Generalized causal effect estimands, including the Mann-Whitney parameter and causal net benefit, provide flexible summaries of treatment effects in randomized experiments with non-Gaussian or multivariate outcomes. We develop a unified design-based inference framework for regression adjustment and variance estimation of a broad class of generalized causal effect estimands defined through pairwise contrast functions. Leveraging the theory of U-statistics and finite-population asymptotics, we establish the consistency and asymptotic normality of regression estimators constructed from individual pairs and per-unit pair averages, even when the working models are misspecified. Consequently, these estimators are model-assisted rather than model-based. In contrast to classical average treatment effect estimands, we show that for nonlinear contrast functions, covariate adjustment preserves consistency but does not admit a universal efficiency guarantee. For inference, we demonstrate that standard heteroskedasticity-robust and cluster-robust variance estimators are generally inconsistent in this setting. As a remedy, we prove that a complete two-way cluster-robust variance estimator, which fully accounts for pairwise dependence and reverse comparisons, is consistent.

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