Experts Gather to Explore New Horizons in Health Technology Assessment

Under the guidance of the Department of Industrial Technology of the Ministry of Economic Affairs (MOEA), the Science and Technology Law Institute (STLI) organized the webinar themed “New Horizons in Health Technology Assessment – Global HTA Forward-Looking Strategies” on September 12 in cooperation with GeneOnline. The two speakers included Dr. Eunjoo Pacifici, Chair & Associate Professor of the Department of Regulatory and Quality Sciences, University of Southern California, and Dr. Fei-Yuan Sharon Hsiao, Professor at the Graduate Institute of Clinical Pharmacy at National Taiwan University. 

In his welcome remarks, Dr. Lu Cheng-Yen, Legal Researcher of STLI, highlighted that many countries are facing the challenge of optimizing the use of drugs, biologics, medical devices and diagnostic tools to maximize healthcare benefits within their limited resources and budgets. Systematic assessments and analyses that comply with scientific, legal, and ethical principles are therefore essential. Following the implementation of the National Health Insurance (NHI) system in 1995, Taiwan has been working on health technology assessment (HTA) to review medical technologies and products to facilitate accurate policy decisions, ensure rational resource allocation, and maintain healthcare quality. Notably, the inauguration of the Center for Health Policy and Technology Assessment (CHPTA) in January 2024 marked a new milestone for Taiwan in the field of HTA. 

Related article: Taiwan’s Biotech Industry Directives: Six Strategic Aspects of AI Empowerment, Smart Healthcare, and Global Expansion 

The 1962 Kefauver-Harris Amendments Sets Foundation for Modern Clinical Trials

As health technology assessment must include systematic analyses of the function, efficacy, and safety of medical products, clinical trials are undoubtedly a critical part of the process. Prof. Pacifici, drawing on her extensive experience in drug clinical development and regulatory review, explained the evolution and development of clinical trials in the United States. 

She began by pointing out that the current drug evaluation and clinical trial system in the U.S. originated from the Kefauver-Harris Amendments in 1962, which strictly required that drugs and biologics must have their safety and efficacy verified through clinical trials before marketing. Moreover, the Amendments introduced requirements for pre-clinical testing, informed consent of patients, adverse event reporting, GMP regulations for manufacturing and quality control, and FDA factory inspections, laying a solid foundation for a modern drug review mechanism.

Emerging Challenges and the Evolving Clinical Trial Landscape

Clinical trials have been expanding by leaps and bounds in the 21st century. Since the inception of ClinicalTrials.gov in 2000, the number of clinical trials registered on the database has surged more than 100-fold over the past 20 years, and the amount of capital invested in clinical R&D by global biopharma companies has continued to soar. Meanwhile, it is also worth noting that many pharma companies are outsourcing their clinical trials to contract research organizations (CROs). 

According to Prof. Pacifici, although data reveal a continuous expansion of the scale of clinical trials, it still could not overcome the high costs of drug R&D. On average, a new drug takes 10 to 14 years to complete its clinical trials and enter the market, along with the cost of about $2.6 billion. However, in her own words, “the success rate is not getting better.” Only about 10% or less of drugs can reach fruition in all three phases of trials and eventually win FDA approval for marketing.

To overcome this predicament, the pharma industry has been experimenting with new approaches such as umbrella trials, basket trials and adaptive design, which move away from the traditional three-phase model. Later, the industry also introduced decentralized or virtual clinical trials to reduce the number of patient visits needed, thus improving efficiency and avoiding trial suspension in the event of major public health crises. Nevertheless, Pacifici reminded attendees that these new designs also pose new challenges, such as maintaining compliance with trial protocols and ensuring data integrity.

Challenges of Diversity and the Growing Importance of Real-World Data

Prof. Pacifici also talked about diversity issues in her speech. The FDA has recently updated its guidance document requiring pharma companies to include underrepresented groups such as African Americans, ethnic minorities, and pregnant women in their clinical trials to improve the generalizability of the results. Although the over-representation of Americans (especially whites) persists, she noted a significant increase in the participation of Asian populations. Yet she stressed that diversity does not only refer to demographic factors such as age, gender, race, ethnicity and place of residence, but also to non-demographic ones including the presence of comorbidities, organ dysfunction, disabilities, rare diseases, and extreme BMIs.

The use of real-world data (RWD) in clinical research has become increasingly popular in the biopharma industry. According to Prof. Pacifici, traditional clinical trials, with their strict eligibility criteria and highly controlled environments, may not adequately reflect patients’ actual experiences, thus affecting the external validity of the results. The advent of electronic health records (EHRs) and mobile health apps has allowed researchers to collect RWD from patients in large quantities, capturing patients’ real conditions and better catering to their heterogeneity. However, RWD can be messy and not necessarily robust enough to be analyzed. Also, data from sources such as insurance claims and hospital bills are not intended for research, which could undermine RWD’s credibility.

Despite the challenges ahead, the FDA is seeking to incorporate RWD into its regulatory decisions. Pacifici also believes that RWD and the resulting real-world evidence (RWE) could lead to a paradigm shift in HTA, whereby instead of waiting until the completion of all three phases of clinical trials, regulators may grant conditional approval based on limited information and continue to collect post-market RWD to complement conventional trials.

