Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals
Abstract Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of...
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Veröffentlicht in: | American journal of epidemiology 2023-08, Vol.192 (8), p.1415-1423 |
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creator | Rojas-Saunero, L Paloma Young, Jessica G Didelez, Vanessa Ikram, M Arfan Swanson, Sonja A |
description | Abstract
Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of a causal effect on dementia risk: the “controlled direct effect” and the “total effect.” We provide definitions and discuss the “censoring” assumptions needed for identification in either case and their link to familiar statistical methods. We illustrate concepts in a hypothetical randomized trial on smoking cessation in late midlife, and emulate such a trial using observational data from the Rotterdam Study, the Netherlands, 1990–2015. We estimated a total effect of smoking cessation (compared with continued smoking) on 20-year dementia risk of 2.1 (95% confidence interval: −0.1, 4.2) percentage points and a controlled direct effect of smoking cessation on 20-year dementia risk had death been prevented of −2.7 (95% confidence interval: −6.1, 0.8) percentage points. Our study highlights how analyses corresponding to different causal questions can have different results, here with point estimates on opposite sides of the null. Having a clear causal question in view of the competing event and transparent and explicit assumptions are essential to interpreting results and potential bias. |
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Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of a causal effect on dementia risk: the “controlled direct effect” and the “total effect.” We provide definitions and discuss the “censoring” assumptions needed for identification in either case and their link to familiar statistical methods. We illustrate concepts in a hypothetical randomized trial on smoking cessation in late midlife, and emulate such a trial using observational data from the Rotterdam Study, the Netherlands, 1990–2015. We estimated a total effect of smoking cessation (compared with continued smoking) on 20-year dementia risk of 2.1 (95% confidence interval: −0.1, 4.2) percentage points and a controlled direct effect of smoking cessation on 20-year dementia risk had death been prevented of −2.7 (95% confidence interval: −6.1, 0.8) percentage points. Our study highlights how analyses corresponding to different causal questions can have different results, here with point estimates on opposite sides of the null. Having a clear causal question in view of the competing event and transparent and explicit assumptions are essential to interpreting results and potential bias.</description><identifier>ISSN: 0002-9262</identifier><identifier>EISSN: 1476-6256</identifier><identifier>DOI: 10.1093/aje/kwad090</identifier><identifier>PMID: 37139580</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Bias ; Causality ; Cigarette smoking ; Confidence intervals ; Death ; Dementia ; Dementia - epidemiology ; Dementia disorders ; Drug addiction ; Goals ; Humans ; Mortality ; Practice of Epidemiology ; Questions ; Risk management ; Smoking ; Smoking - adverse effects ; Smoking - epidemiology ; Smoking cessation ; Smoking Cessation - methods ; Statistical analysis ; Statistical methods</subject><ispartof>American journal of epidemiology, 2023-08, Vol.192 (8), p.1415-1423</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-93935cc20be2ff8a3831d86757d2bf59b56244e252b8062e56e09133141c71e23</citedby><cites>FETCH-LOGICAL-c441t-93935cc20be2ff8a3831d86757d2bf59b56244e252b8062e56e09133141c71e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37139580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rojas-Saunero, L Paloma</creatorcontrib><creatorcontrib>Young, Jessica G</creatorcontrib><creatorcontrib>Didelez, Vanessa</creatorcontrib><creatorcontrib>Ikram, M Arfan</creatorcontrib><creatorcontrib>Swanson, Sonja A</creatorcontrib><title>Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals</title><title>American journal of epidemiology</title><addtitle>Am J Epidemiol</addtitle><description>Abstract
Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of a causal effect on dementia risk: the “controlled direct effect” and the “total effect.” We provide definitions and discuss the “censoring” assumptions needed for identification in either case and their link to familiar statistical methods. We illustrate concepts in a hypothetical randomized trial on smoking cessation in late midlife, and emulate such a trial using observational data from the Rotterdam Study, the Netherlands, 1990–2015. We estimated a total effect of smoking cessation (compared with continued smoking) on 20-year dementia risk of 2.1 (95% confidence interval: −0.1, 4.2) percentage points and a controlled direct effect of smoking cessation on 20-year dementia risk had death been prevented of −2.7 (95% confidence interval: −6.1, 0.8) percentage points. Our study highlights how analyses corresponding to different causal questions can have different results, here with point estimates on opposite sides of the null. Having a clear causal question in view of the competing event and transparent and explicit assumptions are essential to interpreting results and potential bias.