“Comparative evaluation of immunogenicity of bivalent oral poliovirus vaccine (bOPV) and monovalent oral poliovirus vaccine type 1 (mOPV1) when administered in the EPI schedule with a dose of inactivated polio vaccine (IPV) at week 14 and assessment of immunogenicity of IPV only schedule in the EPI: A multicentric open label randomized controlled trialâ€

This study requires collection of cord blood at thetime of delivery and enrolment of healthy newborns within 24 hours of birth.Most study institutions being referral centres do not have a consistentrelationship between a regular antenatal check-up and the mother reporting fordelivery to the same institution. Taking consent during antenatal/pre-labourperiod does not work effectively in most situations. So a 3-stage process isplanned to obtain a written informed consent for study participation:

 Antenatal/Pre-labour period: The study team inpaediatrics department will have a close liaison with the department ofobstetrics. A trained study staff/counsellor will be available in the antenatalclinic to meet the expecting mothers during their 37 week or later visits. Thisstudy staff, besides the usual counselling, will explain to the expectingmother about the importance of vaccination for the new born baby and details ofthe vaccine study being undertaken in the institution. The staff will alsoinform that a small quantity of blood (about 3.0 ml) will be collected from theplacental side of the umbilical cord after birth of the baby for regular testson newborn and potentially for testing polio and pentavalent (DTwP-HepB-Hib) antibodies.The mother will be assured that she will be provided with complete detailsabout the study again once the baby is born and that she and the family willhave sufficient time and opportunity to decide whether or not she will accepther baby’s participation in the study. If not, no testing related to the studywill be performed.

 Oral consent for cord blood: Cord blood is routinelycollected in some institutions for blood group testing and newborn baby screening.An oral consent will be taken from the parents/LAR for cord blood collectionafter informing them that the blood will also be used to test for polioantibodies if parents/LAR agrees for her baby’s participation in a poliovaccine study; which will be completely explained after the baby is born. Ifnot, the collected blood will not be tested for polio and Pentavalent(DTwP-HepB-Hib) antibodies.

 Written informed consent: All babies delivered in thestudy institution during the enrolment period will be assessed for theeligibility criteria. If a baby fulfils the eligibility criteria, a completeinformed consent process will be followed as per the national regulatoryrequirement. The study staff will approach the parent/LAR only once the motherand baby are stabilized after delivery [usually 6-8 hours in a normal vaginaldelivery and within 24 hours in lowersegment caesareansection (LSCS)] and the mother is in a healthy frame of mindfor this discussion as judged by the investigator. Parent/LAR will not beapproached for consent if the woman had a difficult delivery, obstructedlabour, LSCS if onaccount of fetal distress/abnormality, any significant postpartumcomplication or a stressful situation where, as judged by the investigator, theprocess may add to the stress. In addition to obtaining written informedconsent, audio-visual recording of the informed consent process for each trialsubject will be done including the procedure of providing information to parent/LARand their understanding of the consent process. Such audio-visual recording andrelated documentation would be preserved for five years as per regulatoryguidelines.

Study visits, procedures & follow up

Immediately after birth, 3.0 ml. cord blood will becollected. Newborn babies fulfilling eligibility criteria and whose parents haveprovided informed consent will be assigned in to one of the three study arms (A,B & C) as per the randomization envelopes A dose of bOPV or mOPV1 will begiven within 24 hours of birth as per the study arm. Birth dose of OPV will beskipped in Arm C. Parents will be advised to avoid any other vaccine from centresother than the study site. For every study infant, an immunization card will beissued indicating the baby to be a study child and that all vaccinations willbe advised and taken care of by the study investigator during this period. Dateof next visit to the study site will be given to the parents when they bringthe baby for the due procedures. Where the newborn is not eligible or parents donot consent to participate, the cord blood will be discarded as per usualhospital procedures.

 To ensure a good follow up and compliance, completeaddress and contact details of the family will be recorded and verified beforethe mother and baby are discharged from the hospital. Reminder telephone contacts/ household visitswill be arranged through a social worker a day before every subsequent visit at6, 10, 14, 18 and 22 weeks.

 At 6 and 10 week visits, a dose of the study vaccinewill be administered as per the study arm. At 14 weeks, one millilitre (ml)blood will be collected from each study participant by venepuncture followed byadministration of vaccine/s as per the study arm. IPV will be givenintramuscularly using AD syringe in the anterolateral side of the right thigh. At18 weeks, 3.0 ml blood will be collected by venepuncture followed by a dose ofIPV to infants in all the study arms. At week 22 one ml of blood will becollected from all infants across all the three arms

 The study subjects will continue getting other (thanpolio) EPI vaccines concurrently. BCG and HepB will be given at birth as perEPI recommendation. Instead of DPT, these infants will be given pentavalentvaccine (DTP + Hep B + Hib) at 6, 10 and 14 weeks.

 After having fulfilled the study requirements at 22weeks, infants will exit the study. A dose of bOPV will be given to all studyparticipants to compensate for any loss in type specific vaccination and willbe referred to the routine vaccination program for the subsequent vaccinationaccording to the national immunization schedule. Parents will be advised thattheir child should also receive additional OPV doses during the SIAs in theirarea.