Vaccine 22 (2004) 766–772 A post-licensure evaluation of the safety of inactivated hepatitis A vaccine (VAQTA ® , Merck) in children and adults Steven Black a,∗ , Henry Shinefield a , John Hansen a , Edwin Lewis a , Ling Su b , Paul Coplan b a Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, USA b Merck Research Laboratories, Blue Bell, PA, USA Received 19 March 2003; received in revised form 9 July 2003; accepted 1 August 2003 Abstract Background: Hepatitis A is a major cause of epidemic hepatitis in the US. In pre-licensure trials, inactivated hepatitis A vaccine (HAV, VAQTA ® , Merck) was shown to be generally well-tolerated and effective in inducing immunity to hepatitis A infection in adults and children over 2 years of age. Following the licensure of this vaccine, we began a Phase IV safety evaluation in adults and in children over 2 years of age. Methods: Safety was assessed by comparing the rates of diagnoses in clinic, emergency and hospital utilization. From April 1997 to December 1998, rates of diagnoses within 30 days for the clinic and emergency setting and 60 days for hospitalization were compared with unexposed follow-up time in the same individuals both before receipt of vaccine and after the 60 days interval post-vaccination. Results: There were a total of approximately 2000 comparisons between the risk and “before” or “after” period. Among them, 106 were found to have statistically significant differences in rates (30 elevated, 76 lowered). Among children/adolescents (2–17 year-old), in the hospitalization category, the only statistically significant elevated risk found was “elective procedures”, as compared with both “before” and “after” periods. In the outpatient visit category for children and adolescents, elevated risks were found for consultation/general medicine/exam when compared with both “before” and “after” periods, and ganglion and viral warts when compared with either “before” or “after” period. Among adults (≥18 year-old), in the outpatient visit category, a statistically significant elevated relative risk was seen for diarrhea/gastroenteritis for both “before” and “after” periods. There were additionally 17 diagnostic categories that showed a statistically significantly elevated relative risk compared with either “before” or “after” period. Except for diarrhea/gastroenteritis, the other eight events were elevated only in one comparison (either “before” or “after”). These eight elevated relative risks might be explained by chance resulting from multiple comparison or seasonal variations. There were no serious adverse events judged by the investigator to be associated with HAV. Conclusion: In this large Phase IV evaluation of the safety of HAV, the vaccine appeared to be generally well-tolerated. These data support the continued routine use of HAV for vaccination in children and adults. © 2003 Elsevier Ltd. All rights reserved. Keywords: Hepatitis A; Vaccine; Safety 1. Introduction Hepatitis A is a major cause of epidemic hepatitis in the US. Outbreaks are often associated with contact with children in day care centers or with infected food handlers [1,2]. In addition, the risk of acquiring hepatitis A is in- creased by travel to areas where the disease is prevalent [3]. In pre-licensure trials, inactivated hepatitis A vaccine (HAV, VAQTA ® , Merck) was shown to be generally well-tolerated and effective in inducing immunity to hepatitis A infection in adults and children over 2 years of age [4]. We report here on a large Phase IV post-licensure evaluation of the safety of inactivated HAV in adults and children over 2 years of age. ∗ Corresponding author. Tel.: +1-510-267-7534; fax: +1-510-267-7524. E-mail address: steve.black@kp.org (S. Black). 2. Methods This was a passive observational study implemented fol- lowing the introduction of inactivated hepatitis A vaccine into routine use within the medical care program of Northern California Kaiser Permanente. The vaccine recipients were 2 years and older, were members of the Kaiser Permanente Medical Care Program (KPMCP), and met the eligibility criteria for HAV according to the product circular. Safety was assessed through identification of adverse events result- ing in medical utilization. These diagnoses were ascertained through the searches of computerized records of outpa- tient clinic visits, emergency room visits, hospitalizations, and from the mortality database of the state of California. Adverse experiences resulting in outpatient clinic visits or emergency room visits were ascertained for 30 days 0264-410X/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2003.08.034