Beyond composite endpoints analysis: Semicompeting risks as an underutilized framework for cancer research

Ina Jazic, Deborah Schrag, Daniel J. Sargent, Sebastien Haneuse

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Composite endpoints (CEP), such as progression-free survival, are commonly used in cancer research. Notwithstanding their popularity, however, CEP analyses suffer from a number of drawbacks, especially when death is combined with a nonterminal event (ie, progression or recurrence), exemplifying the semicompeting risks setting. We investigated the semicompeting risks framework as a complementary analysis strategy that avoids certain drawbacks of CEPs. Methods: The illness-deathmodel under the semicompeting risks framework was compared with standard analysis approaches: CEP analyses and (separate) univariate analyses for each component endpoint. Data froma previously published phase III randomized clinical trial inmetastatic colon cancer including 1419 participants in the N9741 trial (conducted between 1997 and 2003) were used to determine the impact of the loss of information associated with combiningmultiple endpoints, as well as of ignoring the potentially informative role of death. A simulation study was conducted to further explore these issues. Results: Failure to account for critical features of semicompeting risks data can lead to potentially severely misleading conclusions. Advantages of semicompeting risks analyses include a clear delineation of treatment effects on both events, the ability to draw conclusions about a patient's joint risk of the two events, and an assessment of the dependence between the two event types. Conclusions: Embedding and analyzing component outcomes in the semicompeting risks framework, either as a supplement or alternative to CEP analyses, represents an important, underutilized, and feasible opportunity for cancer research.

Original languageEnglish (US)
Article numberdjw154
JournalJournal of the National Cancer Institute
Volume108
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Research
Neoplasms
Phase III Clinical Trials
Colonic Neoplasms
Disease-Free Survival
Randomized Controlled Trials
Recurrence
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Beyond composite endpoints analysis : Semicompeting risks as an underutilized framework for cancer research. / Jazic, Ina; Schrag, Deborah; Sargent, Daniel J.; Haneuse, Sebastien.

In: Journal of the National Cancer Institute, Vol. 108, No. 12, djw154, 01.12.2016.

Research output: Contribution to journalArticle

Jazic, Ina ; Schrag, Deborah ; Sargent, Daniel J. ; Haneuse, Sebastien. / Beyond composite endpoints analysis : Semicompeting risks as an underutilized framework for cancer research. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 12.
@article{1c8bdaa05c0a43e684ed9b1d125ea178,
title = "Beyond composite endpoints analysis: Semicompeting risks as an underutilized framework for cancer research",
abstract = "Background: Composite endpoints (CEP), such as progression-free survival, are commonly used in cancer research. Notwithstanding their popularity, however, CEP analyses suffer from a number of drawbacks, especially when death is combined with a nonterminal event (ie, progression or recurrence), exemplifying the semicompeting risks setting. We investigated the semicompeting risks framework as a complementary analysis strategy that avoids certain drawbacks of CEPs. Methods: The illness-deathmodel under the semicompeting risks framework was compared with standard analysis approaches: CEP analyses and (separate) univariate analyses for each component endpoint. Data froma previously published phase III randomized clinical trial inmetastatic colon cancer including 1419 participants in the N9741 trial (conducted between 1997 and 2003) were used to determine the impact of the loss of information associated with combiningmultiple endpoints, as well as of ignoring the potentially informative role of death. A simulation study was conducted to further explore these issues. Results: Failure to account for critical features of semicompeting risks data can lead to potentially severely misleading conclusions. Advantages of semicompeting risks analyses include a clear delineation of treatment effects on both events, the ability to draw conclusions about a patient's joint risk of the two events, and an assessment of the dependence between the two event types. Conclusions: Embedding and analyzing component outcomes in the semicompeting risks framework, either as a supplement or alternative to CEP analyses, represents an important, underutilized, and feasible opportunity for cancer research.",
author = "Ina Jazic and Deborah Schrag and Sargent, {Daniel J.} and Sebastien Haneuse",
year = "2016",
month = "12",
day = "1",
doi = "10.1093/jnci/djw154",
language = "English (US)",
volume = "108",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Beyond composite endpoints analysis

T2 - Semicompeting risks as an underutilized framework for cancer research

AU - Jazic, Ina

AU - Schrag, Deborah

AU - Sargent, Daniel J.

AU - Haneuse, Sebastien

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Background: Composite endpoints (CEP), such as progression-free survival, are commonly used in cancer research. Notwithstanding their popularity, however, CEP analyses suffer from a number of drawbacks, especially when death is combined with a nonterminal event (ie, progression or recurrence), exemplifying the semicompeting risks setting. We investigated the semicompeting risks framework as a complementary analysis strategy that avoids certain drawbacks of CEPs. Methods: The illness-deathmodel under the semicompeting risks framework was compared with standard analysis approaches: CEP analyses and (separate) univariate analyses for each component endpoint. Data froma previously published phase III randomized clinical trial inmetastatic colon cancer including 1419 participants in the N9741 trial (conducted between 1997 and 2003) were used to determine the impact of the loss of information associated with combiningmultiple endpoints, as well as of ignoring the potentially informative role of death. A simulation study was conducted to further explore these issues. Results: Failure to account for critical features of semicompeting risks data can lead to potentially severely misleading conclusions. Advantages of semicompeting risks analyses include a clear delineation of treatment effects on both events, the ability to draw conclusions about a patient's joint risk of the two events, and an assessment of the dependence between the two event types. Conclusions: Embedding and analyzing component outcomes in the semicompeting risks framework, either as a supplement or alternative to CEP analyses, represents an important, underutilized, and feasible opportunity for cancer research.

AB - Background: Composite endpoints (CEP), such as progression-free survival, are commonly used in cancer research. Notwithstanding their popularity, however, CEP analyses suffer from a number of drawbacks, especially when death is combined with a nonterminal event (ie, progression or recurrence), exemplifying the semicompeting risks setting. We investigated the semicompeting risks framework as a complementary analysis strategy that avoids certain drawbacks of CEPs. Methods: The illness-deathmodel under the semicompeting risks framework was compared with standard analysis approaches: CEP analyses and (separate) univariate analyses for each component endpoint. Data froma previously published phase III randomized clinical trial inmetastatic colon cancer including 1419 participants in the N9741 trial (conducted between 1997 and 2003) were used to determine the impact of the loss of information associated with combiningmultiple endpoints, as well as of ignoring the potentially informative role of death. A simulation study was conducted to further explore these issues. Results: Failure to account for critical features of semicompeting risks data can lead to potentially severely misleading conclusions. Advantages of semicompeting risks analyses include a clear delineation of treatment effects on both events, the ability to draw conclusions about a patient's joint risk of the two events, and an assessment of the dependence between the two event types. Conclusions: Embedding and analyzing component outcomes in the semicompeting risks framework, either as a supplement or alternative to CEP analyses, represents an important, underutilized, and feasible opportunity for cancer research.

UR - http://www.scopus.com/inward/record.url?scp=85016061155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016061155&partnerID=8YFLogxK

U2 - 10.1093/jnci/djw154

DO - 10.1093/jnci/djw154

M3 - Article

C2 - 27381741

AN - SCOPUS:85016061155

VL - 108

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 12

M1 - djw154

ER -