Combining Multivariate Bioassays: Accurate Inference Using Small Sample Asymptotics

For several independent multivariate bioassays performed at different laboratories or locations, the problem of testing the homogeneity of the relative potencies is addressed, assuming the usual slope‐ratio or parallel line assay model. When the homogeneity hypothesis holds, interval estimation of the common relative potency is also addressed. These problems have been investigated in the literature using likelihood‐based methods, under the assumption of a common covariance matrix across the different studies. This assumption is relaxed in this investigation. Numerical results show that the usual likelihood‐based procedures are inaccurate for both of the above problems, in terms of providing inflated type I error probabilities for the homogeneity test, and providing coverage probabilities below the nominal level for the interval estimation of the common relative potency, unless the sample sizes are large, as expected. Correction based on small sample asymptotics is investigated in this article, and this provides significantly more accurate results in the small sample scenario. The results are also illustrated with examples.     

Multistate Survival Models as Transient Electrical Networks

In multistate survival analysis, the sojourn of a patient through various clinical states is shown to correspond to the diffusion of 1 C of electrical charge through an electrical network. The essential comparison has differentials of probability for the patient to correspond to differentials of charge, and it equates clinical states to electrical nodes. Indeed, if the death state of the patient corresponds to the sink node of the circuit, then the transient current that would be seen on an oscilloscope as the sink output is a plot of the probability density for the survival time of the patient. This electrical circuit analogy is further explored by considering the simplest possible survival model with two clinical states, alive and dead (sink), that incorporates censoring and truncation. The sink output seen on an oscilloscope is a plot of the Kaplan–Meier mass function. Thus, the Kaplan–Meier estimator finds motivation from the dynamics of current flow, as a fundamental physical law, rather than as a nonparametric maximum likelihood estimate (MLE). Generalization to competing risks settings with multiple death states (sinks) leads to cause‐specific Kaplan–Meier submass functions as outputs at sink nodes. With covariates present, the electrical analogy provides for an intuitive understanding of partial likelihood and various baseline hazard estimates often used with the proportional hazards model.     

Deconvolution Estimation of Onset of Pregnancy with Replicate Observations

In general, the precise date of onset of pregnancy is unknown and may only be estimated from ultrasound biometric measurements of the embryo. We want to estimate the density of the random variables corresponding to the interval between last menstrual period and true onset of pregnancy. The observations correspond to the variables of interest up to an additive noise. We suggest an estimation procedure based on deconvolution. It requires the knowledge of the density of the noise which is not available. But we have at our disposal another specific sample with replicate observations for twin pregnancies. This allows both to estimate the noise density and to improve the deconvolution step. Convergence rates of the final estimator are studied and compared with other settings. Our estimator involves a cut‐off parameter for which we propose a cross‐validation type procedure. Lastly, we estimate the target density in spontaneous pregnancies with an estimation of the noise obtained from replicate observations in twin pregnancies.     

The Copula Information Criteria

We derive two types of Akaike information criterion (AIC)‐like model‐selection formulae for the semiparametric pseudo‐maximum likelihood procedure. We first adapt the arguments leading to the original AIC formula, related to empirical estimation of a certain Kullback–Leibler information distance. This gives a significantly different formula compared with the AIC, which we name the copula information criterion. However, we show that such a model‐selection procedure cannot exist for copula models with densities that grow very fast near the edge of the unit cube. This problem affects most popular copula models. We then derive what we call the cross‐validation copula information criterion, which exists under weak conditions and is a first‐order approximation to exact cross validation. This formula is very similar to the standard AIC formula but has slightly different motivation. A brief illustration with real data is given.     

Non‐parametric Estimation of Extreme Risk Measures from Conditional Heavy‐tailed Distributions

In this paper, we introduce a new risk measure, the so‐called conditional tail moment. It is defined as the moment of order a ≥ 0 of the loss distribution above the upper α‐quantile where α ∈ (0,1). Estimating the conditional tail moment permits us to estimate all risk measures based on conditional moments such as conditional tail expectation, conditional value at risk or conditional tail variance. Here, we focus on the estimation of these risk measures in case of extreme losses (where α ↓0 is no longer fixed). It is moreover assumed that the loss distribution is heavy tailed and depends on a covariate. The estimation method thus combines non‐parametric kernel methods with extreme‐value statistics. The asymptotic distribution of the estimators is established, and their finite‐sample behaviour is illustrated both on simulated data and on a real data set of daily rainfalls.     

Prediction of Times to Failure of Censored Items for a Simple Step-Stress Model with Regular and Progressive Type I Censoring from the Exponential Distribution

The problem of predicting times to failure of units from the Exponential Distribution which are censored under a simple step-stress model is considered in this article. We discuss two types of censoring—regular and progressive Type I—and two kinds of predictors—the maximum likelihood predictors (MLP) and the conditional median predictors (CMP) for each type of censoring. Numerical examples are used to illustrate the prediction methods. Using simulation studies, mean squared prediction error (MSPE) and prediction intervals are generated for these examples. MLP and the CMP are then compared with respect to MSPE and the prediction interval.     

Asymptotic Comparison Between Constant-stress Testing and Step-stress Testing for Type-I Censored Data from Exponential Distribution

By running the life tests at higher stress levels than normal operating conditions, accelerated life testing quickly yields information on the lifetime distribution of a test unit. The lifetime at the design stress is then estimated through extrapolation using a regression model. In constant-stress testing, a unit is tested at a fixed stress level until failure or the termination time point of the test, while step-stress testing allows the experimenter to gradually increase the stress levels at some pre-fixed time points during the test. In this article, the optimal k-level constant-stress and step-stress accelerated life tests are compared for the exponential failure data under Type-I censoring. The objective is to quantify the advantage of using the step-stress testing relative to the constant-stress one. A log-linear relationship between the mean lifetime parameter and stress level is assumed and the cumulative exposure model holds for the effect of changing stress in step-stress testing. The optimal design point is then determined under C-optimality, D-optimality, and A-optimality criteria. The efficiency of step-stress testing compared to constant-stress testing is discussed in terms of the ratio of optimal objective functions based on the information matrix.