Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Meeting the review family : exploring review types and associated information retrieval requirements

Background and objectives The last decade has witnessed increased recognition of the value of literature reviews for advancing understanding and decision making. This has been accompanied by an expansion in the range of methodological approaches and types of review. However, there remains uncertainty over definitions and search requirements beyond those for the ‘traditional’ systematic review. This study aims to characterise health related reviews by type and to provide recommendations on appropriate methods of information retrieval based on the available guidance. Methods A list of review types was generated from published typologies and categorised into ‘families’ based on their common features. Guidance on information retrieval for each review type was identified by searching pubmed, medline and Google Scholar, supplemented by scrutinising websites of review producing organisations. Results Forty‐eight review types were identified and categorised into seven families. Published guidance reveals increasing specification of methods for information retrieval; however, much of it remains generic with many review types lacking explicit requirements for the identification of evidence. Conclusions Defining review types and utilising appropriate search methods remain challenging. By familiarising themselves with a range of review methodologies and associated search methods, information specialists will be better equipped to select suitable approaches for future projects

Introduction to economic evaluation and health technology assessment

introduction to HTA for clinical engineer

Systematische Übersichtsarbeit unter Verwendung des HTA Core Model® for Rapid Relative Effectiveness Assessment

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population.Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE.Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma.Conclusions: ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.Hintergrund: Stuhl-DNA-Tests zur Früherkennung des kolorektalen Karzinoms (KRK) sind nicht-invasiv und können etablierte KRK-Screening-Verfahren ergänzen. Ziel dieses Health Technology Assessment war die Untersuchung der Wirksamkeit und Sicherheit von CE-zertifizierten Stuhl-DNA-Tests im Vergleich zu anderen Tests für ein Screening einer asymptomatischen KRK-Screening-Population.Methodik: Das Assessment wurde nach den Richtlinien des Europäischen Netzwerks für Health Technology Assessment (EUnetHTA) durchgeführt und schloss eine systematische Literaturrecherche in MEDLINE, Cochrane und EMBASE ein, durchgeführt 2018. Die Hersteller wurden bezüglich der Übermittlung von weiteren Daten kontaktiert. Fünf Patienteninterviews halfen in der Einschätzung möglicher ethischer oder sozialer Aspekte sowie von Patientenerfahrungen und -präferenzen. Wir bewerteten das Verzerrungsrisiko mit QUADAS-2 und verwendeten GRADE, um die Qualität der Evidenz zu bewerten.Ergebnisse: Wir identifizierten drei Studien zur Testgenauigkeit; zwei untersuchten einen Multitarget-Stuhl-DNA-Test (Cologuard®, im Vergleich zu einem fäkalen immunchemischen Test (FIT)) und eine Studie einen kombinierten DNA-Stuhltest (ColoAlert®, im Vergleich zu einem guajakbasierten Stuhlbluttest (gFOBT), Pyruvate Kinase Isoenzyme Typ M2 (M2-PK) und kombiniertem gFOBT/M2-PK). Wir fanden fünf publizierte Erhebungen zur Patientenzufriedenheit, jedoch keine Primärstudien zu den Auswirkungen eines Screenings mit den beiden Tests auf KRK oder die Gesamtmortalität. Beide Stuhl-DNA-Tests zeigten im direkten Vergleich eine höhere Sensitivität für den Nachweis von KRK und (fortgeschrittenen) Adenomen als FIT beziehungsweise gFOBT, wiesen aber eine geringere Spezifität auf. Diese Ergebnisse könnten jedoch vom genauen Typ des jeweils verwendeten FIT abhängen. Die berichteten Testausfallraten waren beim Stuhl-DNA-Test höher als beim FIT. Die Stärke der Evidenz war moderat bis hoch für die Cologuard®-Studien und niedrig bis sehr niedrig für die ColoAlert®-Studie, die sich auf eine frühere, nicht mehr am Markt befindliche Version des Produkts bezieht und die in den Ergebnissen zur Testgenauigkeit nicht zwischen fortgeschrittenen und nicht-fortgeschrittenen Adenomen differenzierte.Schlussfolgerungen: ColoAlert® ist der einzige derzeit in Europa am Markt befindliche Stuhl-DNA-Test und ist zu einem niedrigeren Preis als Cologuard® erhältlich, jedoch fehlt zuverlässige Evidenz. Eine Screening-Studie mit Implementierung der aktuellen Produktversion von ColoAlert® und geeigneten Komparatoren würde daher helfen, diese Screening-Option im europäischen Kontext zu evaluieren