121 results on '"Hulstaert, Frank"'
Search Results
2. Defining the role of real-world data in cancer clinical research: The position of the European Organisation for Research and Treatment of Cancer
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Saesen, Robbe, Van Hemelrijck, Mieke, Bogaerts, Jan, Booth, Christopher M., Cornelissen, Jan J., Dekker, Andre, Eisenhauer, Elizabeth A., Freitas, André, Gronchi, Alessandro, Hernán, Miguel A., Hulstaert, Frank, Ost, Piet, Szturz, Petr, Verkooijen, Helena M., Weller, Michael, Wilson, Roger, Lacombe, Denis, and van der Graaf, Winette T.
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- 2023
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3. Belgian observational survival data (incidence years 2004–2017) and expenditure for innovative oncology drugs in twelve cancer indications
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, Silversmit, Geert, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Hulstaert, Frank, and Verleye, Leen
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- 2023
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4. Survival of patients with unfavorable prognosis cutaneous melanoma with increased use of immunotherapy agents: a population‐based study in Belgium.
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Castanares‐Zapatero, Diego, Verleye, Leen, Devos, Carl, Thiry, Nancy, Silversmit, Geert, Van Damme, Nancy, De Gendt, Cindy, Hulstaert, Frank, and Neyt, Mattias
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OVERALL survival ,PROGNOSIS ,SURVIVAL rate ,IMMUNOTHERAPY ,MELANOMA ,HEALTH insurance - Abstract
Background: Although metastatic cutaneous melanoma is associated with an unfavorable prognosis, innovative therapies including immunomodulating agents and targeted therapies have shown survival benefits in clinical trials. We assessed the impact of the introduction of innovative drugs into clinical practice on the survival of patients with metastatic cutaneous melanoma during the period 2004–2017, in Belgium. The evolution of associated expenses was also analyzed. Methods: This is a retrospective population‐based study using data from the national Belgian Cancer Registry, compulsory health insurance, and administrative survival data. The immunomodulating drugs were ipilimumab, nivolumab and pembrolizumab, while targeted therapies included vemurafenib, dabrafenib and trametinib. Results: We did not identify a trend for improvement over time. Median survival (years) was 1.5 (95% CI: 1.1–1.8) in 2004–2008, 1.1 (95% CI: 0.8–1.5) in 2009–2013, and 1.6 (95% CI: 1.3–2.4) in 2014–2017, respectively. In contrast, survival improved in those with unknown primary tumor localization. In this group, median survival time was 2.0 (95% CI: 1.4–2.9) in the most recent period, while it was 1.1 (95% CI: 0.7–1.3) in 2009–2013, and 0.9 (95% CI: 0.6–1.2) in 2004–2008. The uptake of innovative drugs remained modest, with no drug being used by more than 30% of patients. Yearly expenditure was almost non‐existent, and gradually increased, reaching several million euros in 2014–2017. Conclusion: Patients with metastatic cutaneous melanoma who were diagnosed between 2004 and 2017 showed no apparent improvement in survival. In contrast, increased survival was observed in the subgroup of patients with unknown primary tumor localization. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial
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Declercq, Jozefien, Van Damme, Karel F A, De Leeuw, Elisabeth, Maes, Bastiaan, Bosteels, Cedric, Tavernier, Simon J, De Buyser, Stefanie, Colman, Roos, Hites, Maya, Verschelden, Gil, Fivez, Tom, Moerman, Filip, Demedts, Ingel K, Dauby, Nicolas, De Schryver, Nicolas, Govaerts, Elke, Vandecasteele, Stefaan J, Van Laethem, Johan, Anguille, Sebastien, van der Hilst, Jeroen, Misset, Benoit, Slabbynck, Hans, Wittebole, Xavier, Liénart, Fabienne, Legrand, Catherine, Buyse, Marc, Stevens, Dieter, Bauters, Fre, Seys, Leen J M, Aegerter, Helena, Smole, Ursula, Bosteels, Victor, Hoste, Levi, Naesens, Leslie, Haerynck, Filomeen, Vandekerckhove, Linos, Depuydt, Pieter, van Braeckel, Eva, Rottey, Sylvie, Peene, Isabelle, Van Der Straeten, Catherine, Hulstaert, Frank, and Lambrecht, Bart N
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- 2021
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6. Effectiveness of nirmatrelvir‐ritonavir on severe outcomes of COVID‐19 in the era of vaccination and Omicron: An updated meta‐analysis
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Ombelet, Sien, primary, Castanares‐Zapatero, Diego, additional, Desimpel, Fabian, additional, Hulstaert, Frank, additional, Stordeur, Sabine, additional, and Roberfroid, Dominique, additional
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- 2024
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7. Budgeting of non-commercial clinical trials: development of a budget tool by a public funding agency
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Nevens, Hilde, Harrison, Jillian, Vrijens, France, Verleye, Leen, Stocquart, Nelle, Marynen, Elisabeth, and Hulstaert, Frank
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- 2019
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8. Replacing RCTs with real world data for regulatory decision making: a self-fulfilling prophecy?
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Wieseler, Beate, primary, Neyt, Mattias, additional, Kaiser, Thomas, additional, Hulstaert, Frank, additional, and Windeler, Jürgen, additional
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- 2023
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9. Survival in stage IV ovarian cancer with increased use of debulking surgery and bevacizumab
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Verleye, Leen, primary, Castanares-Zapatero, Diego, additional, Devos, Carl, additional, De Gendt, Cindy, additional, Silversmit, Geert, additional, Van Damme, Nancy, additional, Hulstaert, Frank, additional, Thiry, Nancy, additional, and Neyt, Mattias, additional
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- 2023
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10. Proton Therapy in Children: A Systematic Review of Clinical Effectiveness in 15 Pediatric Cancers
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Leroy, Roos, Benahmed, Nadia, Hulstaert, Frank, Van Damme, Nancy, and De Ruysscher, Dirk
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- 2016
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11. Contingent non-invasive prenatal testing: an opportunity to improve non-genetic aspects of fetal aneuploidy screening
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Gyselaers, Wilfried, Hulstaert, Frank, and Neyt, Mattias
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- 2015
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12. The importance of test accuracy in economic evaluations of companion diagnostics
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Miguel, Lorena San and Hulstaert, Frank
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- 2015
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13. Stereotactic Body Radiotherapy for Lung Cancer: How Much Does it Really Cost?
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Lievens, Yolande, Obyn, Caroline, Mertens, Anne-Sophie, Halewyck, Dries Van, and Hulstaert, Frank
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- 2015
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14. Evidence gaps for drugs and medical devices at market entry in Europe and potential solutions
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Hulstaert, Frank, Pouppez, Céline, Primus-de Jong, Célia, Harkin, Kathleen, and Neyt, Mattias
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Technology Assessment, Biomedical ,Pharmaceutical Preparations ,R347 ,Device Approval ,2019-08 ,Prostheses and Implants ,Drug Approval ,WB 102.5 Evidence-based practice - Abstract
221 p. ill., SCIENTIFIC REPORT 13 -- 1 INTRODUCTION, AIMS AND SCOPE OF THIS REPORT 13 -- 1.1 BACKGROUND 13 -- 1.2 THE REGULATORY SYSTEM OF MEDICINAL PRODUCTS AND MEDICAL DEVICES 17 -- 1.3 HEALTH TECHNOLOGY ASSESSMENT AND COVERAGE OF HEALTHCARE 17 -- 1.4 NEW EU REGULATIONS FOR MEDICAL DEVICES AND PHARMACEUTICALS 19 -- 1.5 AIMS AND SCOPE OF THIS PROJECT 20 -- 2 METHODS 22 -- 3 LEGAL AND ETHICAL CONSIDERATIONS 23 -- 3.1 INTRODUCTION: THE LEGAL AND ETHICAL FRAMEWORKS ON EVIDENCE REQUIREMENTS 23 -- 3.2 METHODOLOGY 24 -- 3.3 APPLICABLE RULES 25 -- 3.4 EVIDENTIARY REQUIREMENTS FOR MEDICINAL PRODUCTS AND MEDICAL DEVICES 28 -- 3.4.1 Ethical rules for the conduct of clinical trials 28 -- 3.4.2 Research and human rights 32 -- 3.4.3 Evidentiary requirements in the marketing authorisation process for medicines 33 -- 3.4.4 Evidentiary requirements in the CE-marking process for high-risk medical devices 47 -- 3.4.5 The role of ethics committees in reviewing the evidence and the Belgian situation 61 -- 3.5 TRANSPARENCY REQUIREMENTS FOR CLINICAL DATA 64 -- 3.5.1 Ethical rules regarding the transparency on clinical trials data 64 -- 3.5.2 Transparency requirements in the regulatory framework for medicines 65 -- 3.5.3 Transparency requirements for Medical devices 69 -- 3.5.4 Transparency of national reimbursement decisions 73 -- 3.5.5 Enforcement and penalties 73 -- 3.6 CONCLUSION / DISCUSSION REGARDING LEGAL FRAMEWORK 75 -- 4 ANALYSIS OF RIZIV-INAMI DOSSIERS 76 -- 4.1 METHODS 76 -- 4.2 FINDINGS 77 -- 4.2.1 Applications for reimbursement of 18 medicinal products 77 -- 4.2.2 Applications for reimbursement of 18 medical devices 81 -- 5 LITERATURE REVIEW 85 -- 5.1 METHODS 85 -- 5.1.1 Search strategy 85 -- 5.1.2 Selection procedure 86 -- 5.1.3 Selection criteria 87 -- 5.2 OVERVIEW OF THE LITERATURE ON MEDICINAL PRODUCTS 87 -- 5.2.1 Introduction 87 -- 5.2.2 Evidence gaps at market entry (and in the post-market period) 93 -- 5.2.3 Evidence gaps and reimbursement decisions 97 -- 5.2.4 Need for more collaboration (e.g. between regulators and HTA bodies) 98 -- 5.2.5 Use of surrogate endpoints 101 -- 5.2.6 Early patient access, conditional marketing authorisation and managed entry agreements 103 -- 5.3 OVERVIEW OF LITERATURE ON MEDICAL DEVICES 105 -- 5.3.1 Introduction 105 -- 5.3.2 The selected publications 109 -- 5.3.3 Recurring issues in the articles: 115 -- 6 DISCUSSION AND POSSIBLE SOLUTIONS 117 -- 6.1 THE TENSION BETWEEN BUSINESS PRIORITIES AND PATIENT BENEFIT 117 -- 6.1.1 The healthcare economy, important but not the scope of this project 117 -- 6.1.2 Hard law or ethical rules to manage business priorities versus patient benefit? 118 -- 6.1.3 The assessment of true innovation requires a direct comparison of patient benefit 119 -- 6.1.4 Horizon scanning and current limitations affecting the impact of early dialogue and common scientific advice 120 -- 6.1.5 The failed promise of post-marketing trials, coverage with evidence development and managed entry agreements 120 -- 6.2 TOWARDS A CLINICAL DEVELOPMENT PATHWAY THAT BETTER MEETS THE DEMANDS OF REGULATORS AND HTA BODIES 124 -- 6.2.1 The need for a better collaboration between regulators and HTA bodies 124 -- 6.2.2 The split between regulators and HTA bodies, an example of inefficient governance? 125 -- 6.3 EVIDENCE GAPS GROUPED ACCORDING TO THE PICOTS FRAMEWORK 125 -- 6.3.1 Population: keep the randomization but include the routine care patients, all evidence in patient subpopulations should be detailed 126 -- 6.3.2 Intervention: knowledge of optimal dose and duration is key, routine care to be reflected as much as possible 126 -- 6.3.3 The (active) comparator: the Helsinki declaration and the EMA 126 -- 6.3.4 Outcomes: focus on patient-relevant outcomes instead of surrogates that are not validated 128 -- 6.3.5 Study design and time periods, the opportunities and risks of relying only on observational real-world data 129 -- 6.3.6 Should the evidence bar be lower for medical devices? 133 -- 6.4 ON TRANSPARENCY AND REPORTING 135 -- 6.4.1 The case of medicinal products 135 -- 6.4.2 The case of medical devices 135 -- 6.5 PUBLISHED POLICY RECOMMENDATIONS 136 -- 7 RECOMMENDATIONS 139 -- 7.1 FOR THE EUROPEAN COMMISSION AND MEMBER STATES GOVERNMENTS 139 -- 7.2 FOR MEDICAL AND SURGICAL SCIENTIFIC SOCIETIES 140 -- 7.3 FOR (HIGH-RISK) MEDICAL DEVICE INDUSTRY 140 -- 7.4 FOR ALL ETHICS COMMITTEES IN BELGIUM AND ABROAD 141 -- 7.5 FOR ALL CONSUMER ORGANISATIONS AND PATIENT ORGANISATIONS 141 -- 7.6 TO RIZIV-INAMI, HTA AGENCIES AND PAYERS 141 -- 7.7 TO RIZIV-INAMI, INTERNATIONAL HTA AGENCIES, AND JOURNAL EDITORS 141 -- APPENDICES 142
