Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children.

BACKGROUND

In clinical trials of Pneumococcal Conjugate Vaccines (PCV), some adverse events have been reported more frequently in the PCV vaccinated. Ten-valent PCV (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010.

OBJECTIVE

We conducted an ecologic register-based study to investigate further the reported adverse events after PCV.

METHODS

This study included data obtained from the Finnish nationwide, population-based registers. First diagnoses of febrile seizures, breath-holding, urticarial rash, asthma and Kawasaki's disease were included as outcomes obtained from the hospital discharge register. Data from Finnish Population Register during 2000-2014 for children age from 3 months to 10 years were used to estimate annual incidence rates. Incidence rate ratios of the outcomes were calculated between the target cohort of children eligible for PCV10 during 2010-2014 and a reference cohort before the NVP introduction (2004-2008).

RESULTS

No increases in the incidence of the adverse events after PCV10 introduction were found except for urticarial rash (incidence rate 2.48 vs. 1.60/1000 pyrs; incidence rate ratio, 1.54;95% CI 1.42-1.67). This increase was seen also in the unvaccinated older age groups in the post-vaccination era. The higher incidence of urticarial rash after the PCV10 introduction was due to the inclusion of diagnoses made in general medicine specialty in the discharge register because of a concomitant administrative change.

CONCLUSION

The results do not support public health concerns related to the previously reported adverse events. Concomitant changes in health care administration and coding introduced bias, which was controlled after further evaluation of the data. We consider this register-based approach with realworld data feasible in the signal validation process after any signal detection.