Brand-specific enhanced safety surveillance of GSK's Fluarix Tetra seasonal influenza vaccine in England: 2017/2018 season.

In compliance with the European Medicine Agency guidance to detect any potential safety concerns associated with influenza vaccination, an enhanced safety surveillance study was conducted in England during the 2017/18 influenza season. The primary objective was to estimate the incidence rates of adverse events occurring within seven days of vaccination with Fluarix Tetra. In nine General Practices, seasonal influenza vaccine was administered to patients according to local guidelines. Events following immunization were collected using customized cards (enhanced component) combined with electronic health records [EHRs] (EHR component) to estimate incidence rates of adverse events experienced post vaccination. The study ran from 01-Sep-2017 to 30-Nov-2017. A total of 23,939 subjects were vaccinated of whom 16,433 received Fluarix Tetra. The cumulative incidence rates of adverse events of interest for Fluarix Tetra were 7.25% [95% CI, 5.95-8.73] for events reported by card alone, and 9.21% [95% CI, 7.37-11.34] when combined with EHR data. The type and frequency of events reported were consistent with the Fluarix Tetra Summary of Product Characteristics. The study supports and confirms the safety profile of Fluarix Tetra. ClinicalTrials.gov number: NCT03278067.

Enhanced Safety Surveillance of Influenza Vaccines in General Practice, 2015-16: Feasibility Study.

BACKGROUND: The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced real-time surveillance of seasonal influenza vaccination. The EMA has specified a list of adverse events of interest to be monitored. The EMA sets out 3 different ways to conduct such surveillance: (1) active surveillance, (2) enhanced passive surveillance, or (3) electronic health record data mining (EHR-DM). English general practice (GP) is a suitable setting to implement enhanced passive surveillance and EHR-DM. OBJECTIVE: This study aimed to test the feasibility of conducting enhanced passive surveillance in GP using the yellow card scheme (adverse events of interest reporting cards) to determine if it has any advantages over EHR-DM alone. METHODS: A total of 9 GPs in England participated, of which 3 tested the feasibility of enhanced passive surveillance and the other 6 EHR-DM alone. The 3 that tested EPS provided patients with yellow (adverse events) cards for patients to report any adverse events. Data were extracted from all 9 GPs' EHRs between weeks 35 and 49 (08/24/2015 to 12/06/2015), the main period of influenza vaccination. We conducted weekly analysis and end-of-study analyses. RESULTS: Our GPs were largely distributed across England with a registered population of 81,040. In the week 49 report, 15,863/81,040 people (19.57% of the registered practice population) were vaccinated. In the EPS practices, staff managed to hand out the cards to 61.25% (4150/6776) of the vaccinees, and of these cards, 1.98% (82/4150) were returned to the GP offices. Adverse events of interests were reported by 113 /7223 people (1.56%) in the enhanced passive surveillance practices, compared with 322/8640 people (3.73%) in the EHR-DM practices. CONCLUSIONS: Overall, we demonstrated that GPs EHR-DM was an appropriate method of enhanced surveillance. However, the use of yellow cards, in enhanced passive surveillance practices, did not enhance the collection of adverse events of interests as demonstrated in this study. Their return rate was poor, data entry from them was not straightforward, and there were issues with data reconciliation. We concluded that customized cards prespecifying the EMA's adverse events of interests, combined with EHR-DM, were needed to maximize data collection. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2016-015469.

Near-Real Time Monitoring of Vaccine Uptake of Pregnant Women in a Primary Care Sentinel Network: Ontological Case Definition Across Heterogeneous Data Sources.

Vaccination against influenza is important in pregnancy for the health of both mother and unborn baby. Influenza introduces risks to pregnancy and to the baby who relies on maternal antibodies for protection. Because the data associated with pregnancy is fragmented across multiple providers of health care, it is challenging to conduct pregnancy-related public health surveillance using a single data source. We report the integration of a novel ontological approach to identifying pregnancies in routine data with a web-based dashboard that feeds back information to general practices in a sentinel network. As a result, practices receive information about how well they are performing influenza vaccination in pregnancy in near-real-time.

Enhanced passive surveillance of influenza vaccination in England, 2016-2017- an observational study using an adverse events reporting card.

Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92-6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93-3.47] and 1.77% [1.42-2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs.

Uptake and impact of vaccinating primary school-age children against influenza: experiences of a live attenuated influenza vaccine programme, England, 2015/16.

