Many causal questions involve interactions between units, also known as interference, for example between individuals in households, students in schools, or firms in markets. In this paper, we formalize the concept of a conditioning mechanism, which provides a framework for constructing valid and powerful randomization tests under general forms of interference. We describe our framework in the context of two-stage randomized designs and apply our approach to a randomized evaluation of an intervention targeting student absenteeism in the School District of Philadelphia. We show improvements over existing methods in terms of computational and statistical power.
We develop finite-population asymptotic theory for covariate adjustment in randomization-based causal inference for 2K factorial designs. In particular, we confirm that both the unadjusted and covariate-adjusted estimators of the factorial effects are asymptotically normal, and the latter is more precise than the former.
We consider the conditional randomization test as a way to account for covariate imbalance in randomized experiments. The test accounts for covariate imbalance by comparing the observed test statistic to the null distribution of the test statistic conditional on the observed covariate imbalance. We prove that the conditional randomization test has the correct significance level and introduce original notation to describe covariate balance more formally. Through simulation, we verify that conditional randomization tests behave like more traditional forms of covariate adjustmet but have the adde…
Under the potential outcomes framework, we introduce matched-pair factorial designs, and propose the matched-pair estimator of the factorial effects. We also calculate the randomization-based covariance matrix of the matched-pair estimator, and provide the "Neymanian" estimator of the covariance matrix.
A benefit of randomized experiments is that covariate distributions of treatment and control groups are balanced on average, resulting in simple unbiased estimators for treatment effects. However, it is possible that a particular randomization yields covariate imbalances that researchers want to address in the analysis stage through adjustment or other methods. Here we present a randomization test that conditions on covariate balance by only considering treatment assignments that are similar to the observed one in terms of covariate balance. Previous conditional randomization tests have only a…
Interference exists when a unit's outcome depends on another unit's treatment assignment. For example, intensive policing on one street could have a spillover effect on neighboring streets. Classical randomization tests typically break down in this setting because many null hypotheses of interest are no longer sharp under interference. A promising alternative is to instead construct a conditional randomization test on a subset of units and assignments for which a given null hypothesis is sharp. Finding these subsets is challenging, however, and existing methods are limited to special cases or …
Split-plot designs find wide applicability in multifactor experiments with randomization restrictions. Practical considerations often warrant the use of unbalanced designs. This paper investigates randomization based causal inference in split-plot designs that are possibly unbalanced. Extension of ideas from the recently studied balanced case yields an expression for the sampling variance of a treatment contrast estimator as well as a conservative estimator of the sampling variance. However, the bias of this variance estimator does not vanish even when the treatment effects are strictly additi…
Mendelian randomization implemented through instrumental variable analysis is frequently discussed in causality and recently the number of applications on real data is increasing. However, there are very few discussions to address modern biomedical questions such as the integration of large scale omics in causality. While in the age of large omics, we face several hundred or thousands of components with little knowledge about the underlying structures, the focus of the field is on small scales and mostly with known structures. The availability of large omic data accentuates the need for techni…
In medical research, a scenario often entertained is randomized controlled $2^2$ factorial design with a binary outcome. By utilizing the concept of potential outcomes, Dasgupta et al. (2015) proposed a randomization-based causal inference framework, allowing flexible and simultaneous estimations and inferences of the factorial effects. However, a fundamental challenge that Dasgupta et al. (2015)'s proposed methodology faces is that the sampling variance of the randomization-based factorial effect estimator is unidentifiable, rendering the corresponding classic "Neymanian" variance estimator s…
The results from Genome-Wide Association Studies (GWAS) on thousands of phenotypes provide an unprecedented opportunity to infer the causal effect of one phenotype (exposure) on another (outcome). Mendelian randomization (MR), an instrumental variable (IV) method, has been introduced for causal inference using GWAS data. Due to the polygenic architecture of complex traits/diseases and the ubiquity of pleiotropy, however, MR has many unique challenges compared to conventional IV methods. We propose a Bayesian weighted Mendelian randomization (BWMR) for causal inference to address these challeng…
Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a causal effect of the exposure on the outcome. Complications arise with a binary exposure that is a dichotomization of a continuous risk factor (for example, hypertension is a dichotomization of blood pressure). This can lead to violation of the exclusion restriction assumption: the genetic variant can influence the outcome via the continuous risk factor even if…
Based on the physical randomization of completely randomized experiments, Rigdon and Hudgens (2015) propose two approaches to obtaining exact confidence intervals for the average causal effect on a binary outcome. They construct the first confidence interval by combining, with the Bonferroni adjustment, the prediction sets for treatment effects among treatment and control groups, and the second one by inverting a series of randomization tests. With sample size $n$, their second approach requires performing $O(n^4)$ randomization tests. We demonstrate that the physical randomization also justif…
Given two 2-level factors of interest, a 2^2 split-plot design} (a) takes each of the $2^2=4$ possible factorial combinations as a treatment, (b) identifies one factor as `whole-plot,' (c) divides the experimental units into blocks, and (d) assigns the treatments in such a way that all units within the same block receive the same level of the whole-plot factor. Assuming the potential outcomes framework, we propose in this paper a randomization-based estimation procedure for causal inference from 2^2 designs that are not necessarily balanced. Sampling variances of the point estimates are derive…
Estimating the causal effect of an exposure on an outcome is an important task in many economical and biological studies. Mendelian randomization, in particular, uses genetic variants as instruments to estimate causal effects in epidemiological studies. However, conventional instrumental variable methods rely on some untestable assumptions, which may be violated in real problems. In this paper, we adopt a Bayesian framework and build hierarchical models to incorporate invalid effects of instruments. We introduce an empirical Bayes estimator for which some of the instruments are invalid by util…
We extend the randomization-based causal inference framework in Dasgupta et al. (2015) for general 2^K factorial designs, and demonstrate the equivalence between regression-based and randomization-based inferences. Consequently, we justify the use of regression-based methods in 2^K factorial designs from a finite-population perspective.
