Limitations of the study
encephalitis, autoimmune encephalitis
RECRUITMENT, RECRUITMENT, AUTOIMMUNE ENCEPHALITIS, ENCEPHALITIS
The main limitation of the IgNiTE study is that the predefined sample size was not met, and the primary study objective was therefore not achieved. The study initially planned to recruit 308 participants over a 24-month period. The sample size calculation was based on the anticipated number of annual encephalitis hospital admissions in the UK and the anticipated treatment effect of IVIG, based on a large observational study on autoimmune encephalitis.Overall, 13% (115) of children were assessed to meet to inclusion criteria, but 55% (63) of these children fulfilled exclusion criteria and were thus ineligible. The main reasons for exclusion were prior or planned IVIG treatment as part of routine care (32%), and study timeline restrictions (24%). The use of IVIG as part of routine care demonstrates that some clinicians were already convinced of the benefit of IVIG in childhood encephalitis despite the lack of high-quality evidence and the fact that at the time the trial was undertaken, IVIG was not commissioned for routine use in acute childhood encephalitis. This highlights the importance of ensuring that there is equipoise among treating clinicians when conducting randomised controlled trials.Recruitment to the trial was also impacted by a lower than anticipated consent rate. Of the 52 children who were eligible for enrolment, participation was declined in 65% of cases. This is not unexpected given the requirement for parents or guardians to provide informed consent at an exquisitely sensitive time for the family. Other factors which may have contributed to the low consent rate include the limited time frame for enrolment and the trial duration.Finally, recruitment was impacted by delays in the participating NHS hospitals opening as recruitment sites, due primarily to shortages of research personnel and delays in local approval processes. Nine of the 21 participating hospitals did not recruit any particitpants during the study; 5 of these hospitals were open to recruitment for 6 months or less.