Timely, consistent, transparent assessment of market access evidence: implementing tools based on the HTA Core Model® in a pharmaceutical company.

OBJECTIVES: Evidence requirements and assessment methods access differ between health technology assessment (HTA) agencies. The HTA Core Model® provides a standardized approach to HTA, targeting evidence sharing and collaboration between participating HTA bodies. It is fit for purpose from an industry perspective and was used by pharmaceutical company Roche to develop a framework for internal assessment of evidence required for market access and coverage/reimbursement ("access evidence"). METHODS: Tools were developed to systematically scope, assess, plan, and summarize access evidence generation. The tools were based mainly on the first four HTA Core Model® domains and rolled-out in selected development teams in 2017. Five months after full implementation, the impact of tools was assessed in an internal survey. RESULTS: Systematic access evidence generation started with the Access Evidence Questionnaire, to scope evidence requirements and identify evidence gaps. Findings were summarized in the Access Evidence Metric, which assessed the alignment of available/planned evidence against HTA bodies' requirements and developed scope mitigation strategies. The Access Evidence Plan was then used to plan and document (additional) evidence generation. Once generated, evidence was summarized in the Access Evidence Dossier. A survey of twenty-seven Roche employees involved in evidence generation showed that the tools made discussions around access strategies and evidence more efficient and transparent. CONCLUSIONS: The HTA Core Model® provided a useful framework around which to optimize internal evidence generation and assessment. The benefits of using a standardized HTA approach in industry mirror those expected from implementing the HTA Core Model® in HTA agencies.

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.

Cost effectiveness of oseltamivir treatment for patients with influenza-like illness who are at increased risk for serious complications of influenza: illustration for the Netherlands.

BACKGROUND: Oseltamivir is effective in the treatment of influenza. Utilisation in The Netherlands is limited, but increasing. OBJECTIVE: To estimate the cost effectiveness of oseltamivir treatment (vs symptom relief only) for patients with influenza-like illness (ILI) who are at increased risk for serious complications of influenza. METHODS: A cost-effectiveness analysis was used, building on a previously developed model (decision tree) that was applied for evaluating influenza vaccination and pandemic preparedness plans. Three patient subgroups were assessed (elderly patients [aged > or = 65 years] without chronic disease, elderly patients with chronic disease, and chronically ill, non-elderly patients). Inputs for the model were taken from various sources including a meta-analysis. A societal perspective was adopted and costs were expressed in euro per life-year gained (year 2003 values). Life-years lost were discounted at 4% in accordance with Dutch guidelines. Deterministic and probabilistic sensitivity analyses were employed to assess the robustness of the results. RESULTS: For chronically ill patients with ILI, visits to the GP for oseltamivir treatment were cost saving. For non-chronically ill elderly patients, incremental cost-effectiveness was estimated at 1759 euros per life-year gained. Cost savings and favourable cost effectiveness were robust in a deterministic and stochastic sensitivity analysis. CONCLUSION: Our model-based analysis suggests that at-risk people presenting with ILI to a GP could be offered oseltamivir at favourable cost effectiveness or even cost savings in the Dutch setting compared with symptom relief with analgesics only.

Post-exposure influenza prophylaxis with oseltamivir: cost effectiveness and cost utility in families in the UK.

OBJECTIVES: To assess the cost effectiveness and cost utility of preventing post-exposure influenza infection using the neuraminidase inhibitor oseltamivir from a healthcare payer's perspective in the UK. METHODS: A simulation model was developed, based on clinical trial results and published data, to predict morbidity and mortality due to influenza and to compare oseltamivir post-exposure prophylaxis (PEP) with no prophylaxis within families with members aged >or=13 years. Two scenarios were tested:1. Comparison of patients receiving PEP versus patients not receiving PEP and not being treated with oseltamivir should they become infected. 2. Comparison of patients receiving PEP versus patients not receiving PEP but being treated with oseltamivir should they become infected. The model was run with an attack rate in household contacts of 8% for the base case, with higher rates (up to 30%, representing pandemic conditions) tested in sensitivity analyses. A societal perspective and other key parameters were tested in sensitivity analysis. The year of costing was 2002. The time span for the model was up to 1 year (including one influenza season), but loss of life was included in the QALY calculation and based on expected life expectancy. RESULTS: PEP with oseltamivir results in reduced morbidity (i.e. fewer influenza cases) and associated reductions in complications, hospitalisations and mortality due to influenza. When comparing oseltamivir PEP with no prophylaxis for contact attack rates of 8%, 12% and 30%, the mean costs per QALY gained for scenario one were estimated at 29,938 pounds, 18,697 pounds and 5403 pounds, respectively; the mean costs per case avoided were 467 pounds, 293 pounds and 84 pounds, respectively. The corresponding results for scenario two were 52,202 pounds, 31,610 pounds and 9688 pounds per QALY gained. CONCLUSIONS: PEP with oseltamivir is likely to be a cost-effective strategy for family contacts in the UK from a healthcare payer perspective when influenza-like illness contact attack rates are 8% or higher and the only treatment given is 'usual care'.

Impact of influenza treatment with oseltamivir on health, sleep and daily activities of otherwise healthy adults and adolescents.

