Feasibility of Machine Learning Analysis for the Identification of Patients with Possible Primary Ciliary Dyskinesia

BACKGROUNDSignificant diagnostic delays are common in primary ciliary dyskinesia (PCD), a rare disease that is significantly underdiagnosed. Scalable screening methods could improve early identification and health outcomes. RESEARCH QUESTIONCan machine learning (ML) be used to screen for PCD in pediatric patients? STUDY DESIGN AND METHODSWe evaluated the feasibility of a random forest model to screen for PCD using data from the PCD Foundation Registry and a national claims database. We identified a cohort of pediatric patients with diagnostic codes indicative of conditions potentially associated with PCD, and studied diagnostic, procedural, and pharmaceutical codes associated with PCD to develop ML features. Models were trained on composite claims data from confirmed patients with PCD, patients with Q34.8 (Specific Congenital Malformation of the Respiratory System) diagnosed within six months of an Electron Microscopy procedure (Q34.8+EM), and a randomly-selected, matched control group. Model performance was tested through 5-fold cross-validation. RESULTSUsing 82 confirmed PCD cases and 4,161 matched controls, the model demonstrated variable performance (positive predictive value 0.45-0.73, sensitivity 0.75-0.94). Synthetic data augmentation did not improve results (positive predictive value 0.45-0.67, sensitivity 0.71-1.00). Expanding the dataset to include 319 Q34.8+EM patients and 8,214 controls improved performance (positive predictive value 0.51-0.54, sensitivity 0.82-0.90), suitable for screening. In a cohort of 1.32 million pediatric patients, 7,705 were classified as positive, consistent with the estimated prevalence of PCD (1:7,554). INTERPRETATIONThis study demonstrates the feasibility of using ML to screen for PCD using claims data, even in the absence of a specific International Classification of Disease (ICD) code. Such screening approaches may aid in the identification of individuals who may benefit from timely diagnostic testing and targeted interventions.