OBJECTIVES: We examined data from Cochrane Neonatal reviews to assess whether conditions that constituted KSD were included as key outcomes and how commonly they occurred in the population studied.
METHODS: We identified Cochrane reviews, published till November 2017 that evaluated interventions for neonatal jaundice (NNJ). We extracted the following information at the review and study levels: included population, outcomes assessed (in particular, whether PIOs such as KSD were listed as the primary outcomes), as well as their cumulative incidence in the reviews.
RESULTS: Out of 311 reviews, 11 evaluated interventions for NNJ with 78 randomized controlled trials (RCTs) included. Among the reviews, a total number of 148 outcomes were predefined and 30 (20.3%) were PIOs related to KSD, with 11 (36.7%) listed as primary outcomes. Among the 78 included RCTs (total participants = 8,232), 38 (48.7%) enrolled predominantly high-risk and 40 (51.3%) enrolled predominantly low-risk population. A total number of 431 outcomes were reported, and 40 (9.2%) were PIOs related to KSD (of which 37 were from studies with high-risk infants), with 13 (32.5%) listed as primary outcome. Cumulatively, no infant developed KSD across all studies.
CONCLUSIONS: There is suboptimal representation of PIOs such as KSD in neonatal trials and Cochrane reviews on NNJ. Over half of the trials included populations with very low risk of KSD, which does not represent judicious use of resources. Amidst our continued search for a more reliable surrogate marker for NNJ, studies should evaluate the whole spectrum KSD alongside serum bilirubin in high-risk populations with sufficiently significant event rates, as this will make the trial methodologically feasible, with findings that will impact the population concerned.
METHODS: All DDKTRs between January 1, 2015, and December 29, 2020, were included and categorized into 2 groups: EPTS ≤20% and EPTS >20%. Cox regression was performed to evaluate the association of EPTS score and patient survival. The rate of postoperative complications, graft failure and patient survival were compared between 2 groups. Data were analyzed with SPSS v26 and R v4.0.4. The study complies with the Helsinki Congress and the Istanbul Declaration.
RESULTS: We included 159 DDKTRs, with a median follow-up of 25 months (range, 10-60 months). The mean age of those with EPTS ≤20% was 32.2 ± 3.4 years and those with EPTS >20% was 46.0 ± 6.7 years, and the median EPTS score were 16% (range, 12%-18%) and 38% (range, 27%-56.5%), respectively. EPTS score was associated with patient survival (hazard ratio, 1.031; 95% CI 1.010-1.052; P = .003), and the cutoff points of 30% and above were associated with worse survival. It showed good discrimination (C-index, 0.729; 95% CI 0.579-0.878; P = .003) and the optimal cutoff value was 38% (65.5% sensitivity, 68.8% specificity, 17.8% positive predictive value, and 95.8% negative predictive value). Both groups had similar rate of surgical complications (P = .191), graft failure (P = .503), and patient survival (P = .654), but those with EPTS >20% had higher incidence of urinary tract infection (9.3% vs 27.6%, P = .016).
CONCLUSIONS: There was no difference in clinical outcomes using an EPTS cutoff point of 20% but worse patient survival if higher cutoff point was used.
METHODS: We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented.
RESULTS: We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed.
CONCLUSIONS: The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.