The Safety and Immunogenicity Study of Rotavirus Vaccine Simultaneously Vaccinated With MR or MMR Vaccine

1. Quality control plan:

   1. All vaccinators should get professional training held by local Health Bureau, and be qualified by local Health Bureau.
   2. All the clinical trial related staffs are trained by provincial or prefectural Center for Disease Control and prevention (CDC) at the beginning.
   3. Provincial and prefectural CDCs conduct supervision at each step, especially during field vaccination and Adverse Events Following Immunization (AEFI) investigation.
   4. Data valid check is designed to work in the database inputting, double entry and validation is also required.
   5. The field works are conduct under SOP (Standard Operating Procedures), The SOP for vaccination procedures which include vaccinee recruitment and vaccination practice etc. is 'Immunization Work Specification' issued by China Ministry of Health in 2005. The SOP for AEFI surveillance is 'AEFI surveillance guideline' issued by China Ministry of Health in 2010.

2. Statistical plan

   1. Safety evaluation The analytic data include all reactions or events within 30 days after vaccination, compare the incidence of reactions among different vaccines, the statistical method is chi-square.
   2. Immunogenicity evaluation Compare the antibody positive rate and Geometric Mean Concentration between pre-vaccination and post-vaccination, and among different vaccine combinations.

3. safety evaluation method

   At the time of vaccination, vaccinees were instructed to report any adverse event to physicians or vaccination providers. Adverse events that were fatal or that resulted in disability and clusters of events (i.e., notably high numbers of similar adverse events related to a certain vaccine) were required to be reported within 2 hours after their occurrence. The following adverse events were required to be reported within 2 days after their occurrence: anaphylaxis or other allergic reactions occurring within 24 hours after vaccination; fever (axillary temperature, >38.5°C), angioedema, or a local injection-site reaction (diameter, >2.5 cm) occurring within 5 days after vaccination; purpura, an Arthus reaction, febrile convulsion, seizure, or polyneuritis occurring within 15 days after vaccination. Other reactions that were common and minor (e.g., mild pain and fatigue) were not required to be reported.

4. Immunogenicity evaluation

Enzyme-linked immunosorbent assay (abbreviated as ELSIA) is used to quantitatively test immunoglobulin G (IgG) of measles, rubella, mumps, test kit is provided by Virion\Serion company. Rotavirus Immunoglobulin A (RV-IgA) is used to test the antibody of rotavirus.