</description><subject>Bias</subject><subject>Causality</subject><subject>Cigarette smoking</subject><subject>Confidence intervals</subject><subject>Death</subject><subject>Dementia</subject><subject>Dementia - epidemiology</subject><subject>Dementia disorders</subject><subject>Drug addiction</subject><subject>Goals</subject><subject>Humans</subject><subject>Mortality</subject><subject>Practice of Epidemiology</subject><subject>Questions</subject><subject>Risk management</subject><subject>Smoking</subject><subject>Smoking - adverse effects</subject><subject>Smoking - epidemiology</subject><subject>Smoking cessation</subject><subject>Smoking Cessation - methods</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><issn>0002-9262</issn><issn>1476-6256</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc2L1EAQxRtR3HH05F0aBBEkbvVn0qdF47oKK6IoHttOUtnpMUmP3cmK_709zLioB08FVb961KtHyEMGzxkYceq2ePrth-vAwC2yYrLUheZK3yYrAOCF4ZqfkHspbQEYMwrukhNRMmFUBSvytQ5T8h1GP13RDwum2ecGfYl9iEjf4bwJXaJ-oq9wxGn2jn7EhC62G_rFzxtah3GH8375_DrPE3VTR2u3JDfQi-CGdJ_c6XPBB8e6Jp9fn3-q3xSX7y_e1i8ui1ZKNhdGGKHalkODvO8rJyrBukqXqux40yvTKM2lRK54U4HmqDSCYUIwydqSIRdrcnbQ3S3NiF2bj4lusLvoRxd_2uC8_Xsy-Y29CteWgQQhQGeFp0eFGL7vP2FHn1ocBjdhWJLlFRglucj4mjz-B92GJU7ZnxUgTea4LjP17EC1MaQUsb-5hoHdR2dzdPYYXaYf_Wnghv2dVQaeHICw7P6r9Au9CKIG</recordid><startdate>20230804</startdate><enddate>20230804</enddate><creator>Rojas-Saunero, L Paloma</creator><creator>Young, Jessica G</creator><creator>Didelez, Vanessa</creator><creator>Ikram, M Arfan</creator><creator>Swanson, Sonja A</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230804</creationdate><title>Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals</title><author>Rojas-Saunero, L Paloma ; Young, Jessica G ; Didelez, Vanessa ; Ikram, M Arfan ; Swanson, Sonja A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-93935cc20be2ff8a3831d86757d2bf59b56244e252b8062e56e09133141c71e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Bias</topic><topic>Causality</topic><topic>Cigarette smoking</topic><topic>Confidence intervals</topic><topic>Death</topic><topic>Dementia</topic><topic>Dementia - epidemiology</topic><topic>Dementia disorders</topic><topic>Drug addiction</topic><topic>Goals</topic><topic>Humans</topic><topic>Mortality</topic><topic>Practice of Epidemiology</topic><topic>Questions</topic><topic>Risk management</topic><topic>Smoking</topic><topic>Smoking - adverse effects</topic><topic>Smoking - epidemiology</topic><topic>Smoking cessation</topic><topic>Smoking Cessation - methods</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rojas-Saunero, L Paloma</creatorcontrib><creatorcontrib>Young, Jessica G</creatorcontrib><creatorcontrib>Didelez, Vanessa</creatorcontrib><creatorcontrib>Ikram, M Arfan</creatorcontrib><creatorcontrib>Swanson, Sonja A</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of epidemiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rojas-Saunero, L Paloma</au><au>Young, Jessica G</au><au>Didelez, Vanessa</au><au>Ikram, M Arfan</au><au>Swanson, Sonja A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals</atitle><jtitle>American journal of epidemiology</jtitle><addtitle>Am J Epidemiol</addtitle><date>2023-08-04</date><risdate>2023</risdate><volume>192</volume><issue>8</issue><spage>1415</spage><epage>1423</epage><pages>1415-1423</pages><issn>0002-9262</issn><eissn>1476-6256</eissn><abstract>Abstract
Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of a causal effect on dementia risk: the “controlled direct effect” and the “total effect.” We provide definitions and discuss the “censoring” assumptions needed for identification in either case and their link to familiar statistical methods. We illustrate concepts in a hypothetical randomized trial on smoking cessation in late midlife, and emulate such a trial using observational data from the Rotterdam Study, the Netherlands, 1990–2015. We estimated a total effect of smoking cessation (compared with continued smoking) on 20-year dementia risk of 2.1 (95% confidence interval: −0.1, 4.2) percentage points and a controlled direct effect of smoking cessation on 20-year dementia risk had death been prevented of −2.7 (95% confidence interval: −6.1, 0.8) percentage points. Our study highlights how analyses corresponding to different causal questions can have different results, here with point estimates on opposite sides of the null. Having a clear causal question in view of the competing event and transparent and explicit assumptions are essential to interpreting results and potential bias.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>37139580</pmid><doi>10.1093/aje/kwad090</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Bias Causality Cigarette smoking Confidence intervals Death Dementia Dementia - epidemiology Dementia disorders Drug addiction Goals Humans Mortality Practice of Epidemiology Questions Risk management Smoking Smoking - adverse effects Smoking - epidemiology Smoking cessation Smoking Cessation - methods Statistical analysis Statistical methods |
title | Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals |
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