European Health Technology Assessment Research Articles

HT1 - Similarities and Differences in European HTA Evidence Requirements: One for All or One for None?

To determine similarities in requirements and timeline alignment in health technology assessment (HTA) submissions across Europe. Current country differences challenge harmonization and parallel scientific advice with regulatory bodies. Submission guidance from HTA bodies in the UK (England and Wales; Scotland), France, Germany, The Netherlands, Belgium, Denmark, Finland, Norway, Sweden, Poland and Portugal were reviewed. Evidence requirements (e.g., therapeutic benefit, patient benefit, economic evaluations) and timelines for submissions were identified and compared. Requirements of assessment of therapeutic benefit, patient benefit, systematic literature reviews and dossier submissions were consistent across countries. Economic assessment criteria vary across countries. The UK, France, Norway, and Germany recommend a payer perspective and others recommend some form of a societal perspective (Poland, Denmark, Finland, Sweden, and the Netherlands). Differences in preferences for economic perspective drive further differences in economic analyses recommended by HTA bodies. Most HTA bodies suggest cost-utility analysis (CUA) but some a cost-effectiveness analysis (CEA), adding complexity to the development of global economic models and country adaptations. All countries recommend a budget impact model and the Nordics propose a cost calculation. In terms of health-related quality of life evaluation, all countries recommend both generic and disease-specific measures. There is a high degree of variability in mean time from submission to reimbursement across countries. Most countries report an expected mean of 180 days from submission to reimbursement; however, in practice this can extend in some countries to approximately one year (360-400 days). Exceptions include the Netherlands and Denmark, which report an expected 90 days from submission to reimbursement and Germany is the outlier with 12-month free pricing from the time of submission. Despite several similar requirements for HTA submissions to multiple countries, harmonization is challenged by differences in both economic evaluations and submission to reimbursement timelines.

Testing a new taxonomic model for the assessment of medical devices: Is it plausible and applicable? Insights from HTA reports and interviews with HTA institutions in Europe

ObjectiveMedical devices (MDs) encompass a broad and heterogeneous range of technologies. While practices vary considerably across countries, MDs often find application in patient care with little or no evaluation of their effectiveness and safety following market approval. A recently proposed taxonomy of MDs considered devices from the viewpoint of Health Technology Assessment (HTA). The aim of the work presented here was to test its plausibility and applicability by considering real-world HTA practices. MethodsHTA reports on MDs from European institutions were collected in a systematic manner and the evaluated devices and/or related procedures were matched to a position on the taxonomy. Following this, representatives from 16 European HTA institutions were asked about the usefulness of the taxonomy in semi-structured interviews. Results1237 HTA reports (2004–2015) from 33 European institutions were included in the sample. The majority of reports was on technologies from the taxonomic positions initially estimated as having high relevance. Most of the experts interviewed stated that they found the taxonomy useful, particularly regarding its potential to aid in selecting technologies for assessment and to highlight potential methodological particularities per taxonomic position. ConclusionsOverall, the distribution of identified reports on the matrix confirmed that the initial estimation of the relevance and necessity of HTA provided in the taxonomic model is plausible. In addition, interviews with representatives of European HTA institutions showed that the taxonomy could be useful.

Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line (1L) treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in Germany: Data from the FIRE-3 (AIO KRK-0306) study.

