{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:52:23Z","timestamp":1782971543491,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022B1515020094"],"award-info":[{"award-number":["2022B1515020094"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["72074229"],"award-info":[{"award-number":["72074229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2024,11,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hypothetical strategy is a common strategy for handling intercurrent events (IEs). No current guideline or study considers treatment\u2013IE interaction to target the estimand in any one IE\u2010handling strategy. Based on the hypothetical strategy, we aimed to (1) assess the performance of three estimators with different considerations for the treatment\u2013IE interaction in a simulation and (2) compare the estimation of these estimators in a real trial. Simulation data were generalized based on realistic clinical trials of Alzheimer's disease. The estimand of interest was the effect of treatment with no IE occurring under the hypothetical strategy. Three estimators, namely, G\u2010estimation with and without interaction and IE\u2010ignored estimation, were compared in scenarios where the treatment\u2013IE interaction effect was set as \u221250% to 50% of the main effect. Bias was the key performance measure. The real case was derived from a randomized trial of methadone maintenance treatment. Only G\u2010estimation with interaction exhibited unbiased estimations regardless of the existence, direction or magnitude of the treatment\u2013IE interaction in those scenarios. Neglecting the interaction and ignoring the IE would introduce a bias as large as 0.093 and 0.241 (true value, \u22121.561) if the interaction effect existed. In the real case, compared with G\u2010estimation with interaction, G\u2010estimation without interaction and IE\u2010ignored estimation increased the estimand of interest by 33.55% and 34.36%, respectively. This study highlights the importance of considering treatment\u2013IE interaction in the estimand framework. In practice, it would be better to include the interaction in the estimator by default.<\/jats:p>","DOI":"10.1002\/sim.10212","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T23:26:26Z","timestamp":1725578786000},"page":"4850-4860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Causal Mediation Approach to Account for Interaction of Treatment and Intercurrent Events: Using Hypothetical Strategy"],"prefix":"10.1002","volume":"43","author":[{"given":"Kunpeng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Statistics, School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"Center for Migrant Health Policy Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-9699","authenticated-orcid":false,"given":"Xiangliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"Center for Migrant Health Policy Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"Center for Migrant Health Policy Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"Center for Migrant Health Policy Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-8890","authenticated-orcid":false,"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"Center for Migrant Health Policy Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use \u201cAddendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials \u201d(2019)."},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-070146","article-title":"Evaluating How Clear the Questions Being Investigated in Randomised Trials Are: Systematic Review of Estimands","volume":"378","author":"Cro S.","year":"2022","journal-title":"BMJ"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2022.2081599"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1705"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.329.7456.15"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004265367"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007312153"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13145"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17709-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr077003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000664"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biodatasci-092820-114757"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-020-04546-1"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-021-00297-6"},{"key":"e_1_2_10_16_1","volume-title":"Explanation in Causal Inference: Methods for Mediation and Interaction","author":"VanderWeele T. 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