Table 2.

Influenza vaccine surveillance outside the EU.

Country	Initiative	Characteristics (including strengths and limitations)	Example of applications
US	VAERS	Health-care providers and vaccine recipients can report any significant health problem following vaccination. VAERS data are monitored to detect new, unusual or rare adverse events and possible safety signals that warrant further evaluation in other studies. Approximately 30,000 VAERS reports are made each year, of which 85−90% are classified as mild (events such as fever, sore arm, and crying or mild irritability) and the remainder are classified as serious, but are rarely proven to be caused by the administered vaccine.28 Strengths: its extensive scope and power to detect rare events. Limitations include under- or over-reporting, biased reporting, inconsistency in reporting, inability to assess causality or confirm diagnosis, and inability to calculate the incidence or prevalence of an AEFI.27	Annual rapid cycle analysis is used to perform near real-time surveillance of influenza vaccine safety, with weekly monitoring of vaccination records and the occurrence of pre-specified adverse events.27 Traditional, retrospective vaccine safety studies are also conducted based on issues identified by the medical literature or reports to VAERS. Following reports in Australia, the CDC and FDA instigated enhanced surveillance for febrile seizure in children for all influenza vaccines; VAERS records were monitored daily for all possible febrile seizure cases in children <5 years, whilst VSD investigators performed weekly rapid cycle analysis for seizures following influenza vaccine.35
Canada	CANVAS	The main outcomes of interest are the occurrence of a new health problem or exacerbation of any existing condition severe enough to cause work or school absenteeism, prevent daily activities or require a medical consultation. Over 20,000 individuals participate in active surveillance each year; events occurring at a rate of <1 per 1000 can be detected. Participants receive a web-based survey 8 days after vaccination and any medically attended events are followed up by telephone call.29 In 2016, 29,252 adults and parents of immunized children were enrolled in the system, with a survey response rate of 67%.	Evaluation of >20,000 health care workers vaccinated during the 2011 and 2012 influenza seasons, via online questionnaire sent 8 days after vaccination.36 Response rate of 69%; participants who reported a severe event were contacted by a nurse for validation purposes. Questionnaire was able to detect events at a frequency of 1 per 1000.36
Australia	Adverse Drug Reactions Unit	Notifications are either sent directly or via state health departments. Reports are triaged and reviewed and a causality rating is assigned to each AEFI. Serious, severe, or unexpected events are referred to the Medical Officer. All notifications are reviewed at 6 weekly meetings.	Between January 2000 to September 2002, the reporting rate of AEFI with seasonal influenza vaccine was 3.3 per 100,000 doses in adults 40−64 years of age and 1.4 per 100,000 doses in adults ≥65 years.30 Injection site reactions and allergic reactions were most commonly reported.
	SAEFVIC	Enables regional voluntary reporting in the state of Victoria. Established in 2007 and comprises a passive surveillance system coupled with clinical services.37	AEFVIC highlighted a possible increase in allergy-related AEFI with 2015 seasonal trivalent influenza vaccines in Australia. An investigation identified a relative risk for allergy-related AEFI of 2.4 per 100,000 vaccine doses in 2015; almost double that seen in 2011−2014 (relative risk of 1.3/100,000), with no difference between vaccine brands.38 These findings highlighted the potential for changes in reactogenicity following an update of the influenza vaccine strains, emphasising the importance of continued pharmacovigilance.38
	WAVSS	Established in 2011 (built upon the SAEFVIC model) to monitor vaccine safety.39 Enables regional voluntary reporting of suspected AEFI from both the public and Health-care providers in the state of Western Australia.	Develops an annual report of brand-specific AEFI in Western Australia.
New Zealand	CARM	Reports are made on a paper form by post and can be submitted by anyone, although notification by a health care professional is preferred.31 Community doctors submit 65% of reports, hospital doctors submit 17% and pharmacists submit 2%. The Medicines Adverse Reactions Committee meets four times a year to review published material, all fatal reports and selected reports of significant, unusual or serious reactions reported to CARM.	A review of adverse events with inactivated vaccines reported to CARM between 1990 and 1995 found that more reports of fever were made following Hib (16/100,000) vaccination than following hepatitis B (2/100,000) or influenza (1/100,000) vaccination.40
Brazil	ANVISA	Recent enhanced pharmacovigilance initiative to encourage close collaboration between regulators, public health institutes, health care professionals and manufacturers to improve reporting and analysis of AEFI for influenza vaccines.32,33 Instructional material to facilitate spontaneous reporting is provided to vaccinees via vaccination clinics, with emphasis on the importance of detecting and reporting AEs to ANVISA.	The objective is to collect AEFI with seasonal influenza vaccines and generate regular reports of adverse events.
Global	WHO survey	Global survey to identify active and passive AEFI surveillance systems for pregnant women and infants. Involves 154 representatives from National Pharmacovigilance Centers and a convenience sample of 31 vaccine safety experts were invited to complete an online survey.34	Responses were received from 51 individuals in 47 countries; responding countries represented all WHO regions and included low-, middle- and high-income countries.34 Eleven countries had active surveillance systems for detection of serious AEFI in pregnant women or their infants, including six low- or middle-income countries. Passive surveillance systems were identified in 39 countries whose birth cohorts comprise 56% of the global annual birth cohort, including 23 low- or middle-income countries.34

AEFI: adverse event following immunization; ANVISA: Agencia Nacional de Vigilancia Sanitaria; CANVAS: Canadian National Vaccine Safety; CARM: Centre for Adverse Reactions Monitoring; SAEFVIC: Surveillance of Adverse Events Following Vaccination in the Community; VAERS: Vaccine Adverse Event Reporting System; WAVSS: Western Australian Vaccine Safety Surveillance