Alison Antoine , David Pérol , Mathieu Robain , Thomas Bachelot , Rémy Choquet , William Jacot , Béchir Ben Hadj Yahia , Thomas Grinda , Suzette Delaloge , Christine Lasset , Youenn Drouet
{"title":"利用靶向试验模拟评估 8 种主要转移性乳腺癌药物的实际疗效。","authors":"Alison Antoine , David Pérol , Mathieu Robain , Thomas Bachelot , Rémy Choquet , William Jacot , Béchir Ben Hadj Yahia , Thomas Grinda , Suzette Delaloge , Christine Lasset , Youenn Drouet","doi":"10.1016/j.ejca.2024.115072","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.</div></div><div><h3>Methods</h3><div>To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected <em>a priori</em> for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.</div></div><div><h3>Results</h3><div>The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.</div></div><div><h3>Conclusion</h3><div>Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation\",\"authors\":\"Alison Antoine , David Pérol , Mathieu Robain , Thomas Bachelot , Rémy Choquet , William Jacot , Béchir Ben Hadj Yahia , Thomas Grinda , Suzette Delaloge , Christine Lasset , Youenn Drouet\",\"doi\":\"10.1016/j.ejca.2024.115072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.</div></div><div><h3>Methods</h3><div>To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected <em>a priori</em> for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.</div></div><div><h3>Results</h3><div>The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.</div></div><div><h3>Conclusion</h3><div>Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.</div></div>\",\"PeriodicalId\":11980,\"journal\":{\"name\":\"European Journal of Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0959804924012036\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924012036","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation
Background
Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.
Methods
To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected a priori for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.
Results
The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.
Conclusion
Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.
期刊介绍:
The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.