Introduction: In 1998, the first licensed rotavirus vaccine was associated with intussusception, an unexpected adverse event, following reports of this condition to an adverse event reporting system. This rotavirus vaccine was withdrawn from the market and newer rotavirus vaccines have been extensively evaluated for an association with intussusception.
Areas covered: We review the different study designs that have been used both pre- and post-licensure to evaluate the association of rotavirus vaccines with intussusception and discuss the pros and cons of each design. Each of these study designs has their own strengths and weaknesses and the choice of the design often depends on the objective and the timing of the study and the resources available. For post-licensure monitoring of rotavirus vaccines, the self-controlled case-series design has become the most commonly used design to monitor this association.
Expert opinion: Use of this common study design has enabled comparison of findings across diverse settings. As new rotavirus vaccines enter the market, use of the self-controlled case-series design will enable examination of this association in a timely manner.
Keywords: Rotavirus vaccine; adverse event following immunization; intussusception; rotavirus.