Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review

BMJ. 2012 May 18;344:e2809. doi: 10.1136/bmj.e2809.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Data Interpretation, Statistical*
  • Follow-Up Studies*
  • Humans
  • Lost to Follow-Up*
  • Patient Dropouts / statistics & numerical data*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Risk
  • Survival Analysis
  • Treatment Outcome