Although technology can deliver enormous benefits, it has long been acknowledged as one of the key drivers of increasing healthcare costs. Access to innovative healthcare may enhance the patient journey, with better treatments resulting in fewer side-effects and an improved quality of life. For the payer, investment in new technologies may lead to better patient outcomes, better patient flow through the system and reduced overall costs. Most countries attending the HAPF are moving toward universal health care (UHC), and as such are grappling with balancing health budgets and reducing health inequalities, although at the same time wanting to enable patient access to innovative healthcare technologies (Reference Mundy, Kearney and Trowman1). Industry also faces the challenge of finding mechanisms to enable health systems in the region to access innovative and clinically beneficial devices and medicines at an affordable price.
With the move toward UHC, policy makers need tools, such as health technology assessment (HTA), to enable them to prioritize which technologies to invest in and add to benefit packages. Decisions around adding a new medicine or device to public health care are not binary and must consider not only the magnitude of the health benefit, but affordability and whether the technology represents value for money (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2). Technologies that may be considered “affordable” in one country may be viewed as high-cost in another, for example medications such as statins, that have a relatively low acquisition cost but treat a patient group with a high burden of disease may be unaffordable in terms of the overall payer's budget. In addition, some technologies and interventions may work well in some countries but not in others due to many reasons including differences in expenditure on, and types of healthcare systems, population composition, socioeconomic characteristics, service delivery, infrastructure, and care pathways.
There is a paucity of literature describing the region's experience of access to high-cost technologies. Although the term high-cost is cited often in the literature and policy discussions, few countries in the world, let alone in the Asia region, use a standard definition of what represents high-cost, and this formed the basis of discussions between HAPF participants (Reference Ferrario, Araja and Bochenek3).
The Asia region has one of the world's highest dependence on out-of-pocket expenditure (4), resulting in a lack of equity and unequal access to beneficial technologies to patients in the public sector compared with those in the private sector (Reference Teerawattananon, Tantivess, Yothasamut, Kingkaew and Chaisiri5). Participants at the HAPF expressed concerns that inequity may increase in the absence of policy change with the development of high-cost technologies such as gene therapy and regenerative medicines (Reference Teerawattananon, Tantivess, Yothasamut, Kingkaew and Chaisiri5).
Discussions during the HAPF revealed that all countries, regardless of the stage of UHC development, found investing in new and innovative high-cost technologies challenging in a healthcare system operating under significant budgetary pressure. High-cost technologies are often associated with significant risk due to uncertainty around the clinical evidence, cost-effectiveness, budget impact, price, or the eligible patient population for break-through technologies. Alternative funding mechanisms such as managed entry schemes (MES) are just one tool increasingly used by decision makers in the region to manage uncertainties in the evidence-base.
Managing Uncertainty with MES
As stated previously, decision making is not binary and with increasing uncertainty in the evidence base, reimbursement decisions for innovative technologies may be trinary, that is, yes, no, or a “maybe” that is linked to some form of MES (Reference McCabe, Edlin and Hall6). MES can reduce risk to payers by reducing the total budget impact or by creating an opportunity for the development of additional evidence to inform future reviews of the funding decision (Reference Edlin, Hall, Wallner and McCabe7). MES are also appealing to manufacturers as products that otherwise might have been rejected can gain early market access. Importantly, MES may also offer an alternative, softer “disinvestment” strategy, in that they offer the opportunity to reassess the clinical and cost-effectiveness before a commitment is made to add them to a benefits package for reimbursement (Reference McCabe, Stafinski, Edlin and Menon8). However, MES are challenging to implement, especially where they are reliant on data collection, and may themselves be costly to implement and administer. Other challenges around the implementation of an MES include the potential for lengthy negotiations, unclear success measures, the complexity of the agreements, and ultimately, how to use the new evidence to inform coverage decisions (Reference Ferrario, Araja and Bochenek3). Therefore, before entering into an arrangement, the need for feasibility and value of an MES should be carefully considered by all stakeholders, including patient representatives and clinicians, in addition to sponsors and payers (Reference Tuffaha and Scuffham9).
