De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers

ABSTRACT Background Regulators and oncology healthcare providers are increasingly interested in using observational studies of real‐world data (RWD) to complement clinical evidence from randomized controlled trials for informed decision‐making. To generate valid evidence, RWD studies must be careful...

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Main Authors: Charles E. Gaber, Armen A. Ghazarian, Paula D. Strassle, Tatiane B. Ribeiro, Maribel Salas, Camille Maringe, Xabier Garcia‐Albeniz, Richard Wyss, Wei Du, Jennifer L. Lund
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70461
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author Charles E. Gaber
Armen A. Ghazarian
Paula D. Strassle
Tatiane B. Ribeiro
Maribel Salas
Camille Maringe
Xabier Garcia‐Albeniz
Richard Wyss
Wei Du
Jennifer L. Lund
author_facet Charles E. Gaber
Armen A. Ghazarian
Paula D. Strassle
Tatiane B. Ribeiro
Maribel Salas
Camille Maringe
Xabier Garcia‐Albeniz
Richard Wyss
Wei Du
Jennifer L. Lund
author_sort Charles E. Gaber
collection DOAJ
description ABSTRACT Background Regulators and oncology healthcare providers are increasingly interested in using observational studies of real‐world data (RWD) to complement clinical evidence from randomized controlled trials for informed decision‐making. To generate valid evidence, RWD studies must be carefully designed to avoid systematic biases. The clone‐censor‐weight (CCW) method has been proposed to address immortal time and other time‐related biases. Methods The objective of this manuscript is to de‐mystify the CCW method for cancer researchers by describing and presenting its core components in an accessible and digestible format, using visualizations and examples from cancer‐relevant studies. The CCW method has been applied in diverse settings, including investigations of the effects of surgery within a certain time after cancer diagnosis, the continuation of annual screening mammography, and chemotherapy duration on survival. Results The method handles complex data wherein the treatment group to which an individual belongs is unknown at the start of follow‐up. The three steps of the CCW method involve cloning or duplicating the patient population and assigning one clone to each treatment strategy, artificially censoring the clones when their observed data are inconsistent with the assigned strategy and weighting the cloned and censored population to address selection bias created by the artificial censoring. Conclusions The CCW method is a powerful tool for designing RWD studies in cancer that are free from time‐related biases and successfully, to the extent possible, emulate features of a randomized clinical trial.
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spelling doaj-art-87d6c8ef59fa4bdb8b9c2a4edb67efb42025-08-20T01:58:46ZengWileyCancer Medicine2045-76342024-12-011323n/an/a10.1002/cam4.70461De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer ResearchersCharles E. Gaber0Armen A. Ghazarian1Paula D. Strassle2Tatiane B. Ribeiro3Maribel Salas4Camille Maringe5Xabier Garcia‐Albeniz6Richard Wyss7Wei Du8Jennifer L. Lund9Department of Pharmacy Systems, Outcomes, and Policy University of Illinois—Chicago Chicago Illinois USAClinical Safety and Pharmacovigilance Daiichi Sankyo Inc., Basking Ridge New Jersey USADivision of Intramural Research National Institute of Minority Health and Health Disparities, National Institutes of Health Bethesda Maryland USADepartment of Epidemiology School of Public Health, University of São Paulo São Paulo BrazilClinical Safety and Pharmacovigilance Daiichi Sankyo Inc., Basking Ridge New Jersey USAInequalities in Cancer Outcomes Network London School of Hygiene and Tropical Medicine London UKRTI Health Solutions Barcelona SpainDivision of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USASchool of Public Health, Southeast University Nanjing ChinaDepartment of Epidemiology Gillings School of Global Public Health, University of North Carolina at Chapel Hill Chapel Hill North Carolina USAABSTRACT Background Regulators and oncology healthcare providers are increasingly interested in using observational studies of real‐world data (RWD) to complement clinical evidence from randomized controlled trials for informed decision‐making. To generate valid evidence, RWD studies must be carefully designed to avoid systematic biases. The clone‐censor‐weight (CCW) method has been proposed to address immortal time and other time‐related biases. Methods The objective of this manuscript is to de‐mystify the CCW method for cancer researchers by describing and presenting its core components in an accessible and digestible format, using visualizations and examples from cancer‐relevant studies. The CCW method has been applied in diverse settings, including investigations of the effects of surgery within a certain time after cancer diagnosis, the continuation of annual screening mammography, and chemotherapy duration on survival. Results The method handles complex data wherein the treatment group to which an individual belongs is unknown at the start of follow‐up. The three steps of the CCW method involve cloning or duplicating the patient population and assigning one clone to each treatment strategy, artificially censoring the clones when their observed data are inconsistent with the assigned strategy and weighting the cloned and censored population to address selection bias created by the artificial censoring. Conclusions The CCW method is a powerful tool for designing RWD studies in cancer that are free from time‐related biases and successfully, to the extent possible, emulate features of a randomized clinical trial.https://doi.org/10.1002/cam4.70461cancer screeningcancer treatmentcausal inferenceobservational studytarget trial emulation
spellingShingle Charles E. Gaber
Armen A. Ghazarian
Paula D. Strassle
Tatiane B. Ribeiro
Maribel Salas
Camille Maringe
Xabier Garcia‐Albeniz
Richard Wyss
Wei Du
Jennifer L. Lund
De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
Cancer Medicine
cancer screening
cancer treatment
causal inference
observational study
target trial emulation
title De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
title_full De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
title_fullStr De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
title_full_unstemmed De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
title_short De‐Mystifying the Clone‐Censor‐Weight Method for Causal Research Using Observational Data: A Primer for Cancer Researchers
title_sort de mystifying the clone censor weight method for causal research using observational data a primer for cancer researchers
topic cancer screening
cancer treatment
causal inference
observational study
target trial emulation
url https://doi.org/10.1002/cam4.70461
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