Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Structuration, standardisation et enrichissement par traitement automatique du langage des données relatives au cancer au sein de l'entrepôt de données de santé de l'Assistance Publique -Hôpitaux de Paris

Cancer is a public health issue for which the improvement of care relies, among other levers, on the use of clinical data warehouses (CDWs). Their use involves overcoming obstacles such as the quality, standardization and structuring of the care data stored there. The objective of this thesis was to demonstrate that it is possible to address the challenges of secondary use of data from the Assistance Publique - Hôpitaux de Paris (AP-HP) CDW regarding cancer patients, and for various purposes such as monitoring the safety and quality of care, and performing observational and experimental clinical research. First, the identification of a minimal data set enabled to concentrate the effort of formalizing the items of interest specific to the discipline. From 15 identified items, 4 use cases from distinct medical perspectives were successfully developed: automation of calculations of safety and quality of care required for the international certification of health establishments , clinical epidemiology regarding the impact of public health measures during a pandemic on the delay in cancer diagnosis, decision support regarding the optimization of patient recruitment in clinical trials, development of neural networks regarding prognostication by computer vision. A second condition necessary for the CDW use in oncology is based on the optimal and interoperable formalization between several CDWs of this minimal data set. As part of the French PENELOPE initiative aiming at improving patient recruitment in clinical trials, the thesis assessed the added value of the oncology extension of the OMOP common data model. This version 5.4 of OMOP enabled to double the rate of formalization of prescreening criteria for phase I to IV clinical trials. Only 23% of these criteria could be automatically queried on the AP-HP CDW, and this, modulo a positive predictive value of less than 30%. This work suggested a novel methodology for evaluating the performance of a recruitment support system: based on the usual metrics (sensitivity, specificity, positive predictive value, negative predictive value), but also based on additional indicators characterizing the adequacy of the model chosen with the CDW related (rate of translation and execution of queries). Finally, the work showed how natural language processing related to the CDW data structuring could enrich the minimal data set, based on the baseline tumor dissemination assessment of a cancer diagnosis and on the histoprognostic characteristics of tumors. The comparison of textual extraction performance metrics and the human and technical resources necessary for the development of rules and machine learning systems made it possible to promote, for a certain number of situations, the first approach. The thesis identified that automatic rule-based preannotation before a manual annotation phase for training a machine learning model was an optimizable approach. The rules seemed to be sufficient for textual extraction tasks of a certain typology of entities that are well characterized on a lexical and semantic level. Anticipation and modeling of this typology could be possible upstream of the textual extraction phase, in order to differentiate, depending on each type of entity, to what extent machine learning should replace the rules. The thesis demonstrated that a close attention to a certain number of data science challenges allowed the efficient use of a CDW for various purposes in oncology.Le cancer est un enjeu de santé publique dont l’amélioration de la prise en charge repose, entre autres leviers, sur l’exploitation d’entrepôts de données de santé (EDS). Leur utilisation implique la maîtrise d’obstacles tels que la qualité, la standardisation et la structuration des données de soins qui y sont stockées. L’objectif de cette thèse était de démontrer qu’il est possible de lever les verrous d’utilisation secondaire des données de l’EDS de l’Assistance Publique - Hôpitaux de Paris (AP-HP) concernant des patients atteints de cancer à diverses finalités telles que le pilotage de la sécurité et de la qualité des soins, et les projets de recherche clinique observationnelle et expérimentale. En premier lieu, l’identification d’un jeu de données minimales a permis de concentrer l’effort de formalisation des items d’intérêt propres à la discipline. A partir de 15 items identifiés, 4 cas d’usages relevant de perspectives médicales distinctes ont pu être développés avec succès : pilotage concernant l’automatisation de calculs d’indicateurs de sécurité et de qualité des soins nécessaires à la certification internationale des établissements de santé, épidémiologie clinique concernant l’impact des mesures de santé publique en temps de pandémie sur le retard diagnostic des cancers, aide à la décision concernant l’optimisation du recrutement des patients dans des essais cliniques, développement de réseaux de neurones concernant la pronostication par vision par ordinateur. Une deuxième condition nécessaire à l’exploitation d’un EDS en oncologie repose sur la formalisation optimale et interopérable entre plusieurs EDS de ce jeu de données minimales. Dans le cadre de l’initiative française PENELOPE visant à améliorer le recrutement des patients dans des essais cliniques, la thèse a évalué la plus-value de l’extension oncologie du modèle de données commun OMOP. Cette version 5.4 d’OMOP permettait de doubler le taux de formalisation de critères de préscreening d’essais cliniques de phase I à IV. Seulement 23% de ces critères pouvaient être requetés automatiquement sur l’EDS de l’AP-HP, et ce, modulo une valeur prédictive positive inférieure à 30%. Ce travail propose une méthodologie inédite pour évaluer la performance d'un système d’aide au recrutement : à partir des métriques habituelles (sensibilité, spécificité, valeur prédictive positive, valeur prédictive négative), mais aussi à partir d’indicateurs complémentaires caractérisant l’adéquation du modèle choisi avec l’EDS concerné (taux de traduction et d'exécution des requêtes). Enfin, le travail a permis de montrer le caractère palliatif du traitement automatique du langage naturel concernant la structuration des données d'un EDS en informant le bilan d’extension initial d’un diagnostic de cancer et les caractéristiques histopronostiques des tumeurs. La confrontation des métriques de performance d’extraction textuelle et des ressources humaines et techniques nécessaires au développement de systèmes de règles et d’apprentissage automatique a permis de valoriser, pour un certain nombre de situations, la première approche. La thèse a identifié qu’une préannotation automatique à base de règles avant une phase d’annotation manuelle pour entraînement d’un modèle d’apprentissage machine était une approche optimisable. Les règles semblent suffire pour les tâches d’extraction textuelle d’une certaine typologie d’entités bien caractérisée sur un plan lexical et sémantique. L’anticipation et la modélisation de cette typologie pourrait être possible en amont de la phase d’extraction textuelle, afin de différencier, en fonction de chaque type d’entité, dans quelle mesure l’apprentissage machine devrait suppléer aux règles. La thèse a permis de démontrer qu’une attention portée à un certain nombre de thématiques des sciences des données permettait l’utilisation efficiente d’un EDS et ce, à des fins diverses en oncologie

