Semiparametric regression has become very popular in the field of Statistics over the years. While on one hand more and more sophisticated models are being developed, on the other hand the resulting theory and estimation process has become more and more involved. The main problems that are addressed in this work are related to efficient inferential procedures in general semiparametric regression problems. We first discuss efficient estimation of population-level summaries in general semiparametric regression models. Here our focus is on estimating general population-level quantities that combine the parametric and nonparametric parts of the model (e.g., population mean, probabilities, etc.). We place this problem in a general context, provide a general kernel-based methodology, and derive the asymptotic distributions of estimates of these population-level quantities, showing that in many cases the estimates are semiparametric efficient. Next, motivated from the problem of testing for genetic effects on complex traits in the presence of gene-environment interaction, we consider developing score test in general semiparametric regression problems that involves Tukey style 1 d.f form of interaction between parametrically and non-parametrically modeled covariates. We develop adjusted score statistics which are unbiased and asymptotically efficient and can be performed using standard bandwidth selection methods. In addition, to over come the difficulty of solving functional equations, we give easy interpretations of the target functions, which in turn allow us to develop estimation procedures that can be easily implemented using standard computational methods. Finally, we take up the important problem of estimation in a general semiparametric regression model when covariates are measured with an additive measurement error structure having normally distributed measurement errors. In contrast to methods that require solving integral equation of dimension the size of the covariate measured with error, we propose methodology based on Monte Carlo corrected scores to estimate the model components and investigate the asymptotic behavior of the estimates. For each of the problems, we present simulation studies to observe the performance of the proposed inferential procedures. In addition, we apply our proposed methodology to analyze nontrivial real life data sets and present the results.

It is well known that incorporating auxiliary covariates in the analysis of randomized clinical trials (RCTs) can increase efficiency. Questions still remain regarding how to flexibly incorporate baseline covariates while maintaining valid inference. Recent methodological advances that use semiparametric theory to develop covariate-adjusted inference for RCTs have focused on independent outcomes. In biomedical research, however, cluster randomized trials and longitudinal studies, characterized by correlated responses, are commonly used. We develop methods that flexibly incorporate baseline covariates for efficiency improvement in randomized studies with correlated outcomes. In Chapter 1, we show how augmented estimators may be used for cluster randomized trials, in which treatments are assigned to groups of individuals. We demonstrate the potential for imbalance correction and efficiency improvement through consideration of both cluster- and individual-level covariates. To improve small-sample estimation, we consider several variance adjustments. We evaluate this approach for continuous and binary outcomes through simulation and apply it to the Young Citizens study, a cluster randomized trial of a community behavioral intervention for HIV prevention in Tanzania. Chapter 2 builds upon the previous chapter by deriving semiparametric locally efficient estimators of marginal mean treatment effects when outcomes are correlated. Estimating equations are determined by the efficient score under a mean model for marginal effects when data contain baseline covariates and exhibit correlation. Locally efficient estimators are implemented for longitudinal data with continuous outcomes and clustered data with binary outcomes. Methods are illustrated through application to AIDS Clinical Trial Group Study 398, a longitudinal randomized study that compared various protease inhibitors in HIV-positive subjects. In Chapter 3, we empirically evaluate several covariate-adjusted tests of intervention effects when baseline covariates are selected adaptively and the number of randomized units is small. We demonstrate that randomization inference preserves type I error under model selection while tests based on asymptotic theory break down. Additionally, we show that covariate adjustment typically increases power, except at extremely small sample sizes using liberal selection procedures. Properties of covariate-adjusted tests are explored for independent and multivariate outcomes. We revisit Young Citizens to provide further insight into the performance of various methods in small-sample settings.

Die Schätzung von Quantilen und verwandten Funktionalen wird in zwei inversen Problemen behandelt: dem klassischen Dekonvolutionsmodell sowie dem Lévy-Modell in dem ein Lévy-Prozess beobachtet wird und Funktionale des Sprungmaßes geschätzt werden. Im einem abstrakteren Rahmen wird semiparametrische Effizienz im Sinne von Hájek-Le Cam für Funktionalschätzung in regulären, inversen Modellen untersucht. Ein allgemeiner Faltungssatz wird bewiesen, der auf eine große Klasse von statistischen inversen Problem anwendbar ist. Im Dekonvolutionsmodell beweisen wir, dass die Plugin-Schätzer der Verteilungsfunktion und der Quantile effizient sind. Auf der Grundlage von niederfrequenten diskreten Beobachtungen des Lévy-Prozesses wird im nichtlinearen Lévy-Modell eine Informationsschranke für die Schätzung von Funktionalen des Sprungmaßes hergeleitet. Die enge Verbindung zwischen dem Dekonvolutionsmodell und dem Lévy-Modell wird präzise beschrieben. Quantilschätzung für Dekonvolutionsprobleme wird umfassend untersucht. Insbesondere wird der realistischere Fall von unbekannten Fehlerverteilungen behandelt. Wir zeigen unter minimalen und natürlichen Bedingungen, dass die Plugin-Methode minimax optimal ist. Eine datengetriebene Bandweitenwahl erlaubt eine optimale adaptive Schätzung. Quantile werden auf den Fall von Lévy-Maßen, die nicht notwendiger Weise endlich sind, verallgemeinert. Mittels äquidistanten, diskreten Beobachtungen des Prozesses werden nichtparametrische Schätzer der verallgemeinerten Quantile konstruiert und minimax optimale Konvergenzraten hergeleitet. Als motivierendes Beispiel von inversen Problemen untersuchen wir ein Finanzmodell empirisch, in dem ein Anlagengegenstand durch einen exponentiellen Lévy-Prozess dargestellt wird. Die Quantilschätzer werden auf dieses Modell übertragen und eine optimale adaptive Bandweitenwahl wird konstruiert. Die Schätzmethode wird schließlich auf reale Daten von DAX-Optionen angewendet. / The estimation of quantiles and realated functionals is studied in two inverse problems: the classical deconvolution model and the Lévy model, where a Lévy process is observed and where we aim for the estimation of functionals of the jump measure. From a more abstract perspective we study semiparametric efficiency in the sense of Hájek-Le Cam for functional estimation in regular indirect models. A general convolution theorem is proved which applies to a large class of statistical inverse problems. In particular, we consider the deconvolution model, where we prove that our plug-in estimators of the distribution function and of the quantiles are efficient. In the nonlinear Lévy model based on low-frequent discrete observations of the Lévy process, we deduce an information bound for the estimation of functionals of the jump measure. The strong relationship between the Lévy model and the deconvolution model is given a precise meaning. Quantile estimation in deconvolution problems is studied comprehensively. In particular, the more realistic setup of unknown error distributions is covered. Under minimal and natural conditions we show that the plug-in method is minimax optimal. A data-driven bandwidth choice yields optimal adaptive estimation. The concept of quantiles is generalized to the possibly infinite Lévy measures by considering left and right tail integrals. Based on equidistant discrete observations of the process, we construct a nonparametric estimator of the generalized quantiles and derive minimax convergence rates. As a motivating financial example for inverse problems, we empirically study the calibration of an exponential Lévy model for asset prices. The estimators of the generalized quantiles are adapted to this model. We construct an optimal adaptive quantile estimator and apply the procedure to real data of DAX-options.