Non‐parametric Threshold Estimation for Models with Stochastic Diffusion Coefficient and Jumps

Abstract. We consider a stochastic process driven by diffusions and jumps. Given a discrete record of observations, we devise a technique for identifying the times when jumps larger than a suitably defined threshold occurred. This allows us to determine a consistent non‐parametric estimator of the integrated volatility when the infinite activity jump component is Lévy. Jump size estimation and central limit results are proved in the case of finite activity jumps. Some simulations illustrate the applicability of the methodology in finite samples and its superiority on the multipower variations especially when it is not possible to use high frequency data.     

An efficient sequential design of clinical trials

We propose an efficient group sequential monitoring rule for clinical trials. At each interim analysis both efficacy and futility are evaluated through a specified loss structure together with the predicted power. The proposed design is robust to a wide range of priors, and achieves the specified power with a saving of sample size compared to existing adaptive designs. A method is also proposed to obtain a reduced-bias estimator of treatment difference for the proposed design. The new approaches hold great potential for efficiently selecting a more effective treatment in comparative trials. Operating characteristics are evaluated and compared with other group sequential designs in empirical studies. An example is provided to illustrate the application of the method.     

Operating Characteristics for Group Sequential Trials Monitored Under Fractional Brownian Motion

Brownian motion has been used to derive stopping boundaries for group sequential trials, however, when we observe dependent increment in the data, fractional Brownian motion is an alternative to be considered to model such data. In this article we compared expected sample sizes and stopping times for different stopping boundaries based on the power family alpha spending function under various values of Hurst coefficient. Results showed that the expected sample sizes and stopping times will decrease and power increases when the Hurst coefficient increases. With same Hurst coefficient, the closer the boundaries are to that of O'Brien-Fleming, the higher the expected sample sizes and stopping times are; however, power has a decreasing trend for values start from H = 0.6 (early analysis), 0.7 (equal space), 0.8 (late analysis). We also illustrate study design changes using results from the BHAT study.     

Evaluation of a method for setting confidence intervals on the common mean of two normal populations

Let X₁, , X₂, …, X be distributed N(µ, σ² _x), let Y₁, Y₂, …, Y"_n be distributed N(µ, σ² _y), and let X , X , … X_m, Y₁, Y₂, …, Y_n be mutually independent. In this paper a method for setting confidence intervals on the common mean µ is proposed and evaluated.     

Monte-Carlo Sensitivity Analysis for Controlled Direct Effects Using Marginal Structural Models in the Presence of Confounded Mediators

In randomized trials, investigators are frequently interested in estimating the direct effect of a treatment on an outcome that is not relayed by intermediate variables, in addition to the usual intention-to-treat (ITT) effect. Even if the ITT effect is not confounded due to randomization, the direct effect is not identified when unmeasured variables affect the intermediate and outcome variables. Although the unmeasured variables cannot be adjusted for in the models, it is still important to evaluate the potential bias of these variables quantitatively. This article proposes a sensitivity analysis method for controlled direct effects using a marginal structural model that is an extension of the sensitivity analysis method of unmeasured confounding introduced in the context of observational studies. The proposed method is illustrated using a randomized trial of depression.     

Adaptive Crossover Design for Normal Responses

In a response-adaptive design, we review and update the trial on the basis of outcomes in order to achive a specific goal. In clinical trials our goal is to allocate a larger number of patients to the better treatment. In the present paper, we use a response adaptive design in a two-treatment two-period crossover trial where the treatment responses are continuous. We provide probability measures to choose between the possible treatment combinations AA, AB, BA, or BB. The goal is to use the better treatment combination a larger number of times. We calculate the allocation proportions to the possible treatment combinations and their standard errors. We also derive some asymptotic results and provide solutions on related inferential problems. The proposed procedure is compared with a possible competitor. Finally, we use a data set to illustrate the applicability of our proposed design.     

An experimenter’s view of the application of statistics to cloud-seeding experiments

An experimenter in the field of cloud seeding describes aspects of experiments which he would like statisticians to take into account and suggects Problems which he would like statisficians solve.     

Large sample estimation and prediction for explosive growth curve models

Asymptotic distributions of maximum likelihood estimators for the parameters in explosive growth curve models are derived. Limit distributions of prediction errors when the parameters are estimated are also obtained. The growth curve models are viewed as multivariate time-series models, and the usual time-series methods are used for prediction. Estimation constrained by a hypothesis of homogeneity of growth rates is also considered.