OBJECTIVE: To determine the effect of oseltamivir (75mg twice daily) on time to return to baseline health, sleep and activity in patients with laboratory-confirmed influenza infection. PATIENTS AND METHODS: Data from 1642 otherwise healthy adults (aged 13-64 years), who had experienced a febrile influenza-like illness (>38 degrees C) of up to 36 hours' duration together with at least one respiratory and one systemic/constitutional symptom, were pooled from four randomised, double-blind, placebo-controlled clinical trials. Patients in these trials had been randomised to receive either oseltamivir or placebo for 5 days and had been allowed unlimited use of symptom-relief medications. The primary analysis examined the effect of oseltamivir treatment on patients' general health status, sleep and normal activities as measured by visual analogue scales. Secondary analyses examined the possible effects of gender, influenza type, smoking, employment status and time to treatment (< or = or >24 hours) on these endpoints. RESULTS: Oseltamivir significantly reduced the time taken to return to baseline health, sleep and activity across all pooled patients (p < 0.0001) and increased the proportion of patients returning to full activity within the first 7 days following treatment start. Gender, smoking status, time to treatment, influenza subtype and employment status had no appreciable effect on the effectiveness of oseltamivir. CONCLUSIONS: In otherwise healthy adults, oseltamivir reduces the time to return to pre-illness levels of health, sleep and activity, and may help to decrease the overall burden of influenza on society. This provides an important rationale for the early use of antiviral treatment, such as oseltamivir, for the treatment of influenza in otherwise healthy adults and adolescents.

Influenza treatment with neuraminidase inhibitors: cost-effectiveness and cost-utility in healthy adults in the United Kingdom.

We assessed the cost-effectiveness and cost-utility of treating influenza with neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer's and societal perspective in the United Kingdom. A simulation model was developed to predict morbidity and mortality due to influenza and its specified complications, comparing neuraminidase inhibitors with usual care in an otherwise healthy adult population. Robustness of the results was tested by one-way and multiway as well as probabilistic sensitivity analyses. Treatment with either neuraminidase inhibitor results in reduced morbidity and faster return to normal activities. However, oseltamivir dominates zanamivir in cost-utility analysis due to its lower costs. Comparing oseltamivir with usual care, the costs are pound14.36 per day of normal activity gained and pound5,600 per quality-adjusted life-year gained from the healthcare payer perspective. Oseltamivir dominates usual care from the societal perspective. Treatment with oseltamivir is a cost-effective strategy for otherwise healthy adults in the UK from both the healthcare payer and societal perspective.

Effect of influenza treatment with oseltamivir on health outcome and costs in otherwise healthy children.

OBJECTIVE: To evaluate the effect of treating children with influenza with oseltamivir on health outcomes and costs to healthcare payers. PATIENTS AND DESIGN: Health outcome data from the oseltamivir paediatric clinical development programme plus data from the literature were used in an economic model developed to predict morbidity and mortality due to influenza and its specified complications. Published data on the cost of care in the UK were used to compare oseltamivir with usual care in children aged 1-12 and 1-5 years by estimating cost-effectiveness and cost-utility ratios. RESULTS: Oseltamivir reduced median time to return to normal health and activity by almost 2 days (40% reduction, 67.1 vs 111.7 hours; p < 0.0001) versus placebo. In children aged 1-5 years, a 48% reduction (63.5 vs 121.3 hours; p = 0.0003) was observed. Oseltamivir-treated children who developed otitis media returned to normal health and activity 30% faster (99.6 vs 141.5 hours; p = 0.0517) than the placebo group. In the economic model, oseltamivir in the base-case analysis (assuming 60% diagnostic accuracy, full compliance, and 100% receive and start treatment within 48 hours, standard discounting according to the UK National Institute of Clinical Excellence guidelines) resulted in favourable cost-utility ratios in children aged both 1-12 and 1-5 years, with incremental cost-utility rates of £11 173/quality-adjusted life year (QALY) and oseltamivir being dominant compared with usual care, respectively (year of costing, 2002). Even in conservative scenarios, most cost-utility ratios remained <£30 000/QALY. CONCLUSIONS: Oseltamivir is an effective treatment for children with influenza, allowing faster return to normal health and activity compared with usual care. From the healthcare payer perspective, oseltamivir is a potentially cost-effective strategy for otherwise healthy children.

Pharmacoeconomic assessment of oseltamivir in treating influenza--the case of otherwise healthy Danish adolescents and adults.

OBJECTIVE: To assess the pharmacoeconomics of treating influenza with oseltamivir in healthy Danish adolescents and adults. METHOD: Cost-effectiveness and cost-utility analyses were used to compare oseltamivir to usual care (symptomatic treatment with over the counter (OTC) medicine), considering both the societal and health care payer's perspectives. The population group studied was otherwise healthy adolescents and adults, aged 13 to 64. Danish data were collected to simulate results that are specific to Denmark. The economic model included first- and second-order Monte Carlo simulations. Sensitivity analyses were conducted to test the robustness of the analyses. MAIN OUTCOME MEASURE: The cost-effectiveness study was expressed as gain in cost per day to return to normal activity, and the cost-utility study as cost per QALY (quality adjusted life years) gained. RESULTS: From a societal perspective, oseltamivir was a dominant treatment compared to usual care. From a health care payer's perspective, the cost-effectiveness ratio was 12.3 euros per gain in day to return to normal activity and 5,063 euros/QALY gained. A sensitivity analysis leaving out hospitalisation, complications, and mortality showed increased cost-effectiveness and cost-utility ratios. However, treatment with oseltamivir remained cost-effective, assuming a willingness to pay for health benefits at 26,174 euros/QALY. CONCLUSION: Pharmacoeconomic analyses of influenza treatment with oseltamivir in an otherwise healthy Danish adolescent/adult population show that this treatment saves money for society and is associated with a relatively low cost from a health care payer's perspective. Treatment of influenza with oseltamivir would be cost-effective for healthy adolescents/adults in Denmark.