2023 has been a year of notable change, and the sphere of health economics and outcomes research (HEOR) is no exception. The number and complexity of technologies being launched continues to increase, and generative artificial intelligence (AI) is beginning to signal its potential to transform the landscape in unpredictable ways (don’t worry – this is not “one more piece on AI”!).
The rise of advanced therapy medicinal products (ATMPs) continues, with seven new ATMPs approved by the US Food and Drug Administration (FDA) in 2023.1 These therapies represent just one example of the increasingly advanced, transformative but complex health technologies being developed by manufacturers. From both a regulatory and reimbursement standpoint, such innovative technologies bring us into uncharted waters – requiring time and resources to parse out the impact of their introduction into healthcare systems.
We also see continuing evolution on the part of payers and health technology assessment (HTA) bodies to address the challenge of enabling access while managing affordability and equity. 2023 saw continuing progress in preparations for launch of the European Regulation on Health Technology Assessment, the Institute for Clinical and Economic Review (ICER) Value Assessment Framework update, and, of course, the Inflation Reduction Act in the US.
Our HEOR experts worked steadily throughout the year to contribute to the discussion around the key issues faced by patients, clinicians, payers, and manufacturers. As always, our aim is to communicate insights, best practice, and methodological developments to support and inform healthcare decision-making. Here, we briefly summarize our 2023 insights in the HEOR space, referencing our publications and conference appearances and pulling out our thoughts for 2024.
EU HTA regulation
The EU HTA Regulation (formally “The Regulation [EU] 2021/2282 on health technology assessment”) is an EU-wide initiative to streamline and harmonize parts of the HTA process across the continent. From January 2025, oncology products, ATMPs, and certain medical devices will be affected; other products will be affected from 2028–2030 onwards. However, the feasibility of fully achieving the aims of the EU HTA Regulation in all 27 member states is currently unclear, and its implementation presents a multitude of challenges.
We have kept a keen eye on these developments, having published eight pieces in 2023 specifically covering the Regulation. We focused on the Joint Clinical Assessment (JCA) – the central element of the entire Regulation – and discussed the challenges posed by needing to cover multiple PICOs (patient population, intervention, comparator, outcomes) to meet the requirements and preferences of all EU member states, while the EUnetHTA 21 guidance documents also outline stringent methodological requirements.2 We gave our thoughts on the Joint Scientific Consultation (JSC), another key component of the Regulation, and how the decision to proceed with the JSC may in fact be a strategic one.3
Throughout this tumultuous year (in April4, July5, September6, and after November’s ISPOR Europe7) we have kept tabs on key concerns voiced by representatives of the pharmaceutical industry (and responses from HTA representatives) about the JCA and the way it is looking to be implemented. In the new process, there will be fewer opportunities for manufacturers and assessors to interact; no manufacturer involvement in determining or responding to the final assessment scope; and less time overall for the full process to take place. This is on top of the anticipated complexity of running a JCA that accounts for the particular needs of all member states.
As a large and influential healthcare market in the EU, the attitude and actions taken by Germany will likely interact with the overall consequences of the Regulation across Europe. We spoke with Jürgen Wasem, former chairperson of the AMNOG (Arzneimittelmarkt-Neuordnungsgesetz) Drug Price Arbitration Board, on the recent HTA reforms8 taking shape there. Our piece and follow-up ISPOR presentation9 outlined and highlighted the various effects the German reform is having on the pharmaceutical market and, ultimately, the availability of new therapies.
Legislative developments in the US
A number of pieces of legislation have recently passed through US Congress that are disrupting the landscape – not least the Inflation Reduction Act (IRA).10 With its stated aim of reducing drug costs for Medicare Part B and Part D recipients and the federal government as a whole, the IRA includes (among other things) provisions around how the price of pharmaceuticals is negotiated and introduces the Maximum Fair Price (MFP) aspect of the law. Currently, there is considerable uncertainty around the drug price negotiation process, especially with regard to MFPs for small-molecule and biologic therapies, creating a complex situation for the future of drug commercialization both in the US and globally.11
In our diaries from ISPOR US12, we noted the myriad concerns felt by the industry – over a lack of transparency in the process, the absence of a clear value framework, the limited opportunities to engage with the relevant departments, and the potential effect on pharmaceutical innovation, to name a few. In August13 we looked at how the IRA developments might interact with ICER, a US organization with an increasingly important role in payer discussions in the US – a role that may encompass the drug price negotiations now happening between manufacturers and the Centers for Medicare & Medicaid Services (CMS). Based on our analysis, we suggested that ICER intends to make its assessment reports more relevant to the Medicare population, potentially influencing CMS’ methodological approach to assessing comparative effectiveness. We highlighted our essential takeaways from the update for manufacturers looking to launch products in the US.
