Improving the Applicability of Clinical Evidence to the Asian Setting
The phenomenon of Asian underrepresentation in pharmaceutical research has been well-documented in published literature, and was highlighted by the speakers at ISPOR. Although 60% of the global population resides in Asian regions, pharmaceutical research is mainly conducted in the global North, and only ~17% of trials are conducted in Asia.1,2 However, Asians and people living in Asian regions can exhibit differences in treatment outcomes, for example due to physiological differences from Western patients, as well as differences in healthcare systems and treatment practices.1,2 The use of evidence that reflects the local population in health technology assessment (HTA) would reduce uncertainty in decision-making and facilitate treatment uptake in the local setting.2
While barriers to conducting clinical trials in Asia exist, Dr Louise Goh (Lead Specialist at the Agency for Care Effectiveness [ACE]) clarified that these vary across regions, and that conduct of clinical trials in the Asian setting is generally feasible (Table 1).2 Regardless, adequate Asian representation in global clinical trials may not always be achievable. While there has been increased interest in generating real-world evidence (RWE) to supplement clinical trial data, several challenges exist. For example, there is variation and lack of transparency in how RWE is used to inform decision-making; there are also concerns with the quality, completeness and comparability of outcomes in RWE compared with randomised controlled trials (RCTs).2 Furthermore, in countries where HTA decision-making is shifted upstream in parallel with regulatory decisions, real-world data may be limited at the time of reimbursement consideration.2 RCTs are still the gold standard for estimating treatment effect, and the use of RWE to estimate or validate treatment effects can be susceptible to considerable bias,3 thus necessitating adequate Asian representation in global clinical trials if race or ethnicity are expected to be treatment effect modifiers.
Table 1: Feasibility in conducting clinical trials in Asia despite perceived barriers
Abbreviations: EMA: European Medicines Agency; FDA: Food and Drug Administration; IP: intellectual property; US: United States.
Source: Adapted from APAC ISPOR Issue Panel 3.2
Nonetheless, RWE holds a promising role in various aspects of the HTA decision-making process. For example, besides providing more certainty on the safety and effectiveness of a treatment in an Asian population, RWE can provide input parameters in economic modelling for costs and healthcare resource use, and can also inform the treatment mix in the local setting for budget impact analyses (Figure 1).2 RWE is accepted as a source of evidence for HTA decision-making by ACE in Singapore and by the National Institute for Health and Care Excellence (NICE) in the United Kingdom (UK), albeit generally as supplementary information to complement higher-quality evidence from RCTs.4,5 ACE have noted that the quality of RWE can vary depending on data type and source, and that careful study design is required to mitigate potential bias.6 To this end, NICE have published a framework for RWE in June this year, aiming to outline best practices for planning, conducting and reporting RWE studies.7 This signals NICE’s commitment to drive development of high-quality RWE to improve speed of access and reduce uncertainty in HTA decision-making.8 The release of this framework is expected to provide an opportunity for HTA bodies and pharmaceutical companies alike in Asia to identify and address gaps in local RWE-generation capabilities. My colleague, Andrew Lim, has expounded upon these opportunities in a separate commentary here (‘Using Real-World Evidence in Health Technology Assessment and Regulatory Decisions’).
Figure 1: Role of RWE/RWD in informing HTA decision-making
Abbreviations: HTA: health technology assessment; RWD: real-world data; RWE: real-world evidence.
Source: Adapted from APAC ISPOR Issue Panel 3.2
Capturing the Asian Perspective in Patient-Reported Outcomes
Asian HTA bodies have a clear preference for patient-reported outcomes (PROs) and utilities data that are reflective of the local population.1 However, measuring PROs in a manner that reflects the target population can be difficult. Firstly, PROs are not commonly included as endpoints in clinical trials in Asia – for example, less than one third of clinical trials conducted across 2010–2020 in China included PROs as endpoints.1 Secondly, there is a paucity of locally-validated PROs instruments, and adaptations of existing instruments from Western countries may pose translation and generalisability issues.1 A solution to these challenges could be to use utility data derived from other countries to inform HTA submissions; however, doing so would ignore differences in cultural beliefs and preferences across countries. For example, patients from Japan and Korea tend to be more risk-averse than patients in the US and UK.1 Under the standard gamble method that can be used to derive utilities, it is expected that risk-averse Asian patients would hesitate to engage in gambling, and would assign a higher preference and utility to any given health state than Western patients.1,9
This problem can be partially resolved through the application of country-specific value sets to PRO data from other countries, to reflect local preferences. Mahlich et al. reported that, when country-specific EQ-5D value sets were used to assess the cost-effectiveness of a breakthrough innovation, differences in utilities and incremental quality-adjusted life years were obtained, which resulted in dramatic differences in incremental cost-effectiveness ratios (ICERs) – the ICER using the Japanese value set was almost twice of that when the UK value set was used.9 This has an important impact on determination of the cost-effectiveness profile and pricing of the drug. However, locally relevant value sets may only be available for selected instruments – for example, EQ-5D is the only instrument with a valid value set in Japan.1 In addition, it may still be inappropriate to use PRO data that were measured from a Western population to reflect the experiences of patients in Asia, from whom differences in PRO reporting might be expected. For example, stoicism, which refers to the ability to endure pleasure or pain without showing emotion, is considered a positive trait in Chinese culture; admitting to pain can therefore be considered a sign of weakness.10 As a result, Chinese patients may report pain-related outcomes for a treatment differently compared with Western patients.
There is a need to strengthen local capacities in measuring and valuing PRO endpoints in Asian populations. The increasing focus on generating locally relevant PROs and utilities data in Asia is a promising trend, and will benefit HTA decision-making in the region.
If you would like any further information on the themes presented above, please do not hesitate to contact Jian Yi Choy, Senior Analyst (LinkedIn). Jian Yi Choy is an employee at Costello Medical. The views/opinions expressed are their own and do not necessarily reflect those of Costello Medical’s clients/affiliated partners.