Table 1.

Comparison of different study designs used to monitor the safety of rotavirus vaccines with respect to intussusception.

Study Design	Strengths	Weaknesses
Randomized Controlled Trials	• Randomization minimizes selection bias and helps distribute potential confounders equally • Rigorous follow-up of patients and strict adherence to protocol	• Large sample sizes required for rare events and/or low level risks • Costly • May not reflect real-world conditions
Passive Adverse Event Reporting	• Can capture new or unexpected events	• Expected or baseline rate of the condition, the number of children vaccinated, and completeness of reporting often unknown
Cohort Studies	• Known catchment population enables calculation of rates • Closely monitor for cases of intussusception and record vaccination status for individual cases	• Requires large sample size for rare adverse events • Costly • Susceptible to changes in care/treatment over time • Cohort may not be representative of entire population
Case-Control Evaluations	• Smaller sample size required • Resource efficient	• Potential bias due to control selection and confounders • Study team not blinded to case/control status • Logistical challenges in enrolling controls
Self-Controlled Case-Series Evaluations	• Smaller sample size required • Resource efficient • Controls for individual level confounders	• Complex analytic methods
Ecologic Trends	• Relatively straight-forward to implement	• Trends susceptible to improved surveillance and increased awareness over time especially with rare events