Instrumental variables have been widely used for estimating the causal effect between exposure and outcome. Conventional estimation methods require complete knowledge about all the instruments' validity; a valid instrument must not have a direct effect on the outcome and not be related to unmeasured confounders. Often, this is impractical as highlighted by Mendelian randomization studies where genetic markers are used as instruments and complete knowledge about instruments' validity is equivalent to complete knowledge about the involved genes' functions. In this paper, we propose a method for …
Standard Mendelian randomization analysis can produce biased results if the genetic variant defining the instrumental variable (IV) is confounded and/or has a horizontal pleiotropic effect on the outcome of interest not mediated by the treatment. We provide novel identification conditions for the causal effect of a treatment in presence of unmeasured confounding, by leveraging an invalid IV for which both the IV independence and exclusion restriction assumptions may be violated. The proposed Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification (MR MiSTERI) approach relies…
We study user sentiment (reported via optional surveys) as a metric for fully randomized A/B tests. Both user-level covariates and treatment assignment can impact response propensity. We propose a set of consistent estimators for the average and local treatment effects on treated and respondent users. We show that our problem can be mapped onto the intersection of the missing data problem and observational causal inference, and we identify conditions under which consistent estimators exist. We evaluate the performance of estimators via simulation studies and find that more complicated models d…
Methods have been developed for Mendelian randomization that can obtain consistent causal estimates while relaxing the instrumental variable assumptions. These include multivariable Mendelian randomization, in which a genetic variant may be associated with multiple risk factors so long as any association with the outcome is via the measured risk factors (measured pleiotropy), and the MR-Egger (Mendelian randomization-Egger) method, in which a genetic variant may be directly associated with the outcome not via the risk factor of interest, so long as the direct effects of the variants on the out…
For binary experimental data, we discuss randomization-based inferential procedures that do not need to invoke any modeling assumptions. We also introduce methods for likelihood and Bayesian inference based solely on the physical randomization without any hypothetical super population assumptions about the potential outcomes. These estimators have some properties superior to moment-based ones such as only giving estimates in regions of feasible support. Due to the lack of identification of the causal model, we also propose a sensitivity analysis approach which allows for the characterization o…
Mendelian randomization is the use of genetic variants to make causal inferences from observational data. The field is currently undergoing a revolution fuelled by increasing numbers of genetic variants demonstrated to be associated with exposures in genome-wide association studies, and the public availability of summarized data on genetic associations with exposures and outcomes from large consortia. A Mendelian randomization analysis with many genetic variants can be performed relatively simply using summarized data. However, a causal interpretation is only assured if each genetic variant sa…
Valid estimation of a causal effect using instrumental variables requires that all of the instruments are independent of the outcome conditional on the risk factor of interest and any confounders. In Mendelian randomization studies with large numbers of genetic variants used as instruments, it is unlikely that this condition will be met. Any given genetic variant could be associated with a large number of traits, all of which represent potential pathways to the outcome which bypass the risk factor of interest. Such pleiotropy can be accounted for using standard multivariable Mendelian randomiz…
Regression discontinuity designs (RDDs) are a common quasi-experiment in economics and statistics. The most popular methodologies for analyzing RDDs utilize continuity-based assumptions and local polynomial regression, but recent works have developed alternative assumptions based on local randomization. The local randomization framework avoids modeling assumptions by instead placing assumptions on the assignment mechanism near the cutoff. However, most works have focused on completely randomized assignment mechanisms, which posit that propensity scores are equal for all units near the cutoff. …
Towards more plausible point-identifying assumptions in two-sample Mendelian randomization
Federal University of Pelotas（佩洛塔斯联邦大学）；University of Bristol（布里斯托大学）；University College London（伦敦大学学院）；Norwegian University of Science and Technology（挪威科技大学）
Mendelian randomization is the use of genetic variants as instrumental variables to assess whether a risk factor is a cause of a disease outcome. Increasingly, Mendelian randomization investigations are conducted on the basis of summarized data, rather than individual-level data. These summarized data comprise the coefficients and standard errors from univariate regression models of the risk factor on each genetic variant, and of the outcome on each genetic variant. A causal estimate can be derived from these associations for each individual genetic variant, and a combined estimate can be obta…
