Longitudinal profiles of bounded outcome scores as predictors for disease activity in rheumatoid arthritis patients: a joint modeling approach

A variety of statistical approaches have been suggested in the literature for the analysis of bounded outcome scores (BOS). In this paper, we suggest a statistical approach when BOSs are repeatedly measured over time and used as predictors in a regression model. Instead of directly using the BOS as a predictor, we propose to extend the approaches suggested in [16 E. Lesaffre, D. Rizopoulos, and R. Tsonaka, The logistics-transform for bounded outcome scores, Biostatistics 8 (2007), pp. 72–85. doi: 10.1093/biostatistics/kxj034[Crossref], [PubMed], [Web of Science ®] , [Google Scholar],21 M. Molas and E. Lesaffre, A comparison of the three random effects approaches to analyse repeated bounded outcome scores with an application in a stroke revalidation study, Stat. Med. 27 (2008), pp. 6612–6633. doi: 10.1002/sim.3432[Crossref], [PubMed], [Web of Science ®] , [Google Scholar],28 R. Tsonaka, D. Rizopoulos, and E. Lesaffre, Power and sample size calculations for discrete bounded outcome scores, Stat. Med. 25 (2006), pp. 4241–4252. doi: 10.1002/sim.2679[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]] to a joint modeling setting. Our approach is illustrated on longitudinal profiles of multiple patients’ reported outcomes to predict the current clinical status of rheumatoid arthritis patients by a disease activities score of 28 joints (DAS28). Both a maximum likelihood as well as a Bayesian approach is developed.     

Weighting variables in Kohonen competitive learning algorithms

This paper presents a new variable weight method, called the singular value decomposition (SVD) approach, for Kohonen competitive learning (KCL) algorithms based on the concept of Varshavsky et al. [18 R. Varshavsky, A. Gottlieb, M. Linial, and D. Horn, Novel unsupervised feature filtering of bilogical data, Bioinformatics 22 (2006), pp. 507–513.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]]. Integrating the weighted fuzzy c-means (FCM) algorithm with KCL, in this paper, we propose a weighted fuzzy KCL (WFKCL) algorithm. The goal of the proposed WFKCL algorithm is to reduce the clustering error rate when data contain some noise variables. Compared with the k-means, FCM and KCL with existing variable-weight methods, the proposed WFKCL algorithm with the proposed SVD's weight method provides a better clustering performance based on the error rate criterion. Furthermore, the complexity of the proposed SVD's approach is less than Pal et al. [17 S.K. Pal, R.K. De, and J. Basak, Unsupervised feature evaluation: a neuro-fuzzy approach, IEEE. Trans. Neural Netw. 11 (2000), pp. 366–376.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]], Wang et al. [19 X.Z. Wang, Y.D. Wang, and L.J. Wang, Improving fuzzy c-means clustering based on feature-weight learning, Pattern Recognit. Lett. 25 (2004), pp. 1123–1132.[Crossref], [Web of Science ®] , [Google Scholar]] and Hung et al. [9 W. -L. Hung, M. -S. Yang, and D. -H. Chen, Bootstrapping approach to feature-weight selection in fuzzy c-means algorithms with an application in color image segmentation, Pattern Recognit. Lett. 29 (2008), pp. 1317–1325.[Crossref], [Web of Science ®] , [Google Scholar]].     

Flexible parametric modelling of the hazard function in breast cancer studies

In cancer research, study of the hazard function provides useful insights into disease dynamics, as it describes the way in which the (conditional) probability of death changes with time. The widely utilized Cox proportional hazard model uses a stepwise nonparametric estimator for the baseline hazard function, and therefore has a limited utility. The use of parametric models and/or other approaches that enables direct estimation of the hazard function is often invoked. A recent work by Cox et al. [6 Cox, C., Chu, H., Schneider, M. F. and Munoz, A. 2007. Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution. Stat. Med., 26: 4352–4374. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]] has stimulated the use of the flexible parametric model based on the Generalized Gamma (GG) distribution, supported by the development of optimization software. The GG distribution allows estimation of different hazard shapes in a single framework. We use the GG model to investigate the shape of the hazard function in early breast cancer patients. The flexible approach based on a piecewise exponential model and the nonparametric additive hazards model are also considered.     

