That the central line bundle could receive only a moderate evidence rating may suggest that the GRADE framework, developed mostly for traditional clinical therapies, requires modification for QI interventions. GRADE does not distinguish prospective trials (eg, controlled before-after studies and interrupted time series) from lower-level observational studies. On the other hand, that the two highest quality studies reached different conclusions makes it difficult to conclude that future research would not change the effect estimate, especially given evidence of secular trends and the variability of co-interventions to ensure bundle compliance, which created heterogeneity across studies.