Harsh Parikh

Harsh Parikh, Kentaro Hoffman, Haoqi Sun et al.

Epileptiform activity (EA) is associated with worse outcomes including increased risk of disability and death. However, the effect of EA on the neurologic outcome is confounded by the feedback between treatment with anti-seizure medications (ASM) and EA burden. A randomized clinical trial is challenging due to the sequential nature of EA-ASM feedback, as well as ethical reasons. However, some mechanistic knowledge is available, e.g., how drugs are absorbed. This knowledge together with observational data could provide a more accurate effect estimate using causal inference. We performed a retrospective cross-sectional study with 995 patients with the modified Rankin Scale (mRS) at discharge as the outcome and the EA burden defined as the mean or maximum proportion of time spent with EA in six-hour windows in the first 24 hours of electroencephalography as the exposure. We estimated the change in discharge mRS if everyone in the dataset had experienced a certain EA burden and were untreated. We combined pharmacological modeling with an interpretable matching method to account for confounding and EA-ASM feedback. Our matched groups' quality was validated by the neurologists. Having a maximum EA burden greater than 75% when untreated had a 22% increased chance of a poor outcome (severe disability or death), and mild but long-lasting EA increased the risk of a poor outcome by 14%. The effect sizes were heterogeneous depending on pre-admission profile, e.g., patients with hypoxic-ischemic encephalopathy (HIE) or acquired brain injury (ABI) were more affected. Interventions should put a higher priority on patients with an average EA burden higher than 10%, while treatment should be more conservative when the maximum EA burden is low.

Quinn Lanners, Harsh Parikh, Alexander Volfovsky et al.

Our goal is to produce methods for observational causal inference that are auditable, easy to troubleshoot, accurate for treatment effect estimation, and scalable to high-dimensional data. We describe a general framework called Model-to-Match that achieves these goals by (i) learning a distance metric via outcome modeling, (ii) creating matched groups using the distance metric, and (iii) using the matched groups to estimate treatment effects. Model-to-Match uses variable importance measurements to construct a distance metric, making it a flexible framework that can be adapted to various applications. Concentrating on the scalability of the problem in the number of potential confounders, we operationalize the Model-to-Match framework with LASSO. We derive performance guarantees for settings where LASSO outcome modeling consistently identifies all confounders (importantly without requiring the linear model to be correctly specified). We also provide experimental results demonstrating the method's auditability, accuracy, and scalability as well as extensions to more general nonparametric outcome modeling.

Harsh Parikh, Quinn Lanners, Zade Akras et al.

Recent statistical and reinforcement learning methods have significantly advanced patient care strategies. However, these approaches face substantial challenges in high-stakes contexts, including missing data, inherent stochasticity, and the critical requirements for interpretability and patient safety. Our work operationalizes a safe and interpretable framework to identify optimal treatment regimes. This approach involves matching patients with similar medical and pharmacological characteristics, allowing us to construct an optimal policy via interpolation. We perform a comprehensive simulation study to demonstrate the framework's ability to identify optimal policies even in complex settings. Ultimately, we operationalize our approach to study regimes for treating seizures in critically ill patients. Our findings strongly support personalized treatment strategies based on a patient's medical history and pharmacological features. Notably, we identify that reducing medication doses for patients with mild and brief seizure episodes while adopting aggressive treatment for patients in intensive care unit experiencing intense seizures leads to more favorable outcomes.

Harsh Parikh, Marco Morucci, Vittorio Orlandi et al.

Experimental and observational studies often lack validity due to untestable assumptions. We propose a double machine learning approach to combine experimental and observational studies, allowing practitioners to test for assumption violations and estimate treatment effects consistently. Our framework proposes a falsification test for external validity and ignorability under milder assumptions. We provide consistent treatment effect estimators even when one of the assumptions is violated. However, our no-free-lunch theorem highlights the necessity of accurately identifying the violated assumption for consistent treatment effect estimation. Through comparative analyses, we show our framework's superiority over existing data fusion methods. The practical utility of our approach is further exemplified by three real-world case studies, underscoring its potential for widespread application in empirical research.

Harsh Parikh, Gabriel Levin-Konigsberg, Dominique Perrault-Joncas et al.

Suppose a planner has a pre-trained simulator of a sequential decision problem and the option to run real experiments in the field. The simulator is cheap to query but inherits confounding and drift from its calibration data. Experimentation is unbiased but consumes one real unit per trial. We study when, and how, the planner should supplement the simulator with experiments. We give three results. First, an extended simulation lemma decomposes the simulator's value error into a calibration--deployment shift that randomization can identify and a parametric residual that no further interaction can reduce. Second, the value gap between the simulator-optimal policy and the optimum splits into a local component, on states the deployed policy already visits, and a reachability component, on states it does not. The reachability component stays bounded away from zero at any horizon under purely passive learning. Third, we propose Fisher-SEP, a simulation-aided experimental policy (SEP) that minimizes the posterior predictive variance of a target policy's value, with reward-only and transition-only specializations. Two case studies illustrate the regimes. In a vending-machine supply chain, front-loaded experimentation overtakes posterior updating once the horizon is long enough to amortize the pilot. In an HIV mobile-testing example with a corridor that separates a well-surveilled region from a poorly-surveilled one, only designed exploration reaches the poorly-surveilled region.

