Catherine Legrand

Université Catholique de Louvain - UCLouvain | UCLouvain · Louvain Institute for Data Analysis and Modeling (LIDAM)

Background: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumors is suboptimal. Objectives: To determine whether a short dermoscopy e-learning course (4 hours) in skin tumor diagnosis for PCPs is non-inferior to a long course (12 hours) in selective triage of skin lesions. S...

With the ongoing development of treatments and the resulting increase in survival in oncology, clinical trials based on endpoints such as overall survival may require long follow-up periods to observe sufficient events and ensure adequate statistical power. This increase in follow-up time may compromise the feasibility of the study. The use of surr...

In randomized clinical trials, methods of pairwise comparisons such as the ‘Net Benefit’ or the ‘win ratio’ have recently gained much attention when interests lies in assessing the effect of a treatment as compared to a standard of care. Among other advantages, these methods are usually praised for delivering a treatment measure that can easily han...

Over the last decade, the number of years of life lost (YLL) became a popular tool in biostatistics and epidemiology to measure differences in life expectancy or mortality, primarily thanks to its ease of interpretation and because information on the cause of death is not required. On the other hand, multistate models (MSMs) are a powerful statisti...

Introduction Une importante partie des activités réalisées dans le cadre du développement de vaccins a pour but d'assurer la maintenance de la qualité des vaccins enregistrés malgré les nombreuses modifications dans la chaine de production. L'impact des changements doit pouvoir être évalué sur base de paramètres techniques qui sont utilisés comme i...

Advancements in medicine and biostatistics have already resulted in a better access to insurance for people diagnosed with cancer. This materializes into the “right to be forgotten” adopted in several EU member states, granting access to insurance after a waiting period of at most 10 years starting at the end of the successful therapeutic protocol....

Le 28 février dernier se tenait la Journée internationale des maladies rares. Alors que 6 à 8% de la population belge serait atteinte d’une maladie rare, on estime que 94% de ces maladies rares n’ont pas de traitement. Pour la petite proportion de maladies rares pour lesquelles un traitement est disponible, le processus allant de la découverte d’un...

Background Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients w...

In RCTs with an interest in a long-term efficacy endpoint, the follow-up time necessary to observe the endpoint may be substantial. In order to reduce the expected duration of such trials, early-outcome data may be collected to enrich an interim analysis aimed at stopping the trial early for efficacy. We propose to extend such a design with an addi...

Les prêts immobiliers et professionnels sont généralement accompagnés d'une assurance solde restant dû qui couvre le solde du prêt si le client décède. Face à des clients atteints d'un cancer, les banques et assureurs imposent généralement un surcoût voire même refusent de les assurer, ce qui est vu par ces personnes comme un frein à la propriété o...

Introduction Un outil en biostatistique pour mesurer la différence d’espérance de vie ou de mortalité chez les patients cancéreux est le nombre d’années de vie perdues (YLL), quantifiant le nombre d’années de vie qu’une cohorte de patients a perdu par rapport à la population générale. L’analyse de survie est une classe de modèles avec deux états et...

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diag...

The Massart (J Cancer Policy 15:70-71, 2018) testimonial illustrates the difficulties faced by patients having survived cancer to access mortgage insurance securing home loan. Data collected by national registries nevertheless suggest that excess mortality due to some types of cancer becomes moderate or even negligible after some waiting period. In...

In survival analysis with competing risks, the treatment effect is typically expressed using cause-specific or subdistribution hazard ratios, both relying on proportional hazards assumptions. This paper proposes a nonparametric approach to analyze competing risks data based on generalized pairwise comparisons (GPC). GPC estimate the net benefit, de...

The methodological challenges to effectiveness evaluation of complex interventions has been widely discussed. Bottom-up case management for frail older person was implemented in Belgium, and indeed, it was evaluated as a complex intervention. This paper presents the methodological approach we developed to respond to four main methodological challen...

Medical time-to-event studies frequently include two groups of patients: those who will not experience the event of interest and are said to be “cured” and those who will develop the event and are said to be “susceptible”. However, the cure status is unobserved in (right-)censored patients. While most of the work on cure models focuses on the time-...

Background: Better understanding of risk factors for adverse events during monitored anaesthesia care (MAC) for paediatric gastrointestinal endoscopy may improve outcome in children. Objectives: To identify the prevalence and predictors of adverse events during MAC for paediatric endoscopy. Design: An observational study. Setting: Tertiary u...

Background In uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra‐tumor immune population, compare it to other established biomarkers and to patients' outcome. Methods Primary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed usi...

Background: Adjuvants like AS01B increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase II randomized trial was conducted to characterize the response to AS01B and Alum adjuvanted vaccines. A post-hoc analysis was performed to examine the associations between reactogenicity and in...

