Timeliness of Signal Detection for Adverse Events Following Influenza Vaccination in Young Children: A Simulation Case Study

"Actively seeking the input of consumers renders the gathering of AEFI data accessible to the public and potentially increases trust."

Until recently, post-marketing vaccine safety surveillance in Australia has been passive, with several well-documented limitations resulting in substantial delays. This was illustrated in 2010 following an increase in febrile seizures in young children ultimately determined to be associated with one brand of trivalent influenza vaccine (TIV), Fluvax (CSL Biotherapies). In response, several independent adverse events following immunisation (AEFI) surveillance tools were developed and were ultimately incorporated into a national, active vaccine safety surveillance system under the AusVaxSafety initiative. This simulation study asks how soon after the start of seasonal influenza vaccination would the current AusVaxSafety signal detection system have detected a safety signal, had it been operating in 2010.

The majority of participants in AusVaxSafety are enrolled using the opt-out, electronic data monitoring platform SmartVax, which integrates with practice management software to automatically send SMS (short messaging service, or text)surveys to vaccine recipients or their caregivers as a part of routine care after vaccination. Enrollees receive an SMS from their medical provider 3-5 days following vaccination asking whether any AEFI were experienced and whether medical attention (MA) was sought in relation to the AEFI, as well as a further text containing a link to a brief smartphone survey enquiring after the nature, severity, and duration of the AEFI. The goal is to facilitate rapid appropriate action in the event of any safety signals.

The study simulated solicited responses from caregivers who would have received an SMS survey about adverse events experienced following seasonal influenza vaccination of their children aged 6 months to 5 years. Figures 1-6 in the paper show the simulated 2010 performance of the AusVaxSafety signal detection system under various conditions. In short, the study finds that AusVaxSafety signal detection as it currently operates would have, in all likelihood (>90% probability), delivered a safety signal during March 2010, the first month of vaccine deployment, based on solicited reports of fever and MA following influenza vaccination administered to Western Australia (WA) children 6 months to 5 years of age. Even the most conservative of the scenarios considered indicates that a signal would have been generated, on the basis of reported fever or MA, by March 28 2010, 4 weeks before distribution of vaccine was suspended by the Australian regulator on April 23 2010. In the intervening period, there were more than 50 further presentations to WA emergency departments for febrile convulsions associated with Fluvax and the highly publicised death of a 1-year-old child with febrile convulsions on April 8 2010.

The researchers note that "Vaccine hesitancy and public concern about vaccine safety is a global issue. In Australia, consumer confidence in influenza vaccination diminished after the safety issues with the 2010 influenza vaccine in children....By having active surveillance, which directly surveys the consumers in near real time and makes the results publicly available, active surveillance systems address transparency concerns and contribute to public confidence in the whole immunisation programme..."

The authors conclude that active vaccine safety surveillance leading to rapid detection of a safety signal may have resulted in earlier suspension of Fluvax from the childhood vaccination programme, potentially preventing many febrile convulsions and maintaining public confidence in influenza vaccination for young children.