Real-world evidence of quadrivalent meningococcal conjugate vaccine safety in the United States: a systematic review

Two quadrivalent meningococcal conjugate vaccines (MenACWY) that prevent invasive meningococcal disease caused by N. meningitidis serogroups A, C, Y, and W have been licensed in the U.S. in the past 10–15 years. We systematically reviewed published studies conducted in the U.S. to evaluate the real-world safety evidence of meningococcal conjugate vaccines. We performed a literature search in PubMed of publications from 01/01/2005 to 02/29/2020 and identified 18 studies meeting inclusion criteria. Populations included high-risk persons aged 2 months to 10 years, adolescents/adults aged ≥11 years, pregnant populations, and hematopoietic cell transplant recipients. We extracted information about study setting, study design, exposure, outcomes, comparison group, follow-up/look back period, study population, sample size, available demographic/indication information, results, key conclusion, and reference. These published studies found no new significant safety concerns related to MenACWY. Consideration for future research includes a post-licensure safety evaluation of a new MenACWY product approved in April 2020

Challenges in Phase 4 post-licensure safety studies using real world data in the United States: Hepatitis B vaccine example

Post-licensure vaccine safety studies are essential to identify adverse events that may not have been detected in pre-licensure clinical trials and to address questions that arose during the pre-licensure phase. These studies are increasingly conducted using real-world data collected as part of routine health care delivery. However, design of post-licensure vaccine safety studies involves many pragmatic and scientific decisions, which must be made while balancing diverse stakeholder opinions. Challenges include selecting exposure and comparison groups, deciding on the most appropriate outcome, determining sample size and length of follow-up time, and other analytic considerations. As an example of this process and to inform other post-licensure vaccine safety studies in real-world settings, we discuss our experience with design of an FDA-required Phase 4 post-licensure safety study of a hepatitis B vaccine in a large integrated health care organization in the United States