Intussusception Surveillance After Rotarix Introduction in Mexico
Intussusception Surveillance After Rotarix Introduction in Mexico
GSK Biologicals' rotavirus vaccine, Rotarix™ has been recommended for universal use targeting
 infants through the Expanded Program on Immunization (EPI) in Mexico. This protocol describes
 a Phase IV safety study in Mexico designed to further evaluate the safety profile of Rotarix™
 with regard to intussusception (IS). The data generated by this study will be useful for
 public health officers and policy makers in confirming the safety profile of Rotarix™.
Rationale for amendment 3:

 The findings from the first year of the implementation of the active surveillance showed that
 most Lower Respiratory Tract-Related Post-Neonatal (LRTI) Mortality cases could not be
 included into the study, because most of the grieving parents refused to participate in the
 study. The European Medicines Agency Marketing Authorization Holders (EMEA MAH) also
 generated a substantial amount of additional clinical and post-marketing safety data
 throughout the world, which clearly indicated the absence of any safety signal when
 considering the LTRI-related fatalities. Therefore surveillance for LRTI mortality cases was
 removed from the study design. The number of sites was reduced from approximately 230 to
 about 60 to 90 in order to reflect the above mentioned change that reduced the need for so
 many sites. Additionally, passive surveillance for IS cases through the IMSS database was not
 feasible, due to restrictions of the IMSS internal policies and to the current limitations in
 the databases linkage and structure abilities.

 Lastly, SAEs reporting procedures had to be adjusted according to the Council for
 International Organizations of Medical Sciences (CIOMS) Working Group V, 2001 publication
 such that there will be no expedited safety reporting for this study.

 Design This is a post marketing ,Phase IV, observational, prospective, self-controlled case
 series, vaccine safety study including: a) hospital-based surveillance to monitor for the
 occurrence of IS through active surveillance; b) a self-controlled case series (SCCS)
 design/analysis to assess the temporal association with Rotarix™ of the IS ascertained
 through active surveillance.

 The aim of the active hospital-based surveillance system is to identify all definite IS cases
 in children younger than one year of age (children ineligible on day of first birthday) among
 IMSS members. Surveillance will be conducted in approximately 60 to 90 IMSS health facilities
 with pediatric surgery service.

 Study participation for children fitting the surveillance case definition of IS will include
 parental/guardian/legal representative interview, as well as a review of medical charts and
 vaccination records. Additional medical information will be collected through medical record
 review during hospitalization and after the child has been discharged.
Inclusion Criteria:

 A child's clinical episode will be defined as an IS case and deemed eligible for the study
 if he/she meets the following criteria:

 -  Subject is an IMSS affiliate

 -  Subject is being treated/has been treated/has been referred for treatment at one of
 the IMSS hospitals/medical facilities with IS during the study period.

 -  Male or female child is <one year of age at the time of diagnosis of the IS (child
 becomes ineligible on the day of their first birthday)

 -  Subject is diagnosed with definite IS based on the Brighton criteria

 -  Written informed consent is obtained from the parent/guardian/legal representative of
 the subject Subjects meeting the above criteria will be eligible for inclusion in this
 study regardless of whether or not the subject has had a radiographically or
 surgically confirmed case of IS prior to the current episode.

 Exclusion Criteria:

 Not applicable