Harmonizing the collection of solicited adverse events in prophylactic vaccine clinical trials

Introduction: During the clinical development of a vaccine, study participants are monitored for the occurrence of adverse events (AEs) over a defined period post-vaccination to assess the safety of prophylactic vaccines. Among the safety data collected, a standard practice in prophylactic vaccine clinical trials involves collecting reactogenicity data through daily AE solicitation of pre-defined sets of symptoms (i.e. solicited AEs). Areas covered: This paper aims to propose recommendations to improve and harmonize the collection of active AE solicitation in prophylactic vaccine clinical trials. Expert opinion: We recommend using limited lists of solicited AEs adapted to the vaccine technology and target population. While the US Food and Drug Administration toxicity grading scale is commonly used in adolescents/adults, harmonizing grading criteria in infants/children would facilitate the comparison of vaccines' safety profiles. Solicited systemic AEs should not systematically be considered causally related to vaccination. Collection of solicited AEs should occur in cohorts of a maximum of 1,000 vaccinated participants, as larger cohort sizes do not improve substantially the precision of AE incidence. The incidence of daily solicited AEs should be compared with a control group for improved interpretations of their clinical relevance. These suggestions would improve the characterization of safety profiles of vaccines.