Identification of seizures among adults and children following influenza vaccination using health insurance claims data
Introduction
In Western Australia, an increased risk of febrile convulsions was reported in children under 5 years of age following receipt of the 2010 trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies (Fluvax®, Fluvax Junior®), leading to a temporary suspension of the Western Australia influenza vaccination program for children under 5 years of age [1]. An elevated risk of febrile seizures was also reported in a large United States (US) cohort in the 0–1 days following first dose TIV during the 2010–2011 season and in other studies in the short term following administration of vaccinations including diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type B (DTaP-IPV-Hib), measles, mumps, rubella (MMR), and MMR plus varicella (MMRV) [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. These studies highlight the risk of seizures in children following vaccine-induced fever. Although post-vaccination seizure is less common in adults, seizure has been reported as an adverse event (AE) in adults following influenza vaccination [12], which prompted the inclusion of seizures in adults as an outcome of interest in prospective influenza vaccine surveillance previously done in the US [13]. Monitoring for seizures as a potential AE in post-licensure vaccine safety studies in all age groups contributes to the robustness of the safety monitoring of the US influenza immunization program.
Post-licensure active surveillance of AEs following vaccination or prescription drug use often relies on electronic healthcare data to efficiently and effectively detect and evaluate potential safety signals [14], [15]. The efficiency and validity of these surveillance programs are increased with an algorithm that reliably identifies adverse events using diagnosis codes recorded for medical visits.
Performance of seizure-related diagnosis codes in post-licensure safety studies is variable and may be influenced by several factors, including clinical diagnostic setting and age [16], [17], [18], [19]. A systematic review commissioned by the US Food and Drug Administration (FDA) to validate seizure, convulsion, or epilepsy cases as part of its Mini-Sentinel program pilot found positive predictive values (PPVs) ranging from 21% to 98% [16]. Many of the studies included in the review focused on the pediatric population. Few published studies in adult populations were identified. The PPV of diagnosis codes suggestive of seizure in a study of adult tramadol users within a large US health insurance plan was 21%. [19]. More information is needed on how well seizures among vaccinated adults and children can be identified using electronic healthcare data.
This study objective was to evaluate an algorithm for identification of seizure events using an administrative claims database in a large health plan population of adults and children who received influenza vaccination in the US during the 2009–2010 and 2010–2011 seasons.
Section snippets
Data source and study population
The study population was derived from an electronic healthcare database of a large US insurer developed for research purposes. Accessible information includes demographics and pharmacy, medical, and facility claims, which provide dates on services, procedures, and their accompanying diagnoses. The insured population from which the data are drawn is geographically diverse, comprising approximately 3–4% of the US population. For a subset of approximately 6 million health plan members with medical
Results
224 potential seizure events following 1,091,181 influenza vaccinations were identified for medical record review in the main safety study and were thus eligible for inclusion in the algorithm validation analysis.
Discussion
This study validated an algorithm to identify seizures in vaccinated children and adults within a health insurance claims database using a combination of ICD-9 diagnosis codes, diagnostic setting, and pre-specified lookback and risk periods relative to vaccination. Our findings suggest higher PPVs with ICD-9 codes associated with ED visits (76.9–98.2%) and lower PPVs for the same claims-based criteria when associated with inpatient visits (32.3–64.7%). Lower PPVs were observed in older children
Conclusions
This study evaluated the performance of an algorithm to identify seizures in influenza-vaccinated adults and children using health insurance claims data. This study adds to the literature supporting the reliability of electronic healthcare data in accurately identifying seizure events in the ED setting in vaccinated populations.
Acknowledgements
This study was conducted by Optum Epidemiology and sponsored through a subcontract with America's Health Insurance Plans (AHIP) under contract number 200-2002-00732 from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Ms. Thyagarajan and Dr. Lin are employees of Optum. Ms. Su and Dr. Chan were employees of Optum at the time
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Validation of febrile seizures identified in the Sentinel Post-Licensure Rapid Immunization Safety Monitoring Program
2019, VaccineCitation Excerpt :In contrast, the PPV was very low when seizures were only identified with codes for seizure or other seizure, regardless if codes for fever were required (PPV 20%) or not (PPV 19%). A number of studies have validated the use of ICD-9 codes for identifying post-immunization seizures [4–6,10]. Our PPV estimate of 70%, based on all seizure codes except post-traumatic seizures is nearly equivalent to that of a similar study conducted in the Vaccine Safety Datalink (VSD); the study included 61 potential cases and found a PPV of 77% when using the same codes in the ED and inpatient settings following influenza vaccinations in the same age group [6].
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