Testing for sphericity in a two-way error components panel data model

This article is concerned with sphericity test for the two-way error components panel data model. It is found that the John statistic and the bias-corrected LM statistic recently developed by Baltagi et al. (2011 Baltagi, B. H., Feng, Q., Kao, C. (2011). Testing for sphericity in a fixed effects panel data model. Econometrics Journal 14:25–47.[Crossref], [Web of Science ®] , [Google Scholar])Baltagi et al. (2012 Baltagi, B. H., Feng, Q., Kao, C. (2012). A Lagrange multiplier test for cross-sectional dependence in a fixed effects panel data model. Journal of Econometrics 170:164–177.[Crossref], [Web of Science ®] , [Google Scholar], which are based on the within residuals, are not helpful under the present circumstances even though they are in the one-way fixed effects model. However, we prove that when the within residuals are properly transformed, the resulting residuals can serve to construct useful statistics that are similar to those of Baltagi et al. (2011 Baltagi, B. H., Feng, Q., Kao, C. (2011). Testing for sphericity in a fixed effects panel data model. Econometrics Journal 14:25–47.[Crossref], [Web of Science ®] , [Google Scholar])Baltagi et al. (2012 Baltagi, B. H., Feng, Q., Kao, C. (2012). A Lagrange multiplier test for cross-sectional dependence in a fixed effects panel data model. Journal of Econometrics 170:164–177.[Crossref], [Web of Science ®] , [Google Scholar]). Simulation results show that the newly proposed statistics perform well under the null hypothesis and several typical alternatives.     

On the optimal allocation of active redundancies in series system

This paper studies the allocations of two non identical active redundancies in series systems in terms of the reversed hazard rate order and hazard rate order, which generalizes some results built in Valdés and Zequeira (2003 Valdés, J. E., and R. I. Zequeira 2003. On the optimal allocation of an active redundancy in a two-component series system. Stat. Probab. Lett. 63:325–32.[Crossref], [Web of Science ®] , [Google Scholar], 2006 Valdés, J. E., and R. I. Zequeira 2006. On the optimal allocation of two active redundancies in a two-component series system. Oper. Res. Lett. 34:49–52.[Crossref], [Web of Science ®] , [Google Scholar]).     

Weighted simulated integrated conditional moment tests for parametric conditional distributions of stationary time series processes

In this article, we propose a weighted simulated integrated conditional moment (WSICM) test of the validity of parametric specifications of conditional distribution models for stationary time series data, by combining the weighted integrated conditional moment (ICM) test of Bierens (1984 Bierens, H. J. (1984). Model specification testing of time series regressions. Journal of Econometrics 26:323–353.[Crossref], [Web of Science ®] , [Google Scholar]) for time series regression models with the simulated ICM test of Bierens and Wang (2012 Bierens, H. J., Wang, L. (2012). Integrated conditional moment tests for parametric conditional distributions. Econometric Theory 28:328–362.[Crossref], [Web of Science ®] , [Google Scholar]) of conditional distribution models for cross-section data. To the best of our knowledge, no other consistent test for parametric conditional time series distributions has been proposed yet in the literature, despite consistency claims made by some authors.     

A comparison of alternative methods to construct confidence intervals for the estimate of a break date in linear regression models

