Search

Despite very different aetiologies and clinical expressions, advancing knowledge in the physiopathology and treatment of immune and inflammatory diseases (IID) prompts us to consider them as a whole. These are chronic, often incapacitating and painful illnesses that progress and destroy organs. Management by discipline too often leads to erroneous diagnoses and sometimes inappropriate treatment. More integrated translational research would further understanding of the complex relationships between cytokines and organ damage, which vary with the conditions and patients, making it possible to develop new biomarkers and personalize treatment. The research in France has very many strengths but its organization is fragmented. Better coordinated research into IID, which could be based on creating a strategic valorization field (domaine de valorisation stratégique, DVS) and thematic multi-organization institute (Institut thématique multi-organismes ITMO), would advance patient management.

Resume Malgre des etiologies et expressions cliniques tres diverses, la progression des connaissances dans les domaines de laphysiopathologie et de la therapeutique des pathologies immuno-inflammatoires (P2I)amene a les considerer de facon globale.Ce sont des maladies chroniques, souvent invalidantes et douloureuses, evolutives et destructrices d’organes. Leur prise en charge par discipline conduit trop souvent a des errances diagnostiques avec parfois une prise en charge inadaptee. Une recherche translationnelle plus integree permettrait de mieux comprendre les relations complexes entre cytokines et atteintes d’organes, qui sont variables selon les pathologies et les patients, de developper de nouveaux biomarqueurs et de personnaliser la the rapeutique. La recherche en France presente de tres nombreux atouts mais son organisation est morcelee. Une recherche sur les P2I mieux coordonnee, qui pourrait reposer sur la creation d’un domaine de valorisation strategique (DVS) et d’un institut thematique multi-organisme (ITMO) dedie, permettrait de faire progresser la prise en charge des patients.

Resume La population cible d’un medicament en vue du remboursement peut inclure differentes populations qui peuvent se recouvrir partiellement : la population qui a ete etudiee dans les essais cliniques, celle de l’autorisation de mise sur le marche (AMM), celle du service medical rendu (SMR), celle de l’amelioration du service medical rendu (ASMR), etc. Sa definition qualitative et quantitative implique des enjeux importants en termes de sante publique et economique. Des recommandations ont ete faites afin de clarifier les definitions, d’eclaircir les souhaits des decideurs publics et d’ameliorer les methodes et les sources permettant une quantification des populations cibles.

Resume Les donnees cliniques soumises au Comite des Medicaments a Usage Humain (CHMP) pour autorisation de mise sur le marche manquent frequemment de comparaisons directes pertinentes des produits. Ces comparaisons peuvent permettre aux autorites nationales chargees de l’approbation du remboursement d’apprecier l’Amelioration du Service Medical Rendu (ASMR) d’une substance active nouvelle ou d’une entite pharmaceutique existante en cas d’extension d’indication. Les comparaisons indirectes et comparaisons mixtes sont des procedes issus du domaine de la meta-analyse et concus pour aborder ce probleme. Les comparaisons indirectes ajustees, les meta-regressions, les modeles mixtes, les analyses en reseaux bayesiens regroupent les resultats d’essais controles randomises permettant une synthese quantitative des donnees. La procedure REAL (Relative Effectiveness Assessment of Listed drugs), recemment developpee en France par la Haute Autorite de Sante (HAS), associe une comparaison mixte et un modele d’effet base sur des avis d’experts. Elle est destinee a traduire l’efficacite observee au cours des essais en une efficacite potentielle attendue en France dans la pratique clinique quotidienne.

Frequently, in data packages submitted for Marketing Approval to the CHMP, there is a lack of relevant head-to- head comparisons of medicinal products that could enable national authorities responsible for the approval of reimbursement to assess the Added Therapeutic Value (ASMR) of new clinical entities or line extensions of existing therapies. Indirect or mixed treatment comparisons (MTC) are methods stemming from the field of meta-analysis that have been designed to tackle this problem. Adjusted indirect comparisons, meta-regressions, mixed models, Bayesian network analyses pool results of randomised controlled trials (RCTs), enabling a quantitative synthesis. The REAL procedure, recently developed by the HAS (French National Authority for Health), is a mixture of an MTC and effect model based on expert opinions. It is intended to translate the efficacy observed in the trials into effectiveness expected in day-to-day clinical practice in France.

