@article{lee_gao_ghosh_yang_2024, title={Transporting survival of an HIV clinical trial to the external target populations}, volume={3}, ISSN={["1520-5711"]}, DOI={10.1080/10543406.2024.2330216}, abstractNote={Due to the heterogeneity of the randomized controlled trial (RCT) and external target populations, the estimated treatment effect from the RCT is not directly applicable to the target population. For example, the patient characteristics of the ACTG 175 HIV trial are significantly different from that of the three external target populations of interest: US early-stage HIV patients, Thailand HIV patients, and southern Ethiopia HIV patients. This paper considers several methods to transport the treatment effect from the ACTG 175 HIV trial to the target populations beyond the trial population. Most transport methods focus on continuous and binary outcomes; on the contrary, we derive and discuss several transport methods for survival outcomes: an outcome regression method based on a Cox proportional hazard (PH) model, an inverse probability weighting method based on the models for treatment assignment, sampling score, and censoring, and a doubly robust method that combines both methods, called the augmented calibration weighting (ACW) method. However, as the PH assumption was found to be incorrect for the ACTG 175 trial, the methods that depend on the PH assumption may lead to the biased quantification of the treatment effect. To account for the violation of the PH assumption, we extend the ACW method with the linear spline-based hazard regression model that does not require the PH assumption. Applying the aforementioned methods for transportability, we explore the effect of PH assumption, or the violation thereof, on transporting the survival results from the ACTG 175 trial to various external populations.}, journal={JOURNAL OF BIOPHARMACEUTICAL STATISTICS}, author={Lee, Dasom and Gao, Chenyin and Ghosh, Sujit and Yang, Shu}, year={2024}, month={Mar} }
 @article{lee_ghosh_2023, title={Bayesian Analysis of First-Order Markov Models for Autocorrelated Binary Responses}, volume={17}, ISSN={["1559-8616"]}, DOI={10.1007/s42519-022-00305-4}, abstractNote={In many clinical trials, patient outcomes are often binary-valued which are measured asynchronously over time across various dose levels. To account for autocorrelation among such longitudinally observed outcomes, a first-order Markov model for binary data is developed. Moreover, to account for the asynchronously observed time points, nonhomogeneous models for the transition probabilities are proposed. The transition probabilities are modeled using B-spline basis functions after suitable transformations. Additionally, if the underlying dose-response curve is assumed to be non-decreasing, our model allows for the estimation of any underlying non-decreasing curve based on suitably constructed prior distributions. We also extended our model to the mixed effect model to incorporate individual-specific random effects. Numerical comparisons with traditional models are provided based on simulated data sets, and also practical applications are illustrated using real data sets.}, number={1}, journal={JOURNAL OF STATISTICAL THEORY AND PRACTICE}, author={Lee, Dasom and Ghosh, Sujit}, year={2023}, month={Mar} }
 @article{lee_yang_wang_2022, title={Doubly robust estimators for generalizing treatment effects on survival outcomes from randomized controlled trials to a target population}, volume={10}, ISSN={["2193-3685"]}, DOI={10.1515/jci-2022-0004}, abstractNote={Abstract
               In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population and considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root-
                     
                        
                        
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                   consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer.}, number={1}, journal={JOURNAL OF CAUSAL INFERENCE}, author={Lee, Dasom and Yang, Shu and Wang, Xiaofei}, year={2022}, month={Dec}, pages={415–440} }
 @article{balasubramanian_safdar_sketch_broderick_nelsen_lee_melendres-groves_2022, title={Real-world dosing characteristics and utilization of parenteral treprostinil in the outpatient setting}, volume={12}, ISSN={["2045-8940"]}, DOI={10.1002/pul2.12016}, abstractNote={AbstractReal‐world dosing and titration of parenteral (subcutaneous, SC; intravenous, IV) prostacyclin, a mainstay of pulmonary arterial hypertension (PAH) treatment, is not always consistent with prescribing information or randomized trials and has yet to be adequately characterized. The current study describes real‐world outpatient dosing and titration patterns over time, in PAH patients initiated on SC or IV treprostinil. A longitudinal, cross‐sectional analysis of medication shipment records from US specialty pharmacy services between 2009 and 2018 was conducted to determine dosing and titration patterns of SC or IV treprostinil in the outpatient setting beginning with the patient's first shipment. The