Objective: To assess the reporting, extent, and handling of loss to follow-up and its potential impact on the estimates of the effect of treatment in randomised controlled trials.
Design: Systematic review. We calculated the percentage of trials for which the relative risk would no longer be significant under a number of assumptions about the outcomes of participants lost to follow-up.
Data sources: Medline search of five top general medical journals, 2005-07.
Eligibility criteria: Randomised controlled trials that reported a significant binary primary patient important outcome.
Results: Of the 235 eligible reports identified, 31 (13%) did not report whether or not loss to follow-up occurred. In reports that did give the relevant information, the median percentage of participants lost to follow-up was 6% (interquartile range 2-14%). The method by which loss to follow-up was handled was unclear in 37 studies (19%); the most commonly used method was survival analysis (66, 35%). When we varied assumptions about loss to follow-up, results of 19% of trials were no longer significant if we assumed no participants lost to follow-up had the event of interest, 17% if we assumed that all participants lost to follow-up had the event, and 58% if we assumed a worst case scenario (all participants lost to follow-up in the treatment group and none of those in the control group had the event). Under more plausible assumptions, in which the incidence of events in those lost to follow-up relative to those followed-up is higher in the intervention than control group, results of 0% to 33% trials were no longer significant.
Conclusion: Plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of randomised controlled trials published in top medical journals.