Broadly speaking MES can be categorized into performance-based (outcomes or evidence-generation schemes) or financially based schemes (Figure 1). Outcome-based schemes tie the purchase cost, level, or nature of reimbursement to clinical or intermediate endpoints measured in the future and ultimately related to patients’ quality or quantity of life (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2). The benefit to the payer is that they can provide access to innovative technologies to patients at a discounted net cost, decreasing the financial exposure for potentially under-performing products, and the benefit to manufacturers is access to the market at or near launch (Reference Carlson10).
Fig. 1. Taxonomy of managed entry agreements (Reference Morel, Arickx and Befrits16).
Evidence-generation schemes condition a positive coverage decision on the collection of additional evidence through clinical studies, which might result in continued, expanded, or withdrawn coverage (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2). For example, coverage with evidence development (CED) or access with evidence development where the coverage of a treatment or technology is conditional on data being gathered through a clinical trial or registry to determine its effectiveness (11;Reference Mohr and Tunis12). CED delivers benefits to the payer by providing access to innovative products while additional population level evidence is generated that may support future coverage decisions. The benefit to manufacturers is that they receive market access that otherwise would be denied due to insufficient evidence at time of product launch (Reference Carlson10).
Financially-based schemes are the most common, and arguably straightforward, arrangements (usually for pharmaceuticals), where the cost of a product is reduced either through discounts, rebates or price-volume agreements for a specified patient population without linkage to health outcomes (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2). In countries where cost-effectiveness thresholds exist (explicit or implicit), financial-based risk-sharing schemes may be viewed as agreements that bring the price down to within the willingness-to-pay threshold (Reference Ferrario, Araja and Bochenek3).
Much of the literature describes the experience of MES in Western Europe, Australia, the United States, and Canada, with few data describing the use of MES in the Asia region (Reference Mundy13). The review by Lu et al. (2015) was conducted to identify and characterize alternative market access agreements in the Asia-Pacific region. The search strategy identified 106 MES, with the majority being implemented in Australia (n = 98), with only five in New Zealand and three in South Korea. In keeping with the results of a world-wide study of MES (Reference Carlson, Chen and Garrison14), most of these agreements were for pharmaceuticals, most of which were for oncological indications. The three agreements in place in South Korea were all financially based schemes that targeted entire classes of established medicines, such as hyperlipidemia and hypertensive medications, with large patient groups that would have a great impact on the health budget (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2).
Methods
The sixth HAPF was held from October 29–30, 2018, in Jakarta, Indonesia, with sixty-one invited experts in attendance comprising delegates from public sector HTA agencies, most of whom are embedded within, or funded by the health departments of twelve countries in the Asia region; delegates from thirteen pharmaceutical and medical device companies with interest and experience in Asia; leaders from HTAi; senior public officials from the Indonesian Ministry of Health; and a representative from the World Health Organization.
To inform discussions at the Forum, a background paper was developed with the assistance of the Organizing Committee. The background paper, which will be published on the HTAi website, has a greater discussion around the advantages and disadvantages of MES in general (Reference Mundy13). This article comprised two elements: first, a literature review, which attempted to identify the challenges of countries in the Asia region investing in high-cost technologies, along with the use of MES to enable access. Second, a short survey of both payers (HTA agencies) and industry representatives participating in the 2018 APF was undertaken to capture their experience of alternative access mechanisms, the types of mechanisms, and to elucidate some of the challenges and barriers in the implementation of these schemes.
The HAPF is designed to promote open and constructive dialogue, without fear or favor. As such, Forum meetings are conducted under the Chatham House Rule in which participants are free to share information obtained during the meeting but the identity or affiliation of the person providing the information cannot be revealed (15). This study provides the authors’ summary of the premeeting surveys and discussions among participants during the 2018 HAPF, and does not necessarily represent the consensus view of those attending the meeting, or those of the organizations they represent.
Results
Results from the “HTA Agency” Premeeting Survey
The HTA-agency survey was completed by representatives from nine countries: Indonesia, India, Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. It should be noted that responses to the survey, summarized in Table 1, were provided by individuals, and, therefore, may not accurately reflect the full situation in each agency or country.
