Predicting Therapy Outcomes in Patients With Stress-Related Disorders: Protocol for a Predictive Modeling Study

BACKGROUND: While cognitive behavioral therapy has shown efficacy in treating stress-related disorders, such as adjustment disorder and exhaustion disorder, knowledge about factors contributing to treatment response is limited. Improved identification of such factors could enhance assessment procedures and treatment strategies. In addition, evaluating how traditional prediction methods and machine learning can complement each other may help bridge gaps in understanding and predicting treatment response. OBJECTIVE: This study aims to (1) evaluate putative predictors of treatment response in patients with stress-related disorders using traditional prediction methods and (2) model treatment outcomes using a machine learning approach. This design combines the interpretability of traditional methods with the ability of machine learning to identify complex patterns. METHODS: We will analyze data from a randomized controlled trial comparing 2 internet-delivered treatments, cognitive behavioral therapy versus an active control treatment, for patients diagnosed with adjustment disorder or exhaustion disorder (N=300). Prediction models will be based on pooled data from both treatment arms due to the limited sample size and lack of knowledge on predictors of treatment effects. Putative predictors include sociodemographic and clinical information, clinician-assessed data, self-rated symptoms, and cognitive test scores. The primary outcome of interest is responder status on the Perceived Stress Scale-10, evaluated based on the reliable change index posttreatment. For the traditional approach, univariate logistic regressions will be conducted for each predictor, followed by an ablation study for significant predictors. For the machine learning approach, 4 classifiers (logistic regression with elastic net, random forest, support vector machine, and AdaBoost) will be trained and evaluated. The dataset will be split into training (70%) and testing (30%) sets. Hyperparameter tuning will be conducted using 5-fold cross-validation with randomized search. Model performance will be assessed using balanced accuracy, precision, recall, and area under the curve. RESULTS: All data were collected between April 2021 and September 2022. We hypothesize that key predictors will include younger age, education level, baseline symptom severity, treatment credibility, and history of sickness absence. We anticipate that the machine learning models will outperform a dummy model predicting the majority class and achieve a balanced accuracy of ≥67%, thus indicating clinical usefulness. CONCLUSIONS: This study will contribute to the limited research on predictors of treatment outcome in stress-related disorders. The findings could support the development of more personalized and effective treatments for individuals diagnosed with adjustment disorder or exhaustion disorder, potentially improving clinical practice and patient outcomes. If successful, this dual approach may encourage future studies with larger datasets and the implementation of machine learning models in clinical settings, ultimately enhancing precision in mental health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/65790.

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