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Abstract Background New medicines are increasingly being identified as efficacious across multiple indications. The impact of current pricing and reimbursement policies on launch decisions across these indications remains unclear. Objective This paper, first, maps marketing authorisation and HTA coverage recommendation sequences of multi-indication medicines across Germany, France, England, Scotland, Canada, Australia, and the USA, and, second, evaluates the clinical characteristics, clinical development time and coverage recommendation time of multi-indication medicines, drawing comparisons between the first and subsequent indications of an approved molecule. Methods Medicine approvals by the Food and Drug Administration between 2009–2019 were screened to identify multi-indication products with approved oncology indications. Data on clinical trial characteristics, clinical performance and HTA outcomes were extracted from publicly available regulatory approval and HTA reports. Results Relative to subsequent indications, first indications were more likely to receive conditional marketing authorisation, have an orphan designation, have a single arm phase II pivotal trial and lower MCBS score. Subsequent indications had faster HTA coverage recommendation times in England and Canada. While the majority of first indications received HTA coverage recommendations across all settings, the proportion of subsequent indications with HTA coverage recommendations was lower and uptake varied considerably across settings. Conclusions Discordance in the value of first versus subsequent indications can pose major challenges in systems that define price based on the initial indication. Current pricing and reimbursement systems generate significant fragmentation in the approval and availability of multi-indication products across settings.

Abstract Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany.

Background: Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods: Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer's dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results: A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions: This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany. [ABSTRACT FROM AUTHOR]

Background: This paper reports the process of establishing a transparent, accountable, evidence-based program for introduction of new technologies and clinical practices (TCPs) in a large Australian healthcare network. Many countries have robust evidence-based processes for assessment of new TCPs at national level. However many decisions are made by local health services where the resources and expertise to undertake health technology assessment (HTA) are limited and a lack of structure, process and transparency has been reported.Methods: An evidence-based model for process change was used to establish the program. Evidence from research and local data, experience of health service staff and consumer perspectives were incorporated at each of four steps: identifying the need for change, developing a proposal, implementation and evaluation. Checklists assessing characteristics of success, factors for sustainability and barriers and enablers were applied and implementation strategies were based on these findings. Quantitative and qualitative methods were used for process and outcome evaluation. An action research approach underpinned ongoing refinement to systems, processes and resources.Results: A Best Practice Guide developed from the literature and stakeholder consultation identified seven program components: Governance, Decision-Making, Application Process, Monitoring and Reporting, Resources, Administration, and Evaluation and Quality Improvement. The aims of transparency and accountability were achieved. The processes are explicit, decisions published, outcomes recorded and activities reported. The aim of ascertaining rigorous evidence-based information for decision-making was not achieved in all cases. Applicants proposing new TCPs provided the evidence from research literature and local data however the information was often incorrect or inadequate, overestimating benefits and underestimating costs. Due to these limitations the initial application process was replaced by an Expression of Interest from applicants followed by a rigorous HTA by independent in-house experts.Conclusion: The program is generalisable to most health care organisations. With one exception, the components would be achievable with minimal additional resources; the lack of skills and resources required for HTA will limit effective application in many settings. A toolkit containing details of the processes and sample materials is provided to facilitate replication or local adaptation by those wishing to establish a similar program. [ABSTRACT FROM AUTHOR]