Four different study designs to evaluate vaccine safety were equally validated with contrasting limitations

Glanz, Jason M.; McClure, David L.; Xu, Stanley; Hambidge, Simon J.; Lee, Martin; Kolczak, Margarette S.; Kleinman, Ken; Mullooly, John P.; France, Eric K.

doi:10.1016/j.jclinepi.2005.11.012

« Previous Next »Journal of Clinical Epidemiology
Volume 59, Issue 8 , Pages 808-818, August 2006

Four different study designs to evaluate vaccine safety were equally validated with contrasting limitations

Jason M. Glanz
- Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO, 80237-8066, USA
- Corresponding author. Tel.: 303-636-3118; fax: 303-636-3109.
David L. McClure
- Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO, 80237-8066, USA
Stanley Xu
- Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO, 80237-8066, USA
Simon J. Hambidge
- Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO, 80237-8066, USA
- Community Health Services, Denver Health Medical Center, Denver, CO, USA
- Department of Pediatrics, University of Colorado School of Medicine, Denver, CO, USA
Martin Lee
- UCLA Center for Vaccine Research, Torrance, CA, USA
Margarette S. Kolczak
- Centers for Disease Control and Prevention, Atlanta, GA, USA
Ken Kleinman
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, USA
John P. Mullooly
- Center for Health Research, Northwest Kaiser Permanente, Portland, OR, USA
Eric K. France
- Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO, 80237-8066, USA

Accepted 16 November 2005. published online 17 March 2006.

Abstract

Objective

We conducted a simulation study to empirically compare four study designs [cohort, case–control, risk-interval, self-controlled case series (SCCS)] used to assess vaccine safety.

Study Design and Methods

Using Vaccine Safety Datalink data (a Centers for Disease Control and Prevention-funded project), we simulated 250 case sets of an acute illness within a cohort of vaccinated and unvaccinated children. We constructed the other three study designs from the cohort at three different incident rate ratios (IRRs, 2.00, 3.00, and 4.00), 15 levels of decreasing disease incidence, and two confounding levels (20%, 40%) for both fixed and seasonal confounding. Each of the design-specific study samples was analyzed with a regression model. The design-specific estimates were compared.

Results

The estimates of the case–control, risk-interval, and SCCS designs were within 5% of the true risk parameters or cohort estimates. However, the case–control's estimates were less precise, less powerful, and biased by fixed confounding. The estimates of SCCS and risk-interval designs were biased by unadjusted seasonal confounding.

Conclusions

All the methods were valid designs, with contrasting strengths and weaknesses. In particular, the SCCS method proved to be an efficient and valid alternative to the cohort method.

Keywords: Simulation study, Cohort, Case–control, Risk-interval, Self-controlled case series (SCCS), Bias (epidemiology), Confounding factors (epidemiology)