The Beneluxa Initiative domain task force health technology assessment: a comparison of member countries' past health technology assessments.

OBJECTIVE: This study aimed to compare assessments between Beneluxa Initiative member countries' assessments and identify alignments and divergences. METHODS: A retrospective comparative analysis was performed that investigated (i) number and type of assessed indications (for Austria (AT), Belgium (BE), Ireland (IE), and the Netherlands (NL)); (ii) added benefit conclusions (for BE, IE, and NL); and (iii) the main arguments underlying differences in conclusions (for BE, IE, and NL). Data were retrieved directly from agency representatives and from public HTA reports. European Medicines Agency approved indications were included for drugs assessed between 2016 and 2020, excluding veterinary drugs, generics, and biosimilars. RESULTS: Only 44 (10 percent) of the 444 included indications were assessed by all four member countries. Between any pair of two countries, the overlap was higher, from 63 (AT-NL) to 188 (BE-IE). Added benefit conclusions matched exactly in 62-74 percent of the indications, depending on the countries compared. In the remaining cases, most often a difference of one added benefit level was observed (e.g., higher vs. equal relative effect). Contradictory outcomes were very rare: only three cases were observed (lower vs. higher effect). When assessing the underlying arguments for seven cases with different outcomes, differences were attributable to slight differences in weighing of evidence and uncertainties rather than disagreement on aspects within the assessment itself. CONCLUSIONS: Despite high variability in European HTA procedures, collaboration on HTA between the Beneluxa Initiative member countries is very feasible and would likely not result in added benefit conclusions that would be very different from added benefit conclusions in national procedures.

The Utility of a Rapid Review Evaluation Process to a National HTA Agency.

BACKGROUND AND OBJECTIVE: In Ireland, similar to other jurisdictions, health technology assessment (HTA) is used to inform the health payer's drug reimbursement decisions. These HTAs are conducted by the National Centre for Pharmacoeconomics (NCPE). In 2009, the NCPE introduced the Rapid Review process to identify drugs that do not require further assessment in the form of the previously established full HTA process. METHODS: A retrospective analysis of all Rapid Reviews submitted to the NCPE from 2010 to 2019, inclusive, was conducted. Rapid Review recommendation was recorded (i.e. full HTA required or not required). For those submitted from 2012 to 2019, additional data relating to the drug, economic and clinical evidence-related factors were collected. Multivariable logistic regression methods were used to model the relationship between these factors and the likelihood of requiring a full HTA. An exploratory analysis estimated the additional NCPE appraisal time that would have been required to evaluate all drugs, had the Rapid Review process not been established. RESULTS: Of the 446 Rapid Reviews submitted, approximately half (49.6%) were deemed to require a full HTA. Drugs for cancer indications, drugs designated first-in-class status, and high-cost drugs were positively and significantly associated with the likelihood of requiring a full HTA. No significant association was found for drugs for orphan indications when factors relating to cost and clinical evidence were included in the model. Without the Rapid Review process, an estimated additional 15,631 NCPE appraisal days would have been required to evaluate all drugs submitted over the 10-year period. CONCLUSIONS: This is the first study to use data uniquely available to the NCPE to evaluate factors associated with the requirement for a full HTA following a Rapid Review. The process has reduced the NCPE appraisal time required to evaluate all submissions over the study period. The NCPE's Rapid Review process allows for appropriate resource prioritisation within a national HTA agency.

Pharmaceutical regulation in 15 European countries review.

In the context of pharmaceutical care, policy-makers repeatedly face the challenge of balancing patient access to effective medicines with affordability and rising costs. With the aim of guiding the health policy discourse towards questions that are important to actual and potential patients, this study investigates a broad range of regulatory measures, spanning marketing authorization to generic substitution and resulting price levels in a sample of 16 European health systems (Austria, Belgium, Denmark, England, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Portugal, Scotland, Spain and Sweden). All countries employ a mix of regulatory mechanisms to contain pharmaceutical expenditure and ensure quality and efficiency in pharmaceutical care, albeit with varying configurations and rigour. This variation also influences the extent of publicly financed pharmaceutical costs. Overall, observed differences in pharmaceutical expenditure should be interpreted in conjunction with the differing volume and composition of consumption and price levels, as well as dispensation practices and their impact on measurement of pharmaceutical costs. No definitive evidence has yet been produced on the effects of different cost-containment measures on patient outcomes. Depending on the foremost policy concerns in each country, different levers will have to be used to enable the delivery of appropriate care at affordable prices.

Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis.

INTRODUCTION: Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. METHODS: A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome. RESULTS: The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk. CONCLUSION: Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS.

The payer's perspective: What is the burden of MS and how should the patient's perspective be integrated in health technology assessment conducted for taking decisions on access to care and treatment?

BACKGROUND: In Europe, there exists considerable variability in access to care and treatment for multiple sclerosis (MS). OBJECTIVES: To improve this situation, we identified key issues payers should take into account when making decisions on access to care and treatment for MS. We also give an overview of the different dimensions determining total MS burden and discuss why it is key to integrate the patient's perspective in estimating this burden. RESULTS: The total burden of MS relates to three dimensions: clinical, humanistic and economic. Although the clinical burden is extensively studied, crucial information is still missing about MS pathophysiology, how MS-related symptoms will develop during the disease course and which patients will progress more rapidly. With regard to the humanistic burden, information on patient-reported quality of life systematically collected in clinical trials for registration purposes is still scarce. Early engagement between pharmaceutical companies, the European Medicines Agency and health technology agencies to prospectively identify key evidence needs for the regulatory and reimbursement processes is required as a first step towards more equal access to care and treatment in MS in Europe. Patients' expectations regarding treatment outcomes should be better researched and integrated into decision-making and patients should be counselled in this process.