Dépenses publiques dans une économie à deux pays : Stackelberg versus Nash

National audienceThis paper analyses strategic fiscal policy-making within the context of the standard two-country-two-good real trade model developped by TURNOVSKY (1988). Introducing asymmetry between the two countries and assuming that one country acts as a Stackelberg leader relative to the other one, we compare the welfare issued from the Nash equilibrium and the welfare for each country issued from the Stackelberg equilibrium. It happens that both countries benefi t from Stackelberg equilibrium with respect to the non cooperative equilibrium in the presence of strategic omplementarity, because both governments reduce their public pendings. In this model, strategic interactions depend on the relative value of elasticities of substitution between goods. There may either exist strategic substituability or complementarity.Cet article analyse l'impact sur le bien-être des agents des dépenses publiques nationales dans un modèle réel standard à deux pays lorsqu'un des pays est en position de leader de Stackelberg. Nous présentons l'équilibre de Stackelberg et le comparons à l'équilibre de Nash. Nous montrons que l'existence d'un pays meneur bénéficie au pays suiveur s'il existe des complémentarités stratégiques. Les interactions stratégiques dépendent dans ce modèle des élasticités de sustitution relatives entre les biens

“In conferences, everyone goes ‘health data is the future’ ”: an interview study on challenges in re-using EHR data for research in Clinical Data Warehouses

International audienceMore and more hospital Clinical Data Warehouses (CDWs) are developed to gain access to EHR data. The rapid growth of investments in CDWs suggest a real potential for innovation in healthcare. However, it is still not confirmedthat CDWs will deliver on their promises as researchers working with CDWs face many challenges. To gain a better understanding of these challenges and how to overcome them, we conducted a series of semi-structured interviewswith EHR data experts. In this article, we share some initial results from the ongoing interview study. Two main themes emerged from the analysis of the transcripts of the interviews: the importance of infrastructures in terms ofdata and how it is generated, and the difficulty to make care, clinical research, and data science work together. Finally, based on the experts’ experience, several recommendations were identified when using a CDW

Adverse events reporting in phase 3 oncology clinical trials of checkpoint inhibitors: A systematic review

International audienceIntroduction: This study aimed at exploring adverse events (AEs) reporting in cancer trials involving immune checkpoint inhibitors (ICIs).Method: A systematic review on how ICIs phase 3 trials follow TRIO and 2004 CONSORT harms extension recommendations referring to toxicity was performed by two independent reviewers.Results: Among 46 trials included, 74 % did not present separately grade 3 and grade 4 AEs. Timing of onset and duration were reported in 30 % and 28 %, respectively. AEs occurring in <10 % of patients were only reported in 35 % of studies. Patient-related outcomes (PROs) were analyzed in only 17 % of reports. Eight articles qualified the toxicity profile as "manageable", "tolerable", "well tolerated" or "favorable" despite reporting a rate of grade 3-4 greater than 33 %.Conclusion: Reporting toxicity results is crucial. However, toxicity reporting is highly incomplete in clinical trials. Guidelines, new metrics and incorporation of PROs are needed for a comprehensive knowledge of toxicity profile