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- 2021
15. Mise sur le marché des médicaments et des dispositifs médicaux en Europe : manque de données probantes et solutions possibles : Synthése
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Hulstaert, Frank, Pouppez, Céline, Primus-de Jong, Célia, Harkin, Kathleen, and Neyt, Mattias
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Technology Assessment, Biomedical ,Pharmaceutical Preparations ,R347 ,Device Approval ,2019-08 ,Prostheses and Implants ,Drug Approval ,WB 102.5 Evidence-based practice - Abstract
43 p. ill., Pour obtenir l’autorisation de mise sur le marché européen, tout nouveau médicament doit faire la preuve de sa qualité, de sa sécurité et de son efficacité. Pour les dispositifs médicaux à haut risque (comme p. ex. les implants), les exigences sont moindres. Mais aux yeux de l’assurance maladie, des médecins et des patients, ce qui compte surtout, c’est la valeur du nouveau produit par comparaison aux traitements déjà existants. Le problème est que les études comparatives – et qui mesurent des paramètres significatifs pour les patients – ne sont pas obligatoires pour obtenir une autorisation de mise sur le marché. La principale recommandation du Centre fédéral d’Expertise des Soins de santé (KCE) est que les firmes pharmaceutiques ou de dispositifs médicaux ne conçoivent pas seulement leurs études cliniques pour rencontrer les exigences actuelles de l’accès au marché européen, mais qu’elles collectent aussi, dès le départ, des données comparatives leur permettant de répondre aux demandes des organismes d’assurance maladie nationaux, des médecins et des patients. L’étude du KCE arrive à point nommé, compte tenu des évolutions récentes des différents règlements européens relatifs aux médicaments et aux dispositifs médicaux. SYNTHÈSE 2 -- 1. INTRODUCTION, OBJECTIF ET MÉTHODOLOGIE 4 -- 1.1. L’ACCÈS AU MARCHÉ EST RÉGLEMENTÉ AU NIVEAU EUROPÉEN, ALORS QUE LE REMBOURSEMENT EST FIXÉ PAR LES ÉTATS MEMBRES. 5 -- 1.1.1. Médicaments 5 -- 1.1.2. Dispositifs médicaux 6 -- 1.1.3. Évolution de la réglementation européenne 7 -- 1.2. INITIATIVES QUI ONT AUGMENTÉ LES EVIDENCE GAP ET INITIATIVES VISANT À LES COMBLER 7 -- 1.3. OBJECTIF DE CETTE ÉTUDE ET QUESTIONS DE RECHERCHE 8 -- 1.4. MÉTHODOLOGIE 8 -- 2. CONSIDÉRATIONS ÉTHIQUES ET JURIDIQUES 11 -- 2.1. NORMES ÉTHIQUES EN MATIÈRE D’ÉVIDENCE ET DE TRANSPARENCE 11 -- 2.2. LÉGISLATIONS EUROPÉENNES SUR LES MÉDICAMENTS 12 -- 2.2.1. Exigences en matière de données probantes 12 -- 2.2.2. Procédure d’autorisation des essais cliniques 12 -- 2.2.3. Exigences en matière de transparence 12 -- 2.3. LÉGISLATIONS EUROPÉENNES SUR LES DISPOSITIFS MÉDICAUX 13 -- 2.3.1. Exigences en matière de données probantes 13 -- 2.3.2. Procédure d’autorisation des investigations cliniques 13 -- 2.3.3. Exigences en matière de transparence 14 -- 2.4. ÉVALUATION EUROPÉENNE DES TECHNOLOGIES DE LA SANTÉ 14 -- 3. ANALYSE DES DOSSIERS DE L’INAMI 15 -- 3.1.1. Résultats pour les 18 dossiers d’évaluation de médicaments. 16 -- 3.1.2. Résultats pour les 18 dossiers d’évaluation de dispositifs médicaux 16 -- 4. REVUE DE LITTÉRATURE 16 -- 4.1. MÉDICAMENTS 16 -- 4.2. DISPOSITIFS MÉDICAUX 17 -- 5. DISCUSSION ET POSSIBLES SOLUTIONS 18 -- 5.1. COLLABORATIONS ENTRE LES AUTORITÉS RÉGLEMENTAIRES ET LES AGENCES D’HTA, UN RENFORCEMENT DE LA COLLABORATION EST NÉCESSAIRE 19 -- 5.1.1. Exigences relatives à la population étudiée 22 -- 5.1.2. Exigences relatives à l’intervention étudiée 22 -- 5.1.3. Exigences relatives au comparateur utilisé 22 -- 5.1.4. Exigences relatives aux critères d’évaluation (outcomes) 24 -- 5.1.5. Vers des études cliniques plus efficientes : limites des données observationnelles et des études ‘real world’ 25 -- 5.1.6. Le seuil d’exigence peut-il être abaissé pour les dispositifs médicaux? 26 -- 5.2. EXIGENCES DE TRANSPARENCE 27 -- 5.2.1. En matière de médicaments 27 -- 5.2.2. En matière de dispositifs médicaux 27 -- 5.3. RECOMMANDATIONS PUBLIÉES 27 -- RECOMMANDATIONS 31 -- RÉFÉRENCES 37
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- 2021
16. Markttoegang in Europa voor geneesmiddelen en medische hulpmiddelen: gebrek aan bewijs en mogelijke oplossingen : Synthése
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Hulstaert, Frank, Pouppez, Céline, Primus-de Jong, Célia, Harkin, Kathleen, and Neyt, Mattias
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Technology Assessment, Biomedical ,Pharmaceutical Preparations ,R347 ,Device Approval ,2019-08 ,Prostheses and Implants ,Drug Approval ,WB 102.5 Evidence-based practice - Abstract
43 p. ill., Om een Europese marktvergunning te krijgen, moet voor elk nieuw geneesmiddel de kwaliteit, veiligheid en werkzaamheid worden aangetoond. Voor “hoog-risico” medische hulpmiddelen (bijvoorbeeld implantaten) zijn de eisen minder streng. Voor de ziekteverzekering, de artsen en de patiënten telt vooral de waarde van het nieuwe product in vergelijking met de bestaande behandeling. Dergelijke vergelijkende studies met patiëntrelevante eindpunten zijn echter niet noodzakelijk voor een markttoelating. De belangrijkste aanbeveling van het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) is dat bedrijven die geneesmiddelen of medische hulpmiddelen op de markt brengen, hun klinische studies niet alleen afstemmen op de huidige vereisten voor Europese markttoegang, maar meteen ook vergelijkende gegevens verzamelen zodat ook aan de informatienoden van de nationale zorgbetalers, clinici en patiënten wordt voldaan. Deze studie komt op het juiste moment, gezien de recente evoluties in het regelgevend kader van de Europese Unie. SYNTHESE 2 -- 1. INLEIDING, DOEL EN METHODOLOGIE 4 -- 1.1. MARKTTOEGANG IS EUROPEES GEREGULEERD TERWIJL DE TERUGBETALING DOOR DE -- LIDSTATEN WORDT VASTGELEGD. 4 -- 1.1.1. Geneesmiddelen 5 -- 1.1.2. Medische hulpmiddelen 6 -- 1.1.3. Evolutie in de Europese regelgeving 7 -- 1.2. INITIATIEVEN DIE DE EVIDENCE GAP HEBBEN VERGROOT EN INITIATIEVEN OM DE EVIDENCE GAP TE VERKLEINEN 7 -- 1.3. DOEL VAN DEZE STUDIE EN ONDERZOEKSVRAGEN 8 -- 1.4. METHODOLOGIE 8 -- 2. ETHISCHE EN JURIDISCHE OVERWEGINGEN 11 -- 2.1. ETHISCHE NORMEN ROND HET LEVEREN VAN BEWIJS EN ROND TRANSPARANTIE 11 -- 2.2. EUROPESE WETGEVING INZAKE GENEESMIDDELEN 12 -- 2.2.1. Vereisten wat betreft bewijs 12 -- 2.2.2. Procedure voor de toelating van klinische studies 12 -- 2.2.3. Transparantievereisten 12 -- 2.3. EUROPESE WETGEVING INZAKE MEDISCHE HULPMIDDELEN 13 -- 2.3.1. Vereisten wat betreft bewijs 13 -- 2.3.2. Toelatingsprocedure voor klinisch onderzoek 13 -- 2.3.3. Transparantievereisten 14 -- 2.4. EUROPESE EVALUATIE VAN GEZONDHEIDSTECHNOLOGIE 14 -- 3. ANALYSE VAN DE RIZIV-DOSSIERS 14 -- 3.1.1. Resultaten voor de 18 beoordelingsdossiers voor geneesmiddelen. 16 -- 3.1.2. Resultaten voor de 18 beoordelingsdossiers voor medische hulpmiddelen 16 -- 4. LITERATUURSTUDIE 16 -- 4.1. GENEESMIDDELEN 16 -- 4.2. MEDISCHE HULPMIDDELEN 17 -- 5. DISCUSSIE EN MOGELIJKE OPLOSSINGEN 18 -- 5.1. DE SCHEIDING TUSSEN REGELGEVENDE INSTANTIES EN HTA-INSTANTIES, MEER SAMENWERKING NOODZAKELIJK 19 -- 5.1.1. Vereisten wat betreft de onderzochte populatie 22 -- 5.1.2. Vereisten wat betreft de onderzochte interventie 22 -- 5.1.3. Vereisten wat betreft het gebruikte vergelijkend middel (de comparator) 22 -- 5.1.4. Vereisten wat betreft de uitkomsten (outcomes) 24 -- 5.1.5. Naar meer efficiënte klinische studies, beperkingen van observationele ‘real-world data’ 25 -- 5.1.6. Mag de bewijsdrempel voor medische hulpmiddelen lager liggen? 26 -- 5.2. TRANSPARANTIEVEREISTEN 27 -- 5.2.1. Voor geneesmiddelen 27 -- 5.2.2. Voor medische hulpmiddelen 27 -- 5.3. GEPUBLICEERDE BELEIDSAANBEVELINGEN 27 -- AANBEVELINGEN 31 -- REFERENTIES 37
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- 2021
17. Evidence gaps for drugs and medical devices at market entry in Europe and potential solutions : Synthese
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Hulstaert, Frank, Pouppez, Céline, Primus-de Jong, Célia, Harkin, Kathleen, and Neyt, Mattias
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Technology Assessment, Biomedical ,Pharmaceutical Preparations ,R347 ,Device Approval ,2019-08 ,Prostheses and Implants ,Drug Approval ,WB 102.5 Evidence-based practice - Abstract
38 p. ill., SUMMARY 1 -- 1. INTRODUCTION, OBJECTIVE AND METHODOLOGY 3 -- 1.1. MARKET ACCESS IS REGULATED AT THE EUROPEAN LEVEL, WHILE REIMBURSEMENT IS DETERMINED BY THE MEMBER STATES. 3 -- 1.1.1. Medicinal products 4 -- 1.1.2. Medical devices 5 -- 1.1.3. Changes in the European regulations 5 -- 1.2. INITIATIVES THAT HAVE INCREASED THE EVIDENCE GAP AND INITIATIVES TO REDUCE THE EVIDENCE GAP 6 -- 1.3. OBJECTIVE OF THIS STUDY AND STUDY QUESTIONS 6 -- 2. ETHICAL AND LEGAL CONSIDERATIONS 9 -- 2.1. ETHICAL STANDARDS ON THE PROVISION OF EVIDENCE AND TRANSPARENCY 9 -- 2.2. EUROPEAN LEGISLATION ON MEDICINAL PRODUCTS 10 -- 2.2.1. Evidence requirements 10 -- 2.2.2. Procedure for the authorisation of clinical studies 10 -- 2.2.3. Transparency requirements 10 -- 2.3. EUROPEAN LEGISLATION ON MEDICAL DEVICES 10 -- 2.3.1. Evidence requirements 11 -- 2.3.2. Authorisation procedure for clinical research 11 -- 2.3.3. Transparency requirements 11 -- 2.4. EUROPEAN EVALUATION OF HEALTH TECHNOLOGY 12 -- 3. ANALYSIS OF THE INAMI/RIZIV DOSSIERS 12 -- 3.1.1. Results for the 18 assessment dossiers for medicinal products 13 -- 3.1.2. Results for the 18 assessment dossiers for medical devices 13 -- 4. LITERATURE STUDY 14 -- 4.1. MEDICINAL PRODUCTS 14 -- 4.2. MEDICAL DEVICES 15 -- 5. DISCUSSION AND POSSIBLE SOLUTIONS 16 -- 5.1. THE SEPARATION BETWEEN REGULATORY BODIES AND HTA BODIES; MORE COLLABORATION NECESSARY 16 -- 5.1.1. Study population requirements 19 -- 5.1.2. Requirements regarding the intervention 19 -- 5.1.3. Requirements regarding the comparator 19 -- 5.1.4. Requirements regarding outcomes 21 -- 5.1.5. Toward more efficient clinical studies; limitations of observational ‘real-world data’ 21 -- 5.1.6. Should the threshold of evidence for medical devices be lower? 22 -- 5.2. TRANSPARENCY REQUIREMENTS 23 -- 5.2.1. For medicinal products 23 -- 5.2.2. For medical devices 23 -- 5.3. PUBLISHED POLICY RECOMMENDATIONS 23 -- RECOMMENDATIONS 27 -- REFERENCES 32
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- 2021
18. Infectious diseases epidemiology, quantitative methodology, and clinical research in the midst of the COVID-19 pandemic: Perspective from a European country
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Molenberghs, Geert, primary, Buyse, Marc, additional, Abrams, Steven, additional, Hens, Niel, additional, Beutels, Philippe, additional, Faes, Christel, additional, Verbeke, Geert, additional, Van Damme, Pierre, additional, Goossens, Herman, additional, Neyens, Thomas, additional, Herzog, Sereina, additional, Theeten, Heidi, additional, Pepermans, Koen, additional, Abad, Ariel Alonso, additional, Van Keilegom, Ingrid, additional, Speybroeck, Niko, additional, Legrand, Catherine, additional, De Buyser, Stefanie, additional, and Hulstaert, Frank, additional
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- 2020
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19. Closing the cycle of innovation in healthcare in Europe
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Hulstaert, Frank, primary, Ruether, Alric, additional, Demotes, Jacques, additional, and Melien, Øyvind, additional
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- 2020
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20. MOESM1 of Budgeting of non-commercial clinical trials: development of a budget tool by a public funding agency
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Nevens, Hilde, Harrison, Jillian, Vrijens, France, Verleye, Leen, Stocquart, Nelle, Marynen, Elisabeth, and Hulstaert, Frank
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Additional file 1. Detailed example of the costs of a trial. Calculation of a study budget with separate columns detailing the costs per item, the margin and the overhead (if applicable).
