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Background Enhanced Recovery After Surgery (ERAS ® ) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS ® Society guidelines. We created an ERAS ® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties.

The Core Outcome Set-STAndards for Development (COS-STAD), published in 2017, contains 11 standards (12 criteria) describing minimum design criteria for core outcome set (COS) development. We aimed to identify and appraise all pediatric COS published prior to COS-STAD, and assess methods of child and family involvement in their development. This methodological review included documents that described the development of pediatric COS up to and including 2017. Reviewers independently assessed each COS against COS-STAD criteria, and methods of involvement were synthesized. A total of 56 pediatric COS were identified, meeting a median of five COS-STAD criteria. Nearly all met criteria on COS scope specification for setting, health condition, and population; 41% met criteria for intervention. Standards were more often met for the involvement of researchers/health professionals (64%) than for patients or their representatives (29%). Few met standards for achieving COS consensus (4–23%). Methods of child and family engagement varied and were limited. A large proportion of pediatric COS developed prior to COS-STAD recommendations show gaps in design methodology. Updated and newly developed pediatric COS would benefit from the inclusion of the child and family voice, implementing a priori criteria for COS consensus, and clear reporting.

Background Clinicians, patients, and policy-makers rely on published evidence from clinical trials to help inform decision-making. A lack of complete and transparent reporting of the investigated trial outcomes limits reproducibility of results and knowledge synthesis efforts, and contributes to outcome switching and other reporting biases. Outcome-specific extensions for the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT-Outcomes) and Consolidated Standards of Reporting Trials (CONSORT-Outcomes) reporting guidelines are under development to facilitate harmonized reporting of outcomes in trial protocols and reports. The aim of this review was to identify and synthesize existing guidance for trial outcome reporting to inform extension development. Methods We searched for documents published in the last 10 years that provided guidance on trial outcome reporting using: an electronic bibliographic database search (MEDLINE and the Cochrane Methodology Register); a grey literature search; and solicitation of colleagues using a snowballing approach. Two reviewers completed title and abstract screening, full-text screening, and data charting after training. Extracted trial outcome reporting guidance was compared with candidate reporting items to support, refute, or refine the items and to assess the need for the development of additional items. Results In total, 1758 trial outcome reporting recommendations were identified within 244 eligible documents. The majority of documents were published by academic journals (72%). Comparison of each recommendation with the initial list of 70 candidate items led to the development of an additional 62 items, producing 132 candidate items. The items encompassed outcome selection, definition, measurement, analysis, interpretation, and reporting of modifications between trial documents. The total number of documents supporting each candidate item ranged widely (median 5, range 0–84 documents per item), illustrating heterogeneity in the recommendations currently available for outcome reporting across a large and diverse sample of sources. Conclusions Outcome reporting guidance for clinical trial protocols and reports lacks consistency and is spread across a large number of sources that may be challenging to access and implement in practice. Evidence and consensus-based guidance, currently in development (SPIRIT-Outcomes and CONSORT-Outcomes), may help authors adequately describe trial outcomes in protocols and reports transparently and completely to help reduce avoidable research waste.

Background Systematic reviews of outcome measurement instruments are important tools in the evidence-based selection of these instruments. COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) has developed a comprehensive and widespread guideline to conduct systematic reviews of outcome measurement instruments, but key information is often missing in published reviews. This hinders the appraisal of the quality of outcome measurement instruments, impacts the decisions of knowledge users regarding their appropriateness, and compromises reproducibility and interpretability of the reviews’ findings. To facilitate sufficient, transparent, and consistent reporting of systematic reviews of outcome measurement instruments, an extension of the PRISMA (Preferred Reporting of Items for Systematic reviews and Meta-Analyses) 2020 guideline will be developed: the PRISMA-COSMIN guideline. Methods The PRISMA-COSMIN guideline will be developed in accordance with recommendations for reporting guideline development from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. First, a candidate reporting item list will be created through an environmental literature scan and expert consultations. Second, an international Delphi study will be conducted with systematic review authors, biostatisticians, epidemiologists, psychometricians/clinimetricians, reporting guideline developers, journal editors as well as patients, caregivers, and members of the public. Delphi panelists will rate candidate items for inclusion on a 5-point scale, suggest additional candidate items, and give feedback on item wording and comprehensibility. Third, the draft PRISMA-COSMIN guideline and user manual will be iteratively piloted by applying it to systematic reviews in several disease areas to assess its relevance, comprehensiveness, and comprehensibility, along with usability and user satisfaction. Fourth, a consensus meeting will be held to finalize the PRISMA-COSMIN guideline through roundtable discussions and voting. Last, a user manual will be developed and the final PRISMA-COSMIN guideline will be disseminated through publications, conferences, newsletters, and relevant websites. Additionally, relevant journals and organizations will be invited to endorse and implement PRISMA-COSMIN. Throughout the project, evaluations will take place to identify barriers and facilitators of involving patient/public partners and employing a virtual process. Discussion The PRISMA-COSMIN guideline will ensure that the reports of systematic reviews of outcome measurement instruments are complete and informative, enhancing their reproducibility, ease of use, and uptake.

