NCHR Testimony at the Vaccines and Related Biological Products Advisory Committee Meeting
Thank you for the opportunity to speak today. My name is Dr. Megan Polanin. I am a Senior Fellow at the National Center for Health Research, and I previously trained at Johns Hopkins University School of Medicine. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from industry, so I have no conflicts of interest.
[Respiratory Syncytial Virus (RSV) is a common respiratory virus that has the potential to cause serious symptoms in infants. Approximately 25-40% of affected infants and children develop symptoms of bronchiolitis or pneumonia, and 5-20% will require hospitalization. For children younger than 1 year, it is the most common cause of infection and inflammation in the lungs and the leading cause for hospitalization. In fact, most children are infected at least once by the time they are 2-years-old. Though children who have been infected have partial immunity, there remains a life-long potential for reinfection.
Currently, there are very limited interventions. Ribavirin, the only U.S. licensed drug approved to treat RSV in infants, is not recommended for routine use and has conflicting efficacy evidence. There is also a passive immunization, Palivizumab, that works by helping the child’s immune system to temporarily slow or stop the spread of RSV in the body. The American Academy of Pediatrics currently only recommends this type of vaccine for infants born prematurely and those with certain heart or lung diseases. We fully support the development of new vaccines to prevent RSV disease in seronegative infants.
However, due to the history of vaccine-induced enhanced respiratory disease (ERD), it is important to focus on reducing – if not eliminating – the risk of ERD. We concur with the FDA that this pursuit “must be undertaken with an abundance of caution.” Thus, this Advisory Committee’s discussion about how to optimize safety when conducting preclinical and clinical studies is imperative.]
The recommendations this Advisory Committee makes will likely affect the progression of current and future vaccine candidates, and ultimately, the safety of these products for infants in very early stages of development.
We urge the FDA to recommend extreme caution and not test these vaccines in children before there is a reasonable level of certainty regarding the product’s safety. The World Health Organization (WHO) recommended that the safety and efficacy of vaccines must first be determined in healthy adults and then individuals who have experienced RSV before testing in infants who have never experienced RSV. The FDA and NIH recommended that, in order to test vaccines in seronegative infants, virus replication and reactogenicity profiles must be “acceptable.” We agree. We strongly encourage this Committee to determine the specific profiles that are deemed safe.
Currently, the methods for testing RSV vaccines are limited. Preclinical studies using animal models offer preliminary evidence of effectiveness and safety to inform the appropriateness of introducing vaccines in humans, but cannot completely predict either in humans. Clinical trials in adults can be helpful; however, adults have likely previously experienced multiple RSV infections and adults also have the advantage of a more mature immune system. Although clinical trials in seropositive children can provide information about vaccine reactogenicity, such studies are not conclusive regarding the risk of ERD in seronegative infants.
Due to these significant limitations, once vaccines are deemed sufficiently safe to test on seronegative infants, it will also be important to conduct long-term studies of infants in order to determine whether the vaccine protects infants and young children through a critical period of development. The World Health Organization recommended that follow-up for clinical studies should occur through two RSV seasons in order to gather more data regarding efficacy and endurance of the vaccine. We agree. Such long-term studies are absolutely crucial to ensure that the vaccine is not causing long-term health effects that would otherwise go unrecognized.
In addition, all infants 6 months or younger are recommended to receive at least 5 other vaccines. Thus, testing of this particular vaccine should consider how it might interact with other routine immunizations.
Like any public health strategy, a vaccine’s risks must be weighed against its benefits. Given all the mistrust of vaccines in a substantial minority of Americans, it is especially important to determine how effective the vaccine is at preventing RSV and for how long. If the vaccine does not protect infants and young children through a vulnerable period of development or contributes to negative side effects (such as ERD), then the risks of this vaccine are too high. Given that there have been significant issues with past RSV vaccines, the FDA should ensure that they do not recommend this vaccine prematurely, especially for such a vulnerable population.
In summary, we strongly urge this Advisory Committee to prioritize patient safety and urge the FDA to establish high standards for preclinical and clinical studies.
Centers for Disease Control and Prevention (2017, March 7). Respiratory Syncytial Virus Infection (RSV). Retrieved from https://www.cdc.gov/rsv/.
Food and Drug Administration (2017, May 17). FDA Briefing Document: Development of Vaccines for Prevention of Respiratory Syncytial Virus (RSV) Disease in RSV-Naïve Infants. Retrieved from https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM556495.pdf.
Mayo Clinic. (2014, July 9). Respiratory syncytial virus (RSV). Retrieved from http://www.mayoclinic.org/diseases-conditions/respiratory-syncytial-virus/basics/definition/con-20022497.
Vancouver First Aid. (2016, November 17). What is RSV? Retrieved from https://vancouverfirstaid.ca/what-is-rsv/.