Introduction
Health technology assessments (HTAs) are multidisciplinary policy analyses of drugs, diagnostic tests and medical devices contributing to approval, reimbursement, and rollout of biotechnology and pharmaceutical products (Reference O’Rourke, Oortwijn and Schuller1). For the purposes of this article, we defined health technologies following the Institute for Clinical and Economic Review’s definition, which encompasses healthcare interventions used to improve health or prevent disease (2). HTAs are widely adopted; however, different countries’ assessments display varying level of detail exposing gaps as new health technologies emerge (Reference Fontrier, Visintin and Kanavos3).
Recent innovations warrant revisions to existing evaluative frameworks and implementation guidelines. Many national HTA guidelines, including Canada’s Drug Agency guidelines, do not include evaluative methods for products crossing traditionally defined boundaries underscoring a significant shortcoming (4;5). To the best of our knowledge, it is unclear if national and regional HTA agencies have addressed these revisions, and if so, how.
In this article, we build on the work of, Jiu et al. published in IJTAHC, which advocated for adoption of their innovation of HTA methods framework (Reference Jiu, Hogervorst, Vreman, Mantel-Teeuwisse and Goettsch6). We reviewed the status and challenges of evaluating, remunerating, and implementing emerging health innovations that cannot be placed into currently defined categories. In such cases, emerging health technologies to include health innovations (e.g., novel surgery and gene therapies) as well as what has traditionally been thought of as novel health technologies. The solutions we propose assume the financing structure of a predominantly single-payer public healthcare system that has elements of private financing supplementing its core (e.g., Canada). These emerging health technologies can be reimbursed out of a variety of different possible budget silos both inside and outside the single-payer core leading to the problems suggested by this article. Addressing these repercussions requires a concerted effort to streamline reimbursement processes, enhance coordination among budget silos, and improve the evaluation of emerging health technologies.
Evaluation strategy
Two types of health technologies formed the basis of this article: (1) therapeutic innovations, such as drug-device combination products or nondrug alternatives to prescription drugs (or vice versa) and (2) disruptive health innovations, such as novel surgeries and gene replacement therapies. These categories of interventions were chosen based on our previous work and owing to ambiguities about how to assess them within current HTA frameworks (Reference Fu7).
In a two-step analysis, we first performed a scan of national HTA guidelines, along with databases from organizations such as the International Network of Agencies for HTA, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the European Medical Agency (EMA). We used keywords of “digital technology,” “gene replacement therapy,” “digital pill,” “hybrid technology,” “digital prescription,” “software as a medical device” to identify how different HTA agencies define and assess these products. We identified six sources to develop a list of gaps in the current evaluation, reimbursement, and implementation of these health innovations.
We then sought out case examples of products that fit into one of the two defined categories. We used national HTA guidelines and databases previously reviewed to locate specific interventions flagged as cases. We then reviewed products that have been submitted under the FDA’s De Novo pathway (8), Ontario Health Technology Advisory Committee (OHTAC) (9), and examined products available for view on the top 50 pharmaceutical companies with the largest revenues incurred in fiscal year 2022 (10). For included products, we extracted jurisdiction(s) of adoption, market entry/reimbursement status, and HTA evidence (if any) that supports reimbursement decisions. We then identified current problems in evaluating, reimbursing for, and implementing these interventions and propose some actionable solutions.
The current HTA landscape
We examined 20 HTA guidelines (see Table 1), most of which (16/20, 80 percent) did not have information on economic evaluation or reimbursement relevant to at least one of the two products of interest. Instead, these guidelines focused on general approaches to pharmacoeconomic evaluation and considered drugs and medical devices separate entities. Conversely, a small number (4/20, 20 percent) provided evaluative information to varying degrees with the Australia and EU-EMA guidelines providing definitions related to at least one product of interest.
Table 1. Summary of national and international health technology assessment guidelines
UK, United Kingdom; EU, European Union; EMA, European Medicines Agency; INHTA, the International Network of Agencies for Health Technology Assessment; ISPOR, the Professional Society for Health Economics and Outcomes Research.
