Shaping a research agenda to ensure a successful European health technology assessment: insights generated during the inaugural convention of the European access academy.

OBJECTIVES: Key challenges for a joint European Health Technology Assessment (HTA) include consolidated approaches towards the choice of adequate comparator(s), selection of endpoints that are relevant to patients with a given disease, dealing with remaining uncertainties as well as transparent and consistent management of related processes. We aimed to further crystallize related core domains within these four areas that warrant further research and scrutiny. METHODS: Building on the outcomes of a previously conducted questionnaire survey, four key areas, processes, uncertainty, comparator choice and endpoint selection, were identified. At the inaugural convention of the European Access Academy dedicated working groups were established defining and prioritizing core domains for each of the four areas. The working groups consisted of ~ 10 participants each, representing all relevant stakeholder groups (patients/ clinicians/ regulators/ HTA & payers/ academia/ industry). Story books identifying the work assignments were shared in advance. Two leads and one note taker per working group facilitated the process. All rankings were conducted on an ordinal Likert Response Scale scoring from 1 (low priority) to 7 (high priority). RESULTS: Identified key domains include for processes: i) address (resource-) challenge of multiple PICOs (Patient/ Intervention/ Comparator/ Outcomes), ii) time and capacity challenges, iii) integrating all involved stakeholders, iv) conflicts and aligning between different multi-national stakeholders, v) interaction with health technology developer; for uncertainty: i) early and inclusive collaboration, ii) agreement on feasibility of RCT and acceptance of uncertainty, iii) alignment on closing evidence gaps, iv) capacity gaps; for comparator choice: i) criteria for the choice of comparator in an increasingly fragmented treatment landscape, ii) reasonable number of comparators in PICOs, iii) shape Early Advice so that comparator fulfils both regulatory and HTA needs, iv) acceptability of Indirect Treatment Comparisons (ITC), v) ensure broad stakeholder involvement in comparator selection; for endpoint selection: i) approaching new endpoints; ii) patient preferences on endpoints; iii) position of HTA and other stakeholders; iv) long-term generation and secondary use of data; v) endpoint challenges in RCTs. CONCLUSIONS: The implementation of a joint European HTA assessment is a unique opportunity for a stronger European Health Union. We identified 19 domains related to the four key areas, processes, uncertainty, comparator choice and endpoint selection that urgently need to be addressed for this regulation to become a success.

How can a joint European health technology assessment provide an 'additional benefit' over the current standard of national assessments? : Insights generated from a multi-stakeholder survey in hematology/oncology.

OBJECTIVES: We conducted a multi-stakeholder survey to determine key areas where a joint European health technology assessment (HTA) could provide 'additional benefit' compared to the status quo of many parallel independent national and subnational assessments. METHODS: Leveraging three iterative Delphi cycles, a semiquantitative questionnaire was developed covering evidence challenges and heterogeneity of value drivers within HTAs across Europe with a focus on hematology/oncology. The questionnaire consisted of five sections: i) background information; ii) value drivers in HTA assessments today; iii) evolving evidence challenges; iv) heterogeneity of value drivers across Europe; v) impact of Europe's Beating Cancer Plan (EBCP). The questionnaire was circulated across n = 189 stakeholder institutions comprising HTA and regulatory bodies, clinical oncology associations, patient representatives, and industry associations. RESULTS: N = 30 responses were received (HTA bodies: 9; regulators: 10; patients' and physicians' associations: 3 each; industry: 5). Overall, 17 countries and EU level institutions were represented in the responses. Consistency across countries and stakeholder groups was high. Most relevant value drivers in HTAs today (scale 1, low to 5, high) were clinical trial design (mean 4.45), right endpoints (mean 4.40), and size of comparative effect (mean 4.33). Small patient numbers (mean 4.28) and innovative study designs (mean 4.1) were considered the most relevant evolving evidence challenges. Heterogeneity between regulatory and HTA evidence requirements and heterogeneity of the various national treatment standards and national HTA evidence requirements was high. All clinical and patient participants stated to have been with EBCP initiatives. CONCLUSIONS: For a European HTA to provide an 'additional benefit' over the multitude of existing national assessments key methodological and process challenges need to be addressed. These include approaches to address uncertainty in clinical development; comparator choice; consistency in approaching patient-relevant endpoints; and a transparent and consistent management of both HTA and regulatory procedures as well as their interface, including all involved stakeholder groups.