800 Background: The randomized, phase 3 FIRE-3 trial evaluated 1L FOLFIRI + cetuximab or bevacizumab in patients with RAS wt mCRC; overall survival favored FOLFIRI + cetuximab by > 8 months. The purpose of this analysis was to evaluate the cost-effectiveness of FOLFIRI + cetuximab vs that of FOLFIRI + bevacizumab as 1L treatment for patients in Germany with RAS wt mCRC (including the patient subgroup with RAS wt, left-sided [LS] primary tumors, as LS is a predictive factor). Methods: A standard oncology 3–health-state partitioned survival cost-utility model was developed to analyze the costs and health benefits of FOLFIRI + cetuximab vs those of FOLFIRI + bevacizumab from a German payer perspective based on data from FIRE-3 and the literature. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs) gained. A 3.5% discounting rate was applied to the modeled costs and outcomes. Results: Discounted costs, health gains, and incremental cost-effectiveness ratios (ICERs) for patients with RAS wt (base case) and patients with RAS wt, LS (subgroup) mCRC are summarized in the Table. Probabilistic sensitivity analyses showed that at relevant European willingness-to-pay (WTP) thresholds of €55,000 and €80,000, FOLFIRI + cetuximab had a 64.0% and 81.6% (base case) and 80.5% and 92.4% (subgroup) probability of being cost-effective vs FOLFIRI + bevacizumab, respectively. Clinical trial information: NCT00433927. Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients in Germany with RAS wt mCRC at official WTP thresholds applied by relevant European health technology assessment agencies. The cost-effectiveness of FOLFIRI + cetuximab is more pronounced in the subgroup of patients with RAS wt, LS tumors.[Table: see text]

OP152 Level Of Agreement In EUnetHTA Joint Action 3 Early Dialogues

Introduction:A recent article reported a high level of commonality across European Health Technology Assessment bodies’ (HTABs) positions in former parallel scientific advice procedure. Since 2017, the EUnetHTA joint action 3 (JA3) offers a new early dialogue process involving a higher number of European HTABs. The present analysis aims to describe if the JA3 process modified the level of agreement across HTABs.Methods:A descriptive analysis of the written recommendations provided during every JA3 early dialogues coordinated by the French National Authority for Health (HAS) until November 2017 was conducted. The level of commonality for each HTAB position identified was assessed globally and by domain (population, comparator, outcomes, study design and health economics) and classified as follows: “full agreement” if all HTABs had the same position, “partial agreement” if more than half HTABs had the same position and “disagreement” in all other cases.Results:Four JA3 early dialogues were performed until November 2017: two in oncology, one in neurology and one in metabolic disorders. Between five and nine HTABs from eleven European countries participated. A total of forty-six positions were identified in these four early dialogues: ten on population, five on comparator, fifteen on outcomes, four on study design and twelve on health economics. Of the forty-six positions, full agreement was reached for twenty-eight positions, partial agreement for seventeen positions and only one disagreement was observed. The level of full agreements was highest for questions on comparators (five out of five) and population (nine out of ten) and lower for questions on health economics (six out of 12).Conclusions:Although the JA3 process substantially increased the number of HTABs participating in the early dialogues, this descriptive analysis suggests that the level of agreement remains very high. This may be facilitated by the high level of dialogue and coordination between HTAB ensured by the EUnetHTA process.

ANALYSIS OF DUPLICATION AND TIMING OF HEALTH TECHNOLOGY ASSESSMENTS ON MEDICAL DEVICES IN EUROPE.

Strengthening efforts toward better collaboration plays a pivotal role in the assessment of medical devices to reduce overlap and save resources. This study explored the level of duplication in health technology assessments (HTA) of medical devices in Europe and their respective timing in order to identify areas for better collaboration. An analysis of European HTA reports of medical devices regarding overlaps in topics and timing in relation to market authorization was performed. We conducted a systematic search in the ADVANCE, Centre for Reviews and Dissemination, Syngerus, and POP databases, complemented by hand searching, to identify HTA reports published between 01/2003 and 07/2016 for a preselected cohort group of ten technologies. We analyzed the number of annual assessments per technology and evaluated activity patterns and timing in undertaking the HTA of the different institutes in Europe. The results revealed the amount of duplication in the European HTA production: the number of reports per technology ranged from minimum seven to maximum twenty-two over a time-span of 13.5 years. HTA institutes perform assessments at a similar time range within 5 to 10 years following market authorization. The timing of the initial assessment in relation to the granting of the CE-mark varies according to the particular technology. The findings suggest that efficient collaboration may help to save scarce resources and time of HTA institutes in Europe. Efficient collaboration as such needs to shift the focus beyond the time span of 1 year, and build on each's others work from previous assessments.

