10 years of HTA Quarterly: Looking back to see how far we’ve come

When HTA Quarterly was first published in Spring 2013, the intention was to provide informative and timely expert insights into the challenges facing biopharmaceutical companies from a market access perspective, both in those countries with an established health technology assessment (HTA) requirement, such as Australia, Canada, Germany, the United Kingdom (UK), and the Nordics, and those considering or introducing a more structured approach to market access decision making.

The changing focus of HTA Quarterly

Over the last 10 years, healthcare budgets have been squeezed, market access hurdles have gotten higher, product development has increasingly focused on personalized or targeted treatments for defined subgroups of patients, and the technology involved in both development and delivery of healthcare has evolved in leaps and bounds. Reflecting these changes, HTA Quarterly articles have focused on healthcare system evolution, in particular reforms brought in to control the rapidly growing healthcare spend, while ensuring patients have equitable access to the treatments they need and that provide the greatest benefits. Early articles focused on understanding the healthcare systems in emerging markets (Brazil, Columbia, South Africa, Czech Republic to name a few) and the implications for companies who wish to achieve access and reimbursement for their products in these markets. By contrast, more recent articles focus on policy changes in established HTA markets including the UK, Germany, and the Netherlands, and the impact that the Institute for Clinical and Economic Review (ICER) has had on market access in the United States (US).

Reflecting these changes, the most popular article in 2022 in terms of page views was that exploring the introduction of Joint Clinical Assessment in the European Union and questioning whether pan-European HTA for drugs and medical devices will—at last—become reality. A further article on the same topic, published in the Fall 2022 edition also proved popular. By contrast, the most-read articles in 2021 were predominantly US focused, including ICER’s growing influence on payer decision making, how real-world evidence impacts regulatory decisions in the US, and the launch of the ICER Analytics™ platform. Additionally, while HTA Quarterly aims to address current hot topics, articles published in earlier years are still proving to be of interest today.

Evolution of HTA to keep pace with technological advances

Recent years have seen a boom in advanced therapies, ranging from immunotherapies in oncology to cell and gene therapies, including chimeric antigen receptors (CAR) T-cell therapies for blood cancers and potentially curative gene therapies for hemophilia. While these innovations present exciting opportunities for patients and manufacturers alike, integration of new and innovative treatments into the healthcare system is a challenge for regulatory agencies and HTA authorities, as well as the manufacturers. The standard market access pathways have often had to be adapted to accommodate these innovative and high-cost treatments.

Many of these innovative products also have orphan designation. While there are regulatory incentives for innovation, such as those introduced in Europe in 2000 to incentivize development of orphan drugs (including lower fees and 10 years of market exclusivity after registration), market access remains challenging even where unmet need is greatest. Due to small patient population sizes and oftentimes accelerated marketing authorization, only limited evidence is available to determine the long-term value of these products when market access is first considered. This has led to increasing prevalence of managed-entry agreements that aim to distribute the risk of uncertainty between the budget holder and the pharmaceutical, device, or diagnostics manufacturer. While the simplest of these are financial-based agreements (eg, confidential discounts), more complex performance-based agreements (eg, coverage with evidence development) have become increasingly popular, particularly when negotiating market access for advanced therapies.

From the payer perspective, the use of real-world evidence and pay-for-performance agreements linked to clinical outcomes is anticipated to rise significantly. An example of this is the recent introduction of the UK Innovative Medicines Fund (IMF), covered in the Winter 2022 edition of HTA Quarterly. Modelled on the successful Cancer Drugs Fund framework which launched in 2016, the IMF is a managed access fund which covers the cost of medicines that show significant clinical promise, whilst evidence generation is ongoing and promises “to provide a consistent and transparent managed access process for companies offering promising non-cancer medicines at a responsible price.” With the potential to bring forward funding by up to 5 months compared with routine commissioning, the IMF provides game-changing new drugs that treat disease other than cancer with a route for faster market access. Similarly, two HTA Quarterly articles published in Fall 2020 and Spring 2021 considered market access challenges for advanced therapy medicinal products in Germany from the perspectives of AMNOG assessment and subsequent price negotiation. To diminish the uncertainty regarding clinical value due to limited long-term efficacy and safety data, the Federal Joint Committee (G-BA) can set a fixed term for a mandatory reassessment usually in the range of 1 to 3 years, if additional clinical evidence is to be expected then. During this time, the manufacturer must collect further data to be able to submit new evidence for the reassessment by G-BA.

As budgetary pressures intensify and more high-cost innovative products come to market, manufacturers can gain insights from previous HTA decisions and case studies such as these to determine future directions and invest in evidence-generation strategies that would strengthen a product’s value proposition and minimize long-term uncertainty ahead of payer negotiations.

The ongoing challenge of recognizing value and innovation

A key challenge in obtaining rapid market access at a commercially attractive price has always been how to demonstrate added value compared with the established standard of care. HTA bodies such as the UK’s National Institute for Health and Care Excellence (NICE) carefully consider whether the price put forward by the company is worth it for the benefits the new intervention offers to patients and the health system more broadly; ie, whether the intervention represents value for money. But how value is defined and measured is the topic of ongoing debate.

One of the articles published in the first edition of HTA Quarterly in Spring 2013 looked ahead to the anticipated introduction of value-based pricing (VBP) in the UK. First proposed in 2010, the introduction of VBP was slated for early 2014 and intended to replace the Pharmaceutical Price Regulation Scheme (PPRS), a voluntary scheme under which National Health Service (NHS) expenditure on branded medicines is capped. It was intended that VBP would serve as the new paradigm that would systematically regulate pricing of new branded medications with broader consideration of “value” as a central principle. In particular, under VBP, different types of attributes would have value rather than only mortality and quality of life metrics, such as the ability for products to improve health across the NHS, provide greater therapeutic innovation and improvements when compared to other products within and across therapeutic conditions, tackle diseases identified as having a greater burden, and demonstrate wider societal benefits. However, at the time the article was written, while these general themes had been identified, the criteria to measure these elements had not yet been developed, nor had price assignment processes been determined; the UK Department of Health was still in the process of reaching agreement around the practical and operational details of implementing VBP.

