Methodology and Lessons-Learned from the Efficacy Clinical Trial of the Pentavalent Rotavirus Vaccine in Bangladesh

This study from rural Bangladesh describes the methodology based upon "good clinical practices (GCP)" used to set up a clinical trial for vaccination of infants for prevention of acute gastroenteritis associated with rotavirus. "Given that this was the first trial with clinical outcomes for any rotavirus vaccine conducted in Bangladesh, the methodology, including operation, logistics, and lessons-learned are described in this report" from Vaccine Journal Special Supplement: Rotavirus Vaccines for Children in Developing Countries, April 27 2012.

"The clinical trial was part of an Asian study (Bangladesh and Vietnam) and was conducted from March 2007 to March 2009. Eligible children were identified through a database. A few days after birth field workers hired for this study from the community briefed all mothers about this rotavirus vaccine study. They used a brief information sheet containing the basic information regarding the study vaccine. The information provided to the mothers earlier helped them in understanding the contents of the long consent form in giving consent during enrollment....

Vaccination was organized at 41 fixed-site clinics twice/month. Twelve field-workers routinely visited study participants [1,136 participants] at their homes for nearly two years as part of the safety and efficacy follow-up. Telephone contact was made in case the mothers along with the participants were not available at home due to visit to relatives home for social visit. Field-workers visited all children at 7 days and 14 days after each dose and, subsequently once a month, until the end of the follow-up period. During their routine visits field workers advised parents of study participants to bring their children at the hospital in cases of gastroenteritis (GE)....For the evaluation of safety, all subjects were followed for serious adverse events (SAEs)...For the safety and efficacy follow-up of the study, 12 field workers conducted a total of 26,263 interviews (in person or through telephone)."

There were several factors recognised as key to the completion of the study: "At the beginning of the study, study supervisors discussed about the study with all CHRWs [community health research workers] in their routine fortnightly meetings and they provided the message in the community which was helpful for smooth conduct of the study....The CHRWs were experienced in giving EPI [expanded programme on immunisation] vaccines in the community through their fixed site clinics, so the procedures for identifying infants eligible for vaccination was previously established. Further continuous training to the study staff by the local and international monitors, investigators and supervisors helped to conduct the study maintaining GCP standard. The findings of the monitors during the visit helped in filling out different forms properly later on and to conduct the study according GCP guidelines. Since the rotavirus vaccine was given at the standard times with other EPI vaccines, the new vaccine was readily incorporated into the routine schedule during the same visits. The longstanding relationship of the CHRW with the communities they served facilitated the communications about the study with the parents of the eligible infants....

This was the first vaccine trial in a rural setting in Bangladesh where online data entry was done. It has several advantages like rapid entry of data, less transcribing error and quick feed back from the central database for any inconsistencies. Data file is closed when the data set is finalized....Having Health and Demographic Surveillance System (HDSS) identification number was instrumental for the assessment. HDSS consists of regular cross-sectional censuses and longitudinal registration of vital events. This system assigns identification numbers as birth registration. All staff members underwent training to insure that they understood the nature of the study, the importance of accurate data collection and their performance was monitored by supervisors...."

Researchers found that from this study that a vaccine clinical efficacy study, with GCP standards, can be conducted while maintaining high quality and coverage at the community level. "The conduct of the study in this area with a long standing HDSS and relationship with the communities, in which the communities benefit from the services of the institution, facilitates the ability to conduct such studies."