The fourth edition of the European Network for Health Technology Assessment Forum: highlights and outcomes.

The European Network for Health Technology Assessment (EUnetHTA) organizes an annual Forum with stakeholders to receive feedback on its activities, processes, and outputs produced. The fourth edition of the EUnetHTA Forum brought together representatives of HTA bodies, patient organizations, healthcare professionals (HCPs), academia, payers, regulators, and industry. The aim of this paper is to provide an overview of the highlights presented at the 2019 EUnetHTA Forum, reporting the main items and themes discussed in the plenary panel and breakout sessions. The leading topic was the concept of unmet medical need seen from different stakeholders' perspectives. Breakout sessions covered the joint production of assessment reports and engagement with payers, patients, and HCPs. Synergies, pragmatism, and inclusiveness across Member States and stakeholders were emphasized as leading factors to put in place a collaboration that serves the interest of patients and public health in a truly European spirit.

IS THE EUNETHTA HTA CORE MODEL® FIT FOR PURPOSE? EVALUATION FROM AN INDUSTRY PERSPECTIVE.

OBJECTIVES: The HTA Core Model® was developed to improve the transferability of health technology assessment (HTA) between settings. The model has been used by HTA agencies but is also of interest to manufacturers, for improving internal evidence generation and communicating with other HTA stakeholders. To establish if the model is fit for purpose from an industry perspective, the pharmaceutical company Roche, collaborating with the European Network for HTA (EUnetHTA), conducted an assessment of the model. METHODS: A questionnaire was developed to evaluate all assessment elements in the HTA Core Model v2.0 for their usefulness in meeting payers' evidence needs and demonstrating value. The questionnaire was completed by country affiliate teams working in evidence generation and reimbursement submissions for pharmaceuticals. Survey results were discussed in workshops to ensure consistency and alignment between teams. RESULTS: The questionnaire was completed by six teams. An additional team from global pricing and market access participated in workshops. Model domains pertaining to the health problem and current technology use, technology description, clinical effectiveness, and economic value were considered most important because they meet payers' evidence needs. Overall, the model was considered useful to improve the efficiency of HTA evidence generation, share evidence internally, and communicate value to payers and HTA agencies. CONCLUSIONS: From an industry perspective, the HTA Core Model provides a useful framework and common terminology for efficient generation of transferable HTA evidence. The timeliness, efficiency, and transparency of HTA processes could be improved by a more standardized approach to HTA across settings.

Leveraging EUnetHTA's conceptual framework to compare HTA decision drivers in France, Italy, and Germany from a manufacturer's point of view.

BACKGROUND: Health Technology Assessments (HTA) procedures differ substantially across the various European countries. We reviewed recent appraisals of a pharmaceutical manufacturer in three major European markets (France; Italy; Germany) and identified and categorized related decision drivers. METHODS: New marketing authorisation between January 2011 and August 2017, and Roche being the Marketing Authorization Holder, were included. Outcome of HTA appraisals by the Haute Autorité de Santé (HAS), Agenzia Italiana del Farmaco (AIFA), and Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) were reviewed. Respective decision drivers were identified and commonalities and differences across the three countries were determined leveraging the EUnetHTA conceptual taxonomy (i.e. the 9 domains of the EUnetHTA core model). RESULTS: Within that time period Roche received European marketing authorization for eight new molecular entities (10 indications, respectively). Outcome of HTA appraisals was heterogeneous across the three countries. However, the four clinical domains of the EUnetHTA core model were driving the national HTA appraisals, with the clinical effectiveness domain being of most importance. Important drivers related to the other three clinical domains included the target patient population (subgroups, Germany), the current management of the condition (unmet need, Italy), the regulatory status (Orphan Designation, Germany), as well as safety considerations (all three countries). Average time between EMA approval and full commercial availability of new medicines was 63 (Germany), 459 (Italy), and 557 days (France). CONCLUSIONS: The clinical domains of the EUnetHTA framework are mainly driven by national HTA appraisals, providing a suitable starting point for further developing a joint European view on value and evidence. Underlying topics and issues still reveal considerable differences.

