Validation of machine learning-based individualized treatment for depressive disorder using target trial emulation

Chi Shin Wu*, Albert C. Yang, Shu Sen Chang, Chia Ming Chang, Yi Hung Liu, Shih Cheng Liao, Hui Ju Tsai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


This study aims to develop and validate the use of machine learning-based prediction models to select individualized pharmacological treatment for patients with depressive disorder. This study used data from Taiwan’s National Health Insurance Research Database. Patients with incident depressive disorders were included in this study. The study outcome was treatment failure, which was defined as psychiatric hospitalization, self-harm hospitalization, emergency visits, or treatment change. Prediction models based on the Super Learner ensemble were trained separately for the initial and the next-step treatments if the previous treatments failed. An individualized treatment strategy was developed for selecting the drug with the lowest probability of treatment failure for each patient as the model-selected regimen. We emulated clinical trials to estimate the effectiveness of individualized treatments. The area under the curve of the prediction model using Super Learner was 0.627 and 0.751 for the initial treatment and the next-step treatment, respectively. Model-selected regimens were associated with reduced treatment failure rates, with a 0.84-fold (95% confidence interval (CI) 0.82–0.86) decrease for the initial treatment and a 0.82-fold (95% CI 0.80–0.83) decrease for the next-step. In emulation of clinical trials, the model-selected regimen was associated with a reduced treatment failure rate.

Original languageEnglish
Article number1316
JournalJournal of Personalized Medicine
Issue number12
StatePublished - Dec 2021


  • Anti-depressive agents
  • Machine learning
  • Precision medicine


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