This article considers constructing confidence intervals for the date of a structural break in linear regression models. Using extensive simulations, we compare the performance of various procedures in terms of exact coverage rates and lengths of the confidence intervals. These include the procedures of Bai (1997 Bai, J. (1997). Estimation of a change point in multiple regressions. Review of Economics and Statistics 79:551–563.[Crossref], [Web of Science ®] , [Google Scholar]) based on the asymptotic distribution under a shrinking shift framework, Elliott and Müller (2007 Elliott, G., Müller, U. (2007). Confidence sets for the date of a single break in linear time series regressions. Journal of Econometrics 141:1196–1218.[Crossref], [Web of Science ®] , [Google Scholar]) based on inverting a test locally invariant to the magnitude of break, Eo and Morley (2015 Eo, Y., Morley, J. (2015). Likelihood-ratio-based confidence sets for the timing of structural breaks. Quantitative Economics 6:463–497.[Crossref], [Web of Science ®] , [Google Scholar]) based on inverting a likelihood ratio test, and various bootstrap procedures. On the basis of achieving an exact coverage rate that is closest to the nominal level, Elliott and Müller's (2007 Elliott, G., Müller, U. (2007). Confidence sets for the date of a single break in linear time series regressions. Journal of Econometrics 141:1196–1218.[Crossref], [Web of Science ®] , [Google Scholar]) approach is by far the best one. However, this comes with a very high cost in terms of the length of the confidence intervals. When the errors are serially correlated and dealing with a change in intercept or a change in the coefficient of a stationary regressor with a high signal-to-noise ratio, the length of the confidence interval increases and approaches the whole sample as the magnitude of the change increases. The same problem occurs in models with a lagged dependent variable, a common case in practice. This drawback is not present for the other methods, which have similar properties. Theoretical results are provided to explain the drawbacks of Elliott and Müller's (2007 Elliott, G., Müller, U. (2007). Confidence sets for the date of a single break in linear time series regressions. Journal of Econometrics 141:1196–1218.[Crossref], [Web of Science ®] , [Google Scholar]) method.     

Likelihood-based panel cointegration test in the presence of a linear time trend and cross-sectional dependence

This article proposes a new likelihood-based panel cointegration rank test which extends the test of Örsal and Droge (2014 Örsal, D. D. K., Droge, B. (2014). Panel cointegration testing in the presence of a time trend. Computational Statistics and Data Analysis 76:377–390.[Crossref], [Web of Science ®] , [Google Scholar]) (henceforth panel SL test) to dependent panels. The dependence is modelled by unobserved common factors which affect the variables in each cross-section through heterogeneous loadings. The data are defactored following the panel analysis of nonstationarity in idiosyncratic and common components (PANIC) approach of Bai and Ng (2004 Bai, J., Ng, S. (2004). A PANIC attack on unit roots and cointegration. Econometrica 72(4):1127–1177.[Crossref], [Web of Science ®] , [Google Scholar]) and the cointegrating rank of the defactored data is then tested by the panel SL test. A Monte Carlo study demonstrates that the proposed testing procedure has reasonable size and power properties in finite samples.     

Learning-based EM algorithm for normal-inverse Gaussian mixture model with application to extrasolar planets

Karlis and Santourian [14 D. Karlis and A. Santourian, Model-based clustering with non-elliptically contoured distribution, Stat. Comput. 19 (2009), pp. 73–83. doi: 10.1007/s11222-008-9072-0[Crossref], [Web of Science ®] , [Google Scholar]] proposed a model-based clustering algorithm, the expectation–maximization (EM) algorithm, to fit the mixture of multivariate normal-inverse Gaussian (NIG) distribution. However, the EM algorithm for the mixture of multivariate NIG requires a set of initial values to begin the iterative process, and the number of components has to be given a priori. In this paper, we present a learning-based EM algorithm: its aim is to overcome the aforementioned weaknesses of Karlis and Santourian's EM algorithm [14 D. Karlis and A. Santourian, Model-based clustering with non-elliptically contoured distribution, Stat. Comput. 19 (2009), pp. 73–83. doi: 10.1007/s11222-008-9072-0[Crossref], [Web of Science ®] , [Google Scholar]]. The proposed learning-based EM algorithm was first inspired by Yang et al. [24 M.-S. Yang, C.-Y. Lai, and C.-Y. Lin, A robust EM clustering algorithm for Gaussian mixture models, Pattern Recognit. 45 (2012), pp. 3950–3961. doi: 10.1016/j.patcog.2012.04.031[Crossref], [Web of Science ®] , [Google Scholar]]: the process of how they perform self-clustering was then simulated. Numerical experiments showed promising results compared to Karlis and Santourian's EM algorithm. Moreover, the methodology is applicable to the analysis of extrasolar planets. Our analysis provides an understanding of the clustering results in the ln?P?ln?M and ln?P?e spaces, where M is the planetary mass, P is the orbital period and e is orbital eccentricity. Our identified groups interpret two phenomena: (1) the characteristics of two clusters in ln?P?ln?M space might be related to the tidal and disc interactions (see [9 I.G. Jiang, W.H. Ip, and L.C. Yeh, On the fate of close-in extrasolar planets, Astrophys. J. 582 (2003), pp. 449–454. doi: 10.1086/344590[Crossref], [Web of Science ®] , [Google Scholar]]); and (2) there are two clusters in ln?P?e space.     