Systematic overview of cost-effectiveness thresholds in ten countries across four continents.

AIM: To provide an overview of thresholds for incremental cost-effectiveness ratios (ICERs) representing willingness-to-pay (WTP) across multiple countries and insights into exemptions pertaining to the ICER (e.g., cancer). To compare ICER thresholds to individual country's estimated ability-to-pay. MATERIALS & METHODS: We included AHRQ/USA, BIQG-GOEG/Austria, CADTH/Canada, DAHTA@DIMDI/Germany, DECIT-CGATS/Brazil, HAS/France, HITAP/Thailand, IQWiG/Germany, LBI-HTA/Austria, MSAC/Australia, NICE/England/Wales and SBU/Sweden. ICER thresholds were derived from systematic literature/website search/expert surveys. WTP was compared with ATP using Spearman's rank correlation. RESULTS: Two general and explicitly acknowledged thresholds (England/Wales, Thailand), implicit thresholds in six countries and different ICER thresholds/decision-making rules in oncology were identified. Correlation between WTP and ability-to-pay was moderate. DISCUSSION: Our overview supports country-specific discussions on WTP and on how to define value(s) within societies.

Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis.

OBJECTIVE: Poor compliance and persistence with bisphosphonates is a concern in postmenopausal osteoporosis due to its negative impact on fracture risk and healthcare costs as well as quality of life. Reducing oral bisphosphonate dosing frequency is one measure available to increase therapy convenience and practicality, with the hope of improving compliance and persistence. This study compared compliance and persistence with weekly and daily bisphosphonate regimens for postmenopausal osteoporosis. METHODS: Administrative claims data (1997-2002) from 30 health plans were used to identify postmenopausal women (> 45 years) with osteoporosis, who had been newly prescribed a once-weekly (QW alendronate 35 mg or 70 mg) or once-daily (QD alendronate 5 mg or 10 mg or risedronate 5 mg) bisphosphonate. QW and QD cohorts were followed for 12 months from initial prescription. Medication possession ratios (MPRs) measured refill compliance during follow-up. Persistence was calculated as the number of days from the initial prescription to a lapse of > 30 days after completion of the previous refill. RESULTS: Data were available for 2741 women (QW, N = 731, QD, N = 2010). QW users had significantly higher medication compliance than QD users (69.2% vs. 57.6% MPR, p < or = 0.0001). QW users persisted with therapy significantly longer than QD users (p < 0.0001) and had higher rates of retention on treatment at 12 months than QD users (44.2% QW; 31.7% QD). Dosing frequency was the strongest predictor of time to discontinuation (p < 0.0001). CONCLUSIONS: Postmenopausal women prescribed a weekly bisphosphonate had significantly better compliance and persistence than those taking more frequent, daily bisphosphonate doses. However, compliance and persistence rates for both regimens were suboptimal, suggesting that less frequent dosing intervals may provide an opportunity to further improve the consistent use of bisphosphonate therapy.

Carvedilol reduces the costs of medical care in severe heart failure: an economic analysis of the COPERNICUS study applied to the United Kingdom.

BACKGROUND: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). METHODS: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per diem (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. RESULTS: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was pound530,771 ( pound44.89 per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was pound3.49 million in the carvedilol group compared with pound4.24 million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group ( pound479,200 vs. pound548,300). Overall, the cost per patient treated in the carvedilol group was pound3948 compared to pound4279 in the placebo group. This equated to a cost of pound385.98 vs. pound434.18, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. CONCLUSIONS: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.