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- 2019
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21. Expanded carrier screening in a reproductive context. Towards a responsible implementation in the healthcare system
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Borry, Pascal, Cassiman, Jean-Jacques, Hulstaert, Frank, Liebaers, Ingeborg, Mortier, Geert, Peeters, Hilde, Van den Bulcke, Marc, Van Nerom, Anne, Van Oyen, Herman, and Verellen-Dumoulin, Christine
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status: published
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- 2017
22. Introduction of high-risk medical devices: national measures that can be taken under the current European legislation to put the patient interest central
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Neyt, Mattias, primary, Baeyens, Hanne, additional, Pouppez, Céline, additional, Slegers, Pierre, additional, Hulstaert, Frank, additional, Stordeur, Sabine, additional, and Vinck, Irm, additional
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- 2017
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23. Publicly funded practice-oriented clinical trials: of importance for healthcare payers
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Neyt, Mattias, primary, Christiaens, Thierry, additional, Demotes, Jacques, additional, Walley, Tom, additional, and Hulstaert, Frank, additional
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- 2016
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24. The importance of test accuracy in economic evaluations of companion diagnostics
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San Miguel, Lorena, primary and Hulstaert, Frank, additional
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- 2015
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25. Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis
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Neyt, Mattias, primary, Hulstaert, Frank, additional, and Gyselaers, Wilfried, additional
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- 2014
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26. Authors’ reply to Morales and Arlett
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Wieseler, Beate, Neyt, Mattias, Kaiser, Thomas, Hulstaert, Frank, and Windeler, Ju¨rgen
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- 2023
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27. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial
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Benoit Misset, Hans Slabbynck, Ursula Smole, Linos Vandekerckhove, Nicolas Dauby, Helena Catharine Aegerter, Nicolas De Schryver, Jozefien Declercq, Catherine Legrand, Levi Hoste, Gil Verschelden, Fre Bauters, Xavier Wittebole, Bastiaan Maes, Eva Van Braeckel, Sébastien Anguille, Catherine Van Der Straeten, Marc Buyse, Sylvie Rottey, Tom Fivez, Dieter Stevens, Stefaan J. Vandecasteele, Maya Hites, Elke Govaerts, I Peene, Karel Van Damme, Simon Tavernier, Frank Hulstaert, Roos Colman, Stefanie De Buyser, Elisabeth De Leeuw, Jeroen Van der Hilst, Filip Moerman, Fabienne Liénart, Leen J M Seys, Leslie Naesens, Filomeen Haerynck, Ingel K. Demedts, Cedric Bosteels, Victor Bosteels, Pieter Depuydt, Johan Van Laethem, Bart N. Lambrecht, Internal Medicine, Supporting clinical sciences, Faculty of Medicine and Pharmacy, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, UCL - SSH/LIDAM/ISBA - Institut de Statistique, Biostatistique et Sciences Actuarielles, Van Laethem, Johan/0000-0002-2490-216X, Hoste, Levi/0000-0001-9733-1049, Naesens, Leslie/0000-0003-1715-0665, Declercq , Jozefien, Van Damme, Karel F. A., De Leeuw, Elisabeth, Maes, Bastiaan, Bosteels, Cedric, Tavernier, Simon J., De Buyser, Stefanie, Colman, Roos, Hites, Maya, Verschelden, Gil, Fivez, Tom, Moerman , Filip, Demedts, Ingel K., Dauby, Nicolas, De Schryver, Nicolas, Govaerts , Elke, Vandecasteele, Stefaan J., Van Laethem, Johan, Anguille, Sebastien, VAN DER HILST, Jeroen, Misset, Benoit, Slabbynck, Hans, Wittebole, Xavier, Lienart, Fabienne, LEGRAND, Catherine, BUYSE, Marc, Stevens, Dieter, Bauters, Fre, Seys, Leen J. M., Aegerter, Helena, Smole, Ursula, Bosteels, Victor, Hoste , Levi, Naesens, Leslie, Haerynck, Filomeen, Vandekerckhove, Linos, Depuydt, Pieter, van Braeckel, Eva, Rottey, Sylvie, Peene, Isabelle, Van Der Straeten, Catherine, Hulstaert, Frank, and Lambrecht, Bart N.
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Male ,Pulmonary and Respiratory Medicine ,Population ,Antibodies, Monoclonal, Humanized ,law.invention ,Belgium ,Randomized controlled trial ,law ,Fraction of inspired oxygen ,medicine ,Humans ,Prospective Studies ,Hypoxia ,education ,Aged ,education.field_of_study ,Interleukin-6 ,SARS-CoV-2 ,business.industry ,Comment ,Hazard ratio ,COVID-19 ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,COVID-19 Drug Treatment ,Blockade ,Oxygen ,Cytokine release syndrome ,Treatment Outcome ,Respiratory failure ,Anesthesia ,Ferritins ,Female ,SOFA score ,Human medicine ,Cytokine Release Syndrome ,Respiratory Insufficiency ,business ,Interleukin-1 - Abstract
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 with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. Methods We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 mu g/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 mu g/L, which had been increasing over the previous 24 h, or lyrnphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 mu g/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 x 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. Findings Between April 4, and Dec 6,2020,342 patients were randomly assigned to IL-1 blockade n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0.94 [95% CI 0.73-1.21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1.00[0-78-1-29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. Interpretation Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Belgian Health Care Knowledge Center; VIB Grand Challenges program The authors acknowledge professional support and committed efforts from various organisations and individuals involved in this trial and thank all trial participants and clinicians involved in patient recruitment at the different participating sites. This study was funded by KCE, and KCE was involved in various aspects of the study design, management, and execution (Nelle Stocquart, Jillian Harrison). The VIB Grand Challenges Program (Sofie Bekaert) funded measurements of cytokines and the Ghent University Special Research Fund (BOF) supported the clinical follow-up of patients at Ghent University Hospital (UZ Ghent). The clinical trial team of the Department of Respiratory Medicine at UZ Ghent (Stefanie Vermeersch, Benedicte Demeyere, Anja Delporte) were involved in protocol development, amendment filing, and eCRF construction. The Health Innovation and Research Institute of UZ Ghent was involved in eCRF design, protocol design, ethical committee reporting, drug dispensing, trial monitoring, data cleaning, and sponsor site management (Charlotte Clauwaert, Dries Loncke, Hanife Kokur, Lieselot Van Landuyt, Joke Tommelein, Hélène De Naeyer). The hospital pharmacy of UZ Ghent dispensed drugs to all study sites (Els Kestens). Team members of the Primary Immune Deficiency laboratory (Karlien Claes, Veronique Debacker, Lisa Roels, Zara Declercq) handled samples from all study sites. The authors acknowledge the insights of the data safety monitoring board (Drs Renaat Peleman, Geert Leroux-Roels, Steven Callens, Frank Vermassen, Piet Hoebeke, Karim Vermaelen, A Dupont, Tomasz Burzykowski, and Marnik Vuylsteke under the chairmanship of SR).
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- 2021
28. Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial
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Beeckman, Dimitri, Fourie, A., Raepsaet, C., Van Damme, N., Manderlier, B., De Meyer, D., Beele, H., Smet, S., Demarré, L., Vossaert, R., de Graaf, R., Verhaeghe, L., Vandergheynst, N., Hendrickx, B., Hanssens, V., Keymeulen, H., Vanderwee, K., Van De Woestijne, J., Verhaeghe, S., Van Hecke, A., Savoye, Isabelle, Harrison, Jillian, Vrijens, France, and Hulstaert, Frank
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Pressure Ulcer ,Journal Article ,prevention and control ,W 1 Serials. Periodicals - Abstract
4-5 Background Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). Objectives To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. Methods This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) – pooled as the treatment group – and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. Results In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41–0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35–0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34–1·68, P = 0·49). Conclusions Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.
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- 2021
29. Les médicaments innovants contre le cancer ont-ils toujours une réelle valeur ajoutée ? : – Synthèse
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Fairon, Nicolas, Hulstaert, Frank, Verleye, Leen, and Silversmit, Geert
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QV 269 Antineoplastic agents. Antineoplastic antibiotics ,R343 ,Technology Assessment, Biomedical ,Neoplasms ,Antineoplastic Agents ,Review ,Randomized Controlled Trials ,2018-02 - Abstract
47 p. ill., Les progrès de la médecine ont permis de nombreuses avancées ; l'arrivée régulière sur le marché de nouveaux médicaments innovants contre le cancer est une bonne chose en soi. Hélas une grande partie de ces médicaments sont remboursés par l’assurance maladie belge sans preuves suffisantes d’un réel bénéfice pour les patients. Le KCE plaide pour un système plus transparent qui mette davantage l’accent sur la véritable valeur ajoutée pour le patient de chaque nouveau médicament. De cette manière, les moyens limités de l'assurance maladie pourront être utilisés de manière plus responsable et plus efficace. 1. INTRODUCTION 7 -- 1.1. LES MÉDICAMENTS CONTRE LE CANCER COÛTENT DE PLUS EN PLUS CHER 7 -- 1.2. LES BÉNÉFICES POUR LES PATIENTS SONT-ILS SUFFISAMMENT PROUVÉS ? 7 -- 1.3. L’OBLIGATION DE CONFIDENTIALITÉ REND LE SYSTÈME DE PLUS EN PLUS OPAQUE 8 -- 2. QUESTIONS ET MÉTHODES DE RECHERCHE 9 -- 2.1. QUESTIONS DE RECHERCHE 9 -- 2.2. COMMENT AVONS-NOUS PROCÉDÉ? 11 -- 2.2.1. Données observationnelles 11 -- 2.2.2. Analyse de la littérature 12 -- 3. ÉVOLUTION DE LA SURVIE GLOBALE ET DE L’IMPACT BUDGÉTAIRE DES MÉDICAMENTS INNOVANTS 13 -- 3.1. REMARQUES PRÉLIMINAIRES 13 -- 3.2. RÉSUMÉ DES RÉSULTATS 14 -- 4. LIMITATIONS DES DONNÉES OBSERVATIONNELLES 20 -- 5. RAPPORT COÛT-EFFICACITÉ 21 -- 6. PISTES POUR MIEUX ÉVALUER LA VALEUR AJOUTÉE DES MÉDICAMENTS INNOVANTS À L’AVENIR 23 -- 6.1. INCERTITUDES ISSUES DES ESSAIS CLINIQUES 23 -- 6.1.1. Les essais contrôlés randomisées restent le ‘gold standard’ 23 -- 6.1.2. La survie n’est pas le principal outcome 24 -- 6.1.3. Les comparateurs ne sont pas toujours adéquats 25 -- 6.1.4. Les résultats se mesurent par substitution 26 -- 6.1.5. La qualité de vie est la grande oubliée des essais cliniques 27 -- 6.2. INCERTITUDES LIÉES AUX MEA 30 -- 6.2.1. Les mécanismes de compensation des MEA et taxes payées par l’industrie pharmaceutique . 31 -- 6.2.2. L’industrie n’est pas encouragée à fournir les données probantes manquantes 32 -- 6.2.3. Les prix confidentiels génèrent un manque de transparence aux conséquences négatives 35 -- 7. QUELQUES AFFIRMATIONS SUPPLÉMENTAIRES QUI MÉRITENT D'ÊTRE NUANCÉES 36 -- 8. CONCLUSION 39
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30. Benefits and costs of innovative oncology drugs in Belgium : Supplement