Another piece of legislation, the Consolidated Appropriations Act, 2023 (H.R. 2617), represents an important shift in the US HEOR space. Together with the 2018 guidance issued by the FDA regarding payer communications, there is now more support than ever for scientific dialogue between health technology developers and decision-makers in the pre- and post-approval phases. In our compendium on both pre-approval information exchange (PIE) and healthcare economic information (HCEI)14, we provided a succinct explanation of these recent developments and gave recommendations on how manufacturers can effectively drive the discussion with payers across the entire timeline.
Real world evidence – increased use and acceptance
The rise of real world data (RWD) is having a significant impact in healthcare.15 Amidst pressure to bring health technology innovations to patients faster, regulatory and HTA bodies – who at one time were rigid in their requirements for clinical trial data demonstrating safety and efficacy – have been more accommodating of evidence generated using RWD (i.e. real world evidence, or RWE). This has opened the door to new approaches to evidence generation for technology appraisals, but also new challenges to effective utilization of RWE that the industry as a whole must tackle together. Our November podcast episode16 featured four of our experts discussing the various ways RWE is leveraged across a product’s lifecycle, with a focus on HEOR and how best to plan for relevant RWE generation.
In April, Value in Health published a five-piece supplement17 focused entirely on the use of RWD in HTA of pharmaceutical products – work that we have developed as part of the EUreccA 2025 workstream. Bringing in experts and stakeholders from different geographies and using several European countries as points of focus, the supplement details the various ways in which RWE is currently used in drug reimbursement. It also engages in a deep discussion around the barriers to RWE acceptance from healthcare decision-makers, and provides practical solutions to these issues. Two key contributors to this project – Lumanity’s HEOR Executive Chair, Ron Akehurst, and Senior Director, Linda Murphy – hosted a panel discussion at ISPOR US12 in May, presenting the content of the EUreccA work at a well-attended session.
Continued innovation of HEOR methods
Moving from a bird’s-eye view and drilling deeper into specific cases, we continued to give our thoughts on the latest methodological developments in conducting robust HEOR analyses. We demonstrated the use of RWE to incorporate the within-year entry of patients in budget impact models – a better reflection of the reality of clinical practice, and an important step in improving the accuracy of budget impact calculations.18 We published a deep dive on how to maximize the validity of indirect treatment comparisons used to estimate the safety and tolerability of health technologies – a crucial approach to conducting technology appraisals, but one for which there is little to no guidance from HTA organizations.19 Our whitepaper on CAR T-cell therapies in the US, UK, and EU4 countries explored key factors that drive reimbursement decision-making in the context of an evolving regulatory environment for these treatments.20 Additionally, our updated paper on the challenges of demonstrating value in the rare disease space provides insights into how to identify them early on and take steps to overcome them.21 Depending on the context, the way these various modeling aspects are handled for a particular health technology can “make” or “break” an appraisal, and are therefore essential to get right.
What to expect from 2024?
Given the potential disruption caused by the EU HTA Regulation, and the lack of clarity and awareness around its implementation22, it is clear that the health technology manufacturers who are best prepared for the next 5 years are those who have: 1) an acute awareness of the developments in the EU Regulation and 2) an informed and coherent evidence generation strategy for their pipeline. Across the industry, a continued dialogue between all stakeholders will be essential to avoid disruption and roadblocks in future assessment under the Regulation. A similar approach must be taken in the US – again, an internally aligned strategy that is key to navigating the continued legislative deliberations and the resulting uncertainty.