Harsh Parikh

In this short note, I outline conditions under which conditioning on Synthetic Control (SC) weights emulates a randomized control trial where the treatment status is independent of potential outcomes. Specifically, I demonstrate that if there exist SC weights such that (i) the treatment effects are exactly identified and (ii) these weights are uniformly and cumulatively bounded, then SC weights are balancing scores.

Yilin Song, Dan M. Kluger, Harsh Parikh et al.

Machine learning predictions are increasingly used to supplement incomplete or costly-to-measure outcomes in fields such as biomedical research, environmental science, and social science. However, treating predictions as ground truth introduces bias while ignoring them wastes valuable information. Prediction-Powered Inference (PPI) offers a principled framework that leverages predictions from large unlabeled datasets to improve statistical efficiency while maintaining valid inference through explicit bias correction using a smaller labeled subset. Despite its potential, the growing PPI variants and the subtle distinctions between them have made it challenging for practitioners to determine when and how to apply these methods responsibly. This paper demystifies PPI by synthesizing its theoretical foundations, methodological extensions, connections to existing statistics literature, and diagnostic tools into a unified practical workflow. Using the Mosaiks housing price data, we show that PPI variants produce tighter confidence intervals than complete-case analysis, but that double-dipping, i.e. reusing training data for inference, leads to anti-conservative confidence intervals and coverages. Under missing-not-at-random mechanisms, all methods, including classical inference using only labeled data, yield biased estimates. We provide a decision flowchart linking assumption violations to appropriate PPI variants, a summary table of selective methods, and practical diagnostic strategies for evaluating core assumptions. By framing PPI as a general recipe rather than a single estimator, this work bridges methodological innovation and applied practice, helping researchers responsibly integrate predictions into valid inference.

Qi Zhang, Harsh Parikh, Ashley Naimi et al.

Method validation and study design in causal inference rely on synthetic data with known counterfactuals. Existing simulators trade off distributional realism, the ability to capture mixed-type and multimodal tabular data, against causal controllability, including explicit control over overlap, unmeasured confounding, and treatment effect heterogeneity. We introduce CausalMix, a variational generative framework that closes this gap by coupling a mixture of Gaussian latent priors with data-type-specific decoders for continuous, binary, and categorical variables. The model incorporates explicit causal controls: an overlap regularizer shaping propensity-score distributions, alongside direct parameterizations of confounding strength and effect heterogeneity. This unified objective preserves fidelity to the observed data while enabling factorial manipulation of causal mechanisms, allowing overlap, confounding strength, and treatment effect heterogeneity to be varied independently at design time. Across benchmarks, CausalMix achieves state-of-the-art distributional metrics on mixed-type tables while providing stable, fine-grained causal control. We demonstrate practical utility in a comparative safety study of metastatic castration-resistant prostate cancer treatments, using CausalMix to compare estimators under calibrated data-generating processes, tune hyperparameters, and conduct simulation-based power analyses under targeted treatment effect heterogeneity scenarios.

Seyedeh Baharan Khatami, Harsh Parikh, Haowei Chen et al.

We address the challenge of inferring causal effects in social network data. This results in challenges due to interference -- where a unit's outcome is affected by neighbors' treatments -- and network-induced confounding factors. While there is extensive literature focusing on estimating causal effects in social network setups, a majority of them make prior assumptions about the form of network-induced confounding mechanisms. Such strong assumptions are rarely likely to hold especially in high-dimensional networks. We propose a novel methodology that combines graph machine learning approaches with the double machine learning framework to enable accurate and efficient estimation of direct and peer effects using a single observational social network. We demonstrate the semiparametric efficiency of our proposed estimator under mild regularity conditions, allowing for consistent uncertainty quantification. We demonstrate that our method is accurate, robust, and scalable via an extensive simulation study. We use our method to investigate the impact of Self-Help Group participation on financial risk tolerance.

