Last-observation-carried-forward imputation method in clinical efficacy trials: review of 352 antidepressant studies

Pharmacotherapy
Stephen B WoolleyJohn W Goethe

Abstract

To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports. Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004). MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services. A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 tria...Continue Reading

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