Pharmaceutical regulation in 15 European countries: review

In the context of pharmaceutical care, policy-makers repeatedly facethe challenge of balancing patient access to effective medicines withaffordability and rising costs. With the aim of guiding the health policydiscourse towards questions that are important to actual and potential patients,this study investigates a broad range of regulatory measures, spanningmarketing authorization to generic substitution and resulting price levels in asample of 16 European health systems (Austria, Belgium, Denmark, England,Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland,Portugal, Scotland, Spain and Sweden).All countries employ a mix of regulatory mechanisms to containpharmaceutical expenditure and ensure quality and efficiency in pharmaceuticalcare, albeit with varying configurations and rigour. This variation alsoinfluences the extent of publicly financed pharmaceutical costs. Overall,observed differences in pharmaceutical expenditure should be interpreted inconjunction with the differing volume and composition of consumption andprice levels, as well as dispensation practices and their impact on measurementof pharmaceutical costs.No definitive evidence has yet been produced on the effects of differentcost-containment measures on patient outcomes. Depending on the foremostpolicy concerns in each country, different levers will have to be used to enablethe delivery of appropriate care at affordable prices.

Direct and indirect economic consequences of multiple sclerosis in Ireland.

INTRODUCTION: Multiple sclerosis (MS) has significant financial consequences for healthcare systems, individual patients and households, and the wider society. This study examines the distribution of MS costs and resource utilisation across cost categories and from various perspectives, as MS disability increases. METHODS: Two hundred and fourteen patients with MS were recruited from a specialist MS outpatient clinic in Ireland and included in an interview-based study on MS-related healthcare resource consumption and costs. Patients were grouped into three categories based on disability: mild [Expanded Disability Status Scale (EDSS) score 0-3.5, n = 114], moderate (EDSS 4.0-6.5, n = 72) and severe (EDSS 7.0-9.5, n = 27). The mean annual direct and indirect costs (in year 2012 values) were estimated using non-parametric bootstrapping. RESULTS: Participants were 66.4 % female, with a mean age of 47.6 years and a mean EDSS score of 3.6. The majority had relapsing-remitting MS (RRMS) (53 %). The mean annual direct (indirect) costs per person were €10,249 (€9,447), €13,045 (€31,806) and €56,528 (€39,440) in mild, moderate and severe MS, respectively. Direct costs are driven by the cost of disease-modifying therapies and professional home help in mild and severe MS, respectively. Between 74 % (severe MS) and 96 % (mild MS) of all direct costs are borne by the healthcare payer, the remainder being incurred by patients, their families or other non-healthcare organisations. CONCLUSIONS: MS is associated with high levels of healthcare resource consumption and costs, and these costs increase with increasing disability. There is potential to significantly reduce the economic burden of MS through interventions that prevent progression from mild or moderate MS to severe MS, help support independent living at home and keep people with MS in the work force.

Relating health-related Quality of Life to disability progression in multiple sclerosis, using the 5-level EQ-5D.

BACKGROUND: Increasing use of the Quality-Adjusted Life-Year to inform resource allocation decision-making has highlighted the importance of relating clinical and health-related quality of life (HRQoL) outcomes in multiple sclerosis (MS) patients. OBJECTIVE AND METHODS: To investigate the relationship between the Expanded Disability Status Scale (EDSS) and HRQoL utility, using the 5-level EQ-5D (EQ-5D-5L). The discriminatory power of the EQ-5D-5L was assessed using Shannon's indices. RESULTS: A linear decline in utility was observed with changes in EDSS score from 0 to 6, after which point the relationship exhibited greater variability. Mean utility values ranged from -0.22 at EDSS 9 to 0.88 at EDSS 0. We found that the discriminative capacity of the EQ-5D-5L was considerably lower for the domains self-care and anxiety/depression, compared with other health-related domains. CONCLUSION: In its first reported use in an MS population, the EQ-5D-5L displayed good discriminatory capacity, although performance differed between the various domains of health, with evidence of a ceiling effect present in the domains of self-care and anxiety/depression. The EQ-5D-5L demonstrated a high correlation with EDSS in our MS cohort up to EDSS 6, after which point the utility valuation of severe health states exhibited much greater variability. Utility estimates from this study may be used in economic evaluations of disease-modifying therapies in MS, to inform resource-allocation decisions.

Health Technology Assessment International 7th Annual Meeting: Dublin, Ireland, 6­9 June 2010.

A record number of delegates from industry, academia and health policy convened at the 7th Annual Meeting of Health Technology Assessment International (HTAi) which was held in Dublin, Ireland in June 2010. The theme of this year's meeting was 'Maximizing the Value of HTA'. The scientific program covered a broad range of topics from coverage with evidence development to timeliness of conducting HTAs, early engagement with stakeholders, value of information analysis, patient involvement and international collaboration. There was also a lively social program with the conference dinner held at the Guinness Storehouse.