Objective Bayesian analysis of counting experiments with correlated sources of background

Searches for faint signals in counting experiments are often encountered in particle physics and astrophysics, as well as in other fields. Many problems can be reduced to the case of a model with independent and Poisson-distributed signal and background. Often several background contributions are present at the same time, possibly correlated. We provide the analytic solution of the statistical inference problem of estimating the signal in the presence of multiple backgrounds, in the framework of objective Bayes statistics. The model can be written in the form of a product of a single Poisson distribution with a multinomial distribution. The first is related to the total number of events, whereas the latter describes the fraction of events coming from each individual source. Correlations among different backgrounds can be included in the inference problem by a suitable choice of the priors.     

The Limited Role of Formal Statistical Inference in Scientific Inference

ABSTRACT

Such is the grip of formal methods of statistical inference—that is, frequentist methods for generalizing from sample to population in enumerative studies—in the drawing of scientific inferences that the two are routinely deemed equivalent in the social, management, and biomedical sciences. This, despite the fact that legitimate employment of said methods is difficult to implement on practical grounds alone. But supposing the adoption of these procedures were simple does not get us far; crucially, methods of formal statistical inference are ill-suited to the analysis of much scientific data. Even findings from the claimed gold standard for examination by the latter, randomized controlled trials, can be problematic.

Scientific inference is a far broader concept than statistical inference. Its authority derives from the accumulation, over an extensive period of time, of both theoretical and empirical knowledge that has won the (provisional) acceptance of the scholarly community. A major focus of scientific inference can be viewed as the pursuit of significant sameness, meaning replicable and empirically generalizable results among phenomena. Regrettably, the obsession with users of statistical inference to report significant differences in data sets actively thwarts cumulative knowledge development.

The manifold problems surrounding the implementation and usefulness of formal methods of statistical inference in advancing science do not speak well of much teaching in methods/statistics classes. Serious reflection on statistics' role in producing viable knowledge is needed. Commendably, the American Statistical Association is committed to addressing this challenge, as further witnessed in this special online, open access issue of The American Statistician.     

A Non-stationary Cox Model

The purpose of this paper is to consider the problem of statistical inference about a hazard rate function that is specified as the product of a parametric regression part and a non-parametric baseline hazard. Unlike Cox's proportional hazard model, the baseline hazard not only depends on the duration variable, but also on the starting date of the phenomenon of interest. We propose a new estimator of the regression parameter which allows for non-stationarity in the hazard rate. We show that it is asymptotically normal at root- n and that its asymptotic variance attains the information bound for estimation of the regression coefficient. We also consider an estimator of the integrated baseline hazard, and determine its asymptotic properties. The finite sample performance of our estimators are studied.     

Semiparametric Stochastic Modeling of the Rate Function in Longitudinal Studies

In longitudinal biomedical studies, there is often interest in the rate functions, which describe the functional rates of change of biomarker profiles. This paper proposes a semiparametric approach to model these functions as the realizations of stochastic processes defined by stochastic differential equations. These processes are dependent on the covariates of interest and vary around a specified parametric function. An efficient Markov chain Monte Carlo algorithm is developed for inference. The proposed method is compared with several existing methods in terms of goodness-of-fit and more importantly the ability to forecast future functional data in a simulation study. The proposed methodology is applied to prostate-specific antigen profiles for illustration. Supplementary materials for this paper are available online.     

Statistical aspects of linkage analysis in interlaboratory studies

This paper investigates statistical issues that arise in interlaboratory studies known as Key Comparisons when one has to link several comparisons to or through existing studies. An approach to the analysis of such a data is proposed using Gaussian distributions with heterogeneous variances. We develop conditions for the set of sufficient statistics to be complete and for the uniqueness of uniformly minimum variance unbiased estimators (UMVUE) of the contrast parametric functions. New procedures are derived for estimating these functions with estimates of their uncertainty. These estimates lead to associated confidence intervals for the laboratories (or studies) contrasts. Several examples demonstrate statistical inference for contrasts based on linkage through the pilot laboratories. Monte Carlo simulation results on performance of approximate confidence intervals are also reported.     

State space mixed models for longitudinal observations with binary and binomial responses

We propose a new class of state space models for longitudinal discrete response data where the observation equation is specified in an additive form involving both deterministic and random linear predictors. These models allow us to explicitly address the effects of trend, seasonal or other time-varying covariates while preserving the power of state space models in modeling serial dependence in the data. We develop a Markov chain Monte Carlo algorithm to carry out statistical inference for models with binary and binomial responses, in which we invoke de Jong and Shephard’s (Biometrika 82(2):339–350, 1995) simulation smoother to establish an efficient sampling procedure for the state variables. To quantify and control the sensitivity of posteriors on the priors of variance parameters, we add a signal-to-noise ratio type parameter in the specification of these priors. Finally, we illustrate the applicability of the proposed state space mixed models for longitudinal binomial response data in both simulation studies and data examples.     

