An official website of the United States government
Summary Nonparametric covariate adjustment is considered for log-rank-type tests of the treatment effect with right-censored time-to-event data from clinical trials applying covariate-adaptive randomization. Our proposed covariate-adjusted log-rank test has a simple explicit formula and a guaranteed efficiency gain over the unadjusted test. We also show that our proposed test achieves universal applicability in the sense that the same formula of test can be universally applied to simple randomization and all commonly used covariate-adaptive randomization schemes such as the stratified permuted block and the Pocock–Simon minimization, which is not a property enjoyed by the unadjusted log-rank test. Our method is supported by novel asymptotic theory and empirical results for Type-I error and power of tests.
more »
« less
Covariate-adaptive randomization inference in matched designs
Abstract It is common to conduct causal inference in matched observational studies by proceeding as though treatment assignments within matched sets are assigned uniformly at random and using this distribution as the basis for inference. This approach ignores observed discrepancies in matched sets that may be consequential for the distribution of treatment, which are succinctly captured by within-set differences in the propensity score. We address this problem via covariate-adaptive randomization inference, which modifies the permutation probabilities to vary with estimated propensity score discrepancies and avoids requirements to exclude matched pairs or model an outcome variable. We show that the test achieves type I error control arbitrarily close to the nominal level when large samples are available for propensity score estimation. We characterize the large-sample behaviour of the new randomization test for a difference-in-means estimator of a constant additive effect. We also show that existing methods of sensitivity analysis generalize effectively to covariate-adaptive randomization inference. Finally, we evaluate the empirical value of combining matching and covariate-adaptive randomization procedures using simulations and analyses of genetic damage among welders and right-heart catheterization in surgical patients.
more »
« less
- Award ID(s):
- 2142146
- PAR ID:
- 10499631
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Journal of the Royal Statistical Society Series B: Statistical Methodology
- Volume:
- 86
- Issue:
- 5
- ISSN:
- 1369-7412
- Format(s):
- Medium: X Size: p. 1312-1338
- Size(s):
- p. 1312-1338
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
We propose a model-free framework for sensitivity analysis of individual treatment effects (ITEs), building upon ideas from conformal inference. For any unit, our procedure reports the Γ-value, a number which quantifies the minimum strength of confounding needed to explain away the evidence for ITE. Our approach rests on the reliable predictive inference of counterfactuals and ITEs in situations where the training data are confounded. Under the marginal sensitivity model of [Z. Tan, J. Am. Stat. Assoc. 101, 1619-1637 (2006)], we characterize the shift between the distribution of the observations and that of the counterfactuals. We first develop a general method for predictive inference of test samples from a shifted distribution; we then leverage this to construct covariate-dependent prediction sets for counterfactuals. No matter the value of the shift, these prediction sets (resp. approximately) achieve marginal coverage if the propensity score is known exactly (resp. estimated). We describe a distinct procedure also attaining coverage, however, conditional on the training data. In the latter case, we prove a sharpness result showing that for certain classes of prediction problems, the prediction intervals cannot possibly be tightened. We verify the validity and performance of the methods via simulation studies and apply them to analyze real datasets.more » « less
-
Abstract Randomization inference is a powerful tool in early phase vaccine trials when estimating the causal effect of a regimen against a placebo or another regimen. Randomization-based inference often focuses on testing either Fisher’s sharp null hypothesis of no treatment effect for any participant or Neyman’s weak null hypothesis of no sample average treatment effect. Many recent efforts have explored conducting exact randomization-based inference for other summaries of the treatment effect profile, for instance, quantiles of the treatment effect distribution function. In this article, we systematically review methods that conduct exact, randomization-based inference for quantiles of individual treatment effects (ITEs) and extend some results to a special case where naïve participants are expected not to exhibit responses to highly specific endpoints. These methods are suitable for completely randomized trials, stratified completely randomized trials, and a matched study comparing two non-randomized arms from possibly different trials. We evaluate the usefulness of these methods using synthetic data in simulation studies. Finally, we apply these methods to HIV Vaccine Trials Network Study 086 (HVTN 086) and HVTN 205 and showcase a wide range of application scenarios of the methods.Rcode that replicates all analyses in this article can be found in first author’s GitHub page athttps://github.com/Zhe-Chen-1999/ITE-Inference.more » « less
-
Summary In many observational studies, the treatment assignment mechanism is not individualistic, as it allows the probability of treatment of a unit to depend on quantities beyond the unit’s covariates. In such settings, unit treatments may be entangled in complex ways. In this article, we consider a particular instance of this problem where the treatments are entangled by a social network among units. For instance, when studying the effects of peer interaction on a social media platform, the treatment on a unit depends on the change of the interactions network over time. A similar situation is encountered in many economic studies, such as those examining the effects of bilateral trade partnerships on countries’ economic growth. The challenge in these settings is that individual treatments depend on a global network that may change in a way that is endogenous and cannot be manipulated experimentally. In this paper, we show that classical propensity score methods that ignore entanglement may lead to large bias and wrong inference of causal effects. We then propose a solution that involves calculating propensity scores by marginalizing over the network change. Under an appropriate ignorability assumption, this leads to unbiased estimates of the treatment effect of interest. We also develop a randomization-based inference procedure that takes entanglement into account. Under general conditions on network change, this procedure can deliver valid inference without explicitly modelling the network. We establish theoretical results for the proposed methods and illustrate their behaviour via simulation studies based on real-world network data. We also revisit a large-scale observational dataset on contagion of online user behaviour, showing that ignoring entanglement may inflate estimates of peer influence.more » « less
-
A common goal in observational research is to estimate marginal causal effects in the presence of confounding variables. One solution to this problem is to use the covariate distribution to weight the outcomes such that the data appear randomized. The propensity score is a natural quantity that arises in this setting. Propensity score weights have desirable asymptotic properties, but they often fail to adequately balance covariate data in finite samples. Empirical covariate balancing methods pose as an appealing alternative by exactly balancing the sample moments of the covariate distribution. With this objective in mind, we propose a framework for estimating balancing weights by solving a constrained convex program, where the criterion function to be optimized is a Bregman distance. We then show that the different distances in this class render identical weights to those of other covariate balancing methods. A series of numerical studies are presented to demonstrate these similarities.more » « less
