Overcoming under-enrolment of a sensitive patient group for an assay study on neonate sepsis

A non-interventional study sought to evaluate the clinical accuracy of an interleukin assay for sepsis diagnosis in neonates. A control cohort was used to establish normative biomarker reference ranges while a treatment cohort assessed the diagnostic performance of the assay in neonates with suspected sepsis. The study was conducted over a two-year period with more than 500 samples collected at 24 sites in the USA.

The study lagged enrolment projections to meet 400 neonatal patients with suspected sepsis within the first year. Less than 10% of patients were enrolled within the first six months with an enrolment rate of 0.53 patients per site. Difficulties with enrolment were due to the highly sensitive patient population. The neonates were less than one month old, and the study required informed consent from both parents within a narrow timeframe.

In collaboration with the sponsor, ICON obtained central IRB approval for a waiver of informed consent. This gave the study access to leftover blood samples from standard of care blood draws. ICON informed sites through local IRBs about the option of applying for a waiver. The waiver of informed consent, and waiver of authorisation for the use and disclosure of protected health information (PHI), were submitted and approved. The use or disclosure of PHI posed no more than minimal risk to individuals. Sites in California were an exception, as waiver of consent is not permitted there. 

Approximately 40% of the sites used the waiver of consent strategy. This led to an increase in enrolment rates from 0.53 to 1.5 patients per site per month over the following seven months, an increase of around 300%. In collaboration with the sponsor, ICON developed new enrollment projections. As a result of this new approach, the study met its enrollment target with more than 400 patients enrolled in the treatment cohort. The last patient enrollment goal was met, demonstrating the effectiveness of this strategy to overcome initial recruitment challenges.