Core Outcome Set For Trials Research Articles

PRACTICE: Development of a Core Outcome Set for Trials of Physical Rehabilitation in Critical Illness.

Rationale Findings from individual trials of physical rehabilitation interventions in critically ill adults have limited potential for meta-analysis and informing clinical decision-making due to heterogeneity in selection and reporting of outcomes used for evaluation. Objective The objective of this study was to determine a core outcome set (COS) for use in all future trials evaluating physical rehabilitation interventions delivered across the critical illness continuum of recovery. Methods An international, two-round, online, modified Delphi consensus process, following recommended standards, was conducted. Participants (N=329) comprised three stakeholder groups (Researchers, n=58 (18%); Clinicians, n=247 (75%); Patients and Caregivers, n=24 (7%)), and represented 26 countries and 9 healthcare professions. Participants rated the importance of a range of relevant outcomes. Outcomes included in the COS were those prioritised of "critical importance" by all three stakeholder groups. Results Survey response rates were 88% (Round 1) and 91% (Round 2). From a total of 32 initial outcomes, the following outcomes reached consensus for inclusion in the COS: Physical Function, Activities of Daily Living, Survival, Health-related Quality of Life, Exercise Capacity, Cognitive Function, Emotional and Mental Wellbeing, and Frailty. Conclusion This study developed a consensus-generated COS for future clinical research evaluating physical rehabilitation interventions in critically ill adults across the continuum of recovery. Ascertaining recommended measurement instruments for these core outcomes is now required to facilitate implementation of the COS. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study

IntroductionThe burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for...

Selection of outcome measurement instruments for a core outcome set for trials aimed at improving appropriate polypharmacy in older people in primary care: a Delphi consensus study.

Despite developing a polypharmacy core outcome set (COS) in primary care, it is not clear how these outcomes should be measured. To select outcome measurement instruments (OMIs) for a COS targeting appropriate polypharmacy in older patients in primary care. Following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, OMIs were identified from a Cochrane review focusing on appropriate polypharmacy. The quality of OMIs was assessed using a published checklist. Subsequently, two rounds of Delphi questionnaires were conducted via the SoGoSurvey® platform, engaging stakeholders (researchers, clinicians and journal editors specialising in geriatric primary care) to achieve consensus on OMIs using a scale encompassing "agree", "disagree", or "unsure". Consensus was achieved if 70% or more participants chose "agree" and 15% or fewer chose "disagree." The quality of 20 OMIs identified from the Cochrane review was evaluated. Seven OMIs were selected based on meeting the COSMIN guideline's minimum requirements. Out of 188 potential participants, 57 (30.3%) consented to participate. Rounds 1 and 2 of Delphi exercises were completed by 50 respondents, achieving agreement on three OMIs: 'number of serious adverse drug reactions (ADRs)' (98%), 'number of deaths' (76%), and 'number of patients who fell' (70%) for measuring 'serious ADRs,' 'mortality,' and 'falls,' respectively. No agreement was reached for 'medication appropriateness,' 'medication side-effects,' 'quality of life,' and 'medication regimen complexity.' OMIs were selected for a limited number of outcomes in the polypharmacy COS. Future research should identify suitable OMIs for the remaining four outcomes.

Surgical Handover Core Outcome Measures (SH-CORE): a protocol for the development of a core outcome set for trials in surgical handover