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Fairon, Nicolas, Hulstaert, Frank, Verleye, Leen, and Silversmit, Geert
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QV 269 Antineoplastic agents. Antineoplastic antibiotics ,R343 ,Technology Assessment, Biomedical ,Neoplasms ,Antineoplastic Agents ,Review ,Randomized Controlled Trials ,2018-02 - Abstract
1116 p. ill., APPENDIX 1. BREAST CANCER 56 -- APPENDIX 1.1. BCR DATA 56 -- Appendix 1.1.1. Descriptive statistics 56 -- Appendix 1.1.2. Uptake of selected drugs 92 -- APPENDIX 1.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 94 -- APPENDIX 1.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 100 -- Appendix 1.3.1. Search medical literature (systematic reviews) 100 -- Appendix 1.3.2. Critical appraisal systematic reviews 104 -- Appendix 1.3.3. Search strategy 107 -- APPENDIX 1.4. ECONOMIC LITERATURE 118 -- Appendix 1.4.1. Search economic literature (HTA reports) 118 -- Appendix 1.4.2. Results economic literature (HTA reports) 121 -- APPENDIX 2. CHRONIC MYELOID LEUKAEMIA 147 -- APPENDIX 2.1. BCR DATA 147 -- Appendix 2.1.1. Descriptive statistics 147 -- Appendix 2.1.2. Uptake of selected drugs 166 -- APPENDIX 2.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 167 -- APPENDIX 2.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 173 -- Appendix 2.3.1. Search medical literature (systematic reviews) 173 -- Appendix 2.3.2. Critical appraisal systematic reviews 177 -- Appendix 2.3.3. Search strategy 180 -- APPENDIX 2.4. ECONOMIC LITERATURE 189 -- Appendix 2.4.1. Search economic literature (HTA reports) 189 -- Appendix 2.4.2. Results economic literature (HTA reports) 192 -- APPENDIX 3. COLORECTAL CANCER 207 -- APPENDIX 3.1. BCR DATA 207 -- Appendix 3.1.1. Descriptive statistics 207 -- Appendix 3.1.2. Uptake of selected drugs 244 -- APPENDIX 3.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 246 -- APPENDIX 3.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 249 -- Appendix 3.3.1. Search medical literature (systematic reviews) 249 -- Appendix 3.3.2. Critical appraisal systematic reviews 256 -- Appendix 3.3.3. Search strategy 258 -- APPENDIX 3.4. ECONOMIC LITERATURE 274 -- Appendix 3.4.1. Search economic literature (HTA reports) 274 -- Appendix 3.4.2. Results economic literature (HTA reports) 276 -- APPENDIX 4. HEAD & NECK CANCER 290 -- APPENDIX 4.1. BCR DATA 290 -- Appendix 4.1.1. Descriptive statistics 290 -- Appendix 4.1.2. Uptake of selected drug 341 -- APPENDIX 4.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 342 -- APPENDIX 4.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 343 -- Appendix 4.3.1. Search medical literature (systematic reviews) 343 -- Appendix 4.3.2. Critical appraisal systematic reviews 346 -- Appendix 4.3.3. Search strategy 347 -- APPENDIX 4.4. ECONOMIC LITERATURE 350 -- Appendix 4.4.1. Search economic literature (HTA reports) 350 -- Appendix 4.4.2. Results economic literature (HTA reports) 352 -- APPENDIX 5. MELANOMA 358 -- APPENDIX 5.1. BCR DATA 358 -- Appendix 5.1.1. Descriptive statistics 358 -- APPENDIX 5.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 419 -- APPENDIX 5.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 421 -- Appendix 5.3.1. Search medical literature (systematic reviews) 421 -- Appendix 5.3.2. Melanoma: Critical appraisal systematic reviews. 426 -- Appendix 5.3.3. Search strategy 428 -- APPENDIX 5.4. ECONOMIC LITERATURE 438 -- Appendix 5.4.1. Search economic literature (HTA reports) 438 -- Appendix 5.4.2. Results economic literature (HTA reports) 441 -- APPENDIX 6. MESOTHELIOMA 471 -- APPENDIX 6.1. BCR DATA 471 -- Appendix 6.1.1. Descriptive statistics 471 -- Appendix 6.1.2. Descriptive statistics 498 -- Appendix 6.1.3. Uptake of selected drugs 525 -- APPENDIX 6.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 525 -- APPENDIX 6.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 525 -- Appendix 6.3.1. Search medical literature (systematic reviews) 525 -- Appendix 6.3.2. Critical appraisal systematic reviews 527 -- Appendix 6.3.3. Search strategy 528 -- APPENDIX 6.4. ECONOMIC LITERATURE 533 -- Appendix 6.4.1. Search economic literature (HTA reports) 533 -- Appendix 6.4.2. Results economic literature (HTA reports) 534 -- APPENDIX 7. MULTIPLE MYELOMA 538 -- APPENDIX 7.1. BCR DATA 538 -- Appendix 7.1.1. Descriptive statistics 538 -- Appendix 7.1.2. Uptake of selected drugs 545 -- APPENDIX 7.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 546 -- APPENDIX 7.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 549 -- Appendix 7.3.1. Search medical literature (systematic reviews) 549 -- Appendix 7.3.2. Critical appraisal systematic reviews 553 -- Appendix 7.3.3. Search strategy 556 -- APPENDIX 7.4. ECONOMIC LITERATURE 562 -- Appendix 7.4.1. Search economic literature (HTA reports) 562 -- Appendix 7.4.2. Results economic literature (HTA reports) 565 -- APPENDIX 8. NON HODGKIN 587 -- APPENDIX 8.1. BCR DATA 587 -- Appendix 8.1.1. Descriptive statistics 587 -- Appendix 8.1.2. Uptake of selected drugs 611 -- APPENDIX 8.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 612 -- APPENDIX 8.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 614 -- Appendix 8.3.1. Search medical literature (systematic reviews) 614 -- Appendix 8.3.2. Critical appraisal systematic reviews 620 -- Appendix 8.3.3. Search strategy 628 -- APPENDIX 8.4. ECONOMIC LITERATURE 664 -- Appendix 8.4.1. Search economic literature (HTA reports) 664 -- Appendix 8.4.2. Results economic literature (HTA reports) 667 -- Appendix 8.4.3. Mantel-cell lymphoma 681 -- APPENDIX 9. NON-SMALL CELL LUNG CANCER 684 -- APPENDIX 9.1. BCR DATA 684 -- Appendix 9.1.1. Descriptive statistics 684 -- Appendix 9.1.2. Uptake of selected drugs 720 -- APPENDIX 9.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 721 -- APPENDIX 9.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 724 -- Appendix 9.3.1. Search medical literature (systematic reviews) 724 -- Appendix 9.3.2. Critical appraisal systematic reviews 732 -- Appendix 9.3.3. Search strategy 736 -- APPENDIX 9.4. ECONOMIC LITERATURE 747 -- Appendix 9.4.1. Search economic literature (HTA reports) 747 -- Appendix 9.4.2. Results economic literature (HTA reports) 751 -- APPENDIX 10. OVARIAN CANCER 786 -- APPENDIX 10.1. BCR DATA 786 -- Appendix 10.1.1. Descriptive statistics 786 -- Appendix 10.1.2. Uptake of selected drugs 873 -- APPENDIX 10.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 874 -- APPENDIX 10.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 876 -- Appendix 10.3.1. Search medical literature (systematic reviews) 876 -- Appendix 10.3.2. Critical appraisal systematic reviews 878 -- Appendix 10.3.3. Search strategy 880 -- APPENDIX 10.4. ECONOMIC LITERATURE 887 -- Appendix 10.4.1. Search economic literature (HTA reports) 887 -- Appendix 10.4.2. Results economic literature (HTA reports) 889 -- APPENDIX 11. PROSTATE CANCER 898 -- APPENDIX 11.1. BCR DATA 898 -- Appendix 11.1.1. Descriptive statistics 898 -- Appendix 11.1.2. Uptake of selected drugs 951 -- APPENDIX 11.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 951 -- APPENDIX 11.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 952 -- Appendix 11.3.1. Search medical literature (systematic reviews) 952 -- Appendix 11.3.2. Critical appraisal systematic reviews 956 -- Appendix 11.3.3. Search strategy 958 -- APPENDIX 11.4. ECONOMIC LITERATURE 965 -- Appendix 11.4.1. Search economic literature (HTA reports) 965 -- Appendix 11.4.2. Results economic literature (HTA reports) 967 -- APPENDIX 12. RENAL CELL CARCINOMA (RCC) 979 -- APPENDIX 12.1. BCR DATA 979 -- Appendix 12.1.1. Descriptive statistics 979 -- Appendix 12.1.2. Uptake of selected drugs 1031 -- APPENDIX 12.2. REIMBURSEMENT CRITERIA FOR SELECTED DRUGS 1033 -- APPENDIX 12.3. MEDICAL LITERATURE: SEARCH FOR EVIDENCE 1037 -- Appendix 12.3.1. Search medical literature (systematic reviews) 1037 -- Appendix 12.3.2. Critical appraisal systematic reviews 1043 -- Appendix 12.3.3. Search strategy 1045 -- APPENDIX 12.4. ECONOMIC LITERATURE 1054 -- Appendix 12.4.1. Search economic literature (HTA reports) 1054 -- Appendix 12.4.2. Results economic literature (HTA reports) 1057 -- APPENDIX 13. OVERVIEW FINDINGS MEDICAL LITERATURE 1083 -- APPENDIX 14. DRUG PRICES 1094 -- APPENDIX 14.1. BREAST CANCER 1095 -- APPENDIX 14.2. CHRONIC MYELOID LEUKAEMIA (CML) 1097 -- APPENDIX 14.3. COLORECTAL CANCER 1100 -- APPENDIX 14.4. HEAD AND NECK CANCER 1102 -- APPENDIX 14.5. MELANOMA 1103 -- APPENDIX 14.6. MESOTHELIOMA 1105 -- APPENDIX 14.7. MULTIPLE MYELOMA 1106 -- APPENDIX 14.8. NON-HODGKIN LYMPHOMA (NHL) 1108 -- APPENDIX 14.9. NON-SMALL-CELL LUNG CARCINOMA (NSCLC). 1110 -- APPENDIX 14.10. OVARIAN CANCER 1112 -- APPENDIX 14.11. PROSTATE CANCER 1114 -- APPENDIX 14.12. RENAL CELL CARCINOMA 1115
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31. Do innovative medicines against cancer always have a real added value? : Synthesis
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Fairon, Nicolas, Hulstaert, Frank, Verleye, Leen, and Silversmit, Geert
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QV 269 Antineoplastic agents. Antineoplastic antibiotics ,R343 ,Technology Assessment, Biomedical ,Neoplasms ,Antineoplastic Agents ,Review ,Randomized Controlled Trials ,2018-02 - Abstract
45 p. ill., FOREWORD 1 -- KEY MESSAGES 2 -- SUMMARY 4 -- 1. INTRODUCTION 6 -- 1.1. CANCER MEDICINE IS BECOMING MORE AND MORE EXPENSIVE 6 -- 1.2. ARE THE BENEFITS FOR THE PATIENT SUFFICIENTLY PROVEN? 6 -- 1.3. THE CONFIDENTIALITY OBLIGATION MAKES THE SYSTEM EVEN LESS TRANSPARENT 7 -- 2. RESEARCH QUESTIONS AND METHODS 8 -- 2.1. RESEARCH QUESTIONS 8 -- 2.2. HOW DID WE PROCEED? 9 -- 2.2.1. Observational data 9 -- 2.2.2. Literature study 10 -- 3. EVOLUTION OF THE OVERALL SURVIVAL AND BUDGETARY IMPACT OF THE INNOVATIVE -- MEDICINES 11 -- 3.1. PRELIMINARY REMARKS 11 -- 3.2. SUMMARY OF RESULTS 12 -- 4. RESTRICTIONS OF OBSERVATIONAL DATA 19 -- 5. COST EFFECTIVENESS 20 -- 6. WAYS TO BETTER ASSESS THE ADDED VALUE OF INNOVATIVE MEDICINES IN THE FUTURE 21 -- 6.1. UNCERTAINTIES IN CLINICAL STUDIES 22 -- 6.1.1. Randomised controlled studies remain the ‘golden standard’ 22 -- 6.1.2. Survival is not always the primary outcome measure 22 -- 6.1.3. New medicines are not always compared with the right treatment 23 -- 6.1.4. The outcome is measured by surrogate endpoints 24 -- 6.1.5. Quality of life is one thing that is often overlooked in clinical studies. 25 -- 6.2. UNCERTAINTIES WITH REGARD TO MEAS 28 -- 6.2.1. Refund mechanisms of the MEAs and taxes paid by the pharmaceutical industry 29 -- 6.2.2. The industry is not encouraged to provide the missing evidence 30 -- 6.2.3. Confidential pricing creates a lack of transparency with negative consequences 32 -- 7. ADDITIONAL STATEMENTS THAT DESERVE THE NECESSARY NUANCE 34 -- 8. CONCLUSION 37 -- RECOMMENDATIONS 38 -- REFERENCES 43
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- 2021
32. Hebben innovatieve geneesmiddelen tegen kanker altijd een echte meerwaarde? : Synthese
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Fairon, Nicolas, Hulstaert, Frank, Verleye, Leen, and Silversmit, Geert
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QV 269 Antineoplastic agents. Antineoplastic antibiotics ,R343 ,Technology Assessment, Biomedical ,Neoplasms ,Antineoplastic Agents ,Review ,Randomized Controlled Trials ,2018-02 - Abstract
