Hepatitis B Vaccination and First Central Nervous System Demyelinating Events: Reanalysis of a Case-Control Study Using the Self-Controlled Case Series Method

Vaccine. 2007 Aug 1;25(31):5938-43. doi: 10.1016/j.vaccine.2007.05.032. Epub 2007 Jun 8.


The hypothesis that hepatitis B vaccination is a risk factor for multiple sclerosis has been discussed at length. The data from an earlier case-control study were reanalyzed using the self-controlled case series method. Using the matched cases from the case-control study, we found a relative incidence of 1.68, 95% CI (0.77-3.68) for the 0-60-day post-vaccination risk period; this compares to an odds ratio of 1.8, 95% CI (0.7-4.6). When an additional 53 unmatched cases not used in the case-control study were included, the relative incidence was 1.35, 95% CI (0.66-2.79). Our results throw further light on the methodological aspects of the case series method. We recommend that, when case-control studies of vaccination and adverse events are planned, case series analyses based on the cases are also undertaken when appropriate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Central Nervous System
  • Central Nervous System Diseases / chemically induced*
  • Central Nervous System Diseases / epidemiology
  • Data Interpretation, Statistical*
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / epidemiology
  • Hepatitis B / prevention & control
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects*
  • Humans
  • Vaccination


  • Hepatitis B Vaccines