Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for healthcare policy and decision making

Objective: Network meta-analyses have extensively been used to compare the effectiveness of multiple interventions for healthcare policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Study design and setting: Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov Chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. Results: We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whilst MMSE at threshold <25/30 appeared to have the best true negative rate. Conclusion: The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making

Integer-valued time series and renewal processes

This research proposes a new but simple model for stationary time series of integer counts. Previous work in the area has focused on mixture and thinning methods and links to classical time series autoregressive moving-average difference equations; in contrast, our methods use a renewal process to generate a correlated sequence of Bernoulli trials. By superpositioning independent copies of such processes, stationary series with binomial, Poisson, geometric, or any other discrete marginal distribution can be readily constructed. The model class proposed is parsimonious, non-Markov, and readily generates series with either short or long memory autocovariances. The model can be fitted with linear prediction techniques for stationary series. Estimation of process parameters based on conditional least squares methods is considered. Asymptotic properties of the estimators are derived. The models sometimes have an autoregressive moving-average structure and we consider the AR(1) count process case in detail. Unlike previous methods based on mixture and thinning tactics, series with negative autocorrelations can be produced

Compound Markov counting processes and their applications to modeling infinitesimally over-dispersed systems

We propose an infinitesimal dispersion index for Markov counting processes. We show that, under standard moment existence conditions, a process is infinitesimally (over-) equi-dispersed if, and only if, it is simple (compound), i.e. it increases in jumps of one (or more) unit(s), even though infinitesimally equi-dispersed processes might be under-, equi- or over-dispersed using previously studied indices. Compound processes arise, for example, when introducing continuous-time white noise to the rates of simple processes resulting in Levy-driven SDEs. We construct multivariate infinitesimally over-dispersed compartment models and queuing networks, suitable for applications where moment constraints inherent to simple processes do not hold.Comment: 26 page

Modelling the joint distribution of competing risks survival times using copula functions

The problem of modelling the joint distribution of survival times in a competing risks model, using copula functions is considered. In order to evaluate this joint distribution and the related overall survival function, a system of non-linear differential equations is solved, which relates the crude and net survival functions of the modelled competing risks, through the copula. A similar approach to modelling dependent multiple decrements was applied by Carriere (1994) who used a Gaussian copula applied to an incomplete double decrement model which makes it difficult to calculate any actuarial functions and draw relevant conclusions. Here, we extend this methodology by studying the effect of complete and partial elimination of up to four competing risks on the overall survival function, the life expectancy and life annuity values. We further investigate how different choices of the copula function affect the resulting joint distribution of survival times and in particular the actuarial functions which are of importance in pricing life insurance and annuity products. For illustrative purposes, we have used a real data set and used extrapolation to prepare a complete multiple decrement model up to age 120. Extensive numerical results illustrate the sensitivity of the model with respect to the choice ofcopula and its parameter(s)