With the benefit of hindsight, we now know that these challenges were seemingly insurmountable; agreement could not be reached on how to operationalize VBP. Instead, it was agreed that a further PPRS would run from January 2014 to December 2018. This was then replaced by the Voluntary Scheme for Branded Medicines Pricing and Access (VPAS), a similar non-contractual agreement that runs from January 2019 until the end of 2023. Under the 2019 VPAS, NHS expenditure on branded medicines must stay within an agreed limit, which rises by 2% per annum from 2018 to 2023. Also included in the VPAS are requirements for the Department of Health and Social Care and NHS England to make improvements to access to medicines over the same period. Expenditure above the agreed limit incurs a flat-rate rebate payment, payable by companies marketing branded generics and biosimilars as well as patent-protected pharmaceuticals. However, the story doesn’t stop there. The rebate has risen from 5.1% in 2020 to 26.5% in 2023, a figure which has generated much criticism and complaints from the pharmaceutical industry that it is unsustainable. On behalf of the industry, the Association of the British Pharmaceutical Industry (ABPI) is proposing a new framework for 2024. The next edition of HTA Quarterly will look at the responses to the 2023 rebate, the fallout, and what might replace it.

Similarly, in other markets, measurement and recognition of innovation has proven to be challenging. In Italy, where recognition of therapeutic innovation for a medicinal product was first introduced by the Italian Medicines Agency (AIFA) in 2007 and refined in 2017, there are clear rules for assessment of therapeutic need, added therapeutic value and quality of evidence, coupled with economic and time-to-market benefits for those products that are deemed innovative. However, analysis of recent outcomes—published in the previous HTA Quarterly—demonstrates that assessment of innovation is not black and white, and the outcome often does not align with the rules.

Conclusion: Change is the only constant

Looking back over the last 10 years of HTA Quarterly highlights recent advances in healthcare provision, in particular development and commercialization of promising, yet high-cost, interventions and the shifts in policy, product assessment and evidence generation requirements that have been driven by efforts to get these products to patients while balancing the books. As reform continues and healthcare systems evolve, biopharma companies (and HTA Quarterly editors) will need to remain vigilant to determine how changes will impact HTA assessments, reimbursement, and market access strategies.

Sources

• ABPI. Voluntary Scheme on branded medicines. https://www.abpi.org.uk/value-and-access/uk-medicine-pricing/voluntary-scheme-on-branded-medicines/ 
• Achieving market access across the globe for CGTs. HTA Quarterly. Spring 2018. https://www.xcenda.com/insights/htaq-spring-2018--market-access-across-the-globe-for-cell-and-gene-therapies 
• Agashe V. Market access for cell and gene therapies in key European countries. HTA Quarterly. Fall 2019. https://www.xcenda.com/insights/htaq-fall-2019-cell-and-gene-in-key-european-countries. 
• Campbell C. Navigating coverage and reimbursement for immunotherapy in oncology: perspectives on challenges and opportunities in the HTA evaluation process. HTA Quarterly. Spring 2017. https://www.xcenda.com/insights/htaq-spring-2017-navigating-coverage-reimbursement-io-oncology 
• Drummond M, Mittendorf T. The new EU regulation on health technology assessment: major change or minor adjustment? HTA Quarterly. Fall 2022. https://www.xcenda.com/insights/htaq-fall-2022-eu-regulation-and-health-technology-assessment 
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• Kang I, Agashe V. Emerging gene therapies for hemophilia in the United States—value drivers in a crystal ball. HTA Quarterly. Summer 2020. https://www.xcenda.com/insights/htaq-summer-2020-emerging-gene-therapies-hemophilia-us-value-drivers 
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• Kulp W, Martel M, Billig S, Schmidt K, Martinez J. Joint clinical assessment in the EU: Pan-European HTA for drugs and medical devices will become reality. HTA Quarterly. Spring 2022. https://www.xcenda.com/insights/htaq-spring-2022-joint-clinical-assessment-eu/ 
• Lidonnici, D. Fifty shades of… innovativeness: The Italian job. HTA Quarterly. Spring 2023. https://www.xcenda.com/sitecore/content/global-settings/insights/xcenda/hta-quarterly/htaq-spring-2023/htaq-spring-2023-italian-innovation 
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• Watts-James J, Hall C. How to get earlier market access in the UK: Use the Innovative Medicines Fund. HTA Quarterly. Winter 2022. https://www.xcenda.com/insights/htaq-winter-2022-how-to-get-earlier-market-access-in-the-uk 
• Watts-James J, Konstanski M, Schepis Martinez J. Orphan drugs: trapped in the lock? A review of the lock system in the Netherlands. HTA Quarterly. Summer 2022. https://www.xcenda.com/insights/htaq-summer-2022-orphan-drugs-trapped-in-the-lock 
• Xcenda. Implementing coverage with evidence development. HTA Quarterly. Spring 2018. https://www.xcenda.com/insights/htaq-spring-2018-implementing-coverage-with-evidence-development 
• Yan A, Loos A. ICER’s growing influence on payer decision making: the impact of ICER assessments on market dynamics and patient access. HTA Quarterly. Winter 2020. https://www.xcenda.com/insights/htaq-winter-2020-icer-payer-decision-making