Elsevier

Vaccine

Volume 31, Issue 48, 19 November 2013, Pages 5700-5705
Vaccine

Applicability of the Brighton Collaboration Case Definition for seizure after immunization in active and passive surveillance in Canada

https://doi.org/10.1016/j.vaccine.2013.09.048Get rights and content

Highlights

  • Canada conducts passive and active syndromic surveillance for vaccine adverse events.

  • We assessed feasibility of applying standard case definitions to reports of seizure.

  • 37% of 2009–2011 cases met Brighton Collaboration case definition (BCCD) for seizure.

  • Applying BCCD was feasible when it was included in adverse event reporting forms.

Abstract

Background

The Canadian Adverse Event Following Immunization Surveillance System (CAEFISS) receives reports via active syndromic surveillance for selected serious AEFI from the Canadian Immunization Monitoring Program Active (IMPACT) and via targeted passive surveillance from Federal/Provincial/Territorial health jurisdictions. Post-immunization seizure is a target of active and passive surveillance. Since 2009, the revised national AEFI reporting forms enable capture of terms specific to several Brighton Collaboration Case Definitions (BCCD) including generalized seizure and fever.

Objective

To evaluate feasibility of applying the BCCD for generalized seizure to adverse event following immunization (AEFI) reports collected by IMPACT and targeted passive surveillance (non-IMPACT).

Methods

Reports to CAEFISS coded as seizure in children <2 years of age (vaccination dates 1998–2011) were reviewed retrospectively. A BCCD level (1–5 or unclassifiable) was assigned. The effects of reporting source (IMPACT versus non-IMPACT), seriousness [serious (e.g., hospitalized) versus non-serious], vaccination year (1998–2008 versus 2009–2011), and data submission method to CAEFISS (electronic versus paper) were assessed by stratified analysis.

Results

There were 459 IMPACT and 908 non-IMPACT cases analyzed, of which 99.6% and 27%, respectively, were serious reports. The revised reporting form that captured the BCCD components (2009–2011) was associated with increased proportions of IMPACT and non-IMPACT cases meeting the BCCD for generalized seizure.

Conclusions

Incorporating the BCCD components (level of consciousness, motor manifestations and fever ≥38 °C) into the national reporting form and guidelines appeared to improve the feasibility of their use in AEFI surveillance. This effect was more pronounced among active syndromic surveillance compared to targeted passive surveillance reports.

Introduction

The success of vaccination programs is being threatened by heightened concerns about vaccine safety as rates of vaccine-preventable diseases decrease [1], [2]. Post-licensure surveillance to detect rare or unexpected adverse events following immunization (AEFI) not detected in clinical trials is critical to the continued success of immunization programs [3], [4], [5]. Passive AEFI surveillance can detect rare adverse events and changes in the known safety profile of vaccines. However, it is prone to reporting bias, under-reporting and inconsistencies in quality of reporting [6], [7], [8], [9]. Active surveillance can ensure complete case ascertainment and standardized data collection but is resource intensive and often limited in scope [10], [11], [12].

Canada employs a combination of active syndromic and targeted passive surveillance for vaccine pharmacovigilance. Active syndromic surveillance is conducted by the Canadian Immunization Monitoring Program Active (IMPACT) network at 12 centers representing nearly 90% of pediatric tertiary care beds in Canada [10]. IMPACT nurse monitors review hospital admissions for selected target diagnoses, including seizure, in real time and determine if a vaccine was given within a defined interval prior to the admission [10], [13]. Targeted passive surveillance (non-IMPACT) is conducted by Federal/Provincial/Territorial (FPT) health jurisdictions primarily via public health where seizure is considered an AEFI of special importance and is a listed event on the national AEFI report form (available online http://www.phac-aspc.gc.ca/im/aefi-essi-form-eng.php) [14]. All notifiable cases, defined as AEFI with a temporal association to a vaccine that is not clearly attributable to another cause, are submitted to the Canadian AEFI Surveillance System (CAEFISS) operated by the Public Health Agency of Canada (PHAC) in collaboration with the FPT health jurisdictions [5], [14]. From 1987 to 2011 CAEFISS received 4510 AEFI reports of seizure, of which 81% were in children <2 years of age and 34% were serious adverse events [15]. Reports from IMPACT (1991–2011) accounted for 15% of all seizures and 42% of serious reports [15].