RWE continues to have an impact on our industry. The extent to which it is adopted and utilized effectively to accelerate patient access depends on how well manufacturers, payers, and decision-makers can identify, with some degree of certainty, the appropriate opportunities for its use. Following the launch of our dedicated practice in 2022 and our ongoing partnership with the PHARMO Institute23, we are well positioned to leverage these opportunities and contribute to the discussions in this fast-moving area.
As we have published24, the potential for machine learning (including generative AI) to transform the healthcare industry comes with countless challenges and question marks. In the context of HEOR, key areas of automation and optimization include performing systematic literature reviews and analyzing RWD – both cases where the efficiency created by machine learning could greatly benefit technology appraisals when working to short timelines. Careful consideration of the limitations of these approaches, coupled with clear guidance from relevant institutions (for example, Cochrane’s recent policy statement25), will be key to harmonizing processes in this fast-moving area.
As noted from our time at ISPOR events7, 12, there is a pressing need for increased recognition of the patient voice in all aspects of HTA, including throughout the evidence generation strategy. A stronger consideration of the patient and carer voice within the decision-making process will help ensure that their preferences and experiences are captured effectively (for example, in the choice of methods to measure health utilities), enhancing the value story of a product and, subsequently, the relevance of a technology appraisal to patients.26
It is as important as ever for manufacturers to produce relevant, high-quality evidence; to communicate it effectively with healthcare decision-makers; and to engage in dialogue early and consistently to ensure patients can access life-changing therapies as soon as possible. Achieving these objectives in our rapidly changing landscape will require a concerted and collaborative effort from all stakeholders involved.
- HiTechHealth. 2023 ATMP Review. 2023. Available at: https://hitech-health.com/2023-atmps-review/. Accessed: 29 January 2024.
- Matthijsse S, Horscroft J, Beavers N, et al. Facing Up to the Challenges of EU Joint Clinical Assessments. 2023. Available at: https://lumanity.com/perspectives/facing-up-to-the-challenges-of-eu-joint-clinical-assessments/. Accessed: 29 January 2024.
- Patel R, Latimer S and Matthijsse S. To JSC or Not to JSC – That Is the Question. 2023. Available at: https://lumanity.com/perspectives/to-jsc-or-not-to-jsc-that-is-the-question/. Accessed: 29 January 2024.
- Kulakova M and Matthijsse S. The EU HTA Regulation. 2023. Available at: https://lumanity.com/perspectives/the-eu-hta-regulation/. Accessed: 29 January 2024.
- Matthijsse S. Learnings from the Latest EUnetHTA 21 HTD Meeting. 2023. Available at: https://lumanity.com/perspectives/learnings-from-the-latest-eunethta-21-htd-meeting/. Accessed: 29 January 2024.
- Roiz J, Latimer S and Matthijsse S. Half-time in the EU HTA Regulation Roll Out. 2023. Available at: https://lumanity.com/perspectives/half-time-in-the-eu-hta-regulation-roll-out/. Accessed: 29 January 2024.
- Breislin E, Boyers A, Primo LG, et al. ISPOR Europe Diaries 2023. 2023. Available at: https://lumanity.com/perspectives/ispor-europe-diaries-2023/. Accessed: 29 January 2024.
- Wasem J, Matthijsse S, Akehurst R and Gladwell D. HTA Reforms in Germany. 2023. Available at: https://lumanity.com/perspectives/hta-reforms-in-germany/. Accessed: 29 January 2024.
- Matthijsse S, Akehurst R, Gladwell D and Wasem J. HTA Reforms in Germany: Implications for Pharmaceutical Pricing and Reimbursement in Germany and the EU. ISPOR Europe 2023. Copenhagen, Denmark. 12–15 November 2023.
- Lumanity. Inflation Reduction Act. 2024. Available at: https://lumanity.com/IRA/. Accessed: 29 January 2024.
- McGee N and Hayes K. European Perspectives of the Inflation Reduction Act. 2023. Available at: https://lumanity.com/perspectives/european-perspectives-of-the-inflation-reduction-act/. Accessed: 29 January 2024.
- Kowalski J, Evans CJ and Murphy L. ISPOR Diaries 2023. 2023. Available at: https://lumanity.com/perspectives/ispor-diaries-2023/. Accessed: 29 January 2024.
