Pub Date : 2024-09-01Epub Date: 2024-06-11DOI: 10.1097/EDE.0000000000001762
Danielle M Crookes, Jacqueline M Torres
{"title":"Migration and Health: Chasing Causality in a Complex World.","authors":"Danielle M Crookes, Jacqueline M Torres","doi":"10.1097/EDE.0000000000001762","DOIUrl":"10.1097/EDE.0000000000001762","url":null,"abstract":"","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-14DOI: 10.1097/EDE.0000000000001768
Ian Shrier
{"title":"Natural effects with a recanting witness: non-identifiability or meaningless estimand?","authors":"Ian Shrier","doi":"10.1097/EDE.0000000000001768","DOIUrl":"10.1097/EDE.0000000000001768","url":null,"abstract":"","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1097/EDE.0000000000001765
Arin L Madenci, Katherine E Kurgansky, Barbra A Dickerman, Hanna Gerlovin, Kerollos Nashat Wanis, Ann D Smith, Ludovic Trinquart, David R Gagnon, Kelly Cho, J Michael Gaziano, Juan P Casas, James M Robins, Miguel A Hernán
Background: Observational studies have reported strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe an attempt to estimate the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data.
Methods: We propose two target trials among persons with diabetes: (1) bariatric operation (vs. no operation) among individuals who have undergone preoperative preparation (lifestyle modifications and screening) and (2) preoperative preparation and a bariatric operation (vs. neither preoperative nor operative component). We emulated both target trials using observational data of US veterans.
Results: Comparing bariatric surgery with no surgery (target trial #1; 8,087 individuals), the 7-year cardiovascular risk was 18.0% (95% CI = 6.9, 32.7) in the surgery group and 18.9% (95% CI = 17.7, 20.1) in the no-surgery group (risk difference -0.9, 95% CI = -12.0, 14.0). Comparing preoperative components plus surgery vs. neither (target trial #2; 10,065 individuals), the 7-year cardiovascular risk was 17.4% (95% CI = 13.6, 22.0) in the surgery group and 18.8% (95% CI = 17.8, 19.9) in the no-surgery group (risk difference -1.4, 95% CI = -5.1, 3.2). Body mass index and hemoglobin A1c were reduced with bariatric interventions in both emulations.
Conclusions: Within limitations of available observational data, our estimates do not provide evidence that bariatric surgery reduces cardiovascular disease and support equipoise for a randomized trial of bariatric surgery for cardiovascular disease prevention.
{"title":"Estimating the Effect of Bariatric Surgery on Cardiovascular Events Using Observational Data?","authors":"Arin L Madenci, Katherine E Kurgansky, Barbra A Dickerman, Hanna Gerlovin, Kerollos Nashat Wanis, Ann D Smith, Ludovic Trinquart, David R Gagnon, Kelly Cho, J Michael Gaziano, Juan P Casas, James M Robins, Miguel A Hernán","doi":"10.1097/EDE.0000000000001765","DOIUrl":"10.1097/EDE.0000000000001765","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have reported strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe an attempt to estimate the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data.</p><p><strong>Methods: </strong>We propose two target trials among persons with diabetes: (1) bariatric operation (vs. no operation) among individuals who have undergone preoperative preparation (lifestyle modifications and screening) and (2) preoperative preparation and a bariatric operation (vs. neither preoperative nor operative component). We emulated both target trials using observational data of US veterans.</p><p><strong>Results: </strong>Comparing bariatric surgery with no surgery (target trial #1; 8,087 individuals), the 7-year cardiovascular risk was 18.0% (95% CI = 6.9, 32.7) in the surgery group and 18.9% (95% CI = 17.7, 20.1) in the no-surgery group (risk difference -0.9, 95% CI = -12.0, 14.0). Comparing preoperative components plus surgery vs. neither (target trial #2; 10,065 individuals), the 7-year cardiovascular risk was 17.4% (95% CI = 13.6, 22.0) in the surgery group and 18.8% (95% CI = 17.8, 19.9) in the no-surgery group (risk difference -1.4, 95% CI = -5.1, 3.2). Body mass index and hemoglobin A1c were reduced with bariatric interventions in both emulations.</p><p><strong>Conclusions: </strong>Within limitations of available observational data, our estimates do not provide evidence that bariatric surgery reduces cardiovascular disease and support equipoise for a randomized trial of bariatric surgery for cardiovascular disease prevention.</p>","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-05DOI: 10.1097/EDE.0000000000001761
Katrina L Kezios, Scott C Zimmerman, Peter T Buto, Kara E Rudolph, Sebastian Calonico, Adina Zeki Al Hazzouri, M Maria Glymour
Life course epidemiology is hampered by the absence of large studies with exposures and outcomes measured at different life stages in the same individuals. We describe when the effect of an exposure ( A ) on an outcome ( Y ) in a target population is identifiable in a combined ("synthetic") cohort created by pooling an early-life cohort including measures of A with a late-life cohort including measures of Y . We enumerate causal assumptions needed for unbiased effect estimation in the synthetic cohort and illustrate by simulating target populations under four causal models. From each target population, we randomly sampled early- and late-life cohorts and created a synthetic cohort by matching individuals from the two cohorts based on mediators and confounders. We estimated the effect of A on Y in the synthetic cohort, varying matching variables, the match ratio, and the strength of association between matching variables and A . Finally, we compared bias in the synthetic cohort estimates when matching variables did not d-separate A and Y to the bias expected in the original cohort. When the set of matching variables includes all variables d-connecting exposure and outcome (i.e., variables blocking all backdoor and front-door pathways), the synthetic cohort yields unbiased effect estimates. Even when matching variables did not fully account for confounders, the synthetic cohort estimate was sometimes less biased than comparable estimates in the original cohort. Methods based on merging cohorts may hasten the evaluation of early- and mid-life determinants of late-life health but rely on available measures of both confounders and mediators.
