Planning a Bayesian early-phase phase I/II study for human vaccines in HER2 carcinomas

Recent innovative statistical approaches for phase I/II clinical trials allow one to jointly model the toxicity and efficacy of a new treatment, taking into account the information gathered during the trial. Prior probabilities are then updated with interim data and thus predictive probabilities become more accurate as the trial progresses. In this study, prior distribution elicited from a physician's opinion on the available dose levels planned for a vaccination dose-finding trial, with human DNA in patients with HER2-positive tumours in terms of toxicity and therapeutic response is presented and discussed. A simulation study was conducted in order to quantify the impact of the choice of prior on study results, i.e. the recommended dose level at the end of the trial.     

Bayesian confidence interval for the risk ratio in a correlated 2 × 2 table with structural zero

This paper studies the construction of a Bayesian confidence interval for the risk ratio (RR) in a 2 × 2 table with structural zero. Under a Dirichlet prior distribution, the exact posterior distribution of the RR is derived, and tail-based interval is suggested for constructing Bayesian confidence interval. The frequentist performance of this confidence interval is investigated by simulation and compared with the score-based interval in terms of the mean coverage probability and mean expected width of the interval. An advantage of the Bayesian confidence interval is that it is well defined for all data structure and has shorter expected width. Our simulation shows that the Bayesian tail-based interval under Jeffreys’ prior performs as well as or better than the score-based confidence interval.     

超法规不作为犯的构成--对先行行为和道德要求形成的作为义务的分析

先行行为和道德义务成立不作为犯有着共同的伦理基础.先行行为所导致的危险是作为的前提条件,而道德义务的成立也必须有足够的危险存在,以致作为的必要,二者都要求作为义务的形成与作为义务人有着必要的内在联系.在当今中国,道德义务的成立有着现实可能性和时代的需要,但它成立的条件与法律有规定的作为义务不同,和先行行为不作为犯构成一样,它必须与当时危险的现实性、紧迫性和作为义务者对危险的排他性支配力等限定性条件相结合,形成严密的构成体系.     

On the estimation problem of periodic autoregressive time series: symmetric and asymmetric innovations

Periodic autoregressive (PAR) models with symmetric innovations are widely used on time series analysis, whereas its asymmetric counterpart inference remains a challenge, because of a number of problems related to the existing computational methods. In this paper, we use an interesting relationship between periodic autoregressive and vector autoregressive (VAR) models to study maximum likelihood and Bayesian approaches to the inference of a PAR model with normal and skew-normal innovations, where different kinds of estimation methods for the unknown parameters are examined. Several technical difficulties which are usually complicated to handle are reported. Results are compared with the existing classical solutions and the practical implementations of the proposed algorithms are illustrated via comprehensive simulation studies. The methods developed in the study are applied and illustrate a real-time series. The Bayes factor is also used to compare the multivariate normal model versus the multivariate skew-normal model.     

Alternatives to post‐processing posterior predictive p values

The posterior predictive p value (ppp) was invented as a Bayesian counterpart to classical p values. The methodology can be applied to discrepancy measures involving both data and parameters and can, hence, be targeted to check for various modeling assumptions. The interpretation can, however, be difficult since the distribution of the ppp value under modeling assumptions varies substantially between cases. A calibration procedure has been suggested, treating the ppp value as a test statistic in a prior predictive test. In this paper, we suggest that a prior predictive test may instead be based on the expected posterior discrepancy, which is somewhat simpler, both conceptually and computationally. Since both these methods require the simulation of a large posterior parameter sample for each of an equally large prior predictive data sample, we furthermore suggest to look for ways to match the given discrepancy by a computation‐saving conflict measure. This approach is also based on simulations but only requires sampling from two different distributions representing two contrasting information sources about a model parameter. The conflict measure methodology is also more flexible in that it handles non‐informative priors without difficulty. We compare the different approaches theoretically in some simple models and in a more complex applied example.     

Penalized maximum likelihood estimation in the modified extended Weibull distribution

We address the issue of performing inference on the parameters that index the modified extended Weibull (MEW) distribution. We show that numerical maximization of the MEW log-likelihood function can be problematic. It is even possible to encounter maximum likelihood estimates that are not finite, that is, it is possible to encounter monotonic likelihood functions. We consider different penalization schemes to improve maximum likelihood point estimation. A penalization scheme based on the Jeffreys’ invariant prior is shown to be particularly useful. Simulation results on point estimation, interval estimation, and hypothesis testing inference are presented. Two empirical applications are presented and discussed.     

On several estimates to the precision parameter of Dirichlet process prior

The article presents careful comparisons among several empirical Bayes estimates to the precision parameter of Dirichlet process prior, with the setup of univariate observations and multigroup data. Specifically, the data are equipped with a two-stage compound sampling model, where the prior is assumed as a Dirichlet process that follows within a Bayesian nonparametric framework. The precision parameter α measures the strength of the prior belief and kinds of estimates are generated on the basis of observations, including the naive estimate, two calibrated naive estimates, and two different types of maximum likelihood estimates stemming from distinct distributions. We explore some theoretical properties and provide explicitly detailed comparisons among these estimates, in the perspectives of bias, variance, and mean squared error. Besides, we further present the corresponding calculation algorithms and numerical simulations to illustrate our theoretical achievements.     

Bayesian borrowing from historical control data in a vaccine efficacy trial

In the context of vaccine efficacy trial where the incidence rate is very low and a very large sample size is usually expected, incorporating historical data into a new trial is extremely attractive to reduce sample size and increase estimation precision. Nevertheless, for some infectious diseases, seasonal change in incidence rates poses a huge challenge in borrowing historical data and a critical question is how to properly take advantage of historical data borrowing with acceptable tolerance to between-trials heterogeneity commonly from seasonal disease transmission. In this article, we extend a probability-based power prior which determines the amount of information to be borrowed based on the agreement between the historical and current data, to make it applicable for either a single or multiple historical trials available, with constraint on the amount of historical information to be borrowed. Simulations are conducted to compare the performance of the proposed method with other methods including modified power prior (MPP), meta-analytic-predictive (MAP) prior and the commensurate prior methods. Furthermore, we illustrate the application of the proposed method for trial design in a practical setting.     

Bayesian estimation for first-order autoregressive model with explanatory variables

In this article, we develop a Bayesian analysis in autoregressive model with explanatory variables. When σ² is known, we consider a normal prior and give the Bayesian estimator for the regression coefficients of the model. For the case σ² is unknown, another Bayesian estimator is given for all unknown parameters under a conjugate prior. Bayesian model selection problem is also being considered under the double-exponential priors. By the convergence of ρ-mixing sequence, the consistency and asymptotic normality of the Bayesian estimators of the regression coefficients are proved. Simulation results indicate that our Bayesian estimators are not strongly dependent on the priors, and are robust.