Imputing longitudinal PROM data at the item and score level in clinical trials

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Abstract Background Missing data in patient-reported outcome measures (PROMs) can affect estimation accuracy and inferential validity, particularly under missing-at-random (MAR) mechanisms. Multiple imputation (MI) is commonly recommended, but the relative performance of item-level and score-level imputation for longitudinal PROM composite scores remains insufficiently understood. Methods We conducted a simulation study based on longitudinal clinical trial PROM data. Predictive mean matching (PMM) and random forest (RF) imputation were evaluated at both the item and score level under empirically calibrated MAR mechanisms. Simulation scenarios varied sample size, overall missingness, and the proportion of unit nonresponse. Performance was assessed using root mean squared error (RMSE), bias magnitude, relative efficiency compared with complete case analysis (CCA), conditional confidence interval coverage, and variance ratio estimates. Results RMSE decreased with increasing sample size and increased with higher proportions of missingness across all methods. Both PMM and RF generally outperformed CCA in terms of RMSE and relative efficiency, particularly under higher missingness. Differences between item-level and score-level imputation were generally modest, although score-level imputation tended to yield slightly lower RMSE and bias magnitudes under more severe missingness conditions. Conditional coverage remained close to nominal levels across most MI settings. Variance tended to be overestimated in some scenarios, although sensitivity analyses with larger numbers of imputations substantially reduced this effect. PMM showed comparatively stable performance across simulation settings. Conclusions Multiple imputation methods generally outperformed complete case analysis for handling longitudinal PROM data under MAR. While score-level imputation sometimes showed slightly more favorable performance than item-level imputation when targeting composite score means, the magnitude of these differences was frequently small in practical terms. PMM provided stable performance across a wide range of settings and represents a reasonable default approach for many applied PROM analyses.