A Systematic Review of Value Criteria for Next-Generation Sequencing/Comprehensive Genomic Profiling to Inform Value Framework Development.

OBJECTIVES: To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making. METHODS: We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF. RESULTS: A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified. CONCLUSIONS: Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies.

Healthcare Payer Perspectives on the Assessment and Pricing of Oncology Multi-Indication Products: Evidence from Nine OECD Countries.

BACKGROUND: New pharmaceuticals are increasingly being developed for use across multiple indications. Countries across Europe and North America have adopted a range of different approaches to capture differences in the value of individual indications. OBJECTIVE: The three aims of this study were (i) to review the price-setting practice over the past 5 years for multi-indication products across England, France, Italy, Spain, Belgium, Switzerland, Turkey, Canada and the USA; (ii) to assess the impact of current practices on launch strategy; and (iii) to identify issues in the implementation of indication-based pricing. METHODS: Ten current and former members of health insurance organisations, healthcare payer organisations or health technology assessment agencies with expertise on pharmaceutical purchasing were invited to participate in semi-structured interviews. Interview transcripts were imported into NVivo 12 for thematic analysis. RESULTS: The majority of countries studied require full assessments upon launch of a new indication. Five different approaches to pricing were identified: weighted pricing, differential discounting, mandatory discount, price anchoring and free pricing. Manufacturers show a tendency to launch first in niche indications with high unmet need to achieve a high price. Stakeholders from England, France, Italy, Belgium and Switzerland consider their current system fit for purpose, while other countries expressed concern over the administrative burden of monitoring products at indication level. CONCLUSIONS: Given the high administrative burden, it is questionable whether indication-based pricing would provide additional public benefit above and beyond current weighted dynamic single pricing and differential discounting practices for multi-indication products.

Launch sequencing of pharmaceuticals with multiple therapeutic indications: evidence from seven countries.

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.

The future of oncology policy.

To ensure the previous progress seen in cancer survival rates continues as we move through the 21st Century it is important to determine future effective policy related to oncology healthcare delivery and funding. Recent successes with, for example, the COVID vaccine response, the decision-making agility exhibited by governments and healthcare systems and the effective use of telehealth and real-world evidence highlight the progress that can be made with pooled efforts and innovative thinking. This shared approach is the basis for the European Beating Cancer Plan which outlines action points for governments and health systems for the period 2021-2025. It focuses on a whole government approach, centred on patients, maximising the potential of new technologies and insights across policy areas including employment, education, transport and taxation, enabling the tackling of cancer drivers in schools, workplaces, research labs, towns and cities and rural communities. Despite the plan there are still concerns that oncology policy has not adequately responded to the pace of innovation and the unique challenges generated by innovative oncological technologies. There needs to be focus on: gaining consensus on the most appropriate methods to assess and price combination therapies and cell and gene therapies, developing effective outcome-based payment models for personalised medicine and developing consensus on the ideal approach for multiple indication pricing. Finally, future policy needs to ensure pharmaceutical companies and other research organisations are adequately rewarded for innovation to ensure continued R&D and the development of innovative oncological products.

Value and Price of Multi-indication Cancer Drugs in the USA, Germany, France, England, Canada, Australia, and Scotland.

PURPOSE: Oncology drugs are often approved for multiple indications, for which their clinical benefit varies. Aligning a single price to this differing value remains a challenge. This study examines the clinical and economic value, price, and reimbursement of multi-indication cancer drugs across seven countries, representing different approaches to value assessment, pricing, and coverage decisions: the USA, Germany, France, England, Canada, Australia, and Scotland. METHODS: Twenty-five multi-indication cancer drugs across 100 indications were identified with US Food and Drug Administration (FDA) approval between 2009 and 2019. For each indication data on Health Technology Assessment (HTA) recommendations, disease prevalence, and drug prices were obtained. Quality-adjusted life years (QALYs) gained, disease prevalence, list prices, and HTA outcomes were then compared across indications and regions. RESULTS: First approved indications provide a higher clinical benefit whilst targeting a smaller patient group than indication extensions. Quality-adjusted life year gains were higher for first (0.99, 95% CI 0.05-3.25) compared to second (0.51, 95% CI 0.02-1.63, p < 0.001) and third (0.58, 95% CI 0.05-2.07, p < 0.01) approved indications. Disease prevalence per 100,000 inhabitants was 20.7 (95% CI 0.2-63.3) for first compared to 27.1 (95% CI 1.5-109.6, p = 0.907) for second and 128.3 (95% CI 3.1-720.1, p < 0.001) for third approved indications. With each approved indication drug prices declined in Germany and France, remained constant in the UK, Canada, and Australia, whilst they increased in the USA. Negative HTA outcomes, clinical restrictions, and managed entry agreements (MEAs) were more frequently observed for indication extensions. CONCLUSIONS: Results suggest that indication development is prioritised according to clinical value and disease prevalence. Countries employ different mechanisms to account for each indication's differential benefit, e.g., weighted-average prices (Germany, France, Australia), differential discounts (England, Scotland), clinical restrictions, and MEAs (England, Scotland, Australia, Canada). Value-based indication-specific pricing can help to align the benefit and price for multi-indication cancer drugs.

Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA.

BACKGROUND: Previous research focused on the clinical evidence supporting new cancer drugs' initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. OBJECTIVES: To examine the clinical trial evidence supporting new targeted cancer drugs' initial and supplementary indication approval in the US, EU, Canada, and Australia. DATA AND METHODS: 25 cancer drugs across 100 indications were identified with FDA approval between 2009-2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07-6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38-8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17-5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14-30.65], p < 0.05) than supplementary indications. Initial indications' pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93-0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09-0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01-1.39], p < 0.05). CONCLUSIONS: Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication's differential clinical and economic value.

Sin taxes and their effect on consumption, revenue generation and health improvement: a systematic literature review in Latin America.

Sin or public health taxes are excise taxes imposed on the consumption of potentially harmful goods for health [sugar-sweetened beverages (SSBs), tobacco, alcohol, among others], aiming to reduce consumption, raise additional revenue and/or improve population health. This paper assesses the extent to which sin taxes (a) can reduce consumption of potentially harmful goods, (b) raise revenue for national health systems and (c) contribute to population health in Latin America. A systematic literature review was conducted on peer-reviewed and grey literature; endpoints included: impact of raising sin taxes on consumption, ability to raise revenue for health and the possibility of population health improvements. Risk of bias for each study was assessed. The synthesis of the literature on sin tax implementation showed improvements in all three endpoints across the study countries. Following the introduction of sin taxes or by simulating their potential impact, nearly all studies explicitly reported that consumption of potentially harmful goods (mainly SSBs and tobacco) declined; revenue was found to have increased in almost all countries, suggesting that there may be additional scope for further tax increase. Simulated improvements in population health have also been shown, by demonstrating a relationship between sin tax increases and reduction in prevalence of diabetes, stroke, heart attacks and associated deaths. However, sin tax effects on health would be better quantified over the long-term. Data quality and availability challenges did place some limitations on sin tax impact assessment. Sin taxes can be effective in reducing consumption of potentially harmful goods, improve population health and generate additional revenue. Promoting further research on this topic should be a priority.