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Articles 1 - 7 of 7
Full-Text Articles in Statistics and Probability
Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu
Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu
Johns Hopkins University, Dept. of Biostatistics Working Papers
In group sequential designs, adjusting for baseline variables and short-term outcomes can lead to increased power and reduced sample size. We derive formulas for the precision gain from such variable adjustment using semiparametric estimators for the average treatment effect, and give new results on what conditions lead to substantial power gains and sample size reductions. The formulas reveal how the impact of prognostic variables on the precision gain is modified by the number of pipeline participants, analysis timing, enrollment rate, and treatment effect heterogeneity, when the semiparametric estimator uses correctly specified models. Given set prognostic value of baseline variables and …
Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum
Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the …
Using Sensitivity Analyses For Unobserved Confounding To Address Covariate Measurement Error In Propensity Score Methods, Kara E. Rudolph, Elizabeth A. Stuart
Using Sensitivity Analyses For Unobserved Confounding To Address Covariate Measurement Error In Propensity Score Methods, Kara E. Rudolph, Elizabeth A. Stuart
Johns Hopkins University, Dept. of Biostatistics Working Papers
Propensity score methods are a popular tool to control for confounding in observational data, but their bias-reduction properties are threatened by covariate measurement error. There are few easy-to-implement methods to correct for such bias. We describe and demonstrate how existing sensitivity analyses for unobserved confounding---propensity score calibration, Vanderweele and Arah's bias formulas, and Rosenbaum's sensitivity analysis---can be adapted to address this problem. In a simulation study, we examined the extent to which these sensitivity analyses can correct for several measurement error structures: classical, systematic differential, and heteroscedastic covariate measurement error. We then apply these approaches to address covariate measurement error …
Censoring Unbiased Regression Trees And Ensembles, Jon Arni Steingrimsson, Liqun Diao, Robert L. Strawderman
Censoring Unbiased Regression Trees And Ensembles, Jon Arni Steingrimsson, Liqun Diao, Robert L. Strawderman
Johns Hopkins University, Dept. of Biostatistics Working Papers
This paper proposes a novel approach to building regression trees and ensemble learning in survival analysis. By first extending the theory of censoring unbiased transformations, we construct observed data estimators of full data loss functions in cases where responses can be right censored. This theory is used to construct two specific classes of methods for building regression trees and regression ensembles that respectively make use of Buckley-James and doubly robust estimating equations for a given full data risk function. For the particular case of squared error loss, we further show how to implement these algorithms using existing software (e.g., CART, …
Matching The Efficiency Gains Of The Logistic Regression Estimator While Avoiding Its Interpretability Problems, In Randomized Trials, Michael Rosenblum, Jon Arni Steingrimsson
Matching The Efficiency Gains Of The Logistic Regression Estimator While Avoiding Its Interpretability Problems, In Randomized Trials, Michael Rosenblum, Jon Arni Steingrimsson
Johns Hopkins University, Dept. of Biostatistics Working Papers
Adjusting for prognostic baseline variables can lead to improved power in randomized trials. For binary outcomes, a logistic regression estimator is commonly used for such adjustment. This has resulted in substantial efficiency gains in practice, e.g., gains equivalent to reducing the required sample size by 20-28% were observed in a recent survey of traumatic brain injury trials. Robinson and Jewell (1991) proved that the logistic regression estimator is guaranteed to have equal or better asymptotic efficiency compared to the unadjusted estimator (which ignores baseline variables). Unfortunately, the logistic regression estimator has the following dangerous vulnerabilities: it is only interpretable when …
Improving Precision By Adjusting For Baseline Variables In Randomized Trials With Binary Outcomes, Without Regression Model Assumptions, Jon Arni Steingrimsson, Daniel F. Hanley, Michael Rosenblum
Improving Precision By Adjusting For Baseline Variables In Randomized Trials With Binary Outcomes, Without Regression Model Assumptions, Jon Arni Steingrimsson, Daniel F. Hanley, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
In randomized clinical trials with baseline variables that are prognostic for the primary outcome, there is potential to improve precision and reduce sample size by appropriately adjusting for these variables. A major challenge is that there are multiple statistical methods to adjust for baseline variables, but little guidance on which is best to use in a given context. The choice of method can have important consequences. For example, one commonly used method leads to uninterpretable estimates if there is any treatment effect heterogeneity, which would jeopardize the validity of trial conclusions. We give practical guidance on how to avoid this …
Sensitivity Of Trial Performance To Delay Outcomes, Accrual Rates, And Prognostic Variables Based On A Simulated Randomized Trial With Adaptive Enrichment, Tiachen Qian, Elizabeth Colantuoni, Aaron Fisher, Michael Rosenblum
Sensitivity Of Trial Performance To Delay Outcomes, Accrual Rates, And Prognostic Variables Based On A Simulated Randomized Trial With Adaptive Enrichment, Tiachen Qian, Elizabeth Colantuoni, Aaron Fisher, Michael Rosenblum
Johns Hopkins University, Dept. of Biostatistics Working Papers
Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator, and investigate its strengths and limitations compared to standard estimators. Through simulation studies, we assess how sensitive the trial performance (Type I error, power, expected sample size, trial duration) is to different design characteristics. Our simulation distributions mimic features of data from the Alzheimer’s Disease Neuroimaging Initiative, and involve …