Validity of using multiple imputation for "unknown" stage at diagnosis in population-based cancer registry data

Background: The multiple imputation approach to missing data has been validated by a number of simulation studies by artificially inducing missingness on fully observed stage data under a prespecified missing data mechanism. However, the validity of multiple imputation has not yet been assessed using real data. The objective of this study was to assess the validity of using multiple imputation for "unknown" prostate cancer stage recorded in the New South Wales Cancer Registry (NSWCR) in real-world conditions. Methods: Data from the population-based cohort study NSW Prostate Cancer Care and Outcomes Study (PCOS) were linked to 2000-2002 NSWCR data. For cases with "unknown" NSWCR stage, PCOS-stage was extracted from clinical notes. Logistic regression was used to evaluate the missing at random assumption adjusted for variables from two imputation models: a basic model including NSWCR variables only and an enhanced model including the same NSWCR variables together with PCOS primary treatment. Cox regression was used to evaluate the performance of MI. Results: Of the 1864 prostate cancer cases 32.7% were recorded as having "unknown" NSWCR stage. The missing at random assumption was satisfied when the logistic regression included the variables included in the enhanced model, but not those in the basic model only. The Cox models using data with imputed stage from either imputation model provided generally similar estimated hazard ratios but with wider confidence intervals compared with those derived from analysis of the data with PCOS-stage. However, the complete-case analysis of the data provided a considerably higher estimated hazard ratio for the low socioeconomic status group and rural areas in comparison with those obtained from all other datasets. Conclusions: Using MI to deal with "unknown" stage data recorded in a population-based cancer registry appears to provide valid estimates. We would recommend a cautious approach to the use of this method elsewhere.