arXiv subjects

Dominique-Laurent Couturier

Publications and source records attributed to Dominique-Laurent Couturier.

7 recordsLinked to original sources

arXiv2026

Days Alive at Home vs Out of Hospital: Why the Difference Matters for Trial Endpoints

Days Alive and Out of Hospital (DAOH) and Days Alive at Home (DAH) are increasingly used as patient-centred primary outcomes in perioperative trials, and a recent editorial has advocated DAOH for its simplicity and reliance on routinely collected data. We argue that the choice between these endpoints affects power, treatment effect estimation and missing data, and should be made at the design stage with these consequences in mind. By treating days in nursing homes or rehabilitation facilities as equivalent to days at home, DAOH assumes that being out of hospital is a valid surrogate for good recovery, an assumption that patient perspectives, including those from the NOTACS trial, call into question. Choosing DAH over DAOH therefore involves a trade-off between measuring what matters to patients more accurately and the added burden of tracking discharge destination, including a greater risk of missing data. If an intervention affects only length of stay, readmission or mortality, the two endpoints yield the same expected treatment effect, and the extra burden of tracking discharge destination brings no benefit. If it instead enables more patients to return directly home rather than to a care facility, DAOH may conceal this benefit and lose statistical power. We propose a baseline-adjusted DAH, which counts only days spent in a setting representing an escalation of care relative to the patient's baseline, as a better proxy for recovery that also accommodates hospital-at-home and virtual ward services.

stat.AP↗

arXiv2026

A fast, flexible simulation framework for Bayesian adaptive designs -- the R package BATSS

The use of Bayesian adaptive designs for randomised controlled trials has been hindered by the lack of software readily available to statisticians. We have developed a new software package (Bayesian Adaptive Trials Simulator Software - BATSS for the statistical software R, which provides a flexible structure for the fast simulation of Bayesian adaptive designs for clinical trials. We illustrate how the BATSS package can be used to define and evaluate the operating characteristics of Bayesian adaptive designs for various different types of primary outcomes (e.g., those that follow a normal, binary, Poisson or negative binomial distribution) and can incorporate the most common types of adaptations: stopping treatments (or the entire trial) for efficacy or futility, and Bayesian response adaptive randomisation - based on user-defined adaptation rules. Other important features of this highly modular package include: the use of (Integrated Nested) Laplace approximations to compute posterior distributions, parallel processing on a computer or a cluster, customisability, adjustment for covariates and a wide range of available conditional distributions for the response.

stat.CO↗

arXiv2026

Beyond the Composite: Enhancing Trial Analysis through a Divide & Conquer Approach to 'Days Alive and at Home': Insights from the NOTACS trial

"Days alive and at home" (DAH) is a recent patient-centered outcome measure for perioperative trials, defined as the number of days a patient spends at home during the follow-up period. DAH typically follows a zero-inflated, left-skewed, bi-modal distribution. Other increasingly used complex endpoints, such as days alive without a ventilator, share these statistical features arising from combining survival with another clinically relevant count outcome into a single, comprehensive measure. A key challenge for DAH and similar endpoints is the lack of a readily identifiable distributional form, which complicates the statistical design of trials using it as the primary endpoint, particularly regarding the robustness of sample size calculations and final analyses where the central limit theorem might not be suitable. Using 200 data points from the interim data of the NOTACS trial (ISRCTN14092678), whose primary endpoint was DAH, we developed a novel 'Divide & Conquer' model that breaks DAH into distinct parts modeled individually. To our knowledge, such a model has not been used before for DAH. We demonstrate that our approach significantly improves model fit compared to existing alternatives, enabling more suitable DAH data generation that can be used for simulation-based sample size calculations and evaluation of operating characteristics of the statistical test(s). Beyond NOTACS, our work has large potential to inform the design and analysis of other trials using DAH or similar complex endpoints.

stat.ME↗

arXiv2026

Component over Composite: Mitigating Type I Error Inflation when Imputing "Days Alive and at Home"

