LAUSR

OBJECTIVE To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for the consideration of study limitations (risk of bias) due to missing participant outcome data for time-to-event outcomes in intervention studies. STUDY DESIGN AND SETTING We developed this guidance through an iterative process that included membership consultation, feedback, presentation and iterative discussion at meetings of the GRADE Working Group. RESULTS The GRADE working group has published guidance on how to account for missing participant outcome data in binary and continuous outcomes. When analysing time-to-event outcomes (e.g. overall survival, time-to-treatment failure) data of participants for whom the outcome of interest (e.g. death, relapse) has not been observed are dealt with through censoring. To do so, standard methods require that censored individuals are representative for those remaining in the study. Two types of censoring can be distinguished, end of study censoring and censoring because of missing data, commonly named loss to follow-up censoring. However, both types are not distinguishable with the usual information on censoring available to review authors. Dealing with individuals for whom data is missing during follow-up in the same way as individuals for whom full follow-up is available at the end of the study increases the risk of bias. Considerable differences in the treatment arms in the distribution of censoring over time (early versus late censoring), the overall degree of missing follow-up data and the reasons why individuals were lost to follow-up may reduce the certainty in study results. With often only very limited data available, review and guideline authors are required to make transparent and well-considered judgements when judging risk of bias of individual studies and then come to an overall grading decision for the entire body of evidence. CONCLUSION Concern for risk of bias resulting from censoring of participants for whom follow-up data is missing in the underlying studies of a body of evidence can be expressed in the study limitations (risk of bias) domain of the GRADE approach.