In 2009, the Brighton Collaboration case definitions (BCCD) were adopted as the national case definitions and a revised AEFI reporting form was introduced to enable standardized reporting for several BCCD including generalized seizure, and to better capture details of the reported event [14]. The BCCD have been increasingly applied to active and passive AEFI surveillance systems [16], [17], [18]. The reliability and applicability of BCCD (including generalized seizure and fever) were assessed in active and passive AEFI surveillance in the United States [17], [18]. However, data supporting their applicability to post-market surveillance in different countries are lacking.

Seizure reports submitted to CAEFISS for vaccines administered from 1998 to 2011 to children ages 0–23 months were reviewed to describe and compare clinical characteristics of cases submitted by IMPACT and non-IMPACT sources and to evaluate feasibility of applying the BCCD for generalized seizure to IMPACT and non-IMPACT surveillance.

Section snippets

Study design and subjects

This was a retrospective study of de-identified reports in CAEFISS with a primary diagnosis of seizure after immunization. Subjects included children who were vaccinated between January 1, 1998 and December 31, 2011 and were 0–23 months of age at the time of vaccination. Exclusion criteria included: reports where seizure was not the primary diagnosis (e.g., encephalitis), reports with fatal outcome due to the small number and the associated risk of patients being identifiable, and reports from

Results

In total, 1460 unique records of seizure were extracted from the CAEFISS database. There were 93 exclusions: 58 were considered not to be seizures, had an alternate neurological diagnosis (e.g., encephalitis) or were ≥2 years of age, 6 were fatal cases and 29 were reports from market authorization holders. The final sample included 459 IMPACT and 908 non-IMPACT cases. The mean annual reporting rate for post-immunization seizure was 13.6 per 100,000 children <2 years of age. Among non-IMPACT

Discussion

This retrospective review of post-immunization seizure reports in children 0–23 months of age is one of only a few studies to assess the application of the BCCD to AEFI surveillance and the first to assess the BCCD in the Canadian AEFI Surveillance System. Canada's combined system of targeted passive reporting and active syndromic surveillance for serious adverse events differs from the United States where passive and active surveillance [Vaccine Adverse Event Reporting System (VAERS) versus

Conclusions

This study highlighted the strengths and limitations of Canada's vaccine pharmacovigilance system. We found that recent reports for febrile seizures (2009–2011) were more likely to meet the international case definition of seizure, particularly among cases reported by IMPACT. These findings suggest that AEFI reporting forms that elicit information required for the Brighton Collaboration case definition and systematic data collection contribute to high data quality. While applying BCCD to

Funding

This surveillance activity is conducted as part of the Canadian Immunization Monitoring Program Active, a national surveillance initiative managed by the Canadian Paediatric Society and conducted by the IMPACT network of pediatric investigators on behalf of the Public Health Agency of Canada's Centre for Immunization and Respiratory Infectious Diseases. Funding for AEFI surveillance is provided by the PHAC. The PHAC was involved in the review and approval of the manuscript.

Authors’ contributions

Dr. Karina Top had the lead role in study design, protocol development, data extraction and analysis and in writing the manuscript. She approved the final submitted version.

Dr. Cora Constantinescu contributed to the data extraction and development of the analysis plan. She reviewed and revised the manuscript and approved the final submitted version.

Ms. Julie Laflèche was involved in the protocol development, data extraction and analysis and reviewed and revised the manuscript. She approved the

Acknowledgements

The authors wish to thank Ms. Donna MacKinnon-Cameron and Dr. Bruce Smith for expert statistical advice and acknowledge the expert assistance of the Monitor Liaison (Heather Samson), IMPACT nurse monitors, staff of the IMPACT Data Centre (Debbe Heayn, Kim Marty, Wenli Zhang), and staff in Vaccine Safety at PHAC's Centre for Immunization and Respiratory Infectious Diseases. The authors thank the FPT Health Jurisdictions that submit data to CAEFISS and the members of the Vaccine Vigilance Working

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    For members of the Canadian Immunization Monitoring Program, Active. See Appendix A for the list of investigators.

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