Table 1. Survey Results from Payer Agencies
The definition of high-cost, in terms of the health expenditure per capita of their country, varied from country to country, and was reasonably consistent whether describing the investment in a device or a medicine. Based on the results of the survey, most countries make high-cost healthcare technology investment decisions on a case-by-case basis. Only Malaysia, China, and the Philippines have a working definition of “high-cost.” The Malaysian Ministry of Health defines high cost as individual technologies that cost more than US$50,000, whereas in the Philippines, any individual healthcare technology (pharmaceutical, device or procedure) that exceeds US$2,000 or fifteen times the per capita health expenditure is considered very expensive and likely to cause “catastrophic health expenditure” to households. China has recently developed policy around access to high-cost devices. Very high-cost devices, such as proton and heavy ion radiation therapy and other high technological radiation therapies that cost more than US$5 million, are overseen by the Ministry of Health, whereas devices such as magnetic resonance imaging and surgical robots that cost US$1–5 million are overseen by provincial health bureaus. Although Thailand, South Korea, and Taiwan do not have an explicit high-cost technology policy, they do require proof of value-for-money before approving coverage of (mainly pharmaceutical) healthcare technologies (Reference Lu, Lupton, Rakowsky, Babar, Ross-Degnan and Wagner2). Although currently lacking, Vietnam is interested in developing an explicit threshold, which could then be used for decisions on coverage and price negotiation for selected high-cost medicines. Although only a guide and not an explicit value, in South Korea treatment costs exceeding one times gross domestic product per capita would be considered a high cost medication. A fixed threshold is not used in South Korea as the cost of the new technology needs to be considered relative to any existing comparative technology, and the context is important, with consideration given to the nature of the disorder and the burden of disease, for example, disease prevalence may be low, so although the beneficial technology is expensive, the impact on the total health budget is minimized.
The challenges faced by countries when investing in high-cost technologies are as varied as the region's populations, economies and health systems, and include: legislative, regulatory, and budgetary constraints, the lack of evidence supporting new technologies, patient affordability, and socio-cultural barriers. Access to data to assist in decision making was flagged as the biggest issue faced by several countries, whether it was a lack of quantitative data (safety, effectiveness, and especially cost-effectiveness data), or poor-quality data and uncertainty around how to collect data, especially on an individual patient level. One of the flow-on effects of the lack of data, is that there is a degree of uncertainty around the value for money of these high-cost technologies in the local setting. Uncertainty was cited as the major reason that the Philippines has not prioritized access to/investing in high-cost technologies, rather, it is concentrating on the provision of basic population health services. The need for real-world data was reiterated by several respondents, and it was acknowledged that the collection of appropriate data may be hindered by limited resources.
A lack of qualitative evidence to inform decision making, especially around the acceptability of new technologies, was also identified as an issue, particularly when considering that many of the countries in the region, have large, heterogeneous populations with a range of socio-cultural characteristics. One interesting point raised by Thailand was the advent of co-dependent technologies, which may result in a lack of access when one side of the co-dependent equation is missing, for example, access to a high-cost drug is blocked when patient access to the mutational analysis to identify a specific genetic mutation is not available.
Experience with Managed Entry Schemes
Several countries indicated that they had a written policy regarding the implementation of MES in place but only for certain conditions or technologies. Of the five countries without such a policy, three intend to develop one within the next 1–2 years, development was not on the immediate horizon for one country but there was interest in the concept, and one country had no plans to develop a policy. Although the Philippines does not have an explicit policy, it does have Medicines Access Programs in place in selected public facilities; which applies to all technologies not just high-cost ones that can use financial-based schemes. Similarly, Taiwan does not have an MES policy in place, but has a price-volume agreement for some high budgetary impact pharmaceuticals. In addition, Taiwan recently drafted policy for drugs that cost > 500 million NTD per year (US$16.6 million), which requires the drug to be reimbursed for an approved indication in a reference country (Canada, Australia, United Kingdom) along with data describing measurable efficacy endpoints, and any serious adverse events associated with the drug, as well as an estimate of the cost of managing these adverse events.
