD patients from clinical trials for depression treatment, we show that our approach favorably compares with state-of-the-art approaches. Specifically, the model produced an 8% absolute and 23% relative improvement over random treatment allocation. This is potentially clinically significant, given the large number of patients with MDD. Therefore, the model can bring about a much desired leap forward in the way depression is treated today.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Area Under Curve
  • Clinical Decision-Making / methods*
  • Clinical Trials as Topic
  • Deep Learning*
  • Depression / drug therapy*
  • Depressive Disorder, Major / drug therapy*
  • Drug Therapy, Combination / methods
  • Humans
  • Precision Medicine / methods
  • Remission Induction
  • Treatment Outcome

Substances

  • Antidepressive Agents

Grants and funding

AK and AR were supported by the Chief Scientist Office, Israeli Ministry of Health (CSO-MOH, IL url: https://www.health.gov.il/English/Pages/HomePage.aspx) as part of grant #3-000015730 within Era-PerMed. DB, CA, JM, RF and GT were also funded by the Canadian arm of this grant (ERA-Permed Vision 2020 supporting IMADAPT), with DB, CA, JM, RF funded via their involvement in Aifred Health, which was subcontracted to complete work as part of this grant. This was the grant which served as the primary funder of this work. The funders (the granting agencies) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.