47 p. ill., Medische ontwikkelingen hebben tot veel vooruitgang geleid en het feit dat er regelmatig nieuwe, innovatieve geneesmiddelen tegen kanker op de markt komen is een reden tot vreugde. Helaas wordt een groot deel van deze kankermedicijnen reeds terugbetaald door de Belgische ziekteverzekering zonder dat de echte voordelen voor de patiënten voldoende bewezen zijn. Het KCE dringt erop aan om tot een meer transparant systeem te komen dat de nadruk legt op de werkelijke meerwaarde van elk nieuw kankergeneesmiddel voor de patiënt. Op die manier kunnen de beperkte middelen van de ziekteverzekering op een meer verantwoorde en efficiënte manier worden gebruikt. VOORWOORD 1 -- KERN BOODSCHAPPEN 2 -- SAMENVATTING 5 -- 1. INLEIDING 7 -- 1.1. GENEESMIDDELEN TEGEN KANKER WORDEN STEEDS DUURDER 7 -- 1.2. ZIJN DE VOORDELEN ERVAN VOOR DE PATIËNT VOLDOENDE BEWEZEN? 7 -- 1.3. DE VERPLICHTING TOT VERTROUWELIJKHEID MAAKT HET SYSTEEM STEEDS -- ONDOORZICHTIGER 8 -- 2. ONDERZOEKSVRAGEN EN METHODEN 9 -- 2.1. ONDERZOEKSVRAGEN 9 -- 2.2. HOE ZIJN WE TE WERK GEGAAN? 11 -- 2.2.1. Observationele gegevens 11 -- 2.2.2. Literatuuroverzicht 12 -- 3. EVOLUTIE VAN DE TOTALE OVERLEVING EN BUDGETTAIRE IMPACT VAN DE INNOVATIEVE -- GENEESMIDDELEN 13 -- 3.1. VOORAFGAANDE OPMERKINGEN 13 -- 3.2. SAMENVATTING VAN DE RESULTATEN 14 -- 4. BEPERKINGEN VAN OBSERVATIONELE DATA 20 -- 5. KOSTENEFFECTIVITEIT 21 -- 6. PISTES OM DE MEERWAARDE VAN INNOVATIEVE GENEESMIDDELEN IN DE TOEKOMST -- BETER TE BEOORDELEN 23 -- 6.1. ONZEKERHEDEN IN DE KLINISCHE STUDIES 23 -- 6.1.1. Gerandomiseerde gecontroleerde studies blijven de ‘gouden standaard’ 23 -- 6.1.2. Overleving is niet altijd de primaire uitkomstmaat 24 -- 6.1.3. Nieuwe geneesmiddelen worden niet altijd met de juiste behandeling vergeleken 25 -- 6.1.4. De uitkomsten worden gemeten door surrogaateindpunten 26 -- 6.1.5. Wat in het bijzonder over het hoofd wordt gezien in klinische studies is de levenskwaliteit 27 -- 6.2. ONZEKERHEDEN IN VERBAND MET MEA'S 30 -- 6.2.1. Compensatiemechanismen van de MEA’s en door de farmaceutische industrie betaalde heffingen 31 -- 6.2.2. De industrie wordt niet aangemoedigd om de ontbrekende bewijskrachtige gegevens te -- verstrekken 32 -- 6.2.3. Vertrouwelijke prijzen zorgen voor een gebrek aan transparantie met negatieve gevolgen 35 -- 7. BIJKOMENDE STATEMENTS DIE DE NODIGE NUANCE VERDIENEN 36 -- 8. CONCLUSIE 39 -- AANBEVELINGEN 40 -- REFERENTIES 45
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- 2021
33. Rapid review of the evidence on a covid-19 booster dose after a primary vaccination schedule
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Jespers, Vicky, Leroy, Roos, Hulstaert, Frank, Wyndham Thomas, Chloé, Van Montfort, Tessa, Van Damme, Pierre, Dogné, Jena-Michel, Soentjens, Patrick, and Ramaekers, Dirk
- Subjects
COVID-19 [Supplementary Concept] ,WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases ,Vaccination ,Review - Abstract
58 p. ill.c Au moment où nous écrivons cet avis, la Belgique est bien avancée dans sa campagne de vaccination, avec un taux d’adhésion élevé par rapport à d'autres pays. Sur le plan technologique, les vaccins que nous avons pu utiliser sont hautement efficaces et sûrs ; ils sont proposés à toute personne âgée de 12 ans et plus, essentiellement via les centres de vaccination. Les personnes complètement vaccinées sont largement protégées contre les infections graves et les décès dus au SARS-CoV-2, y compris ceux dus au variant delta actuellement dominant. La plupart des personnes non vaccinées sont pour leur part toujours exposées au risque d'hospitalisation et de formes graves de la maladie. Il est donc primordial de poursuivre les efforts pour convaincre les personnes qui refusent le vaccin, afin de les protéger, elles et leurs proches. Ce rapport offre une vision d'ensemble des données probantes actuellement disponibles. Elles proviennent de diverses études cliniques : études sur les cas de percée vaccinale (breakthrough infections), sur la réponse immunitaire après primo-vaccination, sur la réponse immunitaire et la sécurité de la vaccination hétérologue et sur l’administration d’une dose de rappel (booster). Nous y avons également inclus un aperçu des études actuellement en cours en Belgique. Enfin, nous évoquerons les différentes prises de position politiques au niveau international au sujet de cette dose de rappel. 1 PRÉFACE 5 -- 2 RÉSUMÉ ET RECOMMANDATIONS POLITIQUES 6 -- 3 REVIEW OF THE EVIDENCE 11 -- 3.1 BACKGROUND 11 -- 3.2 LITERATURE SEARCH 13 -- 3.3 BREAKTHROUGH INFECTIONS 13 -- 3.3.1 Literature 13 -- 3.3.2 Definition 13 -- 3.3.3 Incidence of breakthrough infections – international data 14 -- 3.3.4 Incidence of breakthrough infections – national data 16 -- 3.3.5 Variants identification 17 -- 3.4 EFFECTIVENESS AND IMMUNE RESPONSE AFTER TWO DOSES OF VACCINE 18 -- 3.4.1 Literature search 18 -- 3.4.2 Effectiveness in general population, healthcare workers and elderly residents 19 -- 3.4.3 Immune response in transplant patients 19 -- 3.4.4 Immune response in patients with immunesuppressive conditions 20 -- 3.4.5 Patients receiving dialysis 22 -- 3.5 SAFETY OF HETEROLOGOUS COVID-19 VACCINE SCHEDULES 22 -- 3.6 EFFECTIVENESS AND SAFETY AFTER THREE DOSES OF COVID-19 VACCINE 27 -- 3.6.1 Literature search 27 -- 3.6.2 Healthy adults 27 -- 3.6.3 Lymphoid malignancies 29 -- 3.6.4 Hemodialysis 30 -- 3.6.5 Organ transplant recipients 34 -- 3.6.6 Overview of side effects for the retrieved studies 38 -- 4 INTERNATIONAL OVERVIEW OF RECOMMENDATIONS ON AN EXTRA/BOOSTER VACCINE DOSE 40 -- 4.1 CANADA 41 -- 4.2 DENMARK 41 -- 4.3 FRANCE 41 -- 4.4 GERMANY 42 -- 4.5 ISRAEL 42 -- 4.6 MALTA 43 -- 4.7 THE NETHERLANDS 43 -- 4.8 SWEDEN 43 -- 4.9 UNITED KINGDOM 44 -- 4.10 UNITED STATES 45 -- 5 ONGOING CLINICAL TRIALS 46 -- 5.1 BELGIAN PLANNED AND ONGOING STUDIES USING CENTRAL LAB TESTING 46 -- 5.2 INTERNATIONAL STUDIES 47 -- 6 APPENDIX 49 -- 7 REFERENCES 54
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- 2021
34. Benefits and costs of innovative oncology drugs in Belgium (2004-2017)
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Neyt, Mattias, Devos, Carl, Thiry, Nancy, De Gendt, Cindy, Van Damme, Nancy, Castanares-Zapatero, Diego, Fairon, Nicolas, Hulstaert, Frank, Verleye, Leen, and Silversmit, Geert
- Subjects
QV 269 Antineoplastic agents. Antineoplastic antibiotics ,R343 ,Technology Assessment, Biomedical ,Neoplasms ,Antineoplastic Agents ,Review ,Randomized Controlled Trials ,2018-02 - Abstract
346 p. ill., SCIENTIFIC REPORT 22 -- 1 INTRODUCTION 22 -- 1.1 SETTING THE SCENE 22 -- 1.1.1 Increasing expenditures for oncology drugs 22 -- 1.1.2 The increasing cancer drug prices 23 -- 1.1.3 Patient benefit, no longer a hard requirement for marketing authorisation 24 -- 1.2 ARE THE EXTRA EXPENDITURES ASSOCIATED WITH PATIENT BENEFITS? 26 -- 1.2.1 Cancer drugs as one of many contributors to cancer survival 26 -- 1.2.2 Small and uncertain patient benefit of new cancer medicines 27 -- 2 OBJECTIVES 28 -- 2.1 OPPORTUNITY COST OR DISPLACEMENT EFFECT 28 -- 2.2 RESEARCH QUESTIONS 28 -- 3 METHODOLOGY 29 -- 3.1 PART 1: DATABASES, STATISTICAL ANALYSES, AND PRESENTATION OF RESULTS 29 -- 3.1.1 Belgian Cancer Registry (BCR) data selection and linkage with Intermutualistic Agency (IMA) data and vital status 29 -- 3.1.1.1 Selection of the study population in the Belgian Cancer Registry database 29 -- 3.1.1.2 Linkage with health insurance data 32 -- 3.1.1.3 Vital status 32 -- 3.1.2 Statistical analyses 33 -- 3.1.2.1 Descriptive analyses 33 -- 3.1.2.2 Survival analysis 33 -- 3.1.2.3 Statistical software 34 -- 3.1.3 Graphics and Tables 34 -- 3.2 PART 2: SELECTION OF DRUGS 35 -- 3.2.1 Selection criteria and process 35 -- 3.2.2 Selected cancer types and drugs 37 -- 3.3 PART 3: LITERATURE SEARCHES 37 -- 3.3.1 Search medical literature 37 -- 3.3.2 Search economic literature 38 -- 3.4 PART 4: RIZIV REIMBURSEMENT CRITERIA 39 -- 4 RESULTS PER CANCER TYPE 40 -- 4.1 BREAST CANCER 40 -- 4.1.1 Introduction 40 -- 4.1.2 Observational data 42 -- 4.1.2.1 Patient characteristics, survival and expenditures 42 -- 4.1.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 47 -- 4.1.3 Medical literature: efficacy 48 -- 4.1.3.1 HER2(+) Breast cancer: neo-adjuvant and adjuvant setting (pertuzumab) 48 -- 4.1.3.2 HER2(+) Breast cancer: metastatic disease or locally advanced disease – first line (pertuzumab) 49 -- 4.1.3.3 HER2(+) Breast cancer: metastatic disease or locally advanced disease – second line (pertuzumab, trastuzumab emtansine) 49 -- 4.1.3.4 HER2(-) Breast cancer: metastatic disease or locally advanced disease 50 -- 4.1.3.5 Discussion 50 -- 4.1.4 Economic literature: cost-effectiveness 51 -- 4.1.5 Summary 57 -- 4.2 CHRONIC MYELOID LEUKAEMIA 59 -- 4.2.1 Introduction 59 -- 4.2.2 Observational data 60 -- 4.2.2.1 Patient characteristics, survival and expenditures 60 -- 4.2.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 67 -- 4.2.3 Medical literature: efficacy 67 -- 4.2.3.1 First-line treatment 68 -- 4.2.3.2 Second- and third-line treatment 70 -- 4.2.3.3 Discussion 70 -- 4.2.4 Economic literature: cost-effectiveness 71 -- 4.2.5 Summary 76 -- 4.3 COLORECTAL CANCER 78 -- 4.3.1 Introduction 78 -- 4.3.2 Observational data 79 -- 4.3.2.1 Patient characteristics, survival and expenditures 79 -- 4.3.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 84 -- 4.3.3 Medical literature: efficacy 84 -- 4.3.3.1 First-line treatment 85 -- 4.3.3.2 Second-line (or later) treatment 86 -- 4.3.3.3 Discussion 87 -- 4.3.4 Economic literature: cost-effectiveness 87 -- 4.3.5 Summary 91 -- 4.4 HEAD AND NECK CANCER 93 -- 4.4.1 Introduction 93 -- 4.4.2 Observational data 94 -- 4.4.2.1 Patient characteristics, survival and expenditures 94 -- 4.4.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 100 -- 4.4.3 Medical literature: efficacy 100 -- 4.4.3.1 Discussion 102 -- 4.4.4 Economic literature: cost-effectiveness 103 -- 4.4.5 Summary 106 -- 4.5 MELANOMA 107 -- 4.5.1 Introduction 107 -- 4.5.2 Observational data 108 -- 4.5.2.1 Patient characteristics, survival and expenditures 108 -- 4.5.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 119 -- 4.5.3 Medical literature: efficacy 120 -- 4.5.3.1 BRAF and MEK inhibitors melanoma 121 -- 4.5.3.2 Immunotherapy in melanoma 122 -- 4.5.3.3 Discussion 123 -- 4.5.4 Economic literature: cost-effectiveness 124 -- 4.5.5 Summary 129 -- 4.6 MESOTHELIOMA 132 -- 4.6.1 Introduction 132 -- 4.6.2 Observational data 132 -- 4.6.2.1 Patient characteristics, survival and expenditures 132 -- 4.6.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 139 -- 4.6.3 Medical literature: efficacy 139 -- 4.6.3.1 Discussion 140 -- 4.6.4 Economic literature: cost-effectiveness 141 -- 4.6.5 Summary 142 -- 4.7 MULTIPLE MYELOMA 143 -- 4.7.1 Introduction 143 -- 4.7.2 Observational data 145 -- 4.7.2.1 Patient characteristics, survival and expenditures 145 -- 4.7.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 150 -- 4.7.3 Medical literature: efficacy 150 -- 4.7.3.1 Multiple Myeloma: First-line treatment in adult patients ineligible for stem-cell -- transplantation 151 -- 4.7.3.2 Multiple myeloma: first-line treatment in adult patients eligible for stem-cell -- transplant 152 -- 4.7.3.3 Multiple myeloma: treatment of relapsed or refractory disease 152 -- 4.7.3.4 Discussion 153 -- 4.7.4 Economic literature: cost-effectiveness 154 -- 4.7.5 Summary 158 -- 4.8 NON-HODGKIN LYMPHOMA 160 -- 4.8.1 Introduction 160 -- 4.8.2 Observational data 161 -- 4.8.2.1 Patient characteristics, survival and expenditures 161 -- 4.8.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 175 -- 4.8.3 Medical literature: efficacy 176 -- 4.8.3.1 CLL/SLL 176 -- 4.8.3.2 DLBCL 178 -- 4.8.3.3 Mantle cell lymphoma 179 -- 4.8.3.4 Discussion 181 -- 4.8.4 Economic literature: cost-effectiveness 183 -- 4.8.4.1 Chronic lymphocytic leukaemia 183 -- 4.8.4.2 Mantel-cell lymphoma 188 -- 4.8.5 Summary 190 -- 4.8.5.1 CLL/SLL 190 -- 4.8.5.2 DLBCL 191 -- 4.8.5.3 Mantle cell lymphoma 192 -- 4.9 NON-SMALL CELL LUNG CANCER 193 -- 4.9.1 Introduction 193 -- 4.9.2 Observational data 194 -- 4.9.2.1 Patient characteristics, survival and expenditures 194 -- 4.9.