For drug-device combination products, Australian and European Union guidelines reference “codependent technologies” and “integral medical devices,” respectively (11;12). Moreover, the Government of Canada, reference drug-device products as “combination products” (5). These definitions are similar, referring to products that have health technology and drug components, where both are integral to product action. Notably, this definition was not included in the Canadian HTA guidelines, but rather, found in Government of Canada publications. As for health technologies replacing a drug, we found a subset from two ISPOR articles (Reference Hsu, Wang and Lee13;Reference Yan, Balijepalli, Gullapalli and Druyts14). This subset comprised “Software as a Medical Device” where software is intended to be used for medical purposes without being part of a hardware medical device. Of the four HTA guidelines that provided information related to the products of interest, those of Australia, The Netherlands, and Norway provided specific economic evaluation or reimbursement guidance (12;15–Reference Kanters, Bouwmans, Van Der Linden, Tan and Hakkaart-van Roijen17).
Case studies
Ten health technologies at varying stages of market entry were identified. Half were emerging therapeutic innovations and half were disruptive health innovations (see Table 2). We located available HTA reports for all products. Seven health innovations were found to be cost-effective compared to standard of care using an upper willingness-to-pay threshold of $150,000 USD per QALY (Reference Neumann and Kim18). As for the remaining three products with less favorable cost-effectiveness profiles, the OHTAC recommendation against the funding of minimally invasive glaucoma surgery was due to potentially high budget impact (19). Zolgensma® (Onasemnogene abeparvovec), a one-time gene therapy intended to cure spinal muscular atrophy, gained market entry in the United States, EU, and Japan; however, an economic evaluation from The Netherlands found the product to be unlikely cost-effective over the current standard of care Spinraza® (nusinersen) combined with best supportive care practices (Reference Broekhoff, Sweegers, Krijkamp, Mantel-Teeuwisse, Leufkens and Goettsch20). By explicitly modeling potential patient relapses, this study found the Incremental Cost-Effectiveness Ratio (ICER) for Zolgensma® to increase by up to sixfold if relapse occurs within 10 years (Reference Broekhoff, Sweegers, Krijkamp, Mantel-Teeuwisse, Leufkens and Goettsch20). Finally, the Canadian Agency for Drugs HTA findings for MiniMed®, a hybrid closed-loop insulin delivery system were inconclusive due to insufficient long-term data on clinical relevance and patient outcomes (21).
Table 2. Case studies of health innovations
I = Therapeutic Innovations; II = Disruptive Health Innovations.
Gaps and potential solutions
The urgency for novel HTA methods grows as emerging health technologies become increasingly complex. This is underscored by Jiu et al.’s perspective paper that developed an evaluative framework to address the need for innovative methods to ensure good evaluative practices within HTA (Reference Jiu, Hogervorst, Vreman, Mantel-Teeuwisse and Goettsch6). This framework serves as a structured approach for assessing the value, efficacy, safety, and cost-effectiveness of emerging health technologies, providing a systematic way to navigate the complexities of healthcare decision making.
The identified HTA limitations in Table 2 provides a list of shortcomings related to funding models, reimbursement mechanisms, and evaluative procedures unique to emerging therapeutic innovations and novel health technologies. Examination of these limitations helped to identify the following gaps and potential solutions.
Lack of definitions for two product categories
The absence of standardized definitions may cause inconsistent evaluation of products. HTA should function as a structured and systematic approach to evaluation.
Potential solution
Define combination products and health technology replacing drugs within the HTA along with establishing jurisdictional guidelines specific to these products including how to calculate alternative Incremental Cost-Effectiveness Ratios (ICERs). Simulate a proxy health technology that embodies all the components of the hybrid technology under evaluation for comparison purposes.
Potentially inappropriate comparators chosen for cost-effectiveness analyses
Using prescription drug alone as the comparator for health technologies intended as drug alternatives may overlook costs such as training and device failure. As such, this approach may not capture the full cost-effectiveness profile of these novel technologies. An example of such technology is Abilify MyCite®, a combination of Aripiprazole with an ingestible tracker for treating certain mental health disorders (Reference Chopra, Boskovic, Kulkarni and Cochran22). One ICER is not sufficient to understand the cost-effectiveness of a device with both drug and device components.
