Pediatrics · Medical Literature
A study within a trial evaluating supplemental, reinforced risk-based training to reduce implementation barriers in a pediatric multicenter randomized controlled trial.
Abstract
High-quality conduct of clinical trials depends on strict adherence to both regulatory protocols and trial-specific procedures to ensure data integrity and participant safety. Standard methods utilized to train research staff have limitations, including lack of specificity and declining impact over time. We developed a Supplemental, Reinforced, Risk-Based Training (SRRBT) program, designed to target study-specific challenges and provide ongoing reinforcement. Our objective was to evaluate whether SRRBT improves protocol adherence. SRRBT was executed as a cluster-randomized, educational implementation study embedded in a multicenter clinical trial. We compared standard training with and without the addition of SRRBT across 23 clinical sites. SRRBT consisted of five interactive electronic vignettes focusing on trial-specific competencies. The primary outcome was the proportion of eligible participants approached for study participation. Secondary outcomes included consent and enrollment rates, protocol deviations, and completeness of study documentation. Approach rates immediately following training trended higher at SRRBT sites compared to those receiving standard training alone (OR = 3.98, 95% CI [0.87, 18.17], p = 0.074); however, this difference was not statistically significant and attenuated over time, with odds ratios of 2.24 (95% CI [0.78, 6.49], p = 0.14) at six months and 1.38 (95% CI [0.53, 3.59], p = 0.51) at 12 months post-training. SRRBT shows potential in enhancing early site-level protocol adherence but may require ongoing reinforcement to sustain benefits over time. This study highlights the need for continuous, adaptive training approaches in complex clinical trials to maintain high standards of protocol adherence.
Clinical relevance
Does adding a Supplemental, Reinforced, Risk-Based Training (SRRBT) program — consisting of interactive electronic vignettes targeting trial-specific competencies — to standard research staff training improve protocol adherence, reduce protocol deviations, and enhance participant recruitment in a pediatric multicenter randomized controlled trial? __SNAPSHOT__ {"studyDesign":"Cluster-randomized, parallel-group, educational implementation Study Within A Trial (SWAT), embedded prospectively within the PRECISE multicenter RCT","setting":"23 CPCCRN (Collaborative Pediatric Critical Care Research Network)-affiliated pediatric intensive care units across the United States","sampleSize":"23 clinical sites (11 randomized to SRRBT + standard training; 12 to standard training alone); participant-level denominators not reported in available abstract or PMC open-access sections","population":"Research staff (principal investigators, co-investigators, and study coordinators) at pediatric ICU sites enrolling children with sepsis-induced multiple organ dysfunction syndrome (MODS) in the PRECISE trial","intervention":"SRRBT: five interactive electronic vignettes delivered via REDCap, covering trial-specific competencies including eligibility and consent procedures, blood sampling and study drug administration, randomization and protocol deviations, participant withdrawal, and REDCap data entry; participation was voluntary and not protocol-enforced","comparator":"Standard training alone (investigator meetings, monitoring visits, and standard onboarding procedures common to all 23 sites)","primaryOutcome":"Proportion of PRECISE-eligible participants approached for study participation (site-level approach rate)","followUp":"Data locks at three prespecified time points: immediately following SRRBT training series (February 2023), approximately 6 months post-SRRBT (August 2023), and approximately 12 months post-SRRBT (March 2024)","fundingSource":"Government (NIH/NICHD): CPCCRN and PRECISE funded by the Eunice Kennedy Shriver NICHD (PL1HD105462); additional support from Utah Trial Innovation Center (U24TR001597) and Vanderbilt Recruitment Innovation Center (U24TR004432), both funded by NCATS; lead author additionally supported by NICHD career development awards (K12HD113189, K23HD115855)"}
Key findings
For the primary outcome (proportion of PRECISE-eligible participants approached for study participation), approach rates immediately following SRRBT training trended higher at SRRBT sites compared to standard-training-only sites, but this difference was not statistically significant. The precise odds ratio, confidence interval, and p-value for this comparison were not fully reported in the available abstract (the abstract was truncated) or in the open-access PMC sections retrieved; these values are therefore not reported here. For secondary outcomes — including consent rates, enrollment rates, frequency and severity of protocol deviations, completeness of required participant surveys, and completeness of daily study data collection forms — no statistically significant differences between arms were identified per the authors' characterization of a 'nuanced impact.' No formal power calculation was conducted, as sample size was fixed by the number of activated PRECISE sites (n=23). NNT/NNH cannot be calculated from available data. No adverse events or safety signals were identified (educational intervention). Notably, uptake of SRRBT vignettes was voluntary and not protocol-enforced, resulting in variable timing of exposure relative to site activation across the 11 SRRBT sites.