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 199 -- 4.9.3 Medical literature: efficacy 199 -- 4.9.3.1 Anti-EGFR therapy in NSCLC 200 -- 4.9.3.2 ALK inhibitors for non-small cell lung cancer 203 -- 4.9.3.3 Immunotherapy 203 -- 4.9.3.4 Discussion 205 -- 4.9.4 Economic literature: cost-effectiveness 205 -- 4.9.5 Summary 209 -- 4.10 OVARIAN CANCER 211 -- 4.10.1 Introduction 211 -- 4.10.2 Observational data 211 -- 4.10.2.1 Patient characteristics, survival and expenditures 211 -- 4.10.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 220 -- 4.10.3 Medical literature: efficacy 220 -- 4.10.3.1 Bevacizumab in ovarian cancer 221 -- 4.10.3.2 Discussion 222 -- 4.10.4 Economic literature: cost-effectiveness 222 -- 4.10.5 Summary 226 -- 4.11 PROSTATE CANCER 227 -- 4.11.1 Introduction 227 -- 4.11.2 Observational data 227 -- 4.11.2.1 Patient characteristics, survival and expenditures 227 -- 4.11.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 233 -- 4.11.3 Medical literature: efficacy 233 -- 4.11.3.1 Discussion 235 -- 4.11.4 Economic literature: cost-effectiveness 235 -- 4.11.5 Summary 238 -- 4.12 RENAL CELL CARCINOMA (RCC) 239 -- 4.12.1 Introduction 239 -- 4.12.2 Observational data 241 -- 4.12.2.1 Patient characteristics, survival and expenditures 241 -- 4.12.2.2 Drug uptake for a selection of drugs during the first 5 years after diagnosis 247 -- 4.12.3 Medical literature: efficacy 249 -- 4.12.3.1 Targeted therapy – first line treatment 250 -- 4.12.3.2 Targeted therapy – second line treatment 250 -- 4.12.3.3 Immunotherapy 251 -- 4.12.3.4 Discussion 252 -- 4.12.4 Economic literature: cost-effectiveness 253 -- 4.12.5 Summary 259 -- 5 USE OF ANTICANCER DRUGS AT THE END OF LIFE 261 -- 6 SUMMARY 266 -- 7 DISCUSSION 276 -- 7.1 REAL-WORLD OBSERVATIONAL DATA 276 -- 7.1.1 Data from the Belgian Cancer Registry (BCR) and Intermutualistic Agency (IMA) – strengths/limitations and nuance needed 276 -- 7.1.2 Limitations inherent to the use of observational data – no good estimate of treatment effect 280 -- 7.2 LIMITED BENEFITS IN OVERALL SURVIVAL 284 -- 7.3 QOL AS AN IMPORTANT ENDPOINT 287 -- 7.3.1 A patient-relevant endpoint in clinical trials 287 -- 7.3.2 Measuring QoL with a generic utility instrument 287 -- 7.3.3 Improvement needed in measuring and reporting QoL, and using the results in economic evaluations 288 -- 7.3.4 An example to show (the importance of) transparent reporting of QoL data 292 -- 7.4 THE USE OF PROGRESSION-FREE SURVIVAL AS A SURROGATE ENDPOINT 295 -- 7.4.1 Is PFS a valid surrogate for OS?. 295 -- 7.4.2 Can PFS be considered as a surrogate for quality of life? 296 -- 7.4.3 The problem of PFS in economic evaluations 297 -- 7.4.4 Do we try hard enough? Searching for a solution that fits both goals 298 -- 7.5 SUBSTANTIAL INCREASE IN GROSS EXPENDITURES, LIMITED BY REFUNDS AND TAXES 299 -- 7.5.1 Managed entry agreement refunds 299 -- 7.5.2 Taxes and clawback 300 -- 7.6 MANAGED ENTRY AGREEMENT 301 -- 7.6.1 Managed entry agreement – when the exception becomes the rule 301 -- 7.6.2 Incentives to demonstrate survival or QoL benefits for the patients 302 -- 7.6.2.1 Before marketing approval 302 -- 7.6.2.2 After marketing approval 304 -- 7.6.3 Confidential prices 307 -- 7.6.3.1 A short-term advantage creating long-term problems and making the system intransparent 307 -- 7.6.3.2 Confidential prices making economic evaluations and policy decisions intransparent 308 -- 7.7 WHY WE MAINLY RELIED ON UK DOSSIERS FOR INFORMATION ON ECONOMIC EVALUATIONS IN THIS REPORT 309 -- 7.8 THE IMPORTANCE OF THE (DISCOUNT FOR THE) COMPARATOR 311 -- 7.9 DIFFERENT ARGUMENTS USED FROM DIFFERENT PERSPECTIVES 313 -- REFERENCES 317
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- 2021
35. Welke rol kan de MammaPrint® test spelen bij het nemen van beslissingen over adjuvante chemotherapie bij borstkanker in een vroeg stadium? : Synthese
- Author
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San Miguel, Lorena, Dubois, Cécile, Gerkens, Sophie, Harrison, Jillian, and Hulstaert, Frank
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R298 ,Gene Expression Profiling ,Breast Neoplasms ,WP 870 - Breast - - Neoplasms ,2017-01 - Abstract
18 p. ill., INHOUDSTAFEL . 2 -- 1. CONTEXT EN DOELSTELLINGEN VAN DEZE STUDIE 3 -- 2. WAT IS DE MAMMAPRINT®? . 3 -- 2.1. BORSTKANKER IN EEN VROEG STADIUM 4 -- 2.2. BEOORDELING VAN HET KLINISCHE RISICO . 4 -- 2.3. GENEXPRESSIETESTEN 5 -- 3. KLINISCHE DOELTREFFENDHEID VAN DE MAMMAPRINT ® . 6 -- 3.1. DE MINDACT-STUDIE 6 -- 3.2. RESULTATEN 7 -- 3.2.1. Patiëntes met hoog klinisch en laag genomisch risico 7 -- 3.2.2. Laag klinisch en hoog genomisch risico 8 -- 3.2.3. Levenskwaliteit 8 -- 3.2.4. Conclusie 8 -- 4. KOSTENEFFECTIVITEIT VAN DE MAMMAPRINT® 9 -- 4.1. BESCHIKBAAR BEWIJS 9 -- 4.2. KOSTENEFFECTIVITEIT VAN DE MAMMAPRINT 9 -- 5. EXTRAPOLATIE NAAR DE BELGISCHE CONTEXT 10 -- 5.1. GEBRUIKTE GEGEVENS . 10 -- 5.2. RESULTATEN . 10 -- 5.3. RAMING VAN DE KOSTEN VOOR ADJUVANTE CHEMOTHERAPIE 13 -- AANBEVELINGEN 15
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- 2018
36. MammaPrint® test for personalised management of adjuvant chemotherapy decisions in early breast cancer
- Author
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San Miguel, Lorena, Dubois, Cécile, Gerkens, Sophie, Harrison, Jillian, and Hulstaert, Frank
- Subjects
R298 ,Gene Expression Profiling ,Breast Neoplasms ,WP 870 - Breast - - Neoplasms ,2017-01 - Abstract
70 p. ill., SCIENTIFIC REPORT 6 -- 1 INTRODUCTION AND SCOPE 6 -- 2 BREAST CANCER 7 -- 2.1 EPIDEMIOLOGY 7 -- 2.2 PROGNOSIS AND TREATMENT 7 -- 3 MAMMAPRINT® IN EARLY BREAST CANCER 8 -- 3.1 MAMMAPRINT® 8 -- 3.2 METHODS FOR ASSESSMENT OF CLINICAL UTILITY 8 -- 3.3 RESULTS ON THE CLINICAL UTILITY OF MAMMAPRINT® 8 -- 4 SYSTEMATIC LITERATURE REVIEW OF ECONOMIC STUDIES 12 -- 4.1 INTRODUCTION 12 -- 4.2 METHODS 12 -- 4.2.1 Search strategy 12 -- 4.2.2 Selection procedure 12 -- 4.2.3 Selection criteria 12 -- 4.3 OVERVIEW OF ECONOMIC EVALUATIONS 13 -- 4.3.1 Type of economic evaluation 14 -- 4.3.2 Time frame of analyses and discounting 14 -- 4.3.3 Perspective 15 -- 4.3.4 Population 15 -- 4.3.5 Comparators 15 -- 4.3.6 Cost and outcome inputs 15 -- 4.3.7 Modelling 16 -- 4.3.8 Results 17 -- 4.3.9 Sensitivity analysis 22 -- 4.3.10 Conflict of interest 22 -- 4.4 DISCUSSION AND CONCLUSIONS 22 -- 5.2 PATIENTS’ SELECTION 25 -- 5.4.2 Characteristics of the subset of patients for the Belgian context 30 -- 5.4.3 Target population and projection 32 -- 6 CHEMOTHERAPY USE AND RELATED COSTS IN EARLY BREAST CANCER PATIENTS IN BELGIUM 36 -- 6.1 CHEMOTHERAPY COMBINATIONS 36 -- 6.2 OTHER NON-PHARMACOLOGICAL CHEMOTHERAPY-RELATED COSTS 37 -- 6.2.1 Chemotherapy administration 37 -- 6.2.2 Blood tests 37 -- 6.2.3 Costs of prophylaxis or management of common chemotherapy related adverse events (AEs) 38 -- 6.2.4 Other costs 39 -- 6.2.5 Limitations 40 -- 7.1 CLINICAL UTILITY OF MAMMAPRINT® 43 -- 7.1.1 The evidence 43 -- 7.2 GENERALIZABILITY OF ECONOMIC EVALUATIONS TO THE BELGIAN CONTEXT 46 -- APPENDICES 48 -- REFERENCES 67
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- 2018
37. Quel rôle pour le test Mammaprint® dans les décisions de chimiothérapie adjuvante en cas de cancer du sein au stade précoce ? : Synthèse
- Author
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San Miguel, Lorena, Dubois, Cécile, Gerkens, Sophie, Harrison, Jillian, and Hulstaert, Frank
- Subjects
R298 ,Gene Expression Profiling ,Breast Neoplasms ,WP 870 - Breast - - Neoplasms ,2017-01 - Abstract
18 p. ill., SYNTHÈSE 2 -- 1. CONTEXTE ET OBJECTIFS DE CETTE ÉTUDE 3 -- 2. QU’EST-CE QUE LE TEST MAMMAPRINT® ?3 -- 2.1. LE CANCER DU SEIN AU STADE PRÉCOCE 4 -- 2.2. L’ÉVALUATION DU RISQUE CLINIQUE 4 -- 2.3. LES TESTS D’EXPRESSION GÉNIQUE 5 -- 3. EFFICACITÉ CLINIQUE DU MAMMAPRINT® 6 -- 3.1. L’ÉTUDE MINDACT 6 -- 3.2. RÉSULTATS 7 -- 3.2.1. Patientes à risque clinique élevé et risque génomique faible 7 -- 3.2.2. Risque clinique faible et risque génomique élevé 8 -- 3.2.3. Qualité de vie 8 -- 3.2.4. Conclusion 8 -- 4. RAPPORT COÛT-EFFICACITÉ DU MAMMAPRINT® 9 -- 4.1. DONNÉES PROBANTES DISPONIBLES 9 -- 4.2. COÛT-EFFICACITÉ DU MAMMAPRINT® 9 -- 5. EXTRAPOLATION AU CONTEXTE BELGE 10 -- 5.1. DONNÉES UTILISÉES 10 -- 5.2. RÉSULTATS 10 -- 5.3. ESTIMATION DES COÛTS LIÉS À LA CHIMIOTHÉRAPIE ADJUVANTE 14
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- 2018
38. Introduction of high-risk medical devices : national measures that can be taken under the current European legislation to put the patient interest central
- Author
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Neyt, Mattias, Baeyens, Hanne, Pouppez, Céline, Slegers, Pierre, Hulstaert, Frank, Stordeur, Sabine, and Vinck, Imgard
- Subjects
Economics, Medical ,Equipment and Supplies ,Legislation ,Journal Article ,European Union ,W 1 Serials. Periodicals - Abstract
p. 181-188 Background: High-risk medical devices may not always provide a therapeutic added value to patients. In Europe, no proof of efficacy is required to receive a CE label, making it difficult for policymakers to decide on reimbursement of (often expensive) high-risk medical devices. We explore, within the framework of the European legislation, the possibilities at a national level for a guided introduction of such devices. Research design and Methods: HTA and legal experts worked in close collaboration with medical specialists and government representatives making a legal analysis of what is possible under the (revised) European and national legislation. Results: At national level, measures for a better evidence-based introduction can be taken that are not in contradiction with the European regulation. From a legal point of view, all restrictive measures must be justified, necessary and proportional. Several measures are possible, a.o.making use of reference centres, applying the IDEAL framework or the 6-step plan set up by the Dutch Order of Medical Specialists. Conclusions: Within the framework of the (revised) European legislation, measures at national level can be taken to temporarily restrict and follow up the use of high-risk medical devices with a greater focus on the therapeutic added value for the patients. Disclaimer As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.
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- 2017
39. Publicly funded practice-oriented clinical trials : of importance for healthcare payers
- Author
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Neyt, Mattias, Christiaens, Thierry, Demotes, Jacques, Walley, Tom, and Hulstaert, Frank
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Comparative Effectiveness Research ,Pragmatic Clinical Trials ,Health Care Economics and Organizations ,2014-07 ,Journal Article ,W 1 Serials. Periodicals ,health care economics and organizations ,Randomized Controlled Trials - Abstract
p. 551-560 AIM: Many questions of relevance to patients/society are not answered by industry-sponsored clinical trials. We consider whether there are benefits to governments in funding practice-oriented clinical trials. METHODOLOGY: A literature search including publications on institutions' websites was performed and supplemented with information gathered from (inter)national stakeholders. RESULTS: Areas were identified where public funding of clinical trials is of importance for society, such as head-to-head comparisons or medical areas where companies have no motivation to invest. The available literature suggests publicly funded research programs could provide a positive return on investment. The main hurdles (e.g., sufficient funding and absence of equipoise) and success factors (e.g., selection of research questions and research infrastructure) for the successful conduct of publicly funded trials were identified. CONCLUSION: Governments should see public funding of pragmatic practice-oriented clinical trials as a good opportunity to improve the selection and quality of treatments and stimulate efficient use of limited resources.