In finite population causal inference exact randomization tests can be constructed for sharp null hypotheses, i.e. hypotheses which fully impute the missing potential outcomes. Oftentimes inference is instead desired for the weak null that the sample average of the treatment effects takes on a particular value while leaving the subject-specific treatment effects unspecified. Without proper care, tests valid for sharp null hypotheses may be anti-conservative should only the weak null hold, creating the risk of misinterpretation when randomization tests are deployed in practice. We develop a gen…
The method of instrumental variables (IV) provides a framework to study causal effects in both randomized experiments with noncompliance and in observational studies where natural circumstances produce as-if random nudges to accept treatment. Traditionally, inference for IV relied on asymptotic approximations of the distribution of the Wald estimator or two-stage least squares, often with structural modeling assumptions and/or moment conditions. In this paper, we utilize the randomization inference approach to IV inference. First, we outline the exact method, which uses the randomized assignme…
In comparative studies, such as in causal inference and clinical trials, balancing important covariates is often one of the most important concerns for both efficient and credible comparison. However, chance imbalance still exists in many randomized experiments. This phenomenon of covariate imbalance becomes much more serious as the number of covariates $p$ increases. To address this issue, we introduce a new randomization procedure, called pairwise sequential randomization (PSR). The proposed method allocates the units sequentially and adaptively, using information on the current level of imb…
Randomization inference for stepped-wedge designs with noncompliance with application to a palliative care pragmatic trial
University of Chicago（芝加哥大学）；Data Science Institute, University of Chicago（芝加哥大学数据科学研究所）；University of Pennsylvania（宾夕法尼亚大学）；Department of Medicine, University of Pennsylvania（宾夕法尼亚大学医学系）；Department of Mathematics and Statistics, Mississippi State University（密西西比州立大学数学与统计系）；Department of Statistics and Data Science, University of Pennsylvania（宾夕法尼亚大学统计与数据科学系）；Yale School of Public Health（耶鲁公共卫生学院）
A common assumption in causal inference is that random treatment assignment ensures that potential outcomes are independent of treatment, or in one word, unconfoundedness. This paper highlights that randomization and unconfoundedness are separate properties, and neither implies the other. A study with random treatment assignment does not have to be unconfounded, and a study with deterministic assignment can still be unconfounded. A corollary is that a propensity score is not the same thing as a treatment assignment probability. These facts should not be taken as arguments against randomization…
Mendelian randomization (MR) is a popular instrumental variable (IV) approach, in which one or several genetic markers serve as IVs that can sometimes be leveraged to recover valid inferences about a given exposure-outcome causal association subject to unmeasured confounding. A key IV identification condition known as the exclusion restriction states that the IV cannot have a direct effect on the outcome which is not mediated by the exposure in view. In MR studies, such an assumption requires an unrealistic level of prior knowledge about the mechanism by which genetic markers causally affect t…
Under the potential outcomes framework, causal effects are defined as comparisons between potential outcomes under treatment and control. To infer causal effects from randomized experiments, Neyman proposed to test the null hypothesis of zero average causal effect (Neyman's null), and Fisher proposed to test the null hypothesis of zero individual causal effect (Fisher's null). Although the subtle difference between Neyman's null and Fisher's null has caused lots of controversies and confusions for both theoretical and practical statisticians, a careful comparison between the two approaches has…
In non-network settings, encouragement designs have been widely used to analyze causal effects of a treatment, policy, or intervention on an outcome of interest when randomizing the treatment was considered impractical or when compliance to treatment cannot be perfectly enforced. Unfortunately, such questions related to treatment compliance have received less attention in network settings and the most well-studied experimental design in networks, the two-stage randomization design, requires perfect compliance with treatment. The paper proposes a new experimental design called peer encouragemen…
Causal analyses for observational studies are often complicated by covariate imbalances among treatment groups, and matching methodologies alleviate this complication by finding subsets of treatment groups that exhibit covariate balance. It is widely agreed upon that covariate balance can serve as evidence that a matched dataset approximates a randomized experiment, but what kind of experiment does a matched dataset approximate? In this work, we develop a randomization test for the hypothesis that a matched dataset approximates a particular experimental design, such as complete randomization, …