In this paper, we extend the vertical modeling approach for the analysis of survival data with competing risks to incorporate a cured fraction in the population, that is, a proportion of the population for which none of the competing events can occur. The proposed method has three components: the proportion of cure, the risk of failure, irrespectiv...

51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Milan, ITALY, JUN 16-19, 2018

A well‐known problem in classical two‐tailed hypothesis testing is that P‐values go to zero when the sample size goes to infinity, irrespectively of the effect size. This pitfall can make the testing of data consisting of large sample sizes potentially unreliable. In this note, we propose to test for relevant differences to overcome this issue. We...

In survival analysis it often happens that a certain fraction of the subjects under study never experience the event of interest, i.e. they are considered ‘cured’. In the presence of covariates, a common model for this type of data is the mixture cure model, which assumes that the population consists of two subpopulations, namely the cured and the...

Measurement error in the continuous covariates of a model generally yields bias in the estimators. It is a frequent problem in practice, and many correction procedures have been developed for different classes of models. However, in most cases, some information about the measurement error distribution is required. When neither validation nor auxili...

This short note supplements the paper by Glschössl et al. (Eur Actuar J 1:23–41, 2011) with an efficient method allowing actuaries to include continuous covariates in their life tables, such as the sum insured for instance. Compared to the classical approach based on grouped data adopted in the majority of actuarial mortality studies, individual ob...

In many situations in survival analysis, it may happen that a fraction of individuals will never experience the event of interest: They are considered to be cured. The promotion time cure model takes this into account. We consider the case where one or more explanatory variables in the model are subject to measurement error, which should be taken i...

Contrary to what is generally assumed in survival analysis, a fraction of the population under study may never develop the event of interest. This special feature is more and more encountered, and referred to as the presence of a cure fraction. Also, in many studies, patients come at scheduled interviews. The event times are thus not exactly observ...

Models for interval-censored survival data presenting a fraction of “cure” or “immune” patients have recently been proposed in the literature, particularly extending the mixture cure model to interval-censored data. However, little is known about the goodness-of-fit of such models. In a mixture cure model, the survival distribution of the entire po...

In medical applications, time-to-event data is frequently encountered. While classical survival methods are well known and broadly used to analyze such data, they do not take into account two phenomena which appear quite often in practice: the presence of individuals who will never experience the event of interest (they are cured from this event) a...

As part of central statistical monitoring of multicenter clinical trial data, we propose a procedure based on the beta-binomial distribution for the detection of centers with atypical values for the probability of some event. The procedure makes no assumptions about the typical event proportion and uses the event counts from all centers to derive a...

Supporting Info Item

Proportional hazards models are among the most popular regression models in survival analysis. Multi-state models generalize them by jointly considering different types of events and their interrelations, whereas frailty models incorporate random effects to account for unobserved risk factors, possibly shared by clusters of subjects. The integratio...

Frailty models adjust for between-cluster variability in survival data by including a cluster-specific random factor, the frailty term, in the Cox model. The frailty term is assumed to be constant over time. This assumption is questionable in some particular settings, e.g., in cancer clinical trials on chronic myeloid leukaemia. We therefore relax...

In standard survival analysis, it is generally assumed that every individual will experience someday the event of interest. However, this is not always the case, as some individuals may not be susceptible to this event. Also, in medical studies, it is frequent that patients come to scheduled interviews and that the time to the event is only known t...

Data quality may impact the outcome of clinical trials; hence, there is a need to implement quality control strategies for the data collected. Traditional approaches to quality control have primarily used source data verification during on-site monitoring visits, but these approaches are hugely expensive as well as ineffective. There is growing int...

Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not avail...

Background. To investigate the relationship between hemagglutinin-inhibition (HI) antibody levels to the risk of influenza disease, we conducted a correlate of protection analysis using pooled data from previously published randomized trials. Methods. Data on the occurrence of laboratory-confirmed influenza and HI levels pre- and postvaccination we...

The success of a seasonal influenza vaccine efficacy trial depends not only upon the design but also upon the annual epidemic characteristics. In this context, simulation methods are an essential tool in evaluating the performances of study designs under various circumstances. However, traditional methods for simulating time-to-event data are not s...

Dermoscopy is a technique which improves melanoma detection. Optical dermoscopy uses a handheld optical device to observe the skin lesions without recording the images. Sequential digital dermoscopy imaging (SDDI) allows storage of the pictures and their comparison over time. Few studies have compared optical dermoscopy and SDDI from an economic pe...

Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this contex...

Few studies about health-related quality of life (HRQoL) in patients with melanoma have expressed their results in terms of utilities or disability weights (DWs). Utilities are required for calculating quality-adjusted life years and therefore for cost-effectiveness analyses. DWs are useful to assess the burden of diseases through disability-adjust...

Conducting a clinical trial at multiple study centres raises the issue of whether and how to adjust for centre heterogeneity in the statistical analysis. In this paper, we address this issue for multicentre clinical trials with a time-to-event outcome. Based on simulations, we show that the current practice of ignoring centre heterogeneity can be s...

