Missing Data in OHCA Registries: How Imputation Methods Affect Research Conclusions-Paper I

Background/Objectives: Clinical observational studies often encounter missing data, which complicates association evaluation with reduced bias while accounting for confounders. This is particularly challenging in multi-national registries such as those for out-of-hospital cardiac arrest (OHCA), a time-sensitive medical emergency with low survival rates. While various methods for handling missing data exist, observational studies frequently rely on complete-case analysis, limiting representativeness and potentially introducing bias. Our objective was to evaluate the impact of various single imputation methods on association analysis with OHCA registries. Methods: Using a complete dataset (N = 13,274) from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry (1 January 2016-31 December 2020) as reference, we intentionally introduced missing values into selected variables via a Missing At Random (MAR) mechanism. We then compared statistical and machine learning (ML) single imputation methods to assess the association between bystander cardiopulmonary resuscitation (BCPR) and the issuance of a mobile app alert, adjusting for confounders. The impacts of complete-case analysis (CCA) and single imputation methods on conclusions in OHCA research were evaluated. Results: CCA was suboptimal for handling MAR data, resulting in more biased estimates and wider confidence intervals compared to single imputation methods. The missingness-indicator (MxI) method offered a trade-off between bias and ease of implementation. The K-Nearest Neighbours (KNN) method outperformed other imputation approaches, whereas missForest introduced bias under certain conditions. Conclusions: KNN and MxI are easy to use and better alternatives to CCA for reducing bias in observational studies. This study highlights the importance of selecting appropriate imputation methods to ensure reliable conclusions in OHCA research and has broader implications for other registries facing similar missing data challenges.