RSV Prevention in Infants: Promising Products, But at What Cost?

In this month’s issue of Pediatrics, Hutton et al present 2 important studies evaluating the health and economic impacts of maternal vaccination with the RSVpreF vaccine and the immunization of infants with nirsevimab, a monoclonal antibody, for the prevention of respiratory syncytial virus (RSV) disease in infants.^1,2  RSV remains the leading cause of hospitalization in infants, resulting in significant health care costs, and, in some cases, long-term complications and death.³  The findings from these studies were presented to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) and were instrumental in the decision-making regarding recommendations of these products.^4,5 

The primary objective of the 2 studies was similar: To assess the cost-effectiveness of these products for infants in their first RSV season. The authors also examined other important outcomes, such as expected hospitalizations averted at a national level and the number needed to immunize to prevent an RSV-associated hospitalization. Because these studies were performed by the same group of health economists, the methods and the inputs to the models were similar. This is important because, when different groups perform their own models regarding the same product, results are often drastically different.⁶  In this case, we have a reasonable apples-to-apples comparison of the 2 products.

The findings regarding maternal vaccination with RSVpreF suggest that targeted vaccination during pregnancy, specifically timed to coincide with the RSV season, can substantially reduce the incidence of RSV-associated lower respiratory tract infections in infants at a reasonable cost to society. The analysis shows that the cost-effectiveness of this intervention is most favorable when the vaccine is administered between September and January, aligning with the peak RSV season. Under this seasonal strategy, assuming a cost of $295 per dose of vaccine plus administration costs, the incremental cost-effectiveness ratio (ICER), essentially a metric used to help understand if an intervention yields sufficient value to justify its cost, is calculated at $163 513 per quality-adjusted life year (QALY) saved, compared with $396 280 per QALY for year-round vaccination.

The study focused on nirsevimab similarly showed that it is highly effective in preventing RSV-related hospitalizations and other severe outcomes, with an ICER of $153 517 per QALY saved assuming a cost of $495 in the private sector and $395 through the Vaccines for Children program. The investigators also examined cost effectiveness for high-risk infants in their second season. In this analysis, the ICER was highly dependent on the underlying risk of hospitalization. For average risk children, the ICER was $1.6 million per QALY gained, but with a 10-fold increased risk of hospitalization, the ICER is much less at $308 468 per QALY gained. This portion of the analysis was highly influential in crafting the current recommendations for young children in their second season, limiting the recommendation only to the highest-risk children.

For maternal RSVpreF vaccination, the model projected that vaccinating approximately half of all pregnant individuals in the US birth cohort would prevent 45 693 outpatient visits, 15 866 emergency department visits, and 7571 hospitalizations related to RSV each year. The number needed to vaccinate to prevent 1 hospitalization because of RSV LRTI was calculated at 234. For nirsevimab, the results for these secondary outcomes were similar, with the model projecting 7654 hospitalizations averted annually. The number needed to vaccinate for nirsevimab to prevent 1 RSV hospitalization was 128.

A critical aspect to consider in this discussion is the cost associated with these products. Both RSVpreF and nirsevimab are notably expensive. The cost of a single dose of RSVpreF is ∽$295, whereas the cost of nirsevimab is $495.⁷  These costs are considerably higher than those of other routinely administered vaccines, such as the Haemophilus influenzae type b vaccine, which costs about from $12 to $30 per dose in the private sector, or the annual influenza vaccine, which ranges from $19 to $32 per dose.⁷  To put that in the perspective of ICERs, many of the vaccines in the childhood immunization schedule are actually cost-saving to society, meaning there are no additional costs per QALY to society. The higher costs associated with RSVpreF and nirsevimab are among the largest drivers of their ICERs. For instance, in the sensitivity analysis for nirsevimab, if the cost per dose were $50, it would be cost saving. Although it is unlikely we will see the costs drop to that extent in the coming years, with several other RSV-prevention products in the pipeline,⁸  it is conceivable that market forces will bring down the remarkably high costs of these products.

To be clear, ACIP and the American Academy of Pediatrics do not use cost-effectiveness analysis as the only metric by which vaccine recommendations are made. In fact, it is only 1 piece of the decision-making process, or Evidence-to-Recommendations framework, that ACIP considers.⁹  That framework states that consideration should be given to whether a vaccination intervention is a “reasonable and efficient allocation of resources” and recommends considering any available cost-effectiveness research. Other factors, such as safety, effectiveness, and public health burden often play a larger role in the considerations. But how does one determine what is “reasonable and efficient?” Although there is guidance from the Centers for Disease Control and Prevention on presentation of health economic analyses to ACIP,¹⁰  the United States has no threshold for what is considered “too much” when considering ICERs in vaccine recommendation considerations, and few other countries do either. The World Health Organization suggests a threshold of one- to threefold of the per-capita gross domestic product of the country as a threshold for health care interventions, but that is not specific to vaccines. Using this metric, the US gross domestic product per capita is roughly $76 000,¹¹  so the ICERs found in these studies are in line with that. However, there are ethical problems with using thresholds like this when making policy recommendations. For example, using a specific threshold may lead to accepting a less effective intervention to save money.

In summary, the studies by Hutton et al provide critical information to policymakers regarding the use of these highly promising RSV prevention tools. Both maternal vaccination with RSVpreF and the administration of nirsevimab demonstrate significant potential in reducing the burden of RSV. The high costs associated with these products will require those administering these vaccines, such as pediatricians, family physicians, hospitals, and health systems, to be meticulous in their ordering, inventory, and billing management practices to make them feasible to deliver in real-world settings. If these immunizations can be successfully delivered broadly, we will then see the dramatic reductions in the burden from this highly morbid pathogen that these products offer.

ACIP

Advisory Committee on Immunization Practices

ICER

incremental cost-effectiveness ratio

QALY

quality-adjusted life year

RSV

respiratory syncytial virus