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose–concentration–effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight.

Background Despite the critical importance of clinical trials to provide evidence about the effects of intervention for children and youth, a paucity of published high-quality pediatric clinical trials persists. Sub-optimal reporting of key trial elements necessary to critically appraise and synthesize findings is prevalent. To harmonize and provide guidance for reporting in pediatric controlled clinical trial protocols and reports, reporting guideline extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines specific to pediatrics are being developed: SPIRIT-Children (SPIRIT-C) and CONSORT-Children (CONSORT-C). Methods The development of SPIRIT-C/CONSORT-C will be informed by the Enhancing the Quality and Transparency of Health Research Quality (EQUATOR) method for reporting guideline development in the following stages: (1) generation of a preliminary list of candidate items, informed by (a) items developed during initial development efforts and child relevant items from recent published SPIRIT and CONSORT extensions; (b) two systematic reviews and environmental scan of the literature; (c) workshops with young people; (2) an international Delphi study, where a wide range of panelists will vote on the inclusion or exclusion of candidate items on a nine-point Likert scale; (3) a consensus meeting to discuss items that have not reached consensus in the Delphi study and to “lock” the checklist items; (4) pilot testing of items and definitions to ensure that they are understandable, useful, and applicable; and (5) a final project meeting to discuss each item in the context of pilot test results. Key partners, including young people (ages 12–24 years) and family caregivers (e.g., parents) with lived experiences with pediatric clinical trials, and individuals with expertise and involvement in pediatric trials will be involved throughout the project. SPIRIT-C/CONSORT-C will be disseminated through publications, academic conferences, and endorsement by pediatric journals and relevant research networks and organizations. Discussion SPIRIT/CONSORT-C may serve as resources to facilitate comprehensive reporting needed to understand pediatric clinical trial protocols and reports, which may improve transparency within pediatric clinical trials and reduce research waste. Trial Registration The development of these reporting guidelines is registered with the EQUATOR Network: SPIRIT-Children ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials-protocols/#35 ) and CONSORT-Children ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#CHILD ).

Background Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community. Methods Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein. Results Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials. Conclusion This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. Study protocol registration https://doi.org/10.1186/s13063-018-2934-7 .

Purpose Although comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024. Methods The development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement. Results From the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final checklist to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review’s title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts. Conclusion PRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding explanation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA-COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application. Note In order to encourage its wide dissemination this article is freely accessible on the web sites of the journals: Health and Quality of Life Outcomes; Journal of Clinical Epidemiology; Journal of Patient-Reported Outcomes; Quality of Life Research.

[...]the comparison of treatment effects between adults and children was across and not within trials. [...]the results could be explained by residual confounding, despite the meta-regression done by the authors, arising from differences in disease severity, drug dosages, outcome measures, and diagnostic categories. Standards for the design and reporting of pediatric trials would contribute to the development of a methodologically strong and relevant evidence base for pediatric care. [...]adequate reporting will assist end-users in assessing the relevance and applicability of a study's findings (http://www.equator-network.org/).

ObjectiveRemote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC.DesignPhase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days.SettingLevel III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada).PatientsFifteen preterm infants born between 22 and 33 weeks gestational age.InterventionFour cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days.OutcomesThe primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation.ResultsFour cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC.ConclusionsThis study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC.Trial registration number NCT03860701.