生命历程流行病学因缺乏在同一个体的不同生命阶段测量暴露和结果的大型研究而受到阻碍。我们列举了在合成队列中进行无偏效应估计所需的因果假设,并通过模拟四种因果模型下的目标人群进行了说明。我们从每个目标人群中随机抽取早期和晚期人群,并根据中介因素和混杂因素对两个人群中的个体进行匹配,从而创建一个合成人群。我们通过改变匹配变量、匹配率以及匹配变量与 A 之间的关联强度,估计了合成队列中 A 对 Y 的影响。最后,我们比较了当匹配变量没有将 A 和 Y 区分开时,合成队列估计值的偏差与原始队列中的预期偏差。当匹配变量集包括所有将暴露和结果 d 连接起来的变量(即阻断所有后门和前门途径的变量)时,合成队列产生的效应估计值是无偏的。即使在匹配变量没有完全考虑混杂因素的情况下,合成队列估计值的偏差有时也小于原始队列的可比估计值。基于合并队列的方法可以加快对晚年健康的早期和中期决定因素的评估,但需要依赖对混杂因素和中介因素的可用测量。
{"title":"Overcoming Data Gaps in Life Course Epidemiology by Matching Across Cohorts.","authors":"Katrina L Kezios, Scott C Zimmerman, Peter T Buto, Kara E Rudolph, Sebastian Calonico, Adina Zeki Al Hazzouri, M Maria Glymour","doi":"10.1097/EDE.0000000000001761","DOIUrl":"10.1097/EDE.0000000000001761","url":null,"abstract":"<p><p>Life course epidemiology is hampered by the absence of large studies with exposures and outcomes measured at different life stages in the same individuals. We describe when the effect of an exposure ( A ) on an outcome ( Y ) in a target population is identifiable in a combined (\"synthetic\") cohort created by pooling an early-life cohort including measures of A with a late-life cohort including measures of Y . We enumerate causal assumptions needed for unbiased effect estimation in the synthetic cohort and illustrate by simulating target populations under four causal models. From each target population, we randomly sampled early- and late-life cohorts and created a synthetic cohort by matching individuals from the two cohorts based on mediators and confounders. We estimated the effect of A on Y in the synthetic cohort, varying matching variables, the match ratio, and the strength of association between matching variables and A . Finally, we compared bias in the synthetic cohort estimates when matching variables did not d-separate A and Y to the bias expected in the original cohort. When the set of matching variables includes all variables d-connecting exposure and outcome (i.e., variables blocking all backdoor and front-door pathways), the synthetic cohort yields unbiased effect estimates. Even when matching variables did not fully account for confounders, the synthetic cohort estimate was sometimes less biased than comparable estimates in the original cohort. Methods based on merging cohorts may hasten the evaluation of early- and mid-life determinants of late-life health but rely on available measures of both confounders and mediators.</p>","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-06DOI: 10.1097/EDE.0000000000001764
Katherine L Hoffman, Diego Salazar-Barreto, Nicholas T Williams, Kara E Rudolph, Iván Díaz
This tutorial discusses a methodology for causal inference using longitudinal modified treatment policies. This method facilitates the mathematical formalization, identification, and estimation of many novel parameters and mathematically generalizes many commonly used parameters, such as the average treatment effect. Longitudinal modified treatment policies apply to a wide variety of exposures, including binary, multivariate, and continuous, and can accommodate time-varying treatments and confounders, competing risks, loss to follow-up, as well as survival, binary, or continuous outcomes. Longitudinal modified treatment policies can be seen as an extension of static and dynamic interventions to involve the natural value of treatment and, like dynamic interventions, can be used to define alternative estimands with a positivity assumption that is more likely to be satisfied than estimands corresponding to static interventions. This tutorial aims to illustrate several practical uses of the longitudinal modified treatment policy methodology, including describing different estimation strategies and their corresponding advantages and disadvantages. We provide numerous examples of types of research questions that can be answered using longitudinal modified treatment policies. We go into more depth with one of these examples, specifically, estimating the effect of delaying intubation on critically ill COVID-19 patients' mortality. We demonstrate the use of the open-source R package lmtp to estimate the effects, and we provide code on https://github.com/kathoffman/lmtp-tutorial.
