With improved survival of very immature infants, necrotizing enterocolitis has risen in importance as a major cause of morbidity and mortality. However, despite many clinical trials, options for prevention and treatment remain elusive. Presenting features are often non-specific, severe disease is rare, and reliable baseline rates are often unavailable. Inconsistent case definitions, inadequate trial power and quality, and rising costs remain significant problems. Limited understanding of causal biological mechanisms and regulatory ambiguities when products are classified as nutritional substances rather than medicines inhibit targeted drug discovery. The consequences are consensus guidelines defined by clinician bias, research stagnation, and continuing risks to patient safety.
These problems mandate a new approach to clinical research. We propose 1) greater use of routine data to obtain reliable baseline rates and deliver studies with greater efficiency; 2) international adoption of core outcome sets and collaboration for greater power, external validity, and improved trial reporting; 3) parent involvement to improve design and ensure acceptability; 4) industry involvement to speed pathways to impact; 5) embedding comparative effectiveness evaluations into routine care to reduce costs; 6) mechanistic exploration in parallel with trials to inform future research; and 7) collaboration across multiple funders and stakeholders to ascertain long-term outcomes.