Standard and reference-based conditional mean imputation

Marcel Wolbers, Alessandro Noci, Paul Delmar, Craig Gower-Page, Sean Yiu, Jonathan Bartlett

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)


Clinical trials with longitudinal outcomes typically include missing data due to missed assessments or structural missingness of outcomes after intercurrent events handled with a hypothetical strategy. Approaches based on Bayesian random multiple imputation and Rubin's rules for pooling results across multiple imputed data sets are increasingly used in order to align the analysis of these trials with the targeted estimand. We propose and justify deterministic conditional mean imputation combined with the jackknife for inference as an alternative approach. The method is applicable to imputations under a missing-at-random assumption as well as for reference-based imputation approaches. In an application and a simulation study, we demonstrate that it provides consistent treatment effect estimates with the Bayesian approach and reliable frequentist inference with accurate standard error estimation and type I error control. A further advantage of the method is that it does not rely on random sampling and is therefore replicable and unaffected by Monte Carlo error.
Original languageEnglish
Pages (from-to)1246-1257
Number of pages12
JournalPharmaceutical Statistics
Issue number6
Early online date19 May 2022
Publication statusPublished - 30 Nov 2022

Bibliographical note

Funding Information:
Bartlett's contribution was supported by the UK Medical Research Council (Grant MR/T023953/1).


  • estimands
  • longitudinal data
  • reference-based imputation

ASJC Scopus subject areas

  • Statistics and Probability
  • Pharmacology
  • Pharmacology (medical)


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