Consider semi-competing risks data (two times to concurrent events are studied but only one of them is right-censored by the other one) where the link between the times Y and C to non-terminal and terminal events, respectively, is modeled by a family of Archimedean copulas. Moreover, both Y and C are submitted to an independent right censoring vari...

The semi-parametric proportional hazards model with crossed random effects has two important characteristics: it avoids explicit specification of the response time distribution by using semi-parametric models, and it captures heterogeneity that is due to subjects and items. The proposed model has a proportionality parameter for the speed of each te...

Inflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries. We performed an observational stu...

The efficacy assessment of an influenza vaccine often requires conducting large and expensive clinical trials. Specificities of influenza increase the complexity of the study designs, of the subsequent statistical analysis and of the interpretation of the results. They include low attack rates, seasonality, multiplicity and frequent mutations of fl...

e16010 Background: PSA kinetic measures are often reported as prognostic factors for overall survival (OS) in mCRPC pts. The objective of this study is to investigate the prognostic value of various summary measures of pre- and post-treatment PSA kinetics on OS in patients treated with cabazitaxel or mitoxantrone following progression during or aft...

Frailty models are getting more and more popular to account for overdispersion and/or clustering in survival data. When the form of the baseline hazard is somehow known in advance, the parametric estimation approach can be used advantageously. Nonetheless, there is no unified widely available software that deals with the parametric frailty model. T...

Generating survival data with a clustered and multi-state structure is useful to study finite sample properties of multi-state models, competing risks models and frailty models. We propose a simulation procedure based on a copula model for each competing events block, allowing to introduce dependence between times of different transitions and betwe...

Background: Classical monitoring approaches rely on extensive on-site visits and source data verification. These activities are associated with high cost and a limited contribution to data quality. Central statistical monitoring is of particular interest to address these shortcomings. Purpose: This article outlines the principles of central stat...

We propose a way to incorporate frailties into multi-state models to account for clustering in complex survival data. Estimation is possible via maximum penalized partial likelihood. This model can both account for risk differences between groups and model the risk of different events simultaneously

Background Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice. Objectives To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone...

The potential impact of intraoperative analgesics on oncological outcome after radical prostatectomy is debated. Some investigators have suggested that use of opioids favour relapse, whereas regional analgesia and NSAIDs improve oncological outcomes. To evaluate the impact of intraoperative analgesia (epidural and intravenous) on the incidence of b...

Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tom...

Despite the use of standardized protocols in, multi-centre, randomized clinical trials, outcome may vary between centres. Such heterogeneity may alter the interpretation and reporting of the treatment effect. Below, we propose a general frailty modelling approach for investigating, inter alia, putative treatment-by-centre interactions in time-to-ev...

Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value. Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 c...

The armed forces are highly exposed to occupational noise. The aim of this study was to evaluate the prevalence and noise exposures associated with the severity of hearing loss (HL) in a Belgian military population. A cross-sectional study was carried out at the Centre for Medical Expertise (CME) and in four Units of Occupational Medicine (UOM). He...

Algorithm selection is typically based on models of algorithm performance,learned during a separate offline training sequence, which can be prohibitively expensive. In recent work, we adopted an online approach, in which models of the runtime distributions of the available algorithms are iteratively updated and used to guide the allocation of compu...

Whether intraoperative analgesics have an impact on postoperative cancer recurrence is unknown. Some investigations suggest that the opioids could favor relapse and that regional analgesia and nonsteroidal antiinflammatory drugs could improve cancer prognosis. We retrospectively reviewed our series of breast cancer surgery patients. This retrospect...

Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering car...

Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation. To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with...

Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies. To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma. A total of 583 adults with acute asthma were treated with standard care during a < or = 60-minute screening period. Patie...

In many applications, we assume that two random observations x and y are generated according to independent Poisson distributions \hbox{$\PPP(\lambda S)$}𝒫(λS) and \hbox{$\PPP(\mu T)$}𝒫(μT) and we are interested in performing statistical inference on the ratio φ = λ / μ of the two incidence rates. In vaccine efficacy trials, x and y are typically t...

The learning curves of optimisation algorithms, plotting the evolution of the objective vs. runtime spent. can be viewed as a sample of longitudinal data. In this paper we describe mixed-effects modeling, a standard technique in longitudinal data analysis, and give an example of its application to algorithm performance modeling.

For cytostatic agents or when the response assessment is difficult, adaptations to phase II designs may allow a better assessment of therapeutic activity: first by using the progression-free survival rate (PFSR) as primary end-point instead of the response rate, and second by considering progression-free survival (PFS) risk groups based on a progno...

A major issue when proposing a new prognostic index is its generalisibility to daily clinical practice. Validation is therefore required. Most validation techniques assess whether "on average" the results obtained by the prognostic index in classifying patients in a new sample of patients are similar to the results obtained in the construction set....