The 2015/16 influenza season was the third season of the introduction of an intra-nasally administered live attenuated influenza vaccine (LAIV) for children in England. All children aged 2‒6 years were offered LAIV, and in addition, a series of geographically discrete areas piloted vaccinating school-age children 7‒11 years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during 2015/16 followed by influenza B. We measured influenza vaccine uptake and the overall and indirect effect of vaccinating children of primary school -age, by comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6-72.0) was achieved in the five pilot areas for children aged 5‒11 years. In pilot areas, cumulative emergency department respiratory attendances, influenza-confirmed hospitalisations and intensive care unit admissions were consistently lower, albeit mostly non-significantly, in targeted and non-targeted age groups compared with non-pilot areas. Effect sizes were less for adults and more severe endpoints. Vaccination of healthy primary school-age children with LAIV at moderately high levels continues to be associated with population-level reductions in influenza-related respiratory illness. Further work to evaluate the population-level impact of the programme is required.

Incidence of Lower Respiratory Tract Infections and Atopic Conditions in Boys and Young Male Adults: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2015-2016.

BACKGROUND: The Royal College of General Practitioners Research and Surveillance Centre comprises more than 150 general practices, with a combined population of more than 1.5 million, contributing to UK and European public health surveillance and research. OBJECTIVE: The aim of this paper was to report gender differences in the presentation of infectious and respiratory conditions in children and young adults. METHODS: Disease incidence data were used to test the hypothesis that boys up to puberty present more with lower respiratory tract infection (LRTI) and asthma. Incidence rates were reported for infectious conditions in children and young adults by gender. We controlled for ethnicity, deprivation, and consultation rates. We report odds ratios (OR) with 95% CI, P values, and probability of presenting. RESULTS: Boys presented more with LRTI, largely due to acute bronchitis. The OR of males consulting was greater across the youngest 3 age bands (OR 1.59, 95% CI 1.35-1.87; OR 1.13, 95% CI 1.05-1.21; OR 1.20, 95% CI 1.09-1.32). Allergic rhinitis and asthma had a higher OR of presenting in boys aged 5 to 14 years (OR 1.52, 95% CI 1.37-1.68; OR 1.31, 95% CI 1.17-1.48). Upper respiratory tract infection (URTI) and urinary tract infection (UTI) had lower odds of presenting in boys, especially those older than 15 years. The probability of presenting showed different patterns for LRTI, URTI, and atopic conditions. CONCLUSIONS: Boys younger than 15 years have greater odds of presenting with LRTI and atopic conditions, whereas girls may present more with URTI and UTI. These differences may provide insights into disease mechanisms and for health service planning.

Uptake of a Dashboard Designed to Give Realtime Feedback to a Sentinel Network About Key Data Required for Influenza Vaccine Effectiveness Studies.

Dashboards are technologies that bringing together a range of data sources for observational or analytical purposes. We have created a customised dashboard that includes all the key data elements required for monitoring flu vaccine effectiveness (FVE). This delivers a unique dashboard for each primary care provider (general practice) providing data to the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), one of the oldest European surveillance systems. These FVE studies use a test negative case control (TNCC) design. TNCC requires knowledge of practice denominator; vaccine exposure, and results of influenza virology swabs carried out to identify in an influenza-like-illness (ILI), a clinical diagnosis, really is influenza. The dashboard displays the denominator uploaded each week into the surveillance system, compared with the nationally known practice size (providing face-validity for the denominator); it identifies those exposed to the vaccine (by age group and risk category) and virology specimens taken and missed opportunities for surveillance (again by category). All sentinel practices can access in near real time (4 working days in areas) their rates of vaccine exposure and swabs conducted. Initial feedback is positive; 80% (32/40) practices responded positively.

RCGP Research and Surveillance Centre Annual Report 2014-2015: disparities in presentations to primary care.

BACKGROUND: The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) comprises over 100 general practices in England, with a population of around 1 million, providing a public health surveillance system for England and data for research. AIM: To demonstrate the scope of data with the RCGP Annual Report 2014-2015 (May 2014 to April 2015) by describing disparities in the presentation of six common conditions included in the report. DESIGN AND SETTING: This is a report of respiratory and communicable disease incidence from a primary care sentinel network in England. METHOD: Incidence rates and demographic profiles are described for common cold, acute otitis media, pneumonia, influenza-like illness, herpes zoster, and scarlet fever. The impact of age, sex, ethnicity, and deprivation on the diagnosis of each condition is explored using a multivariate logistic regression. RESULTS: With the exception of herpes zoster, all conditions followed a seasonal pattern. Apart from pneumonia and scarlet fever, the odds of presenting with any of the selected conditions were greater for females (P<0.001). Older people had a greater probability of a pneumonia diagnosis (≥75 years, odds ratio [OR] 6.37; P<0.001). Common cold and influenza-like illness were more likely in people from ethnic minorities than white people, while the converse was true for acute otitis media and herpes zoster. There were higher odds of acute otitis media and herpes zoster diagnosis among the less deprived (least deprived quintile, OR 1.32 and 1.48, respectively; P<0.001). CONCLUSION: The RCGP RSC database provides insight into the content and range of GP workload and provides insight into current public health concerns. Further research is needed to explore these disparities in presentation to primary care.

Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results.

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15.

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 end of season results.

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case-control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: -29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway.