Industrial water pollution

Objectives

To identify publications describing criteria for use of composite endpoints for competing risk and to offer guidance regarding when a composite endpoint is appropriate on the basis of competing risks.

Data Sources

We searched MEDLINE, CINAHL, EMBASE, The Cochrane’s Central & Systematic Review databases including the Health Technology Assessment database and the Cochrane’s Methodology register from inception to April 2015, and candidate textbooks, to identify all articles providing guidance on this issue.

Study Selection and Data Extraction

Eligible publications explicitly addressed the issue of a composite outcome to address competing risks. Two reviewers independently screened the titles and abstracts for full text review; independently reviewed full text publications; and abstracted specific criteria authors offered for use of composite endpoints to address competing risks.

Results

Of 63645 titles and abstracts, 166 proved potentially relevant of which 43 publications were included in the final review. Most publications note competing risks as a reason for using composite endpoints without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite endpoints for competing risk. Some advocate using composite endpoints to avoid bias due to competing risks and others suggest that composite endpoints seldom or never be used for this purpose. We recommend using composite endpoints for competing risks only if the competing risk is plausible and if it occurs with sufficiently high frequency to influence the interpretation of the effect of intervention on the endpoint of interest. These criteria will seldom be met. Review of heart failure trials published in the New England Journal of Medicine revealed that many of them use the composite endpoint of death or hospitalization; none of the trials, however, satisfied our criteria.

Conclusion

The existing literature fails to provide clear guidance regarding use of composite endpoint for competing risks. We recommend using composite endpoints for competing risks only if the competing risk is plausible and if it occurs sufficiently often.

This is a serious topic