Most of the countries included in the survey (88.9 percent) have at some time introduced a new health technology using an MES, with only one country, Singapore, reporting no experience at all. Overwhelmingly, an MES was set in place to allow access to pharmaceuticals, with only three countries using an MES to fund access to devices and one to a diagnostic. The types of agreements and technologies approved varied greatly from country-to-country and this may offer an opportunity for collaboration and exchange of information/learnings across the region. In Vietnam, MES, where the manufacturer reduced the price by 50 percent for a limited time, have been applied for some high-cost cancer pharmaceuticals such as erlotinib and sorafenib, as well as an MES allowing patients access to robotic surgery. In Malaysia, MES have been used to fund access to imatinib for chronic myeloid leukemia and brentuximab vedotin for certain hematological malignancies. India commenced a MES for bedaquiline for the treatment of multi-drug resistant TB, and Thailand has used an MES to enable access to imiglucerase for the treatment of Gaucher type I disease. MES in the Philippines have funded high-cost drugs to treat breast cancer (trastuzumab and letrozole) and intravenous immunoglobulin to treat Kawasaki disease, as well as low-cost insulin to treat highly prevalent diabetes.
South Korea is one of the most active countries in the region in implementing MES, with numerous high-cost technologies, including pharmaceuticals, devices and diagnostics, funded and reimbursed. Recent examples include autologous platelet rich plasma, irreversible electroporation for pancreatic cancer, intravitreal autologous platelet concentrate injections for the treatment of macular holes, and autologous peripheral blood stem cells for the treatment of myocardial infarction. In addition, a scheme that grants a 1-year temporary regulatory exemption period, during which time evidence must be generated for the technology to undergo HTA, has recently been implemented. There are currently three high-cost technologies funded under an evidence-generating program: transcatheter aortic valve implantation for severe aortic stenosis (due for evaluation in late 2018), the percutaneous left atrial appendage closure device for stroke prevention, WATCHMAN™, and the next generation sequencing Oncogene panel (both due for evaluation in late 2020). In South Korea, the most prolific agreements in place are risk-sharing arrangements to fund access to orphan drugs and anticancer drugs where no other alternatives to treat life-threatening conditions exist. This scheme was introduced in South Korea in 2013, and as of July 2018, a total of thirty-two drugs have been funded by a variety of mechanisms including coverage with evidence development, expenditure caps or refunds. Since the scheme's inception, only the one risk-sharing agreement for lenalidomide, used to treat multiple myeloma, has been terminated.
The proportion of new healthcare technologies that were funded or reimbursed in the public health system using an MES was unknown or low in most countries, with the exception of South Korea, which has funded thirteen of thirty-four (38 percent) new anti-cancer and orphan drugs under the National Health Insurance scheme using risk-sharing arrangements.
All countries gave multiple reasons as to why an MES approach was considered (see Table 1), with the most common criteria (75 percent) being that the technology in question would have a significant budgetary impact, followed by uncertainty around the economic analysis or cost-effectiveness of the technology (62.5 percent). In South Korea, it was recognized that there is a clinical need for some technologies with limited safety and effectiveness data, especially for the treatment of rare diseases/disorders where there are no other treatment alternatives. In cases such as these, it is incumbent on the government to create a support system that enables technologies with potential, especially for those where there is little incentive for development due to patent or ownership rights.
When evaluating MES outcomes, most countries (75 percent) relied on a single entity, either the public payer, a third party (e.g., academic institution) or the manufacturer, to collect data for analysis. Most countries (87.5 percent) collected patient outcome data such as reductions in morbidity or mortality, with 50 percent collecting health system cost data. Few countries collected data on patient satisfaction, including quality of life, and only one country collected data on a demonstrated disinvestment from other technologies.
Results from the “Industry” Premeeting Survey
A total of ten industry representatives from six different companies completed the survey, summarized in Table 2, with one company reporting no experience in MES, and one company describing their experience in five different countries in the region. Most had experience with financial-based schemes (88 percent) which were usually simple discounts or rebates (86 percent). Only one company had experience with all three types of MES, and few had experience with outcome-based or evidence-generation schemes. Most MES were put in place to increase access to pharmaceuticals, most of which were not in the public domain, with the exception of pembrolizumab, an anti-PD-1 immunotherapy for non–small cell lung carcinoma, discounted by the manufacturer for use in South Korea. Only one device, the WATCHMAN™ left atrial appendage closure device, was funded under an access with evidence agreement in South Korea. Three companies had agreements in place in South Korea and Taiwan, with one company having agreements in Thailand, Hong Kong, and India. The majority of these agreements are still in an active phase and are yet to be completed (62.5 percent).