Using Real-World Data (RWD) in Health Technology Assessment (HTA) Practice: A Comparative Study of 5 HTA Agencies

Objectives: Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs) which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in Health Technology Assessment (HTA) of melanoma drugs by European HTA agencies, differences in RWD use between agencies and across time. Methods: HTA reports published between 01.01.2011 and 31.12.2016 were retrieved from websites of agencies representing 5 jurisdictions: England (NICE), Scotland (SMC), France (HAS), Germany (IQWiG) and the Netherlands (ZIN). A standardized data-extraction form was used to extract information on RWD inclusion for both REAs and CEAs. A panel of senior HTA assessors representing the 5 agencies was consulted to check the robustness of data extracted and interpretation. Results: Fifty-two reports were retrieved. All 52 reports contained REAs; CEAs were present in 25. RWD was included in 28 of 52 REAs (54%); mainly to estimate melanoma prevalence. RWD was included in 22 of 25 (88%) of CEAs; mainly to extrapolate long-term effectiveness and/or identify drug-related costs drugs. Differences emerged between agencies regarding RWD use in REAs; ZIN and IQWiG cited RWD for evidence on prevalence whereas NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. Conclusions: In general, RWD inclusion was higher in CEAs than REAs. It was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD. However, no visible trends for RWD use over time were observed. Future research should explore the use of RWD in HTA of drugs in other disease indications and in conditional reimbursement schemes.

A Comparison of Reimbursement Recommendations by European HTA Agencies: Is There Opportunity for Further Alignment?

Introduction: In Europe and beyond, the rising costs of healthcare and limited healthcare resources have resulted in the implementation of health technology assessment (HTA) to inform health policy and reimbursement decision-making. European legislation has provided a harmonized route for the regulatory process with the European Medicines Agency, but reimbursement decision-making still remains the responsibility of each country. There is a recognized need to move toward a more objective and collaborative reimbursement environment for new medicines in Europe. Therefore, the aim of this study was to objectively assess and compare the national reimbursement recommendations of 9 European jurisdictions following European Medicines Agency (EMA) recommendation for centralized marketing authorization.Methods: Using publicly available data and newly developed classification tools, this study appraised 9 European reimbursement systems by assessing HTA processes and the relationship between the regulatory, HTA and decision-making organizations. Each national HTA agency was classified according to two novel taxonomies. The System taxonomy, focuses on the position of the HTA agency within the national reimbursement system according to the relationship between the regulator, the HTA-performing agency, and the reimbursement decision-making coverage body. The HTA Process taxonomy distinguishes between the individual HTA agency's approach to economic and therapeutic evaluation and the inclusion of an independent appraisal step. The taxonomic groups were subsequently compared with national HTA recommendations.Results: This study identified European national reimbursement recommendations for 102 new active substances (NASs) approved by the EMA from 2008 to 2012. These reimbursement recommendations were compared using a novel classification tool and identified alignment between the organizational structure of reimbursement systems (System taxonomy) and HTA recommendations. However, there was less alignment between the HTA processes and recommendations.Conclusions: In order to move forward to a more harmonized HTA environment within Europe, it is first necessary to understand the variation in HTA practices within Europe. This study has identified alignment between HTA recommendations and the System taxonomy and one of the major implications of this study is that such alignment could support a more collaborative HTA environment in Europe.

Giving Patients a Meaningful Voice in European Health Technology Assessments: The Role of Health Preference Research

Giving Patients a Meaningful Voice in European Health Technology Assessments: The Role of Health Preference Research

Defining and Measuring the Affordability of New Medicines: A Systematic Review.

In many healthcare systems, affordability concerns can lead to restrictions on the use of expensive efficacious therapies. However, there does not appear to be any consensus as to the terminology used to describe affordability, or the thresholds used to determine whether new drugs are affordable. The aim of this systematic review was to investigate how affordability is defined and measured in healthcare. MEDLINE, EMBASE and EconLit databases (2005-July 2016) were searched using terms covering affordability and budget impact, combined with definitions, thresholds and restrictions, to identify articles describing a definition of affordability with respect to new medicines. Additional definitions were identified through citation searching, and through manual searches of European health technology assessment body websites. In total, 27 definitions were included in the review. Of these, five definitions described affordability in terms of the value of a product; seven considered affordability within the context of healthcare system budgets; and 15 addressed whether products are affordable in a given country based on economic factors. However, there was little in the literature to indicate that the price of medicines is considered alongside both their value to individual patients and their budget impact at a population level. Current methods of assessing affordability in healthcare may be limited by their focus on budget impact. A more effective approach may involve a broader perspective than is currently described in the literature, to consider the long-term benefits of a therapy and cost savings elsewhere in the healthcare system, as well as cooperation between healthcare payers and the pharmaceutical industry to develop financing models that support sustainability as well as innovation.

