"We must discuss the protective efficacy of flu shots for seniors"

Restructuring of the protective strategy for the elderly is needed

Cost-effectiveness of adjuvanted vaccination has been confirmed

"Given that the current policy's strength lies in expanding vaccination rates, the future challenge is to enhance protective efficacy. It is now time to discuss not only vaccination coverage but also focus on which vaccines can provide more substantial protection for the elderly; in other words, discussing the 'quality of protection'."

Professor Min Joo Choi of the Division of Infectious Diseases at Korea University Guro Hospital 

Professor Min Joo Choi of the Division of Infectious Diseases at Korea University Guro Hospital proposed this direction for influenza immunization policies for the elderly.

Influenza is a major respiratory infectious disease, causing 3 to 5 million cases of severe illness and up to 650,000 deaths globally each year. In particular, older adults aged 65 and above are classified as a high-risk group facing the highest jeopardy of hospitalization, severe complications, and mortality.  

In South Korea, approximately 70% of influenza-related hospitalizations and over 80% of associated deaths are concentrated among the elderly, whose healthcare expenditure burden also ranks as the highest across all age demographics.

Despite high vaccination rates, the disease burden among older adults remains significant. Due to immunosenescence, the antibody-producing capacity of the elderly post-vaccination is known to range from 40% to 80% of that seen in healthy adults. This implies that conventional standard-dose vaccines may fail to elicit a sufficient immune response in this cohort.

Major developed countries, including the United States, the United Kingdom, and Australia, already preferentially recommend adjuvanted or high-dose influenza vaccines over standard-dose formulations for individuals aged 65 and older. The Korean Society of Infectious Diseases (KSID) also aligned with this direction in its 2023 adult immunization guidelines.

Related to this issue, Professor Choi conducted a comparative study evaluating the cost-effectiveness of an MF59-adjuvanted quadrivalent influenza vaccine (aQIV) among older adults aged 65 and older in South Korea and Taiwan. The findings were recently published in the international peer-reviewed journal Vaccine. The study carries significant clinical and economic weight as a domestic research study concurrently evaluating the clinical efficacy and pharmaco-economic profiles of advanced senior vaccine strategies.  

Cost-effectiveness and health benefits…what's the significance of this economic analysis?

Regarding the implications of the economic analysis spanning cost-effectiveness and health utilities, the study revealed that although the adjuvanted vaccine incurs higher upfront acquisition and administration costs than standard-dose options, it represents a highly cost-effective intervention when accounting for downstream medical cost savings from reductions in influenza-related hospitalizations, complications, and mortality.

Notably, transitioning from standard-dose to adjuvanted vaccines yielded an Incremental Cost-Effectiveness Ratio (ICER) of $2,200 per Quality-Adjusted Life-Year (QALY). This figure sits vastly below the standard domestic willingness-to-pay (WTP) threshold, which is typically tied to South Korea's per capita Gross Domestic Product (GDP) of approximately $36,130. This demonstrates that the derived health utilities significantly outweigh the incremental vaccination expenditures.

​"Our analysis indicates that while acquisition costs increase compared to standard-dose vaccines, a substantial portion of this incremental cost is offset by the mitigation of downstream expenses associated with hospitalizations, complications, and deaths," Professor Choi stated. "We have confirmed that the health benefits gained relative to the added expenditure are highly substantial."  

Cost-effectiveness analysis does not simply compare acquisition prices across vaccine products; rather, it is a health economics methodology that evaluates the holistic value of an immunization strategy by incorporating medical cost offsets alongside quality-of-life improvements derived from a lower burden of preventable infections, clinical complications, hospitalizations, and deaths.

This study included the specific demographic structures, vaccine coverage rates, and healthcare utilization patterns of the elderly cohorts in both South Korea and Taiwan, confirming the stability and robustness of the outcomes through exhaustive sensitivity and scenario analyses. The parameters exerting the greatest influence on the final health economic outcomes were relative vaccine effectiveness (rVE) and vaccine pricing.

​"Even within our sensitivity analyses, relative vaccine effectiveness emerged as the most critical variable, while vaccine cost also exerted a major influence on the overall economic outcomes," Professor Choi explained.

However, Professor Choi urged caution when interpreting comparisons against high-dose influenza formulations.

​"Although our current study reports the adjuvanted vaccine as a cost-saving strategy, evidence directly comparing the two enhanced formulations remains limited," Professor Choi noted. "Any comparative projections against the high-dose vaccine should be viewed as purely exploratory. The significance of this research lies in validating the distinct clinical and economic value proposition of the adjuvanted vaccine over standard-dose options."