Forward Moving Average Representations for MA Processes of Finite Order: Multivariate Stationary and Periodically Correlated

Soltani and Mohammadpour (2006 Soltani , A. R. , Mohammadpour , M. (2006). Moving average representations for multivariate stationary processes. J. Time Ser. Anal. 27(6):831–841.[Crossref], [Web of Science ®] , [Google Scholar]) observed that in general the backward and forward moving average coefficients, correspondingly, for the multivariate stationary processes, unlike the univariate processes, are different. This has stimulated researches concerning derivations of forward moving average coefficients in terms of the backward moving average coefficients. In this article we develop a practical procedure whenever the underlying process is a multivariate moving average (or univariate periodically correlated) process of finite order. Our procedure is based on two key observations: order reduction (Li, 2005 Li , L. M. ( 2005 ). Factorization of moving average spectral densities by state space representations and stacking . J. Multivariate Anal. 96 : 425 – 438 .[Crossref], [Web of Science ®] , [Google Scholar]) and first-order analysis (Mohammadpour and Soltani, 2010 Mohammadpour , M. , Soltani , A. R. ( 2010 ). Forward moving average representation for multivariate MA(1) processes . Commun. Statist. Theory Meth. 39 : 729 – 737 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]).     

Analysis of discrete lifetime data under middle-censoring and in the presence of covariates

‘Middle censoring’ is a very general censoring scheme where the actual value of an observation in the data becomes unobservable if it falls inside a random interval (L, R) and includes both left and right censoring. In this paper, we consider discrete lifetime data that follow a geometric distribution that is subject to middle censoring. Two major innovations in this paper, compared to the earlier work of Davarzani and Parsian [3 N. Davarzani and A. Parsian, Statistical inference for discrete middle-censored data, J. Statist. Plan. Inference 141 (2011), pp. 1455–1462. doi: 10.1016/j.jspi.2010.10.012[Crossref], [Web of Science ®] , [Google Scholar]], include (i) an extension and generalization to the case where covariates are present along with the data and (ii) an alternate approach and proofs which exploit the simple relationship between the geometric and the exponential distributions, so that the theory is more in line with the work of Iyer et al. [6 S.K. Iyer, S.R. Jammalamadaka, and D. Kundu, Analysis of middle censored data with exponential lifetime distributions, J. Statist. Plan. Inference 138 (2008), pp. 3550–3560. doi: 10.1016/j.jspi.2007.03.062[Crossref], [Web of Science ®] , [Google Scholar]]. It is also demonstrated that this kind of discretization of life times gives results that are close to the original data involving exponential life times. Maximum likelihood estimation of the parameters is studied for this middle-censoring scheme with covariates and their large sample distributions discussed. Simulation results indicate how well the proposed estimation methods work and an illustrative example using time-to-pregnancy data from Baird and Wilcox [1 D.D. Baird and A.J. Wilcox, Cigarette smoking associated with delayed conception, J, Am. Med. Assoc. 253 (1985), pp. 2979–2983. doi: 10.1001/jama.1985.03350440057031[Crossref], [Web of Science ®] , [Google Scholar]] is included.     