On the Order of Data Reductions by Ancillarity and by Sufficiency

In the context of frequentist inference there are strong arguments in favour of data reduction by both (a) conditioning on the most appropriate ancillary statistic and (b) restricting attention to a minimal sufficient statistic. However, significantly for the study of the foundations of frequentist inference, there are some examples in which the order of application of these data reductions has an important bearing on the statistical inference of interest. This paper presents a new simple example of this kind.     

Properties and Applications of the Generalized Likelihood as a Summary Function for Prediction Problems

The generalized likelihood plays an important role in parametric inference for prediction and empirical Bayesian models. This paper emphasizes the utility of the generalized likelihood as a summarization procedure in general prediction models. Properties of the generalized likelihood when used in this setting, and examples of its use as a data analytic tool are given in a series of numerical examples.     

Modelling Accelerated Degradation Data Using Wiener Diffusion With A Time Scale Transformation

Engineering degradation tests allow industry to assess the potential life span of long-life products that do not fail readily under accelerated conditions in life tests. A general statistical model is presented here for performance degradation of an item of equipment. The degradation process in the model is taken to be a Wiener diffusion process with a time scale transformation. The model incorporates Arrhenius extrapolation for high stress testing. The lifetime of an item is defined as the time until performance deteriorates to a specified failure threshold. The model can be used to predict the lifetime of an item or the extent of degradation of an item at a specified future time. Inference methods for the model parameters, based on accelerated degradation test data, are presented. The model and inference methods are illustrated with a case application involving self-regulating heating cables. The paper also discusses a number of practical issues encountered in applications. This revised version was published online in July 2006 with corrections to the Cover Date.     

Trend analysis with response incompatible formats and measurement error

The increasing popularity of longitudinal studies, along with the rapid advances in science and technology, has created a potential incompatibility between data formats, which leads to an inference problem when applying conventional statistical methods. This inference problem is further compounded by measurement error, since incompatible data format often arise in the context of measuring latent constructs. Without a systematic study of the impact of scale differences, ad-hoc approaches generally lead to inconsistent estimates and thus, invalid statistical inferences. In this paper, we examine the asymptotic properties and identify conditions that guarantee consistent estimation within the context of a trend analysis with response incompatible formats and measurement error. For model estimation, we introduce two competing methods that use a generalized estimating equation approach to provide inferences for the parameters of interest, and highlight the relative strengths of each method. The approach is illustrated by data obtained from a multi-centre AIDS cohort study (MACS), where a trend analysis of an immunologic marker of HIV infection is of interest.     

When is a seamless study desirable? Case studies from different pharmaceutical sponsors

Background: Inferentially seamless studies are one of the best‐known adaptive trial designs. Statistical inference for these studies is a well‐studied problem. Regulatory guidance suggests that statistical issues associated with study conduct are not as well understood. Some of these issues are caused by the need for early pre‐specification of the phase III design and the absence of sponsor access to unblinded data. Before statisticians decide to choose a seamless IIb/III design for their programme, they should consider whether these pitfalls will be an issue for their programme. Methods: We consider four case studies. Each design met with varying degrees of success. We explore the reasons for this variation to identify characteristics of drug development programmes that lend themselves well to inferentially seamless trials and other characteristics that warn of difficulties. Results: Seamless studies require increased upfront investment and planning to enable the phase III design to be specified at the outset of phase II. Pivotal, inferentially seamless studies are unlikely to allow meaningful sponsor access to unblinded data before study completion. This limits a sponsor's ability to reflect new information in the phase III portion. Conclusions: When few clinical data have been gathered about a drug, phase II data will answer many unresolved questions. Committing to phase III plans and study designs before phase II begins introduces extra risk to drug development. However, seamless pivotal studies may be an attractive option when the clinical setting and development programme allow, for example, when revisiting dose selection. Copyright © 2014 John Wiley & Sons, Ltd.     

Towards Bayesian image analysis

Many of the tasks encountered in image processing can be considered as problems in statistical inference. In particular, they fit naturally into a subjectivist Bayesis framework. In this paper, we describe the Bayesian approach to image analysis. Numerical examples are not included but references are given. It is argued that the Bayesian approach, still in its infancy, has considerable potential for future development.     

