Alternatives Needed for Evaluating RSV Vaccine Impact on Asthma, Wheeze

Justin R. Ortiz, MD

Investigators would like to be able to study the effect of candidate respiratory syncytial virus (RSV) vaccines on recurrent pediatric asthma and wheezing during clinical trials, but a new analysis has found that an alternative is needed because of the large sample sizes required to demonstrate effectiveness.

RSV is a common virus that infects the respiratory tract and is easily spread through sneezing and coughing. Most people will only experience a cold that comes and goes, but for some, especially young children, an infection can be potentially life threatening. Premature infants, babies under 6 months old, children under 2 years of age with chronic lung or heart disease, and those with weakened immune systems, are particularly vulnerable according to the Centers for Disease Control and Prevention (CDC).

In addition, infections during the first months of life can be severe, with some studies showing an association between RSV infection as a young infant and the development of wheezing associated disorders later in life.

“Some, but not all, kids under 5 with recurrent wheezing will have asthma latter,” said co-author Justin R. Ortiz, MD, associate professor at the University of Maryland School of Medicine. “Currently, there are no vaccines against RSV, but many are under development. For public health decision makers and clinicians, it would be important to know whether an RSV vaccine could prevent this condition, in addition to lowering RSV infections.”

Using systematic review and meta-analysis, investigators defined vaccine efficacy, allocation ratio, rate of early severe RSV illness, risk of recurrent wheezing at age 3, and increased risk of RSV infection on recurrent wheezing to compute vaccine trial effect sizes.

Out of the 81 scenarios, 57 were the most plausible, where the lowest sample size required that would detect significant reductions in recurrent wheezing was 6196 mother/infant pairs per trial arm. But of the plausible scenarios, 75% need more than 31,060 mother/infant pairs, while 47% need over 100,000 mother/infant pairs. Studies where outcomes extend to age 5 would need even larger sample sizes.

Ortiz says that vaccine and infectious disease experts have called for clinical trials of candidate respiratory syncytial virus vaccines to include long-term follow-up to assess vaccine effect on recurrent wheeze or asthma, but their study shows that would be impractical because of the necessary sample size to demonstrate effectiveness.

“Observational post licensure studies using administrative databases, such as HMO records linking RSV vaccine receipt to recurrent wheeze or asthma diagnoses may be much more efficient to assess the potential impact of future RSV vaccines on these respiratory conditions,” said Ortiz.

The study, “Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: a sample size analysis,” was published in Vaccine.