Background: Days Alive and at Home (DAH) over a pre-defined follow-up period is a novel post-intervention composite outcome that combines data from at least three components: (i) initial length of hospital stay, (ii) length of total readmissions or other post-discharge care and (iii) mortality. Missing values bring unique challenges to the analysis of trials with the DAH outcome as the three components may have different rates of missingness caused by distinct missing data mechanisms. Current approaches define DAH as missing if any of the components are missing, and proceed with complete cases or Multiple Imputation (MI) of the composite. Methods: Through a simulation study motivated by the NOTACS trial, we compare several methods of handling missing data, including complete case analysis, MI of the composite, and MI of the components when the primary analysis is a Mann-Whitney-Wilcoxon test. Results: MI on the component level has good properties in terms of type I error control and power. We caution against the use of MI on the composite level with Predictive Mean Matching, which can lead to type I error inflation. Conclusions: Given the complex distributional characteristics of DAH, naive approaches such as defining missingness on the composite level and directly imputing the composite with Predictive Mean Matching, can lead to type I error inflation. Imputing on the component level is recommended, suggested future work included imputation approaches that are compatible with more complex definitions of DAH, as well as recommendations for sensitivity analyses to the Missing at Random assumption.

stat.ME↗

arXiv2024

Multivariate Adjustments for Average Equivalence Testing

Multivariate (average) equivalence testing is widely used to assess whether the means of two conditions of interest are `equivalent' for different outcomes simultaneously. The multivariate Two One-Sided Tests (TOST) procedure is typically used in this context by checking if, outcome by outcome, the marginal $100(1-2α$)\% confidence intervals for the difference in means between the two conditions of interest lie within pre-defined lower and upper equivalence limits. This procedure, known to be conservative in the univariate case, leads to a rapid power loss when the number of outcomes increases, especially when one or more outcome variances are relatively large. In this work, we propose a finite-sample adjustment for this procedure, the multivariate $α$-TOST, that consists in a correction of $α$, the significance level, taking the (arbitrary) dependence between the outcomes of interest into account and making it uniformly more powerful than the conventional multivariate TOST. We present an iterative algorithm allowing to efficiently define $α^{\star}$, the corrected significance level, a task that proves challenging in the multivariate setting due to the inter-relationship between $α^{\star}$ and the sets of values belonging to the null hypothesis space and defining the test size. We study the operating characteristics of the multivariate $α$-TOST both theoretically and via an extensive simulation study considering cases relevant for real-world analyses -- i.e.,~relatively small sample sizes, unknown and heterogeneous variances, and different correlation structures -- and show the superior finite-sample properties of the multivariate $α$-TOST compared to its conventional counterpart. We finally re-visit a case study on ticlopidine hydrochloride and compare both methods when simultaneously assessing bioequivalence for multiple pharmacokinetic parameters.

stat.ME↗

arXiv2019

Proportional hazards model with partly interval censoring and its penalized likelihood estimation

This paper considers the problem of semi-parametric proportional hazards model fitting for interval, left and right censored survival times. We adopt a more versatile penalized likelihood method to estimate the baseline hazard and the regression coefficients simultaneously, where the penalty is introduced in order to regularize the baseline hazard estimate. We present asymptotic properties of our estimate, allowing for the possibility that it may lie on the boundary of the parameter space. We also provide a computational method based on marginal likelihood, which allows the regularization parameter to be determined automatically. Comparisons of our method with other approaches are given in simulations which demonstrate that our method has favourable performance. A real data application involving a model for melanoma recurrence is presented and an R package implementing the methods is available.

stat.ME↗

arXiv2011

Zero-inflated truncated generalized Pareto distribution for the analysis of radio audience data

Extreme value data with a high clump-at-zero occur in many domains. Moreover, it might happen that the observed data are either truncated below a given threshold and/or might not be reliable enough below that threshold because of the recording devices. These situations occur, in particular, with radio audience data measured using personal meters that record environmental noise every minute, that is then matched to one of the several radio programs. There are therefore genuine zeros for respondents not listening to the radio, but also zeros corresponding to real listeners for whom the match between the recorded noise and the radio program could not be achieved. Since radio audiences are important for radio broadcasters in order, for example, to determine advertisement price policies, possibly according to the type of audience at different time points, it is essential to be able to explain not only the probability of listening to a radio but also the average time spent listening to the radio by means of the characteristics of the listeners. In this paper we propose a generalized linear model for zero-inflated truncated Pareto distribution (ZITPo) that we use to fit audience radio data. Because it is based on the generalized Pareto distribution, the ZITPo model has nice properties such as model invariance to the choice of the threshold and from which a natural residual measure can be derived to assess the model fit to the data. From a general formulation of the most popular models for zero-inflated data, we derive our model by considering successively the truncated case, the generalized Pareto distribution and then the inclusion of covariates to explain the nonzero proportion of listeners and their average listening time. By means of simulations, we study the performance of the maximum likelihood estimator (and derived inference) and use the model to fully analyze the audience data of a radio station in a certain area of Switzerland.

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