European integration in the era of permissive dissensus: Neofunctionalism and agenda-setting in European health technology assessment and communicable disease control

This article questions the argument that we need a post-functional theory of European integration. We suggest instead that the integrative mechanisms of classical neofunctionalist theory explain advances in European integration in the twenty-first century, especially if incorporated into a broader understanding of policymaking grounded in the multiple streams approach. Neofunctionalist mechanisms, in our understanding, work by changing the contents of the problem, politics and policy streams, systematically biasing all three toward integrative solutions to European problems. We illuminate our argument with two cases of integration in health policy, namely communicable disease control and health technology assessment. In these areas, as with other areas of European Union health policy, substantial European integration has taken place since 2000 despite long-standing member state reluctance to integrate and Lisbon treaty language discouraging integration.

Early Insights from Commercialization of Gene Therapies in Europe.

After years of research and development, gene therapies are now becoming a commercial reality with several products approved by European regulatory authorities [...].

PP096 European Union-Health Technology Assessments For Medical Devices - How To Overcome Reimbursement Divergence

INTRODUCTION:National Health Technology Assessments (HTAs) for medical devices are crucial to regulate the quality and costs of healthcare systems. However, there is diversity in several aspects among European countries. Consequently, controversial results might arise, generating contrary reimbursement decisions. The European Network for Health Technology Assessment (EUnetHTA) is an interface platform for the harmonization of HTA information across Europe. The European Commission expects national uptake of a European HTA. Thus, European HTAs might overcome the diversity of national HTA requirements.METHODS:We aimed to compare German and European HTAs for medical devices regarding processes, methods, timelines, and involvement of medical device companies. Therefore we analyzed guidelines, requirements, and output of EUnetHTA and compared those aspects with the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.RESULTS:We found differences between the European and German HTAs for medical devices regarding timelines, involvement of medical device companies, body of evidence, use of surrogate endpoints, and methodology. European HTAs for medical devices reflect the clinical reality by integrating the existing evidence (including real world data) and by using comprehensive statistical methods for medical devices. In contrast, German HTAs for medical device-based technologies are long lasting and are often restricted to a small body of evidence.CONCLUSIONS:As a conclusion, similar to pharmaceuticals, the European HTA framework might also become a worldwide platform for HTAs of medical device-based technologies with the potential to harmonize reimbursement decisions and patients health care across countries on the basis of clinical reality.

OP50 European Assessments Of Medical Devices: Avenues For Improvement

INTRODUCTION:European collaboration in Health Technology Assessments (HTAs) has gained increasing recognition in recent years, not only on pharmaceutical products but also on high-risk medical devices. For medical devices, quality assessments of efficacy and safety are particularly important due to the weak market authorization in Europe. Strengthening efforts towards better collaboration thus plays a pivotal role to reduce overlap and save resources. This study explored the level of redundancy in HTA assessments of medical devices in Europe in order to identify areas for better collaboration.METHODS:We performed an analysis of European HTA reports of medical devices regarding their timing in relation to market authorization, the respective level of evidence used and the overlaps in topics. The ADVANCE HTA database from 2014 was used to select a cohort group of ten high-risk medical devices. A systematic search was conducted to identify all relevant, European HTA reports investigating the ten devices within a time span of 12 years (2003-2015). We analysed the number of annual assessments per technology and evaluated activity patterns, late and early assessors, and minimum evidence requirements.RESULTS:The results revealed the amount of redundancies in European HTA production: the number of reports per technology ranged from a minimum of five to a maximum of twenty-two over a time-span of 12 years. Within a single year, one technology was assessed up to six times by different HTA institutes in Europe. Out of fourteen countries included in the evaluation, two countries assessed each technology, and seven countries assessed more than seven out of the ten technologies.CONCLUSIONS:The findings indicate that more efficient collaboration is needed to save scarce resources and time of HTA institutes. Efficient collaboration as such needs to shift the focus beyond the time span of one year, and start building on each others work from previous assessments.