sample for analysis included shipment records for 2647 patients (IV = 1040, SC = 1607). Although more patients were started on SC treprostinil than IV, median initial outpatient IV treprostinil dose (11 ng/kg/min at month on therapy one [MOT1]) was consistently and statistically significantly higher than initial outpatient SC dose (7.5 ng/kg/min at MOT1; p < 0.01). However, the SC treprostinil dose acceleration rate (DAR) was more aggressive from MOT1 to MOT6, MOT12, and MOT24, leading to a higher dose achieved at later timepoints. All between‐group DAR differences were statistically significant (p < 0.001). This study provides evidence that real‐world prescribing patterns of parenteral treprostinil in the outpatient setting differs from dosing described in pivotal trials, with important differences between SC and IV administration. Although initial outpatient IV treprostinil dosing was higher, SC titration was accelerated more aggressively and a higher dose was achieved by MOT3 suggesting that factors specific to SC administration (e.g., site pain) may not limit dosing and titration as previously thought.}, number={1}, journal={PULMONARY CIRCULATION}, author={Balasubramanian, Vijay P. and Safdar, Zeenat and Sketch, Margaret R. and Broderick, Meredith and Nelsen, Andrew C. and Lee, Dasom and Melendres-Groves, Lana}, year={2022}, month={Jan} }
 @article{lee_yang_dong_wang_zeng_cai_2022, title={Improving trial generalizability using observational studies}, volume={1}, ISSN={["1541-0420"]}, DOI={10.1111/biom.13609}, abstractNote={Abstract
               Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces the covariate balance between the RCT and OS, therefore improving the trial-based estimator's generalizability. Exploiting semiparametric efficiency theory, we propose a doubly robust augmented calibration weighting estimator that achieves the efficiency bound derived under the identification assumptions. A nonparametric sieve method is provided as an alternative to the parametric approach, which enables the robust approximation of the nuisance functions and data-adaptive selection of outcome predictors for calibration. We establish asymptotic results and confirm the finite sample performances of the proposed estimators by simulation experiments and an application on the estimation of the treatment effect of adjuvant chemotherapy for early-stage non-small-cell lung patients after surgery.}, journal={BIOMETRICS}, author={Lee, Dasom and Yang, Shu and Dong, Lin and Wang, Xiaofei and Zeng, Donglin and Cai, Jianwen}, year={2022}, month={Jan} }
 @article{shapiro_mandras_restrepo-jaramillo_shen_broderick_rao_lee_nelsen_2021, title={Survival and drug persistence in patients receiving inhaled treprostinil at doses greater than 54 mu g (nine breaths) four times daily}, volume={11}, ISSN={["2045-8940"]}, DOI={10.1177/20458940211052228}, abstractNote={Treprostinil is a prostacyclin approved for the treatment of pulmonary arterial hypertension. Commercial data sets indicate that approximately 20–25% of patients are prescribed a higher dose than the maximum recommended dosage of nine breaths per treatment session (bps) (54 μg), four times a day (QID) and numerous studies have demonstrated the safety of doses >9 bps QID. This phase 4, retrospective analysis of specialty pharmacy records assessed the effects of inhaled treprostinil at doses >9 bps QID. Patients receiving inhaled treprostinil between September 2009 and June 2018 were included, and a random sampling of 5000 patients was selected for further analysis. Subjects were grouped based on the highest dose reached for ≥2 months within a rolling six‐month window and were followed for up to three years. Of the total of 5000 patients analyzed, 28.5% received >9 bps QID. Survival rates were significantly higher in the >9 bps QID dosing group for years one, two, and three (P < 0.001). The time to transition to parenteral therapy was significantly longer for those at doses >9 bps (17.5 months) compared to doses ≤9 bps (9.5 moths; P < 0.0001). Drug persistence was also significantly higher for those taking >9 bps at years 1, 2, and 3 (P < 0.0001). Patients receiving inhaled treprostinil at doses >9 bps QID had a higher rate of survival and drug persistence over a three‐year period, suggesting that higher doses may provide clinically relevant benefits while remaining tolerable.}, number={4}, journal={PULMONARY CIRCULATION}, author={Shapiro, Shelley and Mandras, Stacy and Restrepo-Jaramillo, Ricardo and Shen, Eric and Broderick, Meredith and Rao, Youlan and Lee, Dasom and Nelsen, Andrew C.}, year={2021}, month={Oct} }
 @article{lee_lee_jo_choi_2020, title={Bayesian ordinal probit semiparametric regression models: KNHANES 2016 data analysis of the relationship between smoking behavior and coffee intake}, volume={33}, ISSN={["2383-5818"]}, DOI={10.5351/KJAS.2020.33.1.025}, number={1}, journal={KOREAN JOURNAL OF APPLIED STATISTICS}, author={Lee, Dasom and Lee, Eunji and Jo, Seogil and Choi, Taeryeon}, year={2020}, month={Feb}, pages={25–46} }