- Smith M and Meng Y. ICER Value Assessment Framework Update 2023. 2023. Available at: https://lumanity.com/perspectives/icer-value-assessment-framework-update-2023/. Accessed: 29 January 2024.
- Lee J and Cashman L. Opportunities for Enhanced Communication between Manufacturers and US Payers. 2023. Available at: https://lumanity.com/perspectives/opportunities-for-enhanced-communication-between-manufacturers-and-us-payers/. Accessed: 29 January 2024.
- Kerber L. Cutting Through the Noise: Crossing the New Real World Data Landscape. 2022. Available at: https://lumanity.com/perspectives/cutting-through-the-noise-crossing-the-new-real-world-data-landscape/. Accessed: 29 January 2024.
- Lumanity. Podcast: The Importance of Real World Evidence Strategy Planning. 2023. Available at: https://lumanity.com/perspectives/the-importance-of-real-world-evidence-strategy-planning/. Accessed: 29 January 2024.
- Murphy LA, Akehurst R, Solà-Morales O, et al. The Real-World Evidence Workstream in EUreccA 2025: How the Task Was Addressed. Value Health. 2023; 26(4):43-51.
- Neves C, Bruette R and Matthijsse S. Making a Case for Using Real World Data to Model Patient Entry in Budget Impact Analyses. 2023. Available at: https://lumanity.com/perspectives/making-a-case-for-using-real-world-data-to-model-patient-entry-in-budget-impact-analyses/. Accessed: 29 January 2024.
- Candlish J, Smith S, Kearns B and Horgan J. The Challenges of Robustly Estimating Relative Effects on Adverse Events and Discontinuations Via an Indirect Treatment Comparison. 2023. Available at: https://lumanity.com/perspectives/the-challenges-of-robustly-estimating-relative-effects-on-adverse-events-and-discontinuations-via-an-indirect-treatment-comparison/. Accessed: 29 January 2024.
- Vinzent A, Thornton I, Matthijsse S and Smith M. CAR T-Cell Therapies in the US, UK and EU4. 2023. Available at: https://lumanity.com/perspectives/car-t-cell-therapies-in-the-us-uk-and-eu4/. Accessed: 29 January 2024.
- Akehurst R, Murphy L and Chapman A-M. Overcoming Challenges in Demonstrating the Value of Drugs for Treating Rare Diseases. 2023. Available at: https://lumanity.com/perspectives/overcoming-challenges-in-demonstrating-the-value-of-drugs-for-treating-rare-diseases/. Accessed: 29 January 2024.
- Matthijsse S. Unsure About the EU HTA Regulation? 2023. Available at: https://lumanity.com/perspectives/unsure-about-the-eu-hta-regulation/. Accessed: 30 January 2024.
- Lumanity. The PHARMO Institute and Lumanity are Partnering to Invest in new Solutions to Support Enhanced Real World Data Analytics. 2023. Available at: https://lumanity.com/the-pharmo-institute-and-lumanity-are-partnering-to-invest-in-new-solutions-to-support-enhanced-real-world-data-analytics/. Accessed: 30 January 2024.
- Bothe I, Fink A, Mills D and Guethert A. The AI Will See You Now: Opportunities and challenges presented by the use of generative artificial intelligence (AI) across healthcare and the pharma value chain. 2023. Available at: https://lumanity.com/perspectives/the-ai-will-see-you-now-opportunities-and-challenges-presented-by-the-use-of-generative-artificial-intelligence-ai-across-healthcare-and-the-pharma-value-chain/. Accessed: 30 January 2024.
- Cochrane. Cochrane announces new policy on AI generated content. 2024. Available at: https://futurecochrane.org/newnews/cochrane-announces-new-policy-on-ai-generated-content. Accessed: 30 January 2024.
- Schurer M and Chapman A-M. The story behind the numbers: How burden of illness studies add value to HTA submissions. 2022. Available at: https://lumanity.com/perspectives/the-story-behind-the-numbers-how-burden-of-illness-studies-add-value-to-hta-submissions/. Accessed: 30 January 2024.