Melody Y Huang, Harsh Parikh

Randomized Controlled Trials (RCTs) are pivotal in generating internally valid estimates with minimal assumptions, serving as a cornerstone for researchers dedicated to advancing causal inference methods. However, extending these findings beyond the experimental cohort to achieve externally valid estimates is crucial for broader scientific inquiry. This paper delves into the forefront of addressing these external validity challenges, encapsulating the essence of a multidisciplinary workshop held at the Institute for Computational and Experimental Research in Mathematics (ICERM), Brown University, in Fall 2023. The workshop congregated experts from diverse fields including social science, medicine, public health, statistics, computer science, and education, to tackle the unique obstacles each discipline faces in extrapolating experimental findings. Our study presents three key contributions: we integrate ongoing efforts, highlighting methodological synergies across fields; provide an exhaustive review of generalizability and transportability based on the workshop's discourse; and identify persistent hurdles while suggesting avenues for future research. By doing so, this paper aims to enhance the collective understanding of the generalizability and transportability of causal effects, fostering cross-disciplinary collaboration and offering valuable insights for researchers working on refining and applying causal inference methods.

Srikar Katta, Harsh Parikh, Cynthia Rudin et al.

Many modern causal questions ask how treatments affect complex outcomes that are measured using wearable devices and sensors. Current analysis approaches require summarizing these data into scalar statistics (e.g., the mean), but these summaries can be misleading. For example, disparate distributions can have the same means, variances, and other statistics. Researchers can overcome the loss of information by instead representing the data as distributions. We develop an interpretable method for distributional data analysis that ensures trustworthy and robust decision-making: Analyzing Distributional Data via Matching After Learning to Stretch (ADD MALTS). We (i) provide analytical guarantees of the correctness of our estimation strategy, (ii) demonstrate via simulation that ADD MALTS outperforms other distributional data analysis methods at estimating treatment effects, and (iii) illustrate ADD MALTS' ability to verify whether there is enough cohesion between treatment and control units within subpopulations to trustworthily estimate treatment effects. We demonstrate ADD MALTS' utility by studying the effectiveness of continuous glucose monitors in mitigating diabetes risks.

Quinn Lanners, Cynthia Rudin, Alexander Volfovsky et al.

Data fusion techniques integrate information from heterogeneous data sources to improve learning, generalization, and decision making across data sciences. In causal inference, these methods leverage rich observational data to improve causal effect estimation, while maintaining the trustworthiness of randomized controlled trials. Existing approaches often relax the strong no unobserved confounding assumption by instead assuming exchangeability of counterfactual outcomes across data sources. However, when both assumptions simultaneously fail - a common scenario in practice - current methods cannot identify or estimate causal effects. We address this limitation by proposing a novel partial identification framework that enables researchers to answer key questions such as: Is the causal effect positive or negative? and How severe must assumption violations be to overturn this conclusion? Our approach introduces interpretable sensitivity parameters that quantify assumption violations and derives corresponding causal effect bounds. We develop doubly robust estimators for these bounds and operationalize breakdown frontier analysis to understand how causal conclusions change as assumption violations increase. We apply our framework to the Project STAR study, which investigates the effect of classroom size on students' third-grade standardized test performance. Our analysis reveals that the Project STAR results are robust to simultaneous violations of key assumptions, both on average and across various subgroups of interest. This strengthens confidence in the study's conclusions despite potential unmeasured biases in the data.

Harsh Parikh, Gabriel Levin-Konigsberg, Dominique Perrault-Joncas et al.

Treatment effects estimated from randomized controlled trials are local not only to the study population but also to the time at which the trial was conducted. We develop a framework for temporal transportation: extrapolating treatment effects to time periods where no experiment was conducted. We target the transported average treatment effect (TATE) and show that under a separable temporal effects assumption, the TATE decomposes into an observed average treatment effect and a temporal ratio. We provide two identification strategies -- one using replicated trials comparing the same treatments at different times, another using common treatment arms observed across time -- and develop doubly robust, semiparametrically efficient estimators for each. Monte Carlo simulations confirm that both estimators achieve nominal coverage, with the common arm strategy yielding substantial efficiency gains when its stronger assumptions hold. We apply our methods to A/B tests from the Upworthy Research Archive, demonstrating that the two strategies exhibit a variance-bias tradeoff: the common arm approach offers greater precision but may incur bias when treatments interact heterogeneously with temporal factors.

David Arbour, Harsh Parikh, Bijan Niknam et al.

Many common estimators in machine learning and causal inference are linear smoothers, where the prediction is a weighted average of the training outcomes. Some estimators, such as ordinary least squares and kernel ridge regression, allow for arbitrarily negative weights, which improve feature imbalance but often at the cost of increased dependence on parametric modeling assumptions and higher variance. By contrast, estimators like importance weighting and random forests (sometimes implicitly) restrict weights to be non-negative, reducing dependence on parametric modeling and variance at the cost of worse imbalance. In this paper, we propose a unified framework that directly penalizes the level of extrapolation, replacing the current practice of a hard non-negativity constraint with a soft constraint and corresponding hyperparameter. We derive a worst-case extrapolation error bound and introduce a novel "bias-bias-variance" tradeoff, encompassing biases due to feature imbalance, model misspecification, and estimator variance; this tradeoff is especially pronounced in high dimensions, particularly when positivity is poor. We then develop an optimization procedure that regularizes this bound while minimizing imbalance and outline how to use this approach as a sensitivity analysis for dependence on parametric modeling assumptions. We demonstrate the effectiveness of our approach through synthetic experiments and a real-world application, involving the generalization of randomized controlled trial estimates to a target population of interest.