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- 2016
40. Economic evaluation of novel direct acting antiviral (DAA) treatment strategies for chronic hepatitis C
- Author
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Gerkens, Sophie, Thiry, Nancy, Hulstaert, Frank, and Robays, Jo
- Subjects
R276 ,Cost-Benefit Analysis ,2015-08 ,WC 536 Human viral hepatitis ,Antiviral Agents ,Hepatitis C - Abstract
144 p. ill., SCIENTIFIC REPORT 14 -- 1 INTRODUCTION .14 -- 1.1 BACKGROUND 14 -- 1.1.1 Transmission 14 -- 1.1.2 Hepatitis C in Belgium 15 -- 1.1.3 Treatments 16 -- 1.2 OBJECTIVE OF THIS REPORT AND RESEARCH QUESTIONS 17 -- 2 REVIEW OF THE PUBLISHED ECONOMIC EVALUATIONS 18 2.1 INTRODUCTION .18 -- 2.2 METHODS 18 2.2.1 Inclusion and exclusion criteria .18 -- 2.2.2 Search strategy .19 2.2.3 Selection procedure 19 2.2.4 Coverage of the reviews 21 -- 2.3 CLASSIFICATION OF THE ECONOMIC EVALUATIONS 21 -- 2.3.1 Early publications based on emerging and weak evidence 21 -- 2.3.2 Pegylated interferon as an intervention 21 -- 2.3.3 Disease progression after sustained viral response 22 -- 2.3.4 Selected economic evaluations 22 -- 2.4 OVERVIEW OF THE SELECTED ECONOMIC EVALUATIONS 23 -- 2.4.1 Country and study design 23 -- 2.4.2 Perspective .23 -- 2.4.3 Time horizon and discount rate .23 -- 2.4.4 Targeted patient group 23 -- 2.4.5 Intervention and comparators 23 -- 2.4.6 Assumptions used in modelling the HCV natural history .24 2.4.7 Non-liver mortality 25 -- 2.4.8 Quality of life 25 -- 2.5 MAIN RESULTS OF THE ECONOMIC EVALUATIONS 34 -- 2.5.1 Genotype 1 34 -- 2.5.2 Genotype 2 35 -- 2.5.3 Genotype 3 35 -- 2.5.4 Genotype 4 35 -- 2.6 SENSITIVITY AND SUBGROUP ANALYSES .35 -- 2.6.1 Sensitivity analyses .35 -- 2.6.2 Subgroup analyses .35 -- 2.7 DISCUSSION 41 -- 2.7.1 Summary of the results .41 -- 2.7.2 General conclusion .42 -- 3 THE COST-EFFECTIVENESS AND BUDGET IMPACT OF TREATMENT STRATEGIES FOR HEPATITIS C IN BELGIUM 43 -- 3.1 INTRODUCTION .43 -- 3.2 METHODS 43 -- 3.2.1 Design and analytic technique 43 -- 3.2.2 Perspective .44 -- 3.2.3 Time window and discounting 44 -- 3.2.4 Target population .44 -- 3.2.5 Intervention and comparator 45 -- 3.2.6 Model structure and basic assumptions 45 -- 3.2.7 Transition probabilities 48 -- 3.2.8 Performance of non-invasive liver tests 50 -- 3.2.9 Effectiveness of antiviral treatment .52 -- 3.2.10 Disease management, diagnostic tests and treatment costs 53 -- 3.2.11 Utilities 59 -- 3.2.12 Uncertainty 63 -- 3.2.13 Validation of the model 66 -- 3.3 RESULTS 66 -- 3.3.1 Cost-effectiveness analysis.66 -- 3.3.2 Budget impact analysis .72 -- 4 DISCUSSION AND CONCLUSION 80 -- APPPENDICES 83 -- APPENDIX 1. SCENARIO ANALYSES .83 -- APPENDIX 1.1. KCE REPORTS 157 ANTIVIRAL TREATMENT - ANNUAL TRANSITION PROBABILITIES BETWEEN FIBROSIS STAGES103 83 -- APPENDIX 1.2. TABLES OF THE SCENARIO ANALYSES FOR THE COST-EFFECTIVENESS ANALYSES 86 -- REFERENCES . 137
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- 2016
41. Vers un élargissement du remboursement des traitements de l’hépatite C ? : – Résumé
- Author
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Gerkens, Sophie, Thiry, Nancy, Hulstaert, Frank, and Robays, Jo
- Subjects
R276 ,Cost-Benefit Analysis ,2015-08 ,WC 536 Human viral hepatitis ,Antiviral Agents ,Hepatitis C - Abstract
24 p. ill., Les nouveaux médicaments antiviraux contre l’hépatite C sont plus efficaces et ont moins d’effets secondaires que les anciens, mais ils sont aussi très chers: environ 40.000 € par traitement. Pour le moment, ils ne sont remboursés que pour les patients qui ont des lésions avancées du foie et en cas de transplantation hépatique. La Ministre de la Santé a déjà annoncé qu’elle souhaitait élargir leur remboursement, à partir de 2017, aux patients à un stade moins avancé. Le Centre fédéral d’Expertise des soins de santé (KCE) suggère de continuer sur cette voie et d’envisager de traiter toutes les personnes porteuses du virus, étant donné que plus on traite tôt, plus les bénéfices pour la santé sont importants. Un tel élargissement du remboursement devrait toutefois se faire par paliers de manière à garder le budget de l’assurance maladie sous contrôle. Afin d’obtenir une réduction plus importante des prix et de permettre d’élargir plus rapidement le remboursement, d’autres options pourraient être envisagées, comme s’associer avec d’autres pays pour lancer un appel d’offres conjoint. PRÉFACE 1--MESSAGES CLÉS 2--SYNTHÈSE 4--1. CONTEXTE DE CE RAPPORT 5--1.1. L’HÉPATITE C 5--1.2. NOMBRE DE PERSONNES ATTEINTES PAR LE VHC EN BELGIQUE 6--1.3. LES TRAITEMENTS 6--1.4. OBJECTIFS DE CE RAPPORT 7--2. CRITÈRES D’ÉLIGIBILITÉ POUR LE TRAITEMENT 7--2.1. LA SITUATION JUSQU’À AUJOURD’HUI 7--2.2. DÉTERMINER LE STADE DE LA FIBROSE PAR DES TESTS NON INVASIFS ? 7--2.3. DÉTERMINATION DES CRITÈRES D’ÉLIGIBILITÉ 8--3. ANALYSE COÛT-EFFICACITÉ DES DIFFÉRENTES STRATÉGIES ENVISAGEABLES 9--3.1. CINQ STRATÉGIES 9--3.2. MÉTHODE 10--3.3. RÉSULTAT DES ANALYSES COÛT-EFFICACITÉ ET COÛT-UTILITÉ 12--3.4. TRAITEMENT DE L’INCERTITUDE 13--4. IMPACT BUDGÉTAIRE 16--5. VERS UNE ÉRADICATION? 21--5.1. LES USAGERS DE DROGUES INJECTABLES (UDI) 21--5.2. LES MSM (MEN HAVING SEX WITH MEN) 21--5.3. L’IMMIGRATION 21--6. CONCLUSION ET DISCUSSION: VERS UN AUTRE MODÈLE DE REMBOURSEMENT? 22--RECOMMANDATIONS 24
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- 2016
42. Naar een uitbreiding van de terugbetaling van de hepatitis c-behandelingen ? : – Samenvatting
- Author
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Gerkens, Sophie, Thiry, Nancy, Hulstaert, Frank, and Robays, Jo
- Subjects
R276 ,Cost-Benefit Analysis ,2015-08 ,WC 536 Human viral hepatitis ,Antiviral Agents ,Hepatitis C - Abstract
24 p. ill., De nieuwe antivirale middelen tegen hepatitis C zijn meer doeltreffend en hebben minder nevenwerkingen dan de oude, maar zijn ook zeer duur: ongeveer €40.000 per behandeling. Momenteel wordt deze behandeling enkel terugbetaald voor patiënten met gevorderde leverschade en bij levertransplantatie. De minister van Volksgezondheid heeft al aangekondigd dat ze de terugbetaling vanaf 2017 zal uitbreiden naar patiënten met minder gevorderde schade. Het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) pleit ervoor om op de ingeslagen weg verder te gaan, met het oog op het uiteindelijk behandelen van alle besmette patiënten, want hoe eerder men behandelt, hoe groter de gezondheidswinst. Dergelijke uitbreiding van de terugbetaling moet wel stapsgewijs gebeuren, om de uitgaven van de ziekteverzekering onder controle te houden.Om een grotere prijskorting te verkrijgen en om de terugbetaling sneller te kunnen uitbreiden zouden ook andere pistes kunnen worden bewandeld, zoals het lanceren van een openbare aanbesteding, samen met andere landen VOORWOORD 1 -- KERN BOODSCHAPPEN 2 -- SYNTHESE 4 -- 1. CONTEXT VAN DIT RAPPORT 5 -- 1.1. HEPATITIS C 5 -- 1.2. AANTAL PERSONEN BESMET MET HCV IN BELGIË 6 -- 1.3. DE BEHANDELINGEN 6 -- 1.4. DOELSTELLINGEN VAN DIT RAPPORT 7 -- 2. TOELAATBAARHEIDSCRITERIA VOOR DE BEHANDELING 7 -- 2.1. DE SITUATIE TOT VANDAAG 7 -- 2.2. HET STADIUM VAN DE FIBROSE BEPALEN MET NIET-INVASIEVE TESTEN? 7 -- 2.3. BEPALING VAN DE TOELAATBAARHEIDSCRITERIA” 8 -- 3. KOSTENEFFECTIVITEIT VAN DE VERSCHILLENDE STRATEGIEËN 9 -- 3.1. VIJF STRATEGIEËN 9 -- 3.2. METHODE 10 -- 3.3. RESULTAAT VAN DE KOSTENEFFECTIVITEITS- EN KOSTENUTILITEITSANALYSES 12 -- 3.4. AANPAK VAN DE ONZEKERHEID 14 -- 4. BUDGETTAIRE IMPACT 16 -- 5. NAAR EEN UITROEIING? 21 -- 5.1. DE INTRAVENEUZE DRUGGEBRUIKERS (IDU) 21 -- 5.2. MSM (MEN HAVING SEX WITH MEN) 21 -- 5.3. IMMIGRATIE 21 -- 6. CONCLUSIE EN DISCUSSIE : NAAR EEN ANDER TERUGBETALINGSMODEL ? 22 -- AANBEVELINGEN 24
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- 2016
43. Future scenarios about drug development and drug pricing
- Author
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Vandenbroeck, Philippe, Raeymakers, Peter, Wickert, Rachel, Becher, Kim, Goossens, Jo, Cleemput, Irina, Hulstaert, Frank, de Heij, Lydia, and Mertens, Raf
- Subjects
QV 736 Drug industry. Economics of pharmacy. Advertising ,Economics, Pharmaceutical ,2013-03 ,R271 ,Legislation, Drug ,Drug Approval - Abstract
32 p. ill., LIST OF FIGURES 2 -- LIST OF TABLES 2 -- LIST OF ABBREVIATIONS 3 -- SCIENTIFIC REPORT 4 -- 1 INTRODUCTION 4 -- 2 METHODS 5 -- 2.1 THE USE OF SCENARIOS IN THE DRUG PRICING PROJECT 5 -- 2.2 RECRUITMENT OF PARTICIPANTS 6 -- 2.3 INTERVIEWS 6 -- 2.4 ANALYSIS OF THE INTERVIEWS 7 -- 2.4.1 Approach 7 -- 2.4.2 General framing of the drug pricing problematique 7 -- 2.4.3 Building blocks for alternative drug development and pricing mechanisms 10 -- 2.5 THE SCENARIO DEVELOPMENT PROCESS 14 -- 3 RESULTS 15 -- 3.1 RESULTS FROM THE FIRST SCENARIO BUILDING WORKSHOP 15 -- 3.1.1 Refinement of the purpose served by the projected drug development and pricing system 15 -- 3.1.2 Refinement of the collection of functional building blocks 15 -- 3.1.3 Development of scenario seeds 16 -- 3.2 RESULTS FROM THE SECOND SCENARIO BUILDING WORKSHOP 19 -- 3.2.1 Scenario 1 – Needs-oriented Public-Private Partnerships 20 -- 3.2.2 Scenario 2 – Parallel Drug Development Track 20 -- 3.2.3 Scenario 3 – Pay for Patents 21 -- 3.2.4 Scenario 4 – Public Good from A to Z 21 -- 4 CONCLUSION 22
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- 2016
44. Scénarios futurs pour le développement des médicaments et la fixation de leurs prix
- Author
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Vandenbroeck, Philippe, Raeymakers, Peter, Wickert, Rachel, Becher, Kim, Goossens, Jo, Cleemput, Irina, Hulstaert, Frank, de Heij, Lydia, and Mertens, Raf
- Subjects
QV 736 Drug industry. Economics of pharmacy. Advertising ,Economics, Pharmaceutical ,2013-03 ,R271 ,Legislation, Drug ,Drug Approval - Abstract
21 p. ill.
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- 2016
45. Toekomstscenario’s voor de ontwikkeling en prijszetting van geneesmiddelen
- Author
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Vandenbroeck, Philippe, Raeymakers, Peter, Wickert, Rachel, Becher, Kim, Goossens, Jo, Cleemput, Irina, Hulstaert, Frank, de Heij, Lydia, and Mertens, Raf
- Subjects
QV 736 Drug industry. Economics of pharmacy. Advertising ,Economics, Pharmaceutical ,2013-03 ,R271 ,Legislation, Drug ,Drug Approval - Abstract
21 p. ill.