Table 2. Survey Results from iIndustry Participants
The decision-making criteria for the implementation of an MES cited by industry representatives were similar to those cited by the agencies, with significant budgetary impact, uncertainty around cost-effectiveness and high clinical demand being the most frequent. It was, however, unclear whether these criteria simply reflected and reiterated the view of the payer rather than the belief of industry.
The majority of companies were involved in data collection; however, it should be noted that financial-based (discount/rebate) schemes are unlikely to require data collection as a prerequisite. One company only agreed to collect data, whereas the remaining two companiesFootnote a collected data and provided data analysis, one through an independent third party. One of these companies also sponsored a clinical trial for a pharmaceutical in Thailand, with data generated to inform a cost-effectiveness analysis, whereas another provided a postapproval registry. Of the representatives actively involved in data collection, all were interested in patient outcomes such as morbidity and mortality, with two interested in patient satisfaction and quality of life. Others were particularly interested in the clinical usefulness of the technology, and change in patient management, as well as cost-effectiveness data, reduced health system costs and disinvestment opportunities.
Discussion
It was clear from both discussions before and during the HAPF, that a simple definition of what constitutes a “high-cost technology” is not straightforward and will vary from country-to-country. Defining high-cost is context-specific and must consider the diversity of health systems, culture and the stage of UHC development in the country in question, as well as differences in regulatory approval pathways and legislation. Regardless of these differences, common factors that can affect the introduction of a high-cost technology into a country's public health system were identified across the region including: considering the severity and burden of disease; affordability and overall budget impact; the value-add and impact of these high-cost technologies; the need for transparency between all stakeholders especially the patient throughout the entire care pathway and consideration of the time horizon of a technology.
During discussions at the HAPF it was agreed that although technology should be embraced, sometimes simple solutions can be effective. Solutions to increase access to healthcare technologies should be pragmatic, affordable, and sustainable. In addition, it was believed that centers of excellence should be encouraged to reduce duplication of under-used high-cost technologies or services within a country's public health system. This might be achieved by promoting partnerships and collaborations between the public and private health systems, noting that high-cost technologies are often available privately in Asia (and, hence, a source of inequity). It was also agreed that, although difficult, disinvestment is important and should be considered when funding new technologies.
Many countries acknowledged that price negotiation with manufacturers was challenging, and were keen to explore and discuss potential areas for collaboration and learning from each other across the region. Attendees at the HAPF agreed that MES represent a mechanism to allow patient access to healthcare that may otherwise be challenging for a public healthcare system to adopt. However, an MES can be challenging to implement, especially when they are reliant on data collection by third parties with associated issues of data access and patient confidentiality. In addition, MES may themselves be costly to implement and administer. An agreed objective of the MES should be articulated before the scheme commences, clearly articulating that the technology in question may be removed if it does not meet the prespecified criteria (i.e., a “managed exit” from the health system). It was agreed that an MES needs to be fit-for-purpose, and due to the complexity of these agreements, it was believed that mechanisms to provide access to drugs, devices and treatments for rare diseases should be considered separately. In addition, patients need to have realistic expectations when accessing treatments funded by an MES and be made aware of the need for, and their obligation to provide, long-term data.
It was agreed that a consensus statement should be developed, which will include a “road map” for the use of MES in the Asia region. This road map will clearly articulate the “rules of engagement” for all stakeholders—patients, providers, payers, and industry—and will clearly outline the intent and need for MES, clearly identifying the problem that needs to be solved, and how an MES can be part of the solution.
In conclusion, although it is early days in the implementation of MES schemes in the Asia region, they have the potential to play an important role enabling access to new, mainly pharmaceutical, health technologies. The development of a “road map” of managed entry schemes in the region that clearly outlines the intent and need for a MES, and articulates the “rules of engagement” for all stakeholders—patients, providers, payers, and industry—will assist countries to clearly identify the problem that needs to be solved, and how an MES can be part of the solution.
Author ORCIDs
Linda Mundy, 0000-0002-7874-4232
Conflicts of interest
Linda Mundy is the Scientific Secretary for the HTAi Asia Policy Forum and as such is paid for this role by HTAi. Rebecca Trowman is the HTAi Secretariat for all of the HTAi Policy Forums and, as such, is paid for her role as the Asia Policy Forum Secretariat. Prof Kearney is the Chair of the HTAi Asia Policy Forum Organizing Committee and, as such, is paid for this role by HTAi.