Analysis expands beyond disease burden to economic viability

This analysis serves as a sequential follow-up expanding upon the senior influenza immunization strategy research published by Professor Choi in 2022.

In that preceding study, the clinical burden of disease, including total infections, complications, hospitalizations, and deaths, was compared across standard-dose quadrivalent, high-dose quadrivalent, and adjuvanted quadrivalent vaccine strategies targeting the domestic elderly population aged 65 and above. Historical data demonstrate that immunization strategies using enhanced-immunogenicity formulations can substantially reduce the clinical burden of disease in older adults.

To discuss an actionable immunization policy, evidence that extends beyond isolated clinical efficacy is required. To integrate an advanced vaccine strategy into national public health frameworks such as the National Immunization Program (NIP), a robust pharmaco-economic evaluation is concurrently mandatory to substantiate the health utilities generated relative to the incremental fiscal investment.

​"At the time of our 2022 study, real-world clinical experience with adjuvanted and high-dose vaccines within South Korea was highly constrained, and there was significant uncertainty surrounding product pricing, which is a critical variable in any health economic assessment," Professor Choi stated. "As a result, executing a highly reliable cost-effectiveness analysis was technically challenging back then."

Professor Choi added, "As these advanced formulations subsequently became commercially accessible in South Korea, we were able to establish highly realistic pricing assumptions, which ultimately provided the foundation for this comprehensive study."

The study's distinguishing feature is conducting parallel analyses of both South Korea and Taiwan. While historical economic models have predominantly focused on Western populations across North America and Europe, this research actively incorporates the specific demographic architecture and healthcare realities of two prominent Asian nations transitioning into super-aged societies.

​"Although South Korea and Taiwan present distinct variations in senior demographics, influenza epidemiology, and healthcare utilization patterns, both nations share the critical commonality of being super-aged societies," Professor Choi evaluated. "This study bridges the gap in Western-centric data, providing concrete evidence to guide immunization policies that reflect the unique epidemiological characteristics and healthcare environments of the Asian region."  

The need to expand immunization strategies centering around elderly

Professor Choi clarified that, because the research evaluated the general senior population aged 65 and older, the outcomes are not limited to narrow sub-segments of ultra-high-risk patients. However, she noted that these baseline analytical insights for the broader elderly cohort can serve as a foundational benchmark for future discussions regarding risk-stratified or risk-based vaccination paradigms.

​"The strategic center of gravity for public health policies must transition from merely boosting raw coverage rates toward preventative strategies that actively minimize hospitalizations and severe clinical complications," she emphasized. "Over the long term, we require immunization frameworks that evaluate chronological age in tandem with individual patient risk profiles."

She further noted, "If the defining achievement of our current policy is vaccination expansion, our upcoming project must be the optimization of protective efficacy. We have reached a critical junction where public health discussion should extend past quantitative uptake metrics to focus on qualitative clinical protection; specifically, identifying which vaccine platforms offer sufficient protection for our aging population."  

To date, South Korea’s elderly influenza immunization policy has achieved significant operational success in terms of quantitative coverage. Driven by the National Immunization Program (NIP), vaccine accessibility for older adults aged 65 and above has been significantly enhanced, maintaining high population-wide uptake rates.

However, elevated coverage rates do not automatically eliminate the clinical burden of disease among seniors. Due to immunosenescence, older individuals frequently exhibit suboptimal immune responses following vaccination, leaving them vulnerable to post-vaccination breakthrough infections, influenza-related hospitalizations, and secondary complications. Public health experts confirm that despite robust clinical uptake, the burden of severe morbidity and hospitalization within the senior demographic remains a critical public health challenge.  

Professor Choi suggested that policymakers could explore a phased expansion of the prioritized immunization cohort to include adults aged 50 to 64. This specific demographic represents a lifecycle phase in which the prevalence of chronic underlying comorbidities begins to climb, making early reinforcement of preventive strategies prior to advanced age a highly rational policy consideration.

In addition, Professor Choi proposed integrating adult vaccinations within the formal National Health Insurance (NHI) reimbursement as a key long-term project.

Professor Choi noted, "Currently, systematically tracking adult vaccination rates alongside real-world effectiveness remains challenging. We must establish a tracking infrastructure utilizing national health insurance claims databases to evaluate immunization status and clinical real-world outcomes continuously." 

Professor Choi concluded by suggesting that "We need to design precision-targeted adult immunization policies based on accumulated real-world data."