Potential solution
Design a costing framework encompassing both drug and nondrug technologies that provides practical advice to measure costs for combination products. For example, require manufacturers to submit costs separately for the drug and medical device components to make possible calculation of an alternative ICER that examines the incremental costs of the added medical device/drug component – separately from the overall cost of the innovation – combined with the full incremental effects of the innovation. The inclusion of these two ICERS could be informative for decision makers.
Lack of reliable trial or field data resulting in highly sensitive economic evaluation findings
Long-term durability of many innovative treatments cannot be observed due to limited patient follow-up (Reference Chopra, Boskovic, Kulkarni and Cochran22;Reference Delshad, Almario, Fuller, Luong and Spiegel23). This is especially concerning for gene therapies with adenovirus delivery mechanisms such as Roctavian® (Valoctocogene roxaparvovec). Real-world data on treatments are scarce due to small patient populations. Moreover, real-world users of certain innovations often do not mirror the original trial population. For example, trial participants may not be tech-savvy or open to using such products outside of trials (Reference Delshad, Almario, Fuller, Luong and Spiegel23). Field data may be needed to supplement the analysis but often these data are not readily available. This shortcoming leads to miss-estimation of costs associated with the rollout of such innovative health products and potential omission of important patient outcomes (19).
Potential solution
When data are limited, one can conduct comprehensive sensitivity or scenario analysis to gauge long-term treatment durability of treatment effects. This is especially important in scenarios that involve rare disease or products that represent revolutionary treatment for health conditions previously deemed incurable (Reference Angelis, Harker, Cairns, Seo, Legood and Miners24). Qualitative input from individuals with lived experiences through interviews or surveys can provide invaluable insights for reimbursement decisions (Reference Fu7). Alternatively, artificial intelligence/machine learning algorithms can be employed to simulate missing data if other methods are not feasible.
The changing price and features of health innovation products lead to complexity in a one-time-only evaluation
Health innovations that involve medical devices are continuously updated to reflect the changing marketplace. For instance, the manufacturers of Virtual Reality for Pain Relief® revealed that their product and pricing strategy is expected to change as market share grows (Reference Delshad, Almario, Fuller, Luong and Spiegel23).
Potential solution
Guidelines should specify the recommended period of time that HTA bodies should conduct a supplementary economic evaluation for review. Moreover, HTA guideline documents should be updated more frequently (i.e., every 2–3 years) as the health technology landscape changes at an increasing rate.
Varying reimbursement mechanisms and funding silos
In Canada, the evaluation of prescription drugs is governed centrally through Canada’s Drug Agency (CDA) with funding decisions reserved for each Province individually; however, that of medical devices is conducted at the provincial level (see MiniMed® in Table 2). This results in interprovincial variations in evaluation and funding, impacting patient affordability from increasing out-of-pocket costs. When emerging health technologies are reimbursed from differing budget silos, it can lead to disjointed decision-making and inefficient resource utilization.
Potential solution
We suggest outlining flexible reimbursement criteria that accommodate boundary-crossing products or outline exceptions to common rules. HTA processes should incorporate measures of patient affordability to help foresee access impediments as the level of out-of-pocket expenditures rise or fall as the budget silo and corresponding cost-share rate for new advancements shift (Reference Jiu, Hogervorst, Vreman, Mantel-Teeuwisse and Goettsch6).
Future considerations and recommendations
This article overviews existing HTA guidelines and policy analysis on the limitations of current evaluative frameworks for emerging health innovations. Implementing standardized assessment criteria and evidence-based frameworks for evaluating the cost-effectiveness and clinical efficacy of emerging health technologies can help mitigate reimbursement policies that appear inconsistent as these innovations emerge. Moreover, leveraging HTA agencies to provide genre-specific evaluations of such novel products could enhance transparency and credibility in reimbursement processes. Future work should consider devising practical solutions to ensure an informative HTA process.
Acknowledgment
None.
Funding statement
The authors have not declared a specific grant for this article from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interest
The authors have no competing interests to disclose.
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