Evaluating the heterogeneous effect of a modifiable risk factor on suicide: The case of vitamin D deficiency

Objectives To illustrate the use of machine learning methods to search for heterogeneous effects of a target modifiable risk factor on suicide in observational studies. The illustration focuses on secondary analysis of a matched case-control study of vitamin D deficiency predicting subsequent suicide. Methods We describe a variety of machine learning methods to search for prescriptive predictors; that is, predictors of significant variation in the association between a target risk factor and subsequent suicide. In each case, the purpose is to evaluate the potential value of selective intervention on the target risk factor to prevent the outcome based on the provisional assumption that the target risk factor is causal. The approaches illustrated include risk modeling based on the super learner ensemble machine learning method, Least Absolute Shrinkage and Selection Operator (Lasso) penalized regression, and the causal forest algorithm. Results The logic of estimating heterogeneous intervention effects is exposited along with the illustration of some widely used methods for implementing this logic. Conclusions In addition to describing best practices in using the machine learning methods considered here, we close with a discussion of broader design and analysis issues in planning an observational study to investigate heterogeneous effects of a modifiable risk factor.