Valuing Patients’ Voices and Optimizing R&D and Regulatory Processes

To conclude her presentation, Prof. Pacifici mentioned the concept of patient-focused drug development (PFDD). With increased awareness of patient rights and regulatory updates, patients’ voices have become more valued by both industry and regulators, and the FDA is placing more emphasis on patient experience data when reviewing medical products. 

One such example involves drugs for the treatment of Huntington’s disease. Early drug development primarily focused on alleviating patients’ abnormal involuntary movements (chorea), but patient feedback indicated that cognitive impairments were causing more distress to them. These comments have not only prompted pharma companies to adjust their R&D approaches, but regulatory authorities have also improved their review processes by including cognitive impairment as an outcome indicator.

Value Framework for Health Technology Assessment in Taiwan’s Context

Prof. Fei-Yuan Hsiao delivered her presentation on the value framework of HTA in the context of Taiwan’s healthcare system. She first introduced the concept of “Value flower” proposed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), in which each “petal” represents a value dimension, such as quality-adjusted life-years (QALY, for measuring the benefits of medical technology for patients) and net costs (for evaluating the feasibility of coverage), aiming to ensure the availability of drugs to patients, profitability of pharma companies, and the sustainability of the health insurance system.

When evaluating the eligibility of a medical product for coverage, the National Health Insurance Administration (NHIA) mainly takes into account its clinical effectiveness and economic feasibility. During the review process, NHIA will convene a Pharmaceutical Benefit and Reimbursement Scheme (PBRS) Joint Committee Meeting. Apart from representatives from the Taiwan FDA and NHIA, the meeting also includes stakeholders such as healthcare providers, medical experts and members of healthcare associations. Patient representatives may also be in attendance to express their views although they do not have the right to vote.

Supporting Roles of Real-world Data and International Practices

Following up on Prof. Pacifici’s remarks, Prof. Hsiao also mentioned in her presentation the growing importance of RWD in HTA decision-making. In particular, the NHIA may allow conditional reimbursement for innovative products that are approved based on Phase 1 or Phase 2 clinical studies. At the same time, the agency will require manufacturers to provide RWD within two years afterwards for reassessment by the NHIA to justify whether such coverage should continue. This approach recognizes the essential role of real-world evidence in confirming efficacy, allowing products that address unmet medical needs to enter the market earlier, and assisting regulators to effectively control uncertainties in efficacy and financial burdens associated with the NHI coverage.

Speaking about the HTA operation in Taiwan, Hsiao pointed out that the first step is to compare the new product or technology with an existing reference product or standard of care, which is usually the best available therapy covered by the NHI. For breakthrough products with clinical benefits that are significantly better than the reference product, they will be more likely to be approved for reimbursement and more favorable pricing methods. 

Taiwan also draws on the experiences and recommendations of international organizations when evaluating innovative health technologies. Major references include the Canadian Agency for Drugs and Technologies in Health (CADTH), the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, and the National Institute for Health and Care Excellence (NICE) in the United Kingdom. There is also an input platform to collect patients’ views on individual products and their feedback will be included in the official HTA report.

Cost-effectiveness and Financial Impact Assessment for Sustainable NHI Operation

Cost-benefit analysis and budget impact assessment are also integral parts of the HTA process. The former considers the incremental cost-effectiveness ratio (ICER), which refers to the additional cost per QALY gained. Currently, experts in Taiwan usually refer to the guidelines of the World Health Organization (WHO), which suggests a threshold of 1 to 3 times the GDP per capita (equivalent to $32,000 to $96,000 per QALY in Taiwan) as the ratio to determine whether the money spent on a new product achieves the desired effect. The latter evaluates the financial impact on the NHI system of covering a particular medical product to determine whether a reimbursement is appropriate. The NHIA shares the financial risks associated with coverage through price negotiations with pharma companies and the signing of managed entry agreements (MEAs) to ensure the long-term stability of the NHI system.

Panel Discussion on the Challenges and Opportunities of Health Technology Assessment

During the panel discussion, both experts reiterated that real-world evidence will play an important role in HTA in the future, not only to complement traditional clinical trial data to verify the efficacy of medical products, but also to facilitate regulatory decision-making. However, Prof. Pacifici also cited the situation in the U.S. where many medical institutions have incompatible or non-interoperable EHR systems, which may hinder the application of EHRs in HTA.

Both speakers also pointed out that the lack of harmonized global HTA standards constitutes another big challenge nowadays, particularly in terms of economic impact assessment. Prof. Hsiao explained that the economic impact associated with medical technologies is closely related to healthcare systems in different countries. Taking the healthcare systems of the U.S. and Taiwan as examples, the former is private insurance-based, while the latter adopts a single-payer, universal approach covering every citizen. Such a fundamental difference renders it difficult to adopt a standardized HTA strategy for cost-benefit analyses and reimbursement decisions, requiring individual countries to design their own HTA models based on their healthcare environments, budgets, and societal needs.

Prof. Pacifici added that there are significant differences in healthcare systems, legal frameworks, and regulatory capabilities across the globe, which result in the availability of reference products and standards of care varying from country to country, complicating the harmonization of HTA globally. 

Prof. Hsiao also recognized the importance of international partnerships and reiterated Taiwan’s ties with organizations such as the UK’s NICE and Australia’s PBAC. Through knowledge sharing and collaborative endeavors, Taiwan is steadily fine-tuning the global pharmacoeconomic model to meet the needs of its healthcare system and local patients.

Author

Richard Chau