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


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 beta; estimates were compared.


RESULTS
The beta; 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.
Glanz
Jason M
JM
Clinical Research Unit, Kaiser Permanente, P. O. Box 378006, Colorado, Denver, CO 80237-8066, USA. jason.m.glanz@kp.org
McClure
David L
DL
Xu
Stanley
S
Hambidge
Simon J
SJ
Lee
Martin
M
Kolczak
Margarette S
MS
Kleinman
Ken
K
Mullooly
John P
JP
France
Eric K
EK
D000208:Acute Disease; D000293:Adolescent; D015982:Bias; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006302:Health Services Research / Q000379:methods*; D006801:Humans; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects*; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012107:Research Design; D013997:Time Factors
D022542:Measles-Mumps-Rubella Vaccine