Using Frailty Models to Identify the Longitudinal Biomarkers in Survival Analysis

We introduce a score test to identify longitudinal biomarkers or surrogates for a time to event outcome. This method is an extension of Henderson et al. (2000 Henderson , R. , Diggle , P. , Dobson , A. ( 2000 ). Joint modelling of longitudinal measurements and event time data . Biostatistics 1 ( 4 ): 465 – 480 .[Crossref], [PubMed] , [Google Scholar], 2002 Henderson , R. , Diggle , P. , Dobson , A. ( 2002 ). Identification and efficacy of longitudinal markers for survival . Biostatistics 3 ( 1 ): 33 – 50 .[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). In this article, a score test is based on a joint likelihood function which combines the likelihood functions of the longitudinal biomarkers and the survival times. Henderson et al. (2000 Henderson , R. , Diggle , P. , Dobson , A. ( 2000 ). Joint modelling of longitudinal measurements and event time data . Biostatistics 1 ( 4 ): 465 – 480 .[Crossref], [PubMed] , [Google Scholar], 2002 Henderson , R. , Diggle , P. , Dobson , A. ( 2002 ). Identification and efficacy of longitudinal markers for survival . Biostatistics 3 ( 1 ): 33 – 50 .[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) assumed that the same random effect exists in the longitudinal component and in the Cox model and then they can derive a score test to determine if a longitudinal biomarker is associated with time to an event. We extend this work and our score test is based on a joint likelihood function which allows other random effects to be present in the survival function.

Considering heterogeneous baseline hazards in individuals, we use simulations to explore how the factors can influence the power of a score test to detect the association of a longitudinal biomarker and the survival time. These factors include the functional form of the random effects from the longitudinal biomarkers, in the different number of individuals, and time points per individual. We illustrate our method using a prothrombin index as a predictor of survival in liver cirrhosis patients.     

Inference on locally ordered breaks in multiple regressions

We consider issues related to inference about locally ordered breaks in a system of equations, as originally proposed by Qu and Perron (2007 Qu, Z., Perron, P. (2007). Estimating and testing structural changes in multivariate regressions. Econometrica 75:459–502.[Crossref], [Web of Science ®] , [Google Scholar]). These apply when break dates in different equations within the system are not separated by a positive fraction of the sample size. This allows constructing joint confidence intervals of all such locally ordered break dates. We extend the results of Qu and Perron (2007 Qu, Z., Perron, P. (2007). Estimating and testing structural changes in multivariate regressions. Econometrica 75:459–502.[Crossref], [Web of Science ®] , [Google Scholar]) in several directions. First, we allow the covariates to be any mix of trends and stationary or integrated regressors. Second, we allow for breaks in the variance-covariance matrix of the errors. Third, we allow for multiple locally ordered breaks, each occurring in a different equation within a subset of equations in the system. Via some simulation experiments, we show first that the limit distributions derived provide good approximations to the finite sample distributions. Second, we show that forming confidence intervals in such a joint fashion allows more precision (tighter intervals) compared to the standard approach of forming confidence intervals using the method of Bai and Perron (1998 Bai, J., Perron, P. (1998). Estimating and testing linear models with multiple structural changes. Econometrica 66:47–78.[Crossref], [Web of Science ®] , [Google Scholar]) applied to a single equation. Simulations also indicate that using the locally ordered break confidence intervals yields better coverage rates than using the framework for globally distinct breaks when the break dates are separated by roughly 10% of the total sample size.     

An objective Bayesian estimation in a two-period crossover design

Two-period crossover design is one of the commonly used designs in clinical trials. But, the estimation of treatment effect is complicated by the possible presence of carryover effect. It is known that ignoring the carryover effect when it exists can lead to poor estimates of the treatment effect. The classical approach by Grizzle (1965 Grizzle, J.E. (1965). The two-period change-over design and its use in clinical trials. Biometrics 21:467–480. See Grizzle (1974) for corrections.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) consists of two stages. First, a preliminary test is conducted on carryover effect. If the carryover effect is significant, analysis is based only on data from period one; otherwise, analysis is based on data from both periods. A Bayesian approach with improper priors was proposed by Grieve (1985 Grieve, A.P. (1985). A Bayesian analysis of the two-period crossover design for clinical trials. Biometrics 41:979–990.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) which uses a mixture of two models: a model with carryover effect and another without. The indeterminacy of the Bayes factor due to the arbitrary constant in the improper prior was addressed by assigning a minimally discriminatory value to the constant. In this article, we present an objective Bayesian estimation approach to the two-period crossover design which is also based on a mixture model, but using the commonly recommended Zellner–Siow g-prior. We provide simulation studies and a real data example and compare the numerical results with Grizzle (1965 Grizzle, J.E. (1965). The two-period change-over design and its use in clinical trials. Biometrics 21:467–480. See Grizzle (1974) for corrections.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar])’s and Grieve (1985 Grieve, A.P. (1985). A Bayesian analysis of the two-period crossover design for clinical trials. Biometrics 41:979–990.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar])’s approaches.     