- Published
- 2016
46. Towards an expansion of the reimbursement conditions for Hepatitis C therapies? : – Summary
- Author
-
Gerkens, Sophie, Thiry, Nancy, Hulstaert, Frank, and Robays, Jo
- Subjects
R276 ,Cost-Benefit Analysis ,2015-08 ,WC 536 Human viral hepatitis ,Antiviral Agents ,Hepatitis C - Abstract
25 p. ill., FOREWORD 1 -- KEY MESSAGES 2 -- SUMMARY 4 -- 1. BACKGROUND 5 -- 1.1. HEPATITIS C 5 -- 1.2. NUMBER OF HCV-INFECTED PEOPLE IN BELGIUM 6 -- 1.3. THERAPIES 6 -- 1.4. OBJECTIVES OF THIS REPORT 6 -- 2. ELIGIBILITY CRITERIA FOR THE TREATMENT 7 -- 2.1. THE CURRENT SITUATION 7 -- 2.2. DETERMINING THE STAGE OF FIBROSIS THROUGH NON-INVASIVE TESTS? 8 -- 2.3. SETTING THE ELIGIBILITY CRITERIA 8 -- 3. COST-EFFECTIVENESS ANALYSIS OF THE VARIOUS POTENTIAL STRATEGIES 9 -- 3.1. FIVE STRATEGIES 9 -- 3.2. METHOD 10 -- 3.3. RESULT OF THE COST-EFFECTIVENESS AND COST-UTILITY ANALYSES 12 -- 3.4. TREATMENT OF THE UNCERTAINTY 14 -- 4. BUDGET IMPACT 16 -- 5. TOWARDS AN ERADICATION? 22 -- 5.1. INTRAVENOUS DRUG USERS. 22 -- 5.2. MSM (MEN WHO HAVE SEX WITH MEN) 22 -- 5.3. IMMIGRATION 22 -- 6. CONCLUSION AND DISCUSSION: TOWARDS A DIFFERENT REIMBURSEMENT MODEL? 23 -- RECOMMENDATIONS 25
- Published
- 2016
47. Towards a guided and phased introduction of high-risk medical devices in Belgium
- Author
-
Baeyens, Hanne, Pouppez, Céline, Slegers, Pierre, Vinck, Imgard, Hulstaert, Frank, and Neyt, Mattias
- Subjects
R249 ,Device Approval ,Equipement and Supplies ,Government Regulation ,2013-01 ,European Union ,W 82 Biomedical technology (General) - Abstract
85 p. ill., LIST OF FIGURES 2 -- LIST OF TABLES 2 -- LIST OF ABBREVIATIONS 3 -- SCIENTIFIC REPORT 5 -- 1 INTRODUCTION 5 -- 1.1 BACKGROUND 5 -- 1.1.1 What is the problem with the CE marking used in Europe? 5 -- 1.1.2 What is the problem on the Belgian market? 6 -- 1.2 RESEARCH QUESTIONS AND SCOPE OF THE STUDY 7 -- 1.3 METHODOLOGY 7 -- 2 A GENERAL OVERVIEW OF THE EU SYSTEM 9 -- 2.1 SOME DEFINITIONS 9 -- 2.2 THE CLASSIFICATION OF MEDICAL DEVICES 11 -- 2.2.1 EU 11 -- 2.2.2 US 12 -- 2.3 PRE-MARKET EVALUATION OF HIGH-RISK DEVICES AND IMPLANTS 12 -- 2.3.1 EU 12 -- 2.3.2 US 18 -- 2.4 TIME TO MARKET AND REIMBURSEMENT 21 -- 2.5 EXAMPLES OF FAILURES OF THE EU (AND US) SYSTEM 21 -- 3 REGULATORY FRAMEWORK ON A EU LEVEL 25 -- 3.1 OVERALL AIM OF THE EU HEALTH POLICIES 25 -- 3.2 THE FREE MOVEMENT OF GOODS AND THE MEDICAL DEVICES DIRECTIVES 27 -- 3.2.1 The core legislation 27 -- 3.2.2 Proposal for new Regulations 28 -- 3.2.3 The Joint Plan for Immediate Actions 36 -- 3.2.4 Possible restrictions on the free movement of medical devices 38 -- 3.2.5 Case law50 -- 3.3 THE PATIENTS’ RIGHTS IN CROSS-BORDER HEALTHCARE 57 -- 4 EXAMPLES OF MEASURES ON A NATIONAL LEVEL 59 -- 4.1 RESTRICTIONS ON THE DISTRIBUTION 59 -- 4.2 MEDICAL GUIDELINES 60 -- 4.3 PROFESSIONAL AND TRACEABILITY REGISTRIES 61 -- 4.4 LIMITATION OF THE USE OF CERTAIN MEDICAL DEVICES TO REFERENCE CENTRES / SPECIALISTS 63 -- 4.5 HCP’S BEHAVIOR RULES AND LIABILITY 65 -- 4.5.1 Belgium 65 -- 4.5.2 UK 67 -- 4.5.3 The Netherlands 69 -- 4.6 CONCLUSION 69 -- 5 POSSIBLE SOLUTIONS FOR BELGIUM 70 -- 5.1 MEASURES WITHIN THE HARMONIZED FIELDS 71 -- 5.1.1 Non conformity of medical devices 71 -- 5.1.2 Threat to health and safety 71 -- 5.2 MEASURE OUTSIDE THE HARMONISED FIELDS 72 -- 5.2.1 Restrictions on the distribution of medical devices 72 -- 5.2.2 Restrictions on the use of medical devices and the performance of complicated surgeries to implant them 73 -- 5.2.3 Increase HCP’s obligations 75 -- 5.2.4 Improve the use of registries and reinforce post marketing surveillance 76 -- 5.2.5 The IDEAL framework: no surgical innovation without evaluation 77 -- 5.2.6 Selection of the appropriate research design 80 -- 5.3 FINAL REMARK 82 -- REFERENCES 83
- Published
- 2015
48. Hadron therapie bij kinderen : een update van de wetenschappelijke evidentie voor 15 kankers bij kinderen – Synthese
- Author
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Leroy, Roos, Benahmed, Nadia, Hulstaert, Frank, Mambourg, Françoise, Fairon, Nicolas, Van Eycken, Liesbet, and De Ruysscher, Dirk
- Subjects
R235 ,Radiotherapy ,2014-19 ,Proton Therapy ,Heavy Ions ,Review ,WN 250.5.P7 Proton therapy - Abstract
24 p. ill. Biedt protontherapie, een nauwkeurige bestralingstechniek, meer voordeel bij de behandeling van kinderen dan klassieke radiotherapie? Bij protontherapie worden de omliggende weefsels minder blootgesteld aan straling. Daardoor zou het risico op bijkomende tumoren en andere problemen, veroorzaakt door bestraling, lager liggen. Op verzoek van het RIZIV onderzocht het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) of dit laatste uiteindelijk ook betere medische resultaten oplevert bij kinderen. De vraag is zeer actueel, omdat dit jaar de bouw van de eerste Belgische protoncentra werd aangekondigd. De vraag is echter onmogelijk te beantwoorden: ondanks de wereldwijde behandeling van duizenden kinderen zijn er geen goede klinische studies bij kinderen uitgevoerd. Het KCE moest dus concluderen dat de meerwaarde van protontherapie voor de behandeling van kanker bij kinderen nog niet is bewezen. VOORWOORD 1 -- SAMENVATTING 2 -- 1 INTRODUCTIE 2 -- 2 METHODEN .3 -- 3 RESULTATEN 3 -- 4 CONCLUSIES .3 -- INHOUDSOPGAVE .2 -- LIJST MET AFBEELDINGEN 3 -- LIJST VAN AFKORTINGEN & ACRONIEMEN 4 -- 1 INTRODUCTIE 5 -- 1.1 RATIONALE & ONDERZOEKSVRAGEN .5 -- 1.2 WAT IS HADRONTHERAPIE? 5 -- 1.2.1 Protontherapie 6 -- 1.2.2 Radiotherapie met koolstofionen 7 -- 1.3 WAAROM PROTONTHERAPIE BIJ KINDEREN? 7 -- 1.4 PROTONTHERAPIE - DE HEILIGE GRAAL IN DE PEDIATRISCHE RADIOTHERAPIE? 8 -- 2 SYSTEMATISCHE LITERATUURSTUDIE 8 -- 2.1 KLINISCHE EFFECTIVITEIT VAN PROTONTHERAPIE EN GEÏNDICEERD VOOR RADIOTHERAPIE/PROTONTHERAPIE, PER TUMORTYPE 9 -- 2.1.1 Chondrosarcoom van de schedelbasis 9 -- 2.1.2 Chordoom van de schedelbasis & (para)spinaal 9 -- 2.1.3 Craniofaryngeoom 9 -- 2.1.4 Ependymoom .10 -- 2.1.5 Esthesioneuroblastoom .10 -- 2.1.6 Ewingsarcoom 11 -- 2.1.7 Germinoom van het centraal zenuwstelsel .11 -- 2.1.8 Laaggradig glioom (incl. van de visuele banen) 12 -- 2.1.9 Medulloblastoom / Primitieve neuro-ectodermale tumor .13 -- 2.1.10 Niet-reseceerbaar osteosarcoom .13 -- 2.1.11 Bekkensarcoom 13 -- 2.1.12 Parenchymale tumoren van de pijnappelklier 14 -- 2.1.13 Retinoblastoom .14 -- 2.1.14 Rhabdomyosarcoom 15 -- 2.1.15 (Para)spinaal wekedelensarcoom van het 'volwassen type' 15 -- 2.2 KLINISCHE EFFECTIVITEIT VAN RADIOTHERAPIE MET KOOLSTOFIONEN EN GESCHIKTHEID VOOR RADIOTHERAPIE/RADIOTHERAPIE MET KOOLSTOFIONEN (CIRT) 16 -- Niet-reseceerbaar osteosarcoom 16 -- 3 DISCUSSIE 17 -- 4 KERNBOODSCHAPPEN18 -- AANBEVELINGEN 19 -- REFERENTIES 20
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- 2015
49. Vers une introduction contrôlée et graduelle des dispositifs médicaux à haut risque en Belgique : Synthèse
- Author
-
Baeyens, Hanne, Pouppez, Céline, Slegers, Pierre, Vinck, Imgard, Hulstaert, Frank, and Neyt, Mattias
- Subjects
R249 ,Device Approval ,Equipement and Supplies ,Government Regulation ,2013-01 ,European Union ,W 82 Biomedical technology (General) - Abstract
25 p. ill., En Europe, les réglementations sont beaucoup moins strictes pour les dispositifs médicaux que pour les médicaments – et ce même pour les dispositifs à haut risque comme les prothèses de hanche, les pacemakers et les stents coronaires. En effet, pour pouvoir les mettre sur le marché, les fabricants ne doivent pas produire de preuve que ces dispositifs apportent un réel bénéfice au patient. Ils ne sont généralement testés que sur un tout petit nombre de personnes, et leur sécurité laisse parfois aussi à désirer. En attendant qu’une réglementation européenne plus stricte voie le jour, le Centre fédéral d’Expertise des Soins de Santé (KCE) propose quelques mesures que la Belgique pourrait adopter pour protéger ses citoyens contre les possibles dangers et inconvénients de dispositifs à haut risque insuffisamment testés, sans pour autant se mettre en infraction par rapport aux législations européennes. PRÉFACE. 1 -- MESSAGES-CLÉS 2 -- SYNTHÈSE 5 -- 1. CONTEXTE. 7 -- 1.1. OBJECTIF DE L’ÉTUDE 7 -- 1.2. QUESTIONS DE RECHERCHE 7 -- 2. PROBLÉMATIQUE LIÉE À LA RÉGLEMENTATION EUROPÉENNE ACTUELLE 8 -- 2.1. LE LABEL CE DONNE ACCÈS À L’ENSEMBLE DU MARCHÉ EUROPÉEN 8 -- 2.2. ÉVALUATION PRÉ-COMMERCIALISATION 9 -- 2.2.1. Des exigences relatives à la sécurité clinique et à la performance, mais pas à l’efficacité. 9 -- 2.2.2. Un manque de recherches scientifiquement étayées. 9 -- 2.2.3. Une absence de transparence. 10 -- 2.2.4. L’efficacité ne doit être démontrée que pour le remboursement 10 -- 2.3. LES PARADOXES BELGES 11 -- 2.4. L’ACCÈS AU MARCHÉ BEAUCOUP PLUS STRICT AUX ÉTATS-UNIS QUE DANS L’UE.12 -- 3. INITIATIVES EUROPÉENNES EN VUE D’UNE RÉGLEMENTATION PLUS STRICTE13 -- 4. OPTIONS POUR UN ACCÈS CONTRÔLÉ ET PROGRESSIF AU MARCHÉ BELGE15 -- 4.1. MESURES AU NIVEAU DE L’ACCES AU MARCHE ET DE LA MISE EN SERVICE DES DISPOSITIFS (POUR LESQUELLES IL EXISTE UNE LEGISLATION EUROPEENNE = LES « DOMAINES HARMONISES ») 16 -- 4.1.1. Dispositifs médicaux qui ne satisfont pas aux exigences de sécurité et de performance cliniques (« non conformes »), et auxquels le label CE a donc été attribué à tort (art. 8 ou 18 de la Directive 93/42) 16 -- 4.1.2. Dispositifs médicaux mettant en danger la santé et la sécurité des patients (Art. 14b de la Directive 93/42) 16 -- 4.2. MESURES AU NIVEAU DE L’UTILISATION, DE LA DISTRIBUTION, DE LA PROMOTION ET DE LA LIVRAISON DES DISPOSITIFS (= HORS « DOMAINES HARMONISES ») 17 -- 4.2.1. Limitation de la distribution, de la promotion et de la livraison de dispositifs médicaux.17 -- 4.2.2. Limitation de l’usage en routine des dispositifs médicaux 17 -- 4.2.3. L’élargissement des obligations des dispensateurs de soins 19 -- 4.2.4. Améliorer l’utilisation des registres 21 -- RECOMMANDATIONS 23
- Published
- 2015
50. Towards a guided and phased introduction of high-risk medical devices in Belgium : Summary
- Author
-
Baeyens, Hanne, Pouppez, Céline, Slegers, Pierre, Vinck, Imgard, Hulstaert, Frank, and Neyt, Mattias
- Subjects
R249 ,Device Approval ,Equipement and Supplies ,Government Regulation ,2013-01 ,European Union ,W 82 Biomedical technology (General) - Abstract
23 p. ill., FOREWORD 1 -- KEY MESSAGES. 2 -- SUMMARY 4 -- 1. CONTEXT. 6 -- 1.1. OBJECTIVE OF THE STUDY 6 -- 1.2. RESEARCH QUESTIONS 6 -- 2. THE CURRENT EUROPEAN LEGISLATION AND ISSUE 7 -- 2.1. CE LABEL GIVES ACCESS TO THE ENTIRE EUROPEAN MARKET 7 -- 2.2. PRE-MARKET ASSESSMENT 7 -- 2.2.1. Clinical safety and performance is a requirement, efficacy not 7 -- 2.2.2. Lack of scientifically sound research 8 -- 2.2.3. No transparency. 8 -- 2.2.4. Efficacy must only be demonstrated for reimbursement purposes 9 -- 2.3. BELGIAN PARADOX 9 -- 2.4. MARKET ACCESS IN THE US IS FAR STRICTER THAN IN THE EU 10 -- 3. EUROPEAN INITIATIVES FOR A MORE STRINGENT LEGISLATION.12 -- 4. OPTIONS AS REGARDS PHASED, CONTROLLED MARKET ACCESS IN BELGIUM 14 -- 4.1. MEASURES WITH REGARD TO MARKET ACCESS AND THE DEPLOYMENT OF MEDICAL DEVICES (GOVERNED BY EUROPEAN LEGISLATION, THE SO-CALLED 'HARMONISED AREAS') 14 -- 4.1.1. Medical devices that do not meet the clinical safety and performance requirements (‘not in conformity’) and thus wrongfully obtained a CE label (art. 8 or 18 of Directive 93/42)14 -- 4.1.2. Medical devices that put the health and safety of patients at risk (art. 14b of Directive 93/42) 15 -- 4.2. MEASURES WITH REGARD TO THE USE, DISTRIBUTION, PROMOTION AND SUPPLY OF MEDICAL DEVICES (OUTSIDE THE 'HARMONISED AREAS') 16 -- 4.2.1. Restrictions on the distribution, promotion and supply of medical devices 16 -- 4.2.2. Restrictions on the actual use of medical devices 16 -- 4.2.3. Extending the obligations incumbent on care providers 17 -- 4.2.4. Improving the use of registers 20 -- RECOMMENDATIONS 21
- Published
- 2015
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