Cost-effectiveness of recombinant influenza vaccine compared with standard-dose influenza vaccine among adults 50 years of age and older in Hong Kong

This study demonstrates that replacing the standard-dose inactivated influenza vaccine with the recombinant influenza vaccine is cost-effective for adults aged 50 and older in Hong Kong, with the highest cost-effectiveness observed in the 80-and-older age group.

The Gist

Imagine your body is a fortress, and the flu virus is a relentless army of invaders trying to break down the gates. As we get older, the walls of our fortress naturally get a bit weaker, making it harder to fight off these invaders.

For decades, the standard way to protect these aging fortresses has been the Standard-Dose Vaccine (IIV). Think of this as a "standard-issue" shield. It's good, but for older adults, it's often like trying to stop a tank with a paper umbrella. It doesn't always hold up as well as we'd hope.

Recently, scientists developed a new, high-tech shield called the Recombinant Vaccine (RIV). This isn't just a stronger shield; it's built differently. Instead of being grown in chicken eggs (which can sometimes weaken the shield's design), it's built in insect cells, creating a pure, powerful defense that fits the older body much better.

The Big Question:
The researchers in Hong Kong asked a very practical question: Is this fancy, new shield worth the extra money?

They didn't just look at health; they looked at the "wallet impact" for society. They built a giant computer simulation (a "decision tree") to play out thousands of scenarios for three groups of people:

1. The "Younger" Seniors (50+)
2. The "Classic" Seniors (65+)
3. The "Elder" Seniors (80+)

The Results: A Small Price for a Big Win

Here is what they found, translated into everyday terms:

1. The Cost Difference is Tiny
Switching from the standard shield to the high-tech shield costs the average person in Hong Kong only about $5 to $6 USD (roughly 40-50 Hong Kong dollars) more per year.

• Analogy: That's less than the cost of a fancy coffee or a single movie ticket.

2. The Health Payoff is Real
For that tiny extra cost, the high-tech shield prevents many more people from getting sick, going to the hospital, or worse.

• The "80+ Group" is the Star: The study found that for people over 80, this switch is the best deal of all. Because this group is most at risk, the new vaccine saves them the most money in the long run by keeping them out of expensive hospital beds. It's like buying a premium fire extinguisher for the house most likely to catch fire; it pays for itself by preventing a disaster.

3. The "Value for Money" Verdict
In economics, there's a rule of thumb: if a health treatment costs less than three times a country's average yearly income per person, it's considered a "great deal."

• The study found that for all age groups, the new vaccine is well within this "great deal" zone.
• For the 80+ group, the value is so high that the new vaccine is almost certainly the smartest choice for the government's budget.

The "What If" Scenarios

The researchers also played "what if" games (sensitivity analysis) to see if their math would break if things changed.

• What if the vaccine isn't quite as good as we think? Even then, it's still a good deal.
• What if hospital costs go up? The new vaccine becomes even more valuable because it keeps people out of the hospital.
• What if the flu is really bad? The new vaccine shines even brighter.

The Bottom Line

Think of this study as a financial advisor for public health. They looked at the books and said:

"Stop buying the paper umbrella (Standard Vaccine) for our elderly. For just a few dollars more, we can give them a titanium shield (Recombinant Vaccine). It will keep them healthier, keep them out of the hospital, and actually save the system money in the long run. It is the smartest investment we can make."

In short: The new vaccine is a small extra cost for a massive health benefit, especially for the oldest among us. It's a win for health, and a win for the wallet.

Technical Summary

1. Problem Statement

Older adults face a disproportionately high risk of severe influenza complications and mortality. In Hong Kong, the standard inactivated influenza vaccine (IIV), which is egg-based, often induces a weaker immune response in older populations compared to younger, healthier groups, leading to suboptimal protection. While enhanced vaccines, such as the recombinant influenza vaccine (RIV), have demonstrated superior clinical efficacy in reducing illness and hospitalization, there is a lack of local economic evidence to guide policy. Specifically, no study had previously evaluated the cost-effectiveness of replacing IIV with RIV for adults aged ≥50, ≥65, and ≥80 years in Hong Kong to determine if the higher cost of RIV is justified by health gains.

2. Methodology

The study employed a decision tree model to conduct a comparative cost-effectiveness analysis from a societal perspective.