Shared inverse Gaussian frailty models based on additive hazards

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin, or family data), the shared frailty models were suggested. These models are based on the assumption that frailty acts multiplicatively to hazard rate. In this article, we assume that frailty acts additively to hazard rate. We introduce the shared inverse Gaussian frailty models with three different baseline distributions, namely the generalized log-logistic, the generalized Weibull, and exponential power distribution. We introduce the Bayesian estimation procedure using Markov chain Monte Carlo technique to estimate the parameters involved in these models. We apply these models to a real-life bivariate survival dataset of McGilchrist and Aisbett (1991 McGilchrist, C.A., Aisbett, C.W. (1991). Regression with frailty in survival analysis. Biometrics 47:461–466.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) related to the kidney infection data, and a better model is suggested for the data.     

A Prediction-Oriented Criterion for Choosing the Biasing Parameter in Liu Estimation

Distribution-free tests have been proposed in the literature for comparing the hazard rates of two probability distributions when the available samples are complete. In this article, we generalize the test of Kochar (1981 Kochar , S. C. ( 1981 ). A new distribution-free test for the equality of two failure rates . Biometrika 68 : 423 – 426 .[Crossref], [Web of Science ®] , [Google Scholar]) to the case when the available sample is Type-II censored, and then examine its power properties.     

MSE Performance of a Heterogeneous Pre-Test Ridge Regression Estimator

This article describes how diagnostic procedures were derived for symmetrical nonlinear regression models, continuing the work carried out by Cysneiros and Vanegas (2008 Cysneiros , F. J. A. , Vanegas , L. H. ( 2008 ). Residuals and their statistical properties in symmetrical nonlinear models . Statist. Probab. Lett. 78 : 3269 – 3273 .[Crossref], [Web of Science ®] , [Google Scholar]) and Vanegas and Cysneiros (2010 Vanegas , L. H. , Cysneiros , F. J. A. ( 2010 ). Assesment of diagnostic procedures in symmetrical nonlinear regression models . Computat. Statist. Data Anal. 54 : 1002 – 1016 .[Crossref], [Web of Science ®] , [Google Scholar]), who showed that the parameters estimates in nonlinear models are more robust with heavy-tailed than with normal errors. In this article, we focus on assessing if the robustness of this kind of models is also observed in the inference process (i.e., partial F-test). Symmetrical nonlinear regression models includes all symmetric continuous distributions for errors covering both light- and heavy-tailed distributions such as Student-t, logistic-I and -II, power exponential, generalized Student-t, generalized logistic, and contaminated normal. Firstly, a statistical test is shown to evaluating the assumption that the error terms all have equal variance. The results of simulation studies which describe the behavior of the test for heteroscedasticity proposed in the presence of outliers are then given. To assess the robustness of inference process, we present the results of a simulation study which described the behavior of partial F-test in the presence of outliers. Also, some diagnostic procedures are derived to identify influential observations on the partial F-test. As ilustration, a dataset described in Venables and Ripley (2002 Venables , W. N. , Ripley , B. D. ( 2002 ). Modern Applied with S. , 4th ed. New York : Springer .[Crossref] , [Google Scholar]), is also analyzed.     

