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Finding an adequate dose of the drug by revealing the dose–response relationship is very crucial and a challenging problem in the clinical development. The main concerns in dose‐finding study are to identify a minimum effective dose (MED) in anesthesia studies and maximum tolerated dose (MTD) in oncology clinical trials. For the estimation of MED and MTD, we propose two modifications of Firth's logistic regression using reparametrization, called reparametrized Firth's logistic regression (rFLR) and ridge‐penalized reparametrized Firth's logistic regression (RrFLR). The proposed methods are designed by directly reducing the small‐sample bias of the maximum likelihood estimate for the parameter of interest. In addition, we develop a method on how to construct confidence intervals for rFLR and RrFLR using profile penalized likelihood. In the up‐and‐down biased‐coin design, numerical studies confirm the superior performance of the proposed methods in terms of the mean squared error, bias, and coverage accuracy of confidence intervals. [ABSTRACT FROM AUTHOR]

Structural trapping is the primary mechanism for intensive CO2 sequestration in saline aquifers. This is the foundation for increasing global CO2 storage; gradual switch to preferable trapping mechanisms, such as residual saturation, dissolution, and mineral trapping, will require a long-time scale. The major constraints limiting the storage capacity of structural trapping are formation pressure and structure size. Over-pressure owing to CO2 injection causes a disruption of seal integrity indicating a failure in geological sequestration. The other constraint on storage capacity is a spill point determining geological storage volume. Overflowing CO2, after filling the storage volume, migrates upward along the aquifer geometry with buoyancy. This study proposes a methodology to maximize CO2 storage capacity of a geological site with a substructure created by an interbedded calcareous layer below spill point. This study provides various conceptual schemes, i.e., no brine production, simultaneous brine production and pre-injection brine production, for geological CO2 storage. By the comparative analysis, location of brine producer, production rate, and distance between injector and producer are optimized. Therefore, the proposed scheme can enhance CO2 storage capacity by 68% beyond the pressure and migration limits by steering CO2 plume and managing formation pressure. [ABSTRACT FROM AUTHOR]