Abstract
Objectives
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 analyzing time-to-event outcomes
(e.g., overall survival and time-to-treatment failure) data of participants for whom
the outcome of interest (e.g., death and 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 are 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 the study results.
With often only very limited data available, review and guideline authors are required
to make transparent and well-considered judgments 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 are 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.
Keywords
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Article info
Publication history
Published online: September 29, 2020
Accepted:
September 2,
2020
Footnotes
Conflict of interest statement: None.
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