Bayesian adaptive two-stage design for determining person-time in Phase II clinical trials with Poisson data

Adaptive clinical trial designs can often improve drug-study efficiency by utilizing data obtained during the course of the trial. We present a novel Bayesian two-stage adaptive design for Phase II clinical trials with Poisson-distributed outcomes that allows for person-observation-time adjustments for early termination due to either futility or efficacy. Our design is motivated by the adaptive trial from [9 V. Sambucini, A Bayesian predictive two-stage design for Phase II clinical trials, Stat. Med. 27 (2008), pp. 1199–1224. doi: 10.1002/sim.3021[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]], which uses binomial data. Although many frequentist and Bayesian two-stage adaptive designs for count data have been proposed in the literature, many designs do not allow for person-time adjustments after the first stage. This restriction limits flexibility in the study design. However, our proposed design allows for such flexibility by basing the second-stage person-time on the first-stage observed-count data. We demonstrate the implementation of our Bayesian predictive adaptive two-stage design using a hypothetical Phase II trial of Immune Globulin (Intravenous).     

Empirical Likelihood in Causal Inference

This paper discusses the estimation of average treatment effects in observational causal inferences. By employing a working propensity score and two working regression models for treatment and control groups, Robins et al. (1994 Robins , J. M. , Rotnitzky , A. , Zhao , L. P. ( 1994 ). Estimation of regression coefficients when some regressors are not always observed . Journal of the American Statistical Association 89 : 846 – 866 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], 1995 Robins , J. M. , Rotnitzky , A. , Zhao , L. P. ( 1995 ). Analysis of semiparametric regression models for repeated outcomes in the presence of missing data . Journal of the American Statistical Association 90 : 106 – 121 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]) introduced the augmented inverse probability weighting (AIPW) method for estimation of average treatment effects, which extends the inverse probability weighting (IPW) method of Horvitz and Thompson (1952 Horvitz , D. G. , Thompson , D. J. ( 1952 ). A generalization of sampling without replacement from a finite universe . Journal of the American Statistical Association 47 : 663 – 685 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]); the AIPW estimators are locally efficient and doubly robust. In this paper, we study a hybrid of the empirical likelihood method and the method of moments by employing three estimating functions, which can generate estimators for average treatment effects that are locally efficient and doubly robust. The proposed estimators of average treatment effects are efficient for the given choice of three estimating functions when the working propensity score is correctly specified, and thus are more efficient than the AIPW estimators. In addition, we consider a regression method for estimation of the average treatment effects when working regression models for both the treatment and control groups are correctly specified; the asymptotic variance of the resulting estimator is no greater than the semiparametric variance bound characterized by the theory of Robins et al. (1994 Robins , J. M. , Rotnitzky , A. , Zhao , L. P. ( 1994 ). Estimation of regression coefficients when some regressors are not always observed . Journal of the American Statistical Association 89 : 846 – 866 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], 1995 Robins , J. M. , Rotnitzky , A. , Zhao , L. P. ( 1995 ). Analysis of semiparametric regression models for repeated outcomes in the presence of missing data . Journal of the American Statistical Association 90 : 106 – 121 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]). Finally, we present a simulation study to compare the finite-sample performance of various methods with respect to bias, efficiency, and robustness to model misspecification.     

Improving the Power of Tests of Stochastic Dominance

We extend Hansen's (2005) recentering method to a continuum of inequality constraints to construct new Kolmogorov–Smirnov tests for stochastic dominance of any pre-specified order. We show that our tests have correct size asymptotically, are consistent against fixed alternatives and are unbiased against some N^?1/2 local alternatives. It is shown that by avoiding the use of the least favorable configuration, our tests are less conservative and more powerful than Barrett and Donald's (2003) and in some simulation examples we consider, we find that our tests can be more powerful than the subsampling test of Linton et al. (2005 Linton, O., Maasoumi, E., Whang, Y.-J. (2005). Consistent testing for stochastic dominance under general sampling schemes. The Review of Economic Studies 72:735–765.[Crossref], [Web of Science ®] , [Google Scholar]). We apply our method to test stochastic dominance relations between Canadian income distributions in 1978 and 1986 as considered in Barrett and Donald (2003 Barrett, G. F., Donald, S. G. (2003). Consistent tests for stochastic dominance. Econometrica 71: 71–104.[Crossref], [Web of Science ®] , [Google Scholar]) and find that some of the hypothesis testing results are different using the new method.