本教程讨论使用纵向修正治疗政策进行因果推断的方法。这种方法有助于对许多新参数进行数学形式化、识别和估计,并对许多常用参数(如平均治疗效果)进行数学概括。纵向修正治疗策略适用于各种暴露,包括二元、多元和连续暴露,并能适应时变治疗和混杂因素、竞争风险、随访损失以及生存、二元或连续结果。纵向修正治疗策略可被视为静态和动态干预的延伸,涉及治疗的自然价值,与动态干预一样,可用于定义替代估计值,其正向性假设比对应于静态干预的估计值更有可能得到满足。本教程旨在说明纵向修正治疗政策方法的几种实际用途,包括介绍不同的估算策略及其相应的优缺点。我们举例说明了可以使用纵向修正治疗策略回答的各类研究问题。我们对其中一个例子进行了深入探讨,特别是估计延迟插管对 COVID-19 重症患者死亡率的影响。我们演示了使用开源 R 软件包 lmtp 估算效果的方法,并在 https://github.com/kathoffman/lmtp-tutorial 上提供了代码。
{"title":"Studying Continuous, Time-varying, and/or Complex Exposures Using Longitudinal Modified Treatment Policies.","authors":"Katherine L Hoffman, Diego Salazar-Barreto, Nicholas T Williams, Kara E Rudolph, Iván Díaz","doi":"10.1097/EDE.0000000000001764","DOIUrl":"10.1097/EDE.0000000000001764","url":null,"abstract":"<p><p>This tutorial discusses a methodology for causal inference using longitudinal modified treatment policies. This method facilitates the mathematical formalization, identification, and estimation of many novel parameters and mathematically generalizes many commonly used parameters, such as the average treatment effect. Longitudinal modified treatment policies apply to a wide variety of exposures, including binary, multivariate, and continuous, and can accommodate time-varying treatments and confounders, competing risks, loss to follow-up, as well as survival, binary, or continuous outcomes. Longitudinal modified treatment policies can be seen as an extension of static and dynamic interventions to involve the natural value of treatment and, like dynamic interventions, can be used to define alternative estimands with a positivity assumption that is more likely to be satisfied than estimands corresponding to static interventions. This tutorial aims to illustrate several practical uses of the longitudinal modified treatment policy methodology, including describing different estimation strategies and their corresponding advantages and disadvantages. We provide numerous examples of types of research questions that can be answered using longitudinal modified treatment policies. We go into more depth with one of these examples, specifically, estimating the effect of delaying intubation on critically ill COVID-19 patients' mortality. We demonstrate the use of the open-source R package lmtp to estimate the effects, and we provide code on https://github.com/kathoffman/lmtp-tutorial.</p>","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-06DOI: 10.1097/EDE.0000000000001769
{"title":"Erratum: Prediction Under Interventions: Evaluation of Counterfactual Performance Using Longitudinal Observational Data.","authors":"","doi":"10.1097/EDE.0000000000001769","DOIUrl":"10.1097/EDE.0000000000001769","url":null,"abstract":"","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1097/EDE.0000000000001766
Michail Katsoulis, Clemence Leyrat, Aroon Hingorani, Manuel Gomes
{"title":"Bariatric Surgery and Cardiovascular Disease: The Target Trial Emulation Framework Provides Transparency in Articulating the Limits of Observational Studies.","authors":"Michail Katsoulis, Clemence Leyrat, Aroon Hingorani, Manuel Gomes","doi":"10.1097/EDE.0000000000001766","DOIUrl":"10.1097/EDE.0000000000001766","url":null,"abstract":"","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-27DOI: 10.1097/EDE.0000000000001767
Barbara N Harding, Silvia Agramunt, Marie Pedersen, Lisbeth E Knudsen, Jeanette K S Nielsen, John Wright, Marina Vafeiadi, Domenico F Merlo, Leslie Stayner, Kaitlin Kelly-Reif, Ana Espinosa, Mariona Bustamante, Kristine Bjerve Gützkow, Berit Granum, Hans von Stedingk, Per Rydberg, Jan Alexander, Margareta Törnqvist, Manolis Kogevinas
Background: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study.