Resume L’objectif general de l’etude etait d’identifier les mesures devant permettre d’ameliorer la performance de la recherche clinique en France. Methode Grâce a la discussion entre les membres de la table-ronde (composee de medecins investigateurs ; responsables hospitaliers ; representants de promoteurs industriels ; medecins generalistes...), nous avons passe en revue les difficultes que rencontrent la recherche clinique francaise aujourd’hui. Resultats Nous avons identifie quatre champs d’action : 1) la disponibilite des ressources necessaires a la conduite des protocoles de recherche (disponibilite en quantite et en temps, dans les delais les plus brefs) ; 2) la faisabilite, celle de l’essai dans le design de son protocole, celle du recrutement qui depend a la fois du centre/equipe/reseau investigateur et des patients et de l’image qu’ils ont de l’experimentation biomedicale ; 3) la qualification et la motivation des individualites et des metiers associes qui composent l’equipe conduisant les protocoles de recherche ; 4) la fluidite et l’efficacite de l’organisation administrative pour des temps preparatoires au demarrage des essais les plus reduits au profit du temps de realisation de l’essai. Conclusion Cette etude, qui n’a pas la pretention a l’exhaustivite, a montre l’ampleur des efforts pour ameliorer l’organisation francaise d’essais cliniques.

The general objective of this study was to proceed an inventory of measures which could help to improve the efficiency of clinical research in France. Method Thanks to the discussion between the members of the round-table conference (composed of medical doctors (MD)/investigators; hospital managers; representatives of industrial promoters; general practitioners...), we have looked over the difficulties that meets clinical research in France nowadays. Results We identified four fields of action: 1) availibility of resources for carrying out the trials in time and in quality; 2) feasability of the clinical trials, in their design and for the recruitment which depends on both of the investigation centers and patients (what is the image of human testing in the society?); 3) skills and motivation of all the elements of staffs in charge of clinical trials (MD; nurses; and the new jobs in medical research); 4) promptness and efficiency of the administrative organisation for a fast starting up of the trials. Conclusion This study, which doesn’t pretend to sufficiency, shows the gap of improvement for French clinical trials organisation.

The EPIGRAM pharmacoepidemiological study was conducted in general practitioners (GPs) prescribing orlistat (Xenical) in order to describe, under real clinical conditions, the management of obese or overweight patients, as well as a 1-year follow-up of a patient cohort treated with orlistat. A total of 714 GPs participated in this study and recruited a total of 6801 patients. Forty percent were treated with orlistat, 76% were women and 63% presented with a comorbidity. With a mean body mass index of 33.1+/-5.1 kg/m2, 85% of the patients treated with orlistat were in agreement with the indications of this drug. Comparison of patients treated and not treated with orlistat did not allow identification of any key factor able to predict prescription of the treatment. Patients treated with orlistat on inclusion and reviewed at least once by their doctor were followed up for an average of 11 months and a maximum of 23 months. Between 64% and 77% of patients stopped treatment with orlistat during the follow-up period. The treatment cost was the main reason for definitive treatment discontinuation for more than 50% of the patients. The average weight loss was 5% and 9% after 3 and 12 months of treatment, respectively.

Resume L’etude pharmacoepidemiologique EPIGRAM s’est attachee a decrire la prise en charge des patients obeses ou en surpoids et le suivi sur un an des patients traites par orlistat (Xenical®) en medecine generale. Des criteres de qualite specifiques a l’etude ont ete definis pour garantir la validite scientifique des resultats. Ils concernent principalement : la constitution d’un comite scientifique independant, l’echantillonnage des medecins, l’organisation de l’etude et le controle des donnees recueillies. Les controles sur site realises aupres d’un echantillon de 13 % des medecins actifs ont revele que 75 % des donnees controlees etaient documentees dans un dossier source, avec 85 % de concordance. Cent trente mille donnees ont ete controlees pour les seules visites effectivement renseignees, dont 1 % seulement a donne lieu a des demandes de correction. Parmi les patients traites par orlistat, 17 % n’ont pas ete revus par leur medecin apres l’inclusion et 25 % d’entre eux ont pu etre contactes directement a la fin de l’etude.

Round table no. 2 was devoted to the postmarketing evaluation of drugs. The debates involved both the questions posed by postmarketing evaluation and the methods for responding to them. The major categories of questions likely to be posed are as follows: efficacy in actual situations; safety in actual situations; prognostic factors and patients responding; place in the therapeutic strategy; impact on the healthcare care system; the ‘joined’ population (those who actually obtain benefit); and drug utilisation review. In addition, the methodological approaches have been divided into three categories: the experimental approach, the observational approach and the modelling approach. Each of these methodological approaches has been qualified with respect to each of the questions. The objective was neither to establish a classification of the methods according to the level of proof, nor to propose methodological formulae. Instead, the participants applied themselves to describe the strengths and the limits of the different methods for each of the questions in turn. The debates then focused on the process of identification of pertinent questions and appropriate methods. In this context, the round-table participants applied an analysis of the current system of postmarketing study projects and formulated some propositions for their improvement. Finally, the place of existing databases in the postmarketing evaluation was discussed and the participants emphasised the importance of initiating a very detailed assessment of the information that could be provided by such databases before instituting ad hoc studies.