Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations

Veena Manja, Siwar AlBashir, Gordon Guyatt

Research output: Contribution to journalReview article

Abstract

Background Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. Objectives To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. Methods, Data Sources, Study Selection and Data Extraction 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. 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 end points to address competing risks. Results Of 63,645 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 end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points 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 end point 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 end point 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 end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.

Original languageEnglish (US)
Pages (from-to)4-11
Number of pages8
JournalJournal of Clinical Epidemiology
Volume82
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Fingerprint

Publications
Textbooks
Surveys and Questionnaires
Databases
Biomedical Technology Assessment
New England
Information Storage and Retrieval
MEDLINE
Hospitalization
Heart Failure
Medicine
Clinical Trials

Keywords

  • Combined end points
  • Competing risks
  • Composite end points

ASJC Scopus subject areas

  • Epidemiology

Cite this

Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations. / Manja, Veena; AlBashir, Siwar; Guyatt, Gordon.

In: Journal of Clinical Epidemiology, Vol. 82, 01.02.2017, p. 4-11.

Research output: Contribution to journalReview article

@article{2116c13987574ab8bc452fc7cef5a75c,
title = "Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations",
abstract = "Background Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. Objectives To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. Methods, Data Sources, Study Selection and Data Extraction 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. 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 end points to address competing risks. Results Of 63,645 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 end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points 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 end point 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 end point 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 end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.",
keywords = "Combined end points, Competing risks, Composite end points",
author = "Veena Manja and Siwar AlBashir and Gordon Guyatt",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.jclinepi.2016.12.001",
language = "English (US)",
volume = "82",
pages = "4--11",
journal = "Journal of Clinical Epidemiology",
issn = "0895-4356",
publisher = "Elsevier USA",

}

TY - JOUR

T1 - Criteria for use of composite end points for competing risks—a systematic survey of the literature with recommendations

AU - Manja, Veena

AU - AlBashir, Siwar

AU - Guyatt, Gordon

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. Objectives To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. Methods, Data Sources, Study Selection and Data Extraction 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. 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 end points to address competing risks. Results Of 63,645 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 end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points 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 end point 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 end point 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 end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.

AB - Background Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. Objectives To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. Methods, Data Sources, Study Selection and Data Extraction 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. 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 end points to address competing risks. Results Of 63,645 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 end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points 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 end point 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 end point 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 end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.

KW - Combined end points

KW - Competing risks

KW - Composite end points

UR - http://www.scopus.com/inward/record.url?scp=85010383261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010383261&partnerID=8YFLogxK

U2 - 10.1016/j.jclinepi.2016.12.001

DO - 10.1016/j.jclinepi.2016.12.001

M3 - Review article

VL - 82

SP - 4

EP - 11

JO - Journal of Clinical Epidemiology

JF - Journal of Clinical Epidemiology

SN - 0895-4356

ER -