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  1. Many recent developments in causal inference, and functional estimation problems more generally, have been motivated by the fact that classical one-step (first-order) debiasing methods, or their more recent sample-split double machine-learning avatars, can outperform plugin estimators under surprisingly weak conditions. These first-order corrections improve on plugin estimators in a black-box fashion, and consequently are often used in conjunction with powerful off-the-shelf estimation methods. These first-order methods are however provably suboptimal in a minimax sense for functional estimation when the nuisance functions live in Holder-type function spaces. This suboptimality of first-order debiasing has motivated the development of "higher-order" debiasing methods. The resulting estimators are, in some cases, provably optimal over Holder-type spaces, but both the estimators which are minimax-optimal and their analyses are crucially tied to properties of the underlying function space. In this paper we investigate the fundamental limits of structure-agnostic functional estimation, where relatively weak conditions are placed on the underlying nuisance functions. We show that there is a strong sense in which existing first-order methods are optimal. We achieve this goal by providing a formalization of the problem of functional estimation with black-box nuisance function estimates, and deriving minimax lower bounds for this problem. Our results highlight somemore »clear tradeoffs in functional estimation -- if we wish to remain agnostic to the underlying nuisance function spaces, impose only high-level rate conditions, and maintain compatibility with black-box nuisance estimators then first-order methods are optimal. When we have an understanding of the structure of the underlying nuisance functions then carefully constructed higher-order estimators can outperform first-order estimators.« less
    Free, publicly-accessible full text available January 1, 2024
  2. We introduce a new notion of regularity of an estimator called median regularity. We prove that uniformly valid (honest) inference for a functional is possible if and only if there exists a median regular estimator of that functional. To our knowledge, such a notion of regularity that is necessary for uniformly valid inference is unavailable in the literature.
    Free, publicly-accessible full text available January 1, 2024
  3. Causal effects are often characterized with averages, which can give an incomplete picture of the underlying counterfactual distributions. Here we consider estimating the entire counterfactual density and generic functionals thereof. We focus on two kinds of target parameters. The first is a density approximation, defined by a projection onto a finite-dimensional model using a generalized distance metric, which includes f-divergences as well as Lp norms. The second is the distance between counterfactual densities, which can be used as a more nuanced effect measure than the mean difference, and as a tool for model selection. We study nonparametric efficiency bounds for these targets, giving results for smooth but otherwise generic models and distances. Importantly, we show how these bounds connect to means of particular non-trivial functions of counterfactuals, linking the problems of density and mean estimation. We go on to propose doubly robust-style estimators for the density approximations and distances, and study their rates of convergence, showing they can be optimally efficient in large nonparametric models. We also give analogous methods for model selection and aggregation, when many models may be available and of interest. Our results all hold for generic models and distances, but throughout we highlight what happens formore »particular choices, such as L2 projections on linear models, and KL projections on exponential families. Finally we illustrate by estimating the density of CD4 count among patients with HIV, had all been treated with combination therapy versus zidovudine alone, as well as a density effect. Our results suggest combination therapy may have increased CD4 count most for high-risk patients. Our methods are implemented in the freely available R package npcausal on GitHub.« less
    Free, publicly-accessible full text available January 1, 2024
  4. Scholkopf, Bernhard ; Uhler, Caroline ; Zhang, Kun (Ed.)
    In order to test if a treatment is perceptibly different from a placebo in a randomized experiment with covariates, classical nonparametric tests based on ranks of observations/residuals have been employed (eg: by Rosenbaum), with finite-sample valid inference enabled via permutations. This paper proposes a different principle on which to base inference: if — with access to all covariates and outcomes, but without access to any treatment assignments — one can form a ranking of the subjects that is sufficiently nonrandom (eg: mostly treated followed by mostly control), then we can confidently conclude that there must be a treatment effect. Based on a more nuanced, quantifiable, version of this principle, we design an interactive test called i-bet: the analyst forms a single permutation of the subjects one element at a time, and at each step the analyst bets toy money on whether that subject was actually treated or not, and learns the truth immediately after. The wealth process forms a real-valued measure of evidence against the global causal null, and we may reject the null at level if the wealth ever crosses 1= . Apart from providing a fresh “game-theoretic” principle on which to base the causal conclusion, the i-bet has othermore »statistical and computational benefits, for example (A) allowing a human to adaptively design the test statistic based on increasing amounts of data being revealed (along with any working causal models and prior knowledge), and (B) not requiring permutation resampling, instead noting that under the null, the wealth forms a nonnegative martingale, and the type-1 error control of the aforementioned decision rule follows from a tight inequality by Ville. Further, if the null is not rejected, new subjects can later be added and the test can be simply continued, without any corrections (unlike with permutation p-values). Numerical experiments demonstrate good power under various heterogeneous treatment effects. We first describe i-bet test for two-sample comparisons with unpaired data, and then adapt it to paired data, multi-sample comparison, and sequential settings; these may be viewed as interactive martingale variants of the Wilcoxon, Kruskal-Wallis, and Friedman tests.« less
  5. We propose a method for multiple hypothesis testing with familywise error rate (FWER) control, called the i-FWER test. Most testing methods are predefined algorithms that do not allow modifications after observing the data. However, in practice, analysts tend to choose a promising algorithm after observing the data; unfortunately, this violates the validity of the conclusion. The i-FWER test allows much flexibility: a human (or a computer program acting on the human’s behalf) may adaptively guide the algorithm in a data-dependent manner. We prove that our test controls FWER if the analysts adhere to a particular protocol of masking and unmasking. We demonstrate via numerical experiments the power of our test under structured non-nulls, and then explore new forms of masking.