Summary

A medRxiv preprint estimates that ensitrelvir post-exposure prophylaxis for high-risk household contacts in Japan would cost JPY 16.82 million per QALY gained. The model found this was unlikely to meet Japan’s JPY 5 million-per-QALY cost-effectiveness threshold.

A model-based analysis of ensitrelvir as post-exposure prophylaxis for high-risk household contacts in Japan estimates that the treatment would be unlikely to offer good value at the country’s benchmark cost-effectiveness threshold. The medRxiv preprint calculated an incremental cost-effectiveness ratio of JPY 16.82 million per quality-adjusted life-year, or QALY, gained—more than three times the JPY 5 million-per-QALY threshold used in the analysis.

Ensitrelvir is being evaluated here as a medicine given after household exposure to reduce the risk of developing symptomatic COVID-19. The analysis used symptomatic-disease risks from the SCORPIO-PEP trial and combined them with Japanese evidence on hospitalisation, mortality, healthcare costs, quality of life and life expectancy.

Contents

What the model evaluated

The researchers developed a decision-analytic cost-utility model from the perspective of Japan’s public healthcare payer. It compared high-risk household contacts receiving ensitrelvir after exposure with a strategy without the prophylactic treatment.

The model used trial risks of symptomatic COVID-19 through day 10. It then linked prevention of symptomatic disease to longer-term outcomes using Japanese data on hospitalisation, mortality, costs, quality of life and life expectancy. The analysis included deterministic, probabilistic, structural, subgroup and threshold analyses to examine how the result changed when key inputs varied.

A QALY combines length and quality of life into one measure: an additional year in perfect health equals one QALY, while a year lived with reduced health-related quality of life counts for less. The incremental cost-effectiveness ratio, or ICER, expresses the additional cost required to gain one additional QALY compared with the alternative strategy.

The economic analysis was based on published aggregate data and publicly available reimbursement information. The authors also made the complete Python model and analysis outputs available through a public repository.

The main cost-effectiveness result

For each exposed contact, ensitrelvir increased estimated costs by JPY 54,945 and produced a gain of 0.003267 QALYs. Those values generated an ICER of JPY 16.82 million per QALY gained.

In the probabilistic analysis, none of 10,000 simulations was cost-effective at the JPY 5 million-per-QALY threshold. When the researchers applied the overall trial relative risk to the higher-risk baseline population, the ICER increased to JPY 19.24 million per QALY.

The model also calculated a drug acquisition-cost threshold of JPY 11,021 per course. This is the per-course acquisition cost identified by the analysis in relation to its cost-effectiveness benchmark; the source does not provide a separate current acquisition price.

How the estimate changed under different assumptions

The result was sensitive to how long the model assigned a post-acute reduction in quality of life after symptomatic COVID-19. Restricting that utility loss to six months produced an ICER of JPY 23.62 million per QALY. Halving the utility loss raised the estimate to JPY 26.76 million per QALY, while excluding it entirely raised the ICER to JPY 65.51 million per QALY.

The SCORPIO-PEP trial recorded no COVID-19-related hospitalisation or death. Consequently, the analysis modelled downstream benefits through prevention of symptomatic disease rather than using trial-observed reductions in severe outcomes. The authors describe the severe-outcome benefits as model-based extrapolations.

The findings therefore apply specifically to the Japanese public healthcare payer perspective, the high-risk household-contact population represented in the model and the costs, utilities and clinical assumptions used by the researchers. At those current Japanese costs and under the study’s benchmark, the preprint estimates that ensitrelvir post-exposure prophylaxis would not be a cost-effective strategy.

Sources