Bias from the use of generalized estimating equations to analyze incomplete longitudinal binary data

Patient dropout is a common problem in studies that collect repeated binary measurements. Generalized estimating equations (GEE) are often used to analyze such data. The dropout mechanism may be plausibly missing at random (MAR), i.e. unrelated to future measurements given covariates and past measurements. In this case, various authors have recommended weighted GEE with weights based on an assumed dropout model, or an imputation approach, or a doubly robust approach based on weighting and imputation. These approaches provide asymptotically unbiased inference, provided the dropout or imputation model (as appropriate) is correctly specified. Other authors have suggested that, provided the working correlation structure is correctly specified, GEE using an improved estimator of the correlation parameters (‘modified GEE’) show minimal bias. These modified GEE have not been thoroughly examined. In this paper, we study the asymptotic bias under MAR dropout of these modified GEE, the standard GEE, and also GEE using the true correlation. We demonstrate that all three methods are biased in general. The modified GEE may be preferred to the standard GEE and are subject to only minimal bias in many MAR scenarios but in others are substantially biased. Hence, we recommend the modified GEE be used with caution.     

Statistical Inference Enables Bad Science; Statistical Thinking Enables Good Science

ABSTRACT

Scientific research of all kinds should be guided by statistical thinking: in the design and conduct of the study, in the disciplined exploration and enlightened display of the data, and to avoid statistical pitfalls in the interpretation of the results. However, formal, probability-based statistical inference should play no role in most scientific research, which is inherently exploratory, requiring flexible methods of analysis that inherently risk overfitting. The nature of exploratory work is that data are used to help guide model choice, and under these circumstances, uncertainty cannot be precisely quantified, because of the inevitable model selection bias that results. To be valid, statistical inference should be restricted to situations where the study design and analysis plan are specified prior to data collection. Exploratory data analysis provides the flexibility needed for most other situations, including statistical methods that are regularized, robust, or nonparametric. Of course, no individual statistical analysis should be considered sufficient to establish scientific validity: research requires many sets of data along many lines of evidence, with a watchfulness for systematic error. Replicating and predicting findings in new data and new settings is a stronger way of validating claims than blessing results from an isolated study with statistical inferences.     

Randomization-Based Inference within Principal Strata

In randomized studies, treatment comparisons conditional on intermediate post-randomization outcomes using standard analytic methods do not have a causal interpretation. An alternate approach entails treatment comparisons within principal strata defined by the potential outcomes for the intermediate outcome that would be observed under each treatment assignment. In this paper, we develop methods for randomization-based inference within principal strata. The proposed methods are compared with existing large-sample methods as well as traditional intent-to-treat approaches. This research is motivated by HIV prevention studies where few infections are expected and inference is desired within the always-infected principal stratum, i.e., all individuals who would become infected regardless of randomization assignment.     

Multiple comparisons with a control under heteroscedasticity

This article investigates three procedures on the multiple comparisons with a control in the presence of unequal error variances. The advantages of the proposed methods are illustrated through two examples. The performance of the proposed methods and other alternative methods is compared by simulation studies. The results show that the typical methods assuming equal variance will have inflated error rate and may lead to erroneous inference when the equal variance assumption fails. In addition, the simulation study shows that the proposed approaches always control the family-wise error rate at a specified nominal level α, while some established methods are liberal and have inflated error rate in some scenarios.     

Weighted composite quantile regression analysis for nonignorable missing data using nonresponse instrument

Efficient statistical inference on nonignorable missing data is a challenging problem. This paper proposes a new estimation procedure based on composite quantile regression (CQR) for linear regression models with nonignorable missing data, that is applicable even with high-dimensional covariates. A parametric model is assumed for modelling response probability, which is estimated by the empirical likelihood approach. Local identifiability of the proposed strategy is guaranteed on the basis of an instrumental variable approach. A set of data-based adaptive weights constructed via an empirical likelihood method is used to weight CQR functions. The proposed method is resistant to heavy-tailed errors or outliers in the response. An adaptive penalisation method for variable selection is proposed to achieve sparsity with high-dimensional covariates. Limiting distributions of the proposed estimators are derived. Simulation studies are conducted to investigate the finite sample performance of the proposed methodologies. An application to the ACTG 175 data is analysed.     

Reliability of a soccer player based on the bivariate Rayleigh distribution with right censored and ignorable missing data

In this paper, we study the performance of a soccer player based on analysing an incomplete data set. To achieve this aim, we fit the bivariate Rayleigh distribution to the soccer dataset by the maximum likelihood method. In this way, the missing data and right censoring problems, that usually happen in such studies, are considered. Our aim is to inference about the performance of a soccer player by considering the stress and strength components. The first goal of the player of interest in a match is assumed as the stress component and the second goal of the match is assumed as the strength component. We propose some methods to overcome incomplete data problem and we use these methods to inference about the performance of a soccer player.     

Digital Image Processing

Many of the tasks encountered in image processing can be considered as problems in statistical inference. In particular, they fit naturally into a subjectivist Bayesian framework. In this paper, we describe the Bayesian approach to image analysis. Numerical examples are not included but can be found among the references, in the previous Special Issue of this Journal and elsewhere. It is argued that the Bayesian approach, still in its infancy, has considerable potential for future development.