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Vivek Charu

Publications and source records attributed to Vivek Charu.

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Learning Interpretable Point-Based Clinical Risk Scores via Direct Optimization

Many clinical risk scores are deployed as additive rules with nonnegative integer points assigned to relevant binary predictive features. These integer weights not only make the score easier to use in practice but also promote sparsity in the resulting prediction model. Such risk scores are often derived by first fitting a regression model and then rounding the estimated coefficients to the nearest integer after appropriate scaling. This approach is computationally fast but does not guarantee optimality of the resulting score. Alternatively, one may search over all possible integer weights to directly optimize a value function by posing the problem as an integer programming task. However, the associated computational burden can be substantial, especially when the value function is nonconcave or even discontinuous. In this paper, we develop new machine learning algorithms that employ a flexible greedy optimization strategy to learn such additive scoring directly under explicit and sensible optimality objectives. We apply the proposed method to a large electronic health record (EHR) cohort in Epic Cosmos to construct an integer-weighted comorbidity score for measuring the risk of post-discharge mortality. We also conduct a simulation study to examine the finite-sample operating characteristics.

stat.ME

Conditional Inference for Secondary Outcomes Based on the Testing Result for the Primary Outcome in Clinical Trials

In clinical trials, inferences on clinical outcomes are often made conditional on specific selective processes. For instance, only when a treatment demonstrates a significant effect on the primary outcome, further analysis is conducted to investigate its efficacy on selected secondary outcomes. Similarly, inferences may also depend on whether a trial is terminated early at interim stage. While conventional approaches primarily aim to control the family-wise error rate through multiplicity adjustments, they do not necessarily ensure the desired statistical property of the inference result, when the analysis is conducted according to a selective process. For example, the conditional coverage level of a regular confidence interval under a selective processes can be very different from its nominal level even after adjustment for multiple testing. In this paper, we argue that the validity of the inference procedure conditional on selective process is important in many applications. In addition, we propose to construct confidence intervals with correct conditional coverage probability by accounting for related selective process. Specifically, our approach involves a pivotal quantity constructed by inversing the cumulative distribution function of a truncated normal distribution induced by the selective process. Theoretical justification and comprehensive simulations illustrate the effectiveness of this method in realistic settings. We also apply our method to analyze data from the SPRINT, resulting in more conservative but conditionally valid confidence intervals for the average treatment effect than those originally published.

stat.ME

Bootstrapping the Cross-Validation Estimate

Cross-validation is a widely used technique for evaluating the performance of prediction models, ranging from simple binary classification to complex precision medicine strategies. It helps correct for optimism bias in error estimates, which can be significant for models built using complex statistical learning algorithms. However, since the cross-validation estimate is a random value dependent on observed data, it is essential to accurately quantify the uncertainty associated with the estimate. This is especially important when comparing the performance of two models using cross-validation, as one must determine whether differences in estimated error are due to chance. Although various methods have been developed to make inferences on cross-validation estimates, they often have many limitations, such as requiring stringent model assumptions. This paper proposes a fast bootstrap method that quickly estimates the standard error of the cross-validation estimate and produces valid confidence intervals for a population parameter measuring average model performance. Our method overcomes the computational challenges inherent in bootstrapping a cross-validation estimate by estimating the variance component within a random-effects model. It is also as flexible as the cross-validation procedure itself. To showcase the effectiveness of our approach, we conducted comprehensive simulations and real-data analysis across two applications.

stat.ME