Practice implications
This SWAT established that SRRBT, a structured risk-based supplemental training program using scenario-based electronic vignettes, did not produce statistically significant improvements in the primary outcome (approach rate) or any prespecified secondary outcomes over standard research staff training in a pediatric critical care multicenter trial. The authors suggest a 'nuanced impact,' with a non-significant early trend toward higher approach rates at SRRBT sites that was not sustained at 6 or 12 months post-training, consistent with the well-recognized phenomenon of declining training impact over time. The study did not establish that SRRBT reduces protocol deviations, improves consent or enrollment rates, or improves documentation completeness. The findings apply specifically to research coordinators and investigators at CPCCRN-affiliated academic pediatric ICUs conducting a complex immunomodulation trial; generalizability to trials with simpler protocols, non-academic settings, or non-pediatric populations is not established. A critical limitation acknowledged by the authors is the absence of a formal power calculation — with only 23 sites, the SWAT was likely substantially underpowered to detect plausible effect sizes for site-level outcomes. Voluntary and uncontrolled vignette uptake introduced significant implementation heterogeneity, complicating causal interpretation. This review is based on the published abstract and open-access PMC full-text sections; specific effect sizes, confidence intervals, and p-values for the primary and all secondary outcomes were not fully accessible and are not reported. __LIMITATIONS__ Critical underpowering: sample size was fixed at 23 sites with no formal power calculation, making the study substantially underpowered to detect plausible between-arm differences in site-level outcomes,Voluntary, unforced SRRBT uptake with variable timing relative to site activation introduced significant implementation heterogeneity, undermining fidelity to the intended intervention,Allocation was not concealed and blinding was not feasible due to the nature of the educational intervention, creating risk of performance and detection bias,Site-level (cluster) randomization with n=23 clusters limits statistical power and precision; participant-level denominators and full effect sizes are not available in accessible text,The SWAT concluded in February 2023, and site activation varied across the 11 SRRBT sites, with some sites activated before, during, or after the vignette series — compromising dose-response interpretation,Generalizability is limited to CPCCRN-affiliated academic pediatric ICUs conducting a high-complexity, immune-phenotype-guided trial; findings may not apply to simpler trials or community settings,Vignette scores were not treated as protocol adherence outcomes and were not used to assess individual competency, limiting mechanistic insight into whether staff actually learned the intended content,No participant-level clinical outcomes were assessed; all outcomes were process and implementation metrics,Only abstract and partial open-access full-text were available for review; complete results tables, all confidence intervals, and all p-values could not be verified independently __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ SRRBT — a voluntary, scenario-based electronic supplemental training program — did not significantly improve protocol adherence, approach rates, consent rates, or documentation completeness compared to standard training alone across 23 pediatric ICU sites in the PRECISE trial. The study was likely substantially underpowered given its fixed cluster sample size of 23 sites and voluntary uptake design, meaning a meaningful benefit cannot be excluded. Trial methodologists and research teams should view SRRBT as a promising but unproven implementation strategy that requires evaluation in larger, more rigorously controlled settings with enforced participation before adoption as standard practice.