Increasing number of unexpected deaths reported during paediatric clinical trials for vaccines are attributed to negligence by doctors in selection of infants and children who already have a serious health condition. This is where the Institutional Review Board (IRB) or the Ethics Committee (EC) should take complete responsibility to thoroughly scrutinize the trial to be carried out on paediatric subjects.

Although the number of paediatric trials conducted in India is far lower than the adult trials, yet there needs to be strict monitoring to be undertaken at every stage. The EC needs to meet more often to ensure that they closely examine every paediatric trial, assess that inclusion/exclusion criteria carefully and certify the health condition of the child before being cleared for the study. Right now ECs at Hospitals are not able to meet for want of time and are only involved in granting permission for the trial. There is a need for frequent evaluation and IRB should not deter from this practice, Dr Prem Pais, dean, professor of medicine and head, clinical trials division, St John's Medical College told Pharmabiz.

For a vaccine trial, paediatric subjects should be usually in good health condition. However, sometimes it is unanticipated that underlying factors could cause complications. In such cases, death could be attributed to an existing serious health condition where the child was admitted in the hospital for treatment or it could be due to serious adverse events(SAEs) related to an undetectable genetic condition like liver disease or a lung disorder which manifests in infants only during an adult stage. It is extremely difficult for doctors to detect this condition because the infant or the child cannot explain if there is a disorder. Therefore, medical institutions undertaking a paediatric trial should be extra cautious in permitting such subjects for trials, said Dr Pais.

When SAEs are reported, it is the responsibility of the Principal investigator (PI) of the Hospital to inform the IRB which has approved the trial. The PI should also alert the concerned sponsor whose responsibility is to inform the Drugs Control General of India (DCGI). The drug regulator takes on the onus to investigate where the trial team will have to submit the required information about the infant's death and the kind of diagnosis carried out to permit the subject for clinical trial. St. John Medical College reports such deaths immediately to the authorities, informed Dr Pais.

While St John's hospital authorities confirmed that vaccine trials were the only studies held in the facility involving the department of paediatrics, they refused to provide any details about the Wyeth's pneumonia vaccine.

According to reliable sources, the child which succumbed to the Wyeth vaccine trial was suffering from a serious congenital heart disease which was overlooked by the paediatric specialist-while recruiting this child into the study.

The EC at St John's is manned by five doctors, two officials from judiciary, one representative from the non governmental organization and a member from Theosophical Society.

"Annually 150 research proposals come in for human studies and around 50 clinical trails are conducted of which paediatric trials are only one or two," informed Dr Karuna Ramesh Kumar, professor, Department of Clinical Pathology, St John's Medical College Hospital who heads its Ethics Committee.

"India does contribute to all paediatric vaccine trials since we have experienced investigators who have done well with vaccine trials. However, the increase in number of deaths should be thoroughly be investigated for all trials. It is not that the trials cause death since these are multi-centric phase-III studies. It is mandatory that causality assessment is made for all such SAEs and the trial sponsor submit this data to the regulatory authority for necessary action," said Dr Ramananda Nadig, president and vice dean, CREMA.