title: Application of a self-controlled case series study to a database study in children.
abstract: BACKGROUND
  Post-marketing surveillance activities are particularly important for safety issues in children, the elderly, and patients with severe comorbidities since these populations are usually excluded from clinical trials. In addition, using electronic databases for monitoring of safety of marketed products has been of considerable interest.
  
  
  OBJECTIVE
  This study aimed to clarify the advantages and difficulties of the self-controlled case series method relative to cohort studies in pharmacoepidemiological studies in children, using an administrative database, and to explore the impact on results of handling the period eligible for analysis and recurrent events in different ways.
  
  
  METHODS
  Datasets of only individuals who had the outcome of interest were derived from an anonymized hospital administrative database in Japan from April 2003 through August 2011. We calculated incidence rate ratios (IRRs) and their 95 % confidence intervals (CIs) for the risks of diarrhea, bronchitis, and eczema related to palivizumab treatment in young children. The analysis included 'first diagnosed' events or 'multiple' events during an eligible period. An eligible period was defined in two ways: first-time inpatient periods of more than 3 continuous days (EPA); and a continuous period in cases where the interval between visits was below the 75th percentile of the interval between visits for patients with the same diagnosis (EPB).
  
  
  RESULTS
  We extracted data for 70,771 patients and identified 641 who were exposed to palivizumab. The age-adjusted IRRs for diarrhea, bronchitis, and eczema were 3.0 (95 % CI 1.7-5.4), 10.3 (95 % CI 8.0-13.2), and 16.9 (95 % CI 12-23), respectively, in multiple events and the EPB eligible period. The IRRs varied greatly between the two eligible periods.
  
  
  CONCLUSIONS
  This method could be a useful tool in pharmacoepidemiological studies in children. Careful consideration in the handling of inpatient and outpatient periods, including sensitivity analyses, is necessary because this method is a within-individual comparison.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoecho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Hanae
authors.initials: H
authors.lastname: Ueyama
authors.forename: Shiro
authors.initials: S
authors.lastname: Hinotsu
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Urushihara
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D000069455:Palivizumab; D017891:Pharmacoepidemiology / Q000379:methods; D012449:Safety
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069455:Palivizumab