Harsh Parikh, Rachael Ross, Elizabeth Stuart et al.

Randomized controlled trials (RCTs) serve as the cornerstone for understanding causal effects, yet extending inferences to target populations presents challenges due to effect heterogeneity and underrepresentation. Our paper addresses the critical issue of identifying and characterizing underrepresented subgroups in RCTs, proposing a novel framework for refining target populations to improve generalizability. We introduce an optimization-based approach, Rashomon Set of Optimal Trees (ROOT), to characterize underrepresented groups. ROOT optimizes the target subpopulation distribution by minimizing the variance of the target average treatment effect estimate, ensuring more precise treatment effect estimations. Notably, ROOT generates interpretable characteristics of the underrepresented population, aiding researchers in effective communication. Our approach demonstrates improved precision and interpretability compared to alternatives, as illustrated with synthetic data experiments. We apply our methodology to extend inferences from the Starting Treatment with Agonist Replacement Therapies (START) trial -- investigating the effectiveness of medication for opioid use disorder -- to the real-world population represented by the Treatment Episode Dataset: Admissions (TEDS-A). By refining target populations using ROOT, our framework offers a systematic approach to enhance decision-making accuracy and inform future trials in diverse populations.

Harsh Parikh, Carlos Varjao, Louise Xu et al.

The fundamental challenge of drawing causal inference is that counterfactual outcomes are not fully observed for any unit. Furthermore, in observational studies, treatment assignment is likely to be confounded. Many statistical methods have emerged for causal inference under unconfoundedness conditions given pre-treatment covariates, including propensity score-based methods, prognostic score-based methods, and doubly robust methods. Unfortunately for applied researchers, there is no `one-size-fits-all' causal method that can perform optimally universally. In practice, causal methods are primarily evaluated quantitatively on handcrafted simulated data. Such data-generative procedures can be of limited value because they are typically stylized models of reality. They are simplified for tractability and lack the complexities of real-world data. For applied researchers, it is critical to understand how well a method performs for the data at hand. Our work introduces a deep generative model-based framework, Credence, to validate causal inference methods. The framework's novelty stems from its ability to generate synthetic data anchored at the empirical distribution for the observed sample, and therefore virtually indistinguishable from the latter. The approach allows the user to specify ground truth for the form and magnitude of causal effects and confounding bias as functions of covariates. Thus simulated data sets are used to evaluate the potential performance of various causal estimation methods when applied to data similar to the observed sample. We demonstrate Credence's ability to accurately assess the relative performance of causal estimation techniques in an extensive simulation study and two real-world data applications from Lalonde and Project STAR studies.

Babak Salimi, Harsh Parikh, Moe Kayali et al.

Causal inference is at the heart of empirical research in natural and social sciences and is critical for scientific discovery and informed decision making. The gold standard in causal inference is performing randomized controlled trials; unfortunately these are not always feasible due to ethical, legal, or cost constraints. As an alternative, methodologies for causal inference from observational data have been developed in statistical studies and social sciences. However, existing methods critically rely on restrictive assumptions such as the study population consisting of homogeneous elements that can be represented in a single flat table, where each row is referred to as a unit. In contrast, in many real-world settings, the study domain naturally consists of heterogeneous elements with complex relational structure, where the data is naturally represented in multiple related tables. In this paper, we present a formal framework for causal inference from such relational data. We propose a declarative language called CaRL for capturing causal background knowledge and assumptions and specifying causal queries using simple Datalog-like rules.CaRL provides a foundation for inferring causality and reasoning about the effect of complex interventions in relational domains. We present an extensive experimental evaluation on real relational data to illustrate the applicability of CaRL in social sciences and healthcare.

Harsh Parikh, Cynthia Rudin, Alexander Volfovsky

We introduce a flexible framework that produces high-quality almost-exact matches for causal inference. Most prior work in matching uses ad-hoc distance metrics, often leading to poor quality matches, particularly when there are irrelevant covariates. In this work, we learn an interpretable distance metric for matching, which leads to substantially higher quality matches. The learned distance metric stretches the covariate space according to each covariate's contribution to outcome prediction: this stretching means that mismatches on important covariates carry a larger penalty than mismatches on irrelevant covariates. Our ability to learn flexible distance metrics leads to matches that are interpretable and useful for the estimation of conditional average treatment effects.