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Abstract Investigating the causal relationship between exposure and time-to-event outcome is an important topic in biomedical research. Previous literature has discussed the potential issues of using hazard ratio (HR) as the marginal causal effect measure due to noncollapsibility. In this article, we advocate using restricted mean survival time (RMST) difference as a marginal causal effect measure, which is collapsible and has a simple interpretation as the difference of area under survival curves over a certain time horizon. To address both measured and unmeasured confounding, a matched design with sensitivity analysis is proposed. Matching is used to pair similar treated and untreated subjects together, which is generally more robust than outcome modeling due to potential misspecifications. Our propensity score matched RMST difference estimator is shown to be asymptotically unbiased, and the corresponding variance estimator is calculated by accounting for the correlation due to matching. Simulation studies also demonstrate that our method has adequate empirical performance and outperforms several competing methods used in practice. To assess the impact of unmeasured confounding, we develop a sensitivity analysis strategy by adapting the E -value approach to matched data. We apply the proposed method to the Atherosclerosis Risk in Communities Study (ARIC) to examine the causal effect of smoking on stroke-free survival. 

Abstract The Mekong River Basin (MRB) is undergoing unprecedented changes due to the recent acceleration in large-scale dam construction. While the hydrology of the MRB is well understood and the effects of some of the existing dams have been studied, the potential effects of the planned dams on flood pulse dynamics over the entire Lower Mekong remains unexamined. Here, using hydrodynamic model simulations, we show that the effects of flow regulation on downstream river-floodplain dynamics are relatively predictable along the mainstream Mekong, but flow regulations could potentially disrupt the flood dynamics in the Tonle Sap River (TSR) and small distributaries in the Mekong Delta. Results suggest that TSR flow reversal could cease if the Mekong flood pulse is dampened by 50% and delayed by one-month. While flood occurrence in the vicinity of the Tonle Sap Lake and middle reach of the delta could increase due to enhanced low flow, it could decrease by up to five months in other areas due to dampened high flow, particularly during dry years. Further, areas flooded for less than five months and over six months are likely to be impacted significantly by flow regulations, but those flooded for 5–6 months could be impacted the least.