VP181 From National To European Assessment - The German Case

INTRODUCTION:Health Technology Assessment (HTA) processes have become a fundamental part in the lifecycle of new medicines. However, their deep relation with national legislation creates ambiguous and controversial results between the European countries. Can they be standardized across Europe?METHODS:Sources of national differences have been identified in timelines, documents, methods, data interpretation, and conclusions. In order to harmonize and standardize HTA cooperation across Europe the European Network for HTA (EUnetHTA) was established. We analyzed guidelines, requirements, and output of EUnetHTA and noted the differences between those guidelines and the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.RESULTS:The comparison between German and European HTAs highlights that although both procedures follow the rules of Evidence-Based Medicine, differences in Body of Evidence, Comparator, Surrogate Endpoints, Subgroups, and Evidence Synthesis may lead to diverging HTA outcomes. The European HTA framework facilitates the appropriate depiction of clinical reality through comprehensive inclusion of the existing evidence with context specific statistical methods. It might become a worldwide platform for HTA evaluation and discussion.CONCLUSIONS:Only the involvement of both, pharmaceutical companies and HTA bodies within a unified European framework can lead to a mature and transparent procedure with a reliable outcome independent of legal requirements.

EVALUATION OF THE HTA CORE MODEL FOR NATIONAL HEALTH TECHNOLOGY ASSESSMENT REPORTS: COMPARATIVE STUDY AND EXPERIENCES FROM EUROPEAN COUNTRIES.

The health technology assessment (HTA) Core Model® is a tool for defining and standardizing the elements of HTA analyses within several domains for producing structured reports. This study explored the parallels between the Core Model and a national HTA report. Experiences from various European HTA agencies were also investigated to determine the Core Model's adaptability to national reports. A comparison between a national report on Genetic Counseling, produced by the Cellule d'expertise médicale Luxembourg, and the Core Model was performed to identify parallels in terms of relevant and comparable assessment elements (AEs). Semi-structured interviews with five representatives from European HTA agencies were performed to assess their user experiences with the Core Model. The comparative study revealed that 50 percent of the total number (n = 144) of AEs in the Core Model were relevant for the national report. Of these 144 AEs from the Core Model, 34 (24 percent) were covered in the national report. Some AEs were covered only partly. The interviewees emphasized flexibility in using the Core Model and stated that the most important aspects to be evaluated include characteristics of the disease and technology, clinical effectiveness, economic aspects, and safety. In the present study, the national report covered an acceptable number of AEs of the Core Model. These results need to be interpreted with caution because only one comparison was performed. The Core Model can be used in a flexible manner, applying only those elements that are relevant from the perspective of the technology assessment and specific country context.

PP039 Health Utility Values In Renal Cell Carcinoma: A Systematic Review

INTRODUCTION:Advanced or metastatic renal cell-carcinoma (RCC) is associated with poor health outcomes; in particular in those whose disease progressed after first line treatment. A literature review was conducted to elucidate evidence on health-related utility associated with advanced and metastatic RCC.METHODS:A systematic literature search from 2006 onwards (date of search: July 2016) was conducted for studies evaluating health-related quality of life (QoL) and utility outcomes. Searches included Medline, Embase, National Health Service (NHS) Economic Evaluation Database and HTA Database and were supplemented by free internet search for key European Health Technology Assessment reports. Publications were limited to 2006 onwards as previous research (1) revealed no prior relevant evidence.RESULTS:The search yielded 4,178 records. The selection process revealed seventy-eight relevant publications. Generic EuroQol (EQ)-5D scale was most commonly used. Health-state utilities were assessed for specific treatments and at different time points. Mean reported value for patients after failure of one prior systemic therapy ranged from .79 - .62. For patients without progression (on and off-treatment) reported utility values were in range from .80 – .63. Utility in stable patients with adverse events ranged from .71 - .47. For patients with progressive diseases, utility was reported from .71 - .36. Utility for interventions due to skeletal-related events in patients with bone metastasis was reported to range between .46 and .15.CONCLUSIONS:Identified evidence confirms advanced or metastatic RCC leads to significant detriment to patients health-related utility. Further research efforts are warranted to assess health-state utility beyond clinical trial assessment.

