Case-only designs in pharmacoepidemiology: a systematic review

PLoS One. 2012;7(11):e49444. doi: 10.1371/journal.pone.0049444. Epub 2012 Nov 16.


Background: Case-only designs have been used since late 1980's. In these, as opposed to case-control or cohort studies for instance, only cases are required and are self-controlled, eliminating selection biases and confounding related to control subjects, and time-invariant characteristics. The objectives of this systematic review were to analyze how the two main case-only designs - case-crossover (CC) and self-controlled case series (SCCS) - have been applied and reported in pharmacoepidemiology literature, in terms of applicability assumptions and specificities of these designs.

Methodology/principal findings: We systematically selected all reports in this field involving case-only designs from MEDLINE and EMBASE up to September 15, 2010. Data were extracted using a standardized form. The analysis included 93 reports 50 (54%) of CC and 45 (48%) SCCS, 2 reports combined both designs. In 12 (24%) CC and 18 (40%) SCCS articles, all applicable validity assumptions of the designs were fulfilled, respectively. Fifty (54%) articles (15 CC (30%) and 35 (78%) SCCS) adequately addressed the specificities of the case-only analyses in the way they reported results.

Conclusions/significance: Our systematic review underlines that implementation of CC and SCCS designs needs to be more rigorous with regard to validity assumptions, as well as improvement in results reporting.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Cross-Over Studies
  • Drug-Related Side Effects and Adverse Reactions
  • Epidemiologic Research Design*
  • Pharmacoepidemiology / methods*
  • Pharmacoepidemiology / standards
  • Research Design

Grant support

The authors have no support or funding to report.