Article type
Abstract
Background: Handling time-varying exposure is a challenging issue for assessing treatment effect especially in observational studies. In presence of time-varying exposure, valid effect estimation involves well-defined objectives, rigorous design, and proper analysis. However, existing methodological studies often exclusively address analysis models without a holistic perspective. This study aimed to examine the current methods for dealing with time-varying treatments in observational studies and developed practical recommendations
Methods: We searched PubMed from 2000 to 2021 for methodological articles about time-varying treatments, and qualitatively summarized the current methods for handling time-varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts.
Results: Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time-varying treatments, and only a few discussed the overarching methodological process. Generally, there were three methodological components to handle time-varying treatments. These included the specification of treatment which may be categorized as three scenarios (i.e., time-independent treatment, static treatment regime, or dynamic treatment regime); definition of treatment status which could involve three approaches (i.e., intention-to-treat, per-protocol or as-treated approach); and selection of analytic methods. Based on the review results, a methodological workflow and a set of practical recommendations were proposed through 2 consensus meetings.
Conclusion: There is no consensus process of assessing treatment effect in observational studies with time-varying treatments. Previous efforts were dedicated to statistical methods development. Our study proposed a stepwise workflow with practical recommendations to assist the practice in this regard.
Methods: We searched PubMed from 2000 to 2021 for methodological articles about time-varying treatments, and qualitatively summarized the current methods for handling time-varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts.
Results: Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time-varying treatments, and only a few discussed the overarching methodological process. Generally, there were three methodological components to handle time-varying treatments. These included the specification of treatment which may be categorized as three scenarios (i.e., time-independent treatment, static treatment regime, or dynamic treatment regime); definition of treatment status which could involve three approaches (i.e., intention-to-treat, per-protocol or as-treated approach); and selection of analytic methods. Based on the review results, a methodological workflow and a set of practical recommendations were proposed through 2 consensus meetings.
Conclusion: There is no consensus process of assessing treatment effect in observational studies with time-varying treatments. Previous efforts were dedicated to statistical methods development. Our study proposed a stepwise workflow with practical recommendations to assist the practice in this regard.