Methods: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size.
Results: Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth.
Conclusion: Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size.
{"title":"Ethylene Oxide Hemoglobin Adducts in Cord Blood and Offspring's Size at Birth: The NewGeneris European Cohort Study.","authors":"Barbara N Harding, Silvia Agramunt, Marie Pedersen, Lisbeth E Knudsen, Jeanette K S Nielsen, John Wright, Marina Vafeiadi, Domenico F Merlo, Leslie Stayner, Kaitlin Kelly-Reif, Ana Espinosa, Mariona Bustamante, Kristine Bjerve Gützkow, Berit Granum, Hans von Stedingk, Per Rydberg, Jan Alexander, Margareta Törnqvist, Manolis Kogevinas","doi":"10.1097/EDE.0000000000001767","DOIUrl":"10.1097/EDE.0000000000001767","url":null,"abstract":"<p><strong>Background: </strong>Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study.</p><p><strong>Methods: </strong>This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size.</p><p><strong>Results: </strong>Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth.</p><p><strong>Conclusion: </strong>Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size.</p>","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-05DOI: 10.1097/EDE.0000000000001759
Kerollos Nashat Wanis, Aaron L Sarvet
{"title":"Placebo Adherence as a Negative Control Exposure.","authors":"Kerollos Nashat Wanis, Aaron L Sarvet","doi":"10.1097/EDE.0000000000001759","DOIUrl":"10.1097/EDE.0000000000001759","url":null,"abstract":"","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-06DOI: 10.1097/EDE.0000000000001753
Lindsay J Collin, Lance A Waller, Deirdre P Cronin-Fenton, Thomas P Ahern, Michael Goodman, Lauren E McCullough, Anders Kjærsgaard, Kirsten M Woolpert, Rebecca A Silliman, Peer M Christiansen, Bent Ejlertsen, Henrik Toft Sørensen, Timothy L Lash
Purpose: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design.
Methods: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007.
Results: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4).
Conclusions: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.
目的:乳腺癌的 10 年平均相对生存率高达 84%。这种良好的生存率部分归功于生物标志物指导疗法的引入。我们采用趋势中趋势药物流行病学研究设计,估算了两种辅助疗法--他莫昔芬和曲妥珠单抗的引入对人群复发的影响:我们确定了丹麦乳腺癌小组临床数据库中登记的非转移性乳腺癌女性患者的数据。我们采用趋势中趋势的设计方法,估算了(1)1982 年对绝经后雌激素受体(ER)阳性乳腺癌妇女使用他莫昔芬、(2)1999 年对绝经前诊断为 ER 阳性乳腺癌的妇女使用他莫昔芬以及(3)对妇女使用曲妥珠单抗的人群效应:在 1999 年确诊为 ER 阳性乳腺癌的绝经前妇女中引入他莫昔芬的人群效应中,复发风险降低了近一半(OR = 0.52),这与临床试验的证据一致;然而,该估计值并不精确(95% 置信区间 [CI] = 0.25,1.85)。我们观察到,自1982年他莫昔芬问世以来,使用他莫昔芬与复发之间的关系并不精确(OR = 1.24 95% CI = 0.46, 5.11),这与之前临床试验的结果不一致。至于 2007 年引入的曲妥珠单抗,尽管不精确(OR = 0.51; 95% CI = 0.21, 22.4),但估计值也与试验证据一致:我们展示了如何利用新型药物流行病学分析设计来评估基于人群的常规临床护理和治疗进展的有效性,同时也考虑了该方法的一些局限性。
{"title":"The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.","authors":"Lindsay J Collin, Lance A Waller, Deirdre P Cronin-Fenton, Thomas P Ahern, Michael Goodman, Lauren E McCullough, Anders Kjærsgaard, Kirsten M Woolpert, Rebecca A Silliman, Peer M Christiansen, Bent Ejlertsen, Henrik Toft Sørensen, Timothy L Lash","doi":"10.1097/EDE.0000000000001753","DOIUrl":"10.1097/EDE.0000000000001753","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design.</p><p><strong>Methods: </strong>We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007.</p><p><strong>Results: </strong>For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4).</p><p><strong>Conclusions: </strong>We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.</p>","PeriodicalId":11779,"journal":{"name":"Epidemiology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}