• Target Populations: Three distinct age strata were analyzed: adults aged ≥50, ≥65, and ≥80 years.
• Interventions: Comparison between the Recombinant Influenza Vaccine (RIV) and the Standard-dose Inactivated Influenza Vaccine (IIV).
• Model Structure: The model simulated the natural history of influenza, including:
  • Occurrence of influenza infection.
  • Risk stratification (Normal risk vs. High risk based on chronic conditions).
  • Clinical outcomes: Self-care, outpatient visits, hospitalization (with and without ICU admission), and death.
• Data Sources:
  • Epidemiology: Attack rates, hospitalization rates, and case-fatality rates were derived from Hong Kong-specific surveillance data, meta-analyses, and local studies. Where local data was unavailable, proxies from comparable East Asian settings (e.g., Japan, mainland China) were used.
  • Costs: Direct medical costs (vaccination, self-care, outpatient, hospitalization, ICU) were sourced from the Hospital Authority and Sanofi. Indirect costs (productivity losses) were calculated using age-specific labor force participation rates and median wages.
  • Effectiveness: Vaccine efficacy/effectiveness data were synthesized from randomized controlled trials (RCTs) and test-negative design studies. RIV efficacy was inferred by combining IIV efficacy with the relative efficacy of RIV vs. IIV.
  • Utilities: Quality-Adjusted Life Years (QALYs) were calculated using health utility scores from the 2013 National Health Services Survey in China and local life expectancy data.
• Analysis Metrics:
  • Incremental Cost-Effectiveness Ratio (ICER): Calculated as the difference in costs divided by the difference in QALYs.
  • Willingness-to-Pay (WTP) Thresholds: Based on 1x, 2x, and 3x of Hong Kong's 2024 GDP per capita (USD 54,101; 108,203; and 162,304, respectively).
• Sensitivity Analyses:
  • Deterministic: One-way sensitivity analyses (tornado diagrams) to identify influential parameters.
  • Probabilistic: Monte Carlo simulations (1,000 iterations) to generate cost-effectiveness planes and acceptability curves, accounting for parameter uncertainty.

3. Key Contributions

• First Local Economic Evaluation: This is the first study to provide an age-stratified economic evaluation of RIV versus IIV specifically for the Hong Kong population.
• Age-Stratified Policy Guidance: Unlike previous studies that treated older adults as a monolith, this analysis differentiates between ≥50, ≥65, and ≥80 age groups, revealing that cost-effectiveness improves significantly with age.
• Comprehensive Societal Perspective: The model incorporates both direct medical costs and indirect productivity losses, providing a holistic view of the economic burden.
• Robustness Testing: Extensive sensitivity analyses confirm that the conclusions hold true even when key parameters (such as vaccine efficacy and hospitalization rates) are varied within plausible ranges.

4. Key Results

Base Case Analysis:

• Clinical Impact: Replacing IIV with RIV prevented additional influenza cases, outpatient visits, hospitalizations, and deaths across all age groups.
  • ≥50 years: Prevented 13,322 cases and 17 deaths.
  • ≥65 years: Prevented 10,157 cases and 17 deaths.
  • ≥80 years: Prevented 2,321 cases and 4 deaths.
• Cost and QALYs:
  • ≥50 years: RIV cost an additional USD 5.1 per person and gained 0.00012 QALYs. ICER: USD 40,659/QALY.
  • ≥65 years: RIV cost an additional USD 6.0 per person and gained 0.00021 QALYs. ICER: USD 29,077/QALY.
  • ≥80 years: RIV cost an additional USD 3.2 per person and gained 0.00015 QALYs. ICER: USD 21,092/QALY.
• Cost-Effectiveness: All ICERs were well below the 3x GDP per capita threshold (USD 162,304). Even at the strictest threshold (1x GDP), RIV was cost-effective in 57.8% (≥50), 68.7% (≥65), and 79.2% (≥80) of probabilistic simulations.

Sensitivity Analyses:

• Deterministic: The most influential parameter for the ≥50 and ≥65 groups was the relative vaccine efficacy of RIV vs. IIV. For the ≥80 group, the effectiveness of IIV against hospitalization was most critical. Notably, at the lower bound of IIV effectiveness for the ≥80 group, RIV became cost-saving (negative ICER).
• Probabilistic: At the 3x GDP threshold, the probability of RIV being cost-effective was >96% for all age groups.

5. Significance and Implications

• Policy Optimization: The study provides strong evidence for the Hong Kong government and health authorities to prioritize RIV for older adults, particularly those ≥80 years, where the health gain per dollar spent is highest.
• Budgetary Impact: While RIV is more expensive upfront, the reduction in hospitalizations and productivity losses offsets a portion of the cost, making it a viable investment for public health budgets.
• Generalizability: The findings align with similar studies in the US, suggesting that the cost-effectiveness of RIV is robust across different high-income healthcare systems with similar demographic profiles.
• Limitations: The study acknowledges that some parameters relied on non-local data (e.g., outpatient rates from Japan) and that the decision tree model does not capture herd immunity effects, potentially underestimating the total population benefit.

Conclusion: The study concludes that RIV is a cost-effective alternative to IIV for adults aged ≥50, ≥65, and ≥80 in Hong Kong. The economic case is strongest for the oldest age group (≥80), supporting a policy shift toward preferential use of enhanced vaccines for the most vulnerable populations.