title: Accounting for uncertainty due to 'last observation carried forward' outcome imputation in a meta-analysis model.
abstract: Missing outcome data are a problem commonly observed in randomized control trials that occurs as a result of participants leaving the study before its end. Missing such important information can bias the study estimates of the relative treatment effect and consequently affect the meta-analytic results. Therefore, methods on manipulating data sets with missing participants, with regard to incorporating the missing information in the analysis so as to avoid the loss of power and minimize the bias, are of interest. We propose a meta-analytic model that accounts for possible error in the effect sizes estimated in studies with last observation carried forward (LOCF) imputed patients. Assuming a dichotomous outcome, we decompose the probability of a successful unobserved outcome taking into account the sensitivity and specificity of the LOCF imputation process for the missing participants. We fit the proposed model within a Bayesian framework, exploring different prior formulations for sensitivity and specificity. We illustrate our methods by performing a meta-analysis of five studies comparing the efficacy of amisulpride versus conventional drugs (flupenthixol and haloperidol) on patients diagnosed with schizophrenia. Our meta-analytic models yield estimates similar to meta-analysis with LOCF-imputed patients. Allowing for uncertainty in the imputation process, precision is decreased depending on the priors used for sensitivity and specificity. Results on the significance of amisulpride versus conventional drugs differ between the standard LOCF approach and our model depending on prior beliefs on the imputation process. Our method can be regarded as a useful sensitivity analysis that can be used in the presence of concerns about the LOCF process.
authors.affiliation: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Dimitrakopoulou
authors.forename: Orestis
authors.initials: O
authors.lastname: Efthimiou
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
mesh_terms: D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001499:Bayes Theorem; D015982:Bias; D056808:Biostatistics; D006801:Humans; D008390:Markov Chains; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D009010:Monte Carlo Method; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000188:drug therapy; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use; D035501:Uncertainty
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride
keywords: Bayesian meta-analysis; LOCF approach; amisulpride; missing data; randomized controlled trials; schizophrenia