OP78 Patient Involvement In European Health Technology Assessment Focus Group With Cardiac Patients

INTRODUCTION:Involving patients in defining the scope of health technology assessments is recognized as a valuable strategy that ensures that patient-relevant outcomes are considered.The aim of this project was to pilot the focus group approach with cardiac patients in a European rapid assessment on the wearable cardioverter defibrillator, to improve involvement processes, to identify neglected outcomes, and to explore the potential of this methodology for eliciting the patients views on their disease and the wearable cardioverter defibrillator therapy.METHODS:An e-mail was sent to members of the nine regional associations of the Austrian Organization for Heart and Lung Transplant Patients to identify eligible participants. Guiding questions for the discussion were developed based upon a hand search of patient involvement initiatives and a review of appropriate literature. The 4-hour meeting was moderated by a patient support expert and recorded upon approval of participants. The anonymized transcript was analyzed using framework analysis.RESULTS:Ten eligible patients responded, of which five men, aged between 55 and 73 years (mean 65 years) from Austria and Germany, were able to participate. All respondents experienced heart transplantation, and four had received an implantable cardioverter defibrillator before.Participants reported that experiencing a sense of security was crucial to them and that they expected to do sports and live a life with few limitations, despite receiving a therapy. A wearable cardioverter defibrillator was hence not considered a long-term solution due to expected restrictions in living a ‘normal’ life.Challenges included the identification of participants representative of this patient group and the complexity of patient histories.CONCLUSIONS:The focus group approach proved useful in the wearable cardioverter defibrillator assessment. Gathered results informed the inclusion of outcomes relevant to the target group and revealed patients views on health-related quality of life. Lessons learned guide us in further improving patient involvement processes within the European Network for HTA (EUnetHTA) project.

Variation in Health Technology Assessment and Reimbursement Processes in Europe

It has been suggested that differences in health technology assessment (HTA) processes among countries, particularly within Europe, have led to inequity in patient access to new medicines. To provide an up-to-date snapshot analysis of the present status of HTA and reimbursement systems in select European countries, and to investigate the implications of these processes, especially with regard to delays in market and patient access. HTA and reimbursement processes were assessed through a review of published and gray literature, and through a series of interviews with HTA experts. To quantify the impact of differences among countries, we conducted case studies of 12 products introduced since 2009, including 10 cancer drugs. In addition to the differences in HTA and reimbursement processes among countries, the influence of particular sources of information differs among HTA bodies. The variation in the time from the authorization by the European Medicines Agency to the publication of HTA decisions was considerable, both within and among countries, with a general lack of transparency as to why some assessments take longer than others. In most countries, market access for oncology products can occur outside the HTA process, with sales often preceding HTA decisions. It is challenging even for those with considerable personal experience in European HTA processes to establish what is really happening in market access for new drugs. We recommend that efforts should be directed toward improving transparency in HTA, which should, in turn, lead to more effective processes.

PHP374 - Strategic Considerations to Engage in Early Advice with European Health Technology Assessment Bodies

PHP374 - Strategic Considerations to Engage in Early Advice with European Health Technology Assessment Bodies

Health Technology Assessment in the Context of Adaptive Pathways for Medicines in Europe: Challenges and Opportunities.

Adaptive pathways for medicines have gained momentum and, in Europe, adaptive pathways have recently been introduced into the European Medicines Agency (EMA) processes after a successful 2-year pilot. Although the concept, as initially proposed, contained several elements that would have required regulatory reforms, the adaptive pathways program has developed a more pragmatic scope (Box 1). In this article, we explore the main challenges and opportunities adaptive pathways pose from a European health technology assessment (HTA) perspective.