BackgroundSurgical handover is associated with a significant risk of care failures. Existing research displays methodological deficiencies and little consensus on the outcomes that should be used to evaluate interventions in this area. This paper reports a protocol to develop a core outcome set (COS) to support standardisation, comparability, and evidence synthesis in future studies of surgical handover between doctors.MethodsThis study adheres to the Core Outcome Measures in Effectiveness Trials (COMET) initiative guidance for COS development, including the COS-Standards for Development (COS-STAD) and Reporting (COS-STAR) recommendations. It has been registered prospectively on the COMET database and will be led by an international steering group that includes surgical healthcare professionals, researchers, and patient and public partners. An initial list of reported outcomes was generated through a systematic review of interventions to improve surgical handover (PROSPERO: CRD42022363198). Findings of a qualitative evidence synthesis of patient and public perspectives on handover will augment this list, followed by a real-time Delphi survey involving all stakeholder groups. Each Delphi participant will then be invited to take part in at least one online consensus meeting to finalise the COS.Ethics and disseminationThis study was approved by the Royal College of Surgeons in Ireland (RCSI) Research Ethics Committee (202309015, 7th November 2023). Results will be presented at surgical scientific meetings and submitted to a peer-reviewed journal. A plain English summary will be disseminated through national websites and social media. The authors aim to integrate the COS into the handover curriculum of the Irish national surgical training body and ensure it is shared internationally with other postgraduate surgical training programmes. Collaborators will be encouraged to share the findings with relevant national health service functions and national bodies.DiscussionThis study will represent the first published COS for interventions to improve surgical handover, the first use of a real-time Delphi survey in a surgical context, and will support the generation of better-quality evidence to inform best practice.Trial registrationCore Outcome Measures in Effectiveness Trials (COMET) initiative 2675. http://www.comet-initiative.org/Studies/Details/2675.

Using patient and care partner experiences to confirm outcomes of relevance for inclusion in a core outcome set for trials of physical rehabilitation in critical illness: A qualitative interview study

BackgroundIncorporating the perspectives of patients and care partners is crucial in the development of core outcome sets. One effective approach for achieving this involvement is by seeking input to refine the outcomes for consensus.The objectives of the study were to: i) to determine patient and care partner views on outcomes that should be measured in trials of physical rehabilitation interventions across the critical illness recovery continuum; (ii) to map these views with a pre-established list of thirty outcomes for potential inclusion in a core outcome set for these trials; and (iii) to identify any new outcomes that could be considered for inclusion. MethodsA qualitative semistructured telephone interview study was conducted with a convenience sample of post–critical illness patients and care partners, as part of core outcome set development work. Anonymised interview transcripts were analysed using a framework approach, and exemplary narrative quotes from participants were reported used to illustrate outcome reporting. FindingsFourteen participants were recruited (male:female ratio = 8:6, age range [minimum–maximum]: 50–80 years, 13 former patients, one spouse). Time since intensive care unit discharge ranged from less than 1 year to 10 years at the time of interview. Participants described a range of outcomes that could be measured in trials of physical rehabilitation after critical illness that mapped closely with the pre-established list. No new outcomes were introduced by participants during the interviews. Experiences described by participants commonly reflected outcomes related to physical ability and performance, functional level, activities of daily living, and emotional and mental wellbeing. Participants spoke to how the different outcomes directly impacted their day-to-day lives and highlighted their priorities centred around resumption of tasks and activities that had value to them at personal, functional, and societal level. ConclusionQualitative interviews confirmed the relevance of existing outcomes for potential inclusion in a core outcome set for trials of physical rehabilitation interventions across the critical illness recovery continuum. The added significance of our findings is to provide real-world meaning to these outcomes. RegistrationCOMET Initiative, ID288, https://www.comet-initiative.org/studies/details/288.

Representation of published core outcome sets in practice guidelines

ObjectivesA core outcome set (COS) is an agreed standardized set of outcomes that should be measured and reported, as a minimum, in specific areas of health or health care. A COS is developed through a consensus process to ensure health care outcomes to be measured are relevant to decision-makers, including patients and health-care professionals. Use of COS in guideline development is likely to increase the relevance of the guideline to those decision-makers. Previous work has looked at the uptake of COS in trials, systematic reviews, health technology assessments and regulatory guidance but to date there has been no evaluation of the use of COS in practice guideline development. The objective of this study was to investigate the representation of core outcomes in a set of international practice guidelines. Study Design and SettingWe searched for clinical guidelines relevant to ten high-quality COS (with focus on the United Kingdom, Germany, China, India, Canada, Denmark, United States and World Health Organisation). We matched scope between COS and guideline in terms of condition, population and outcome. We calculated the proportion of guidelines mentioning or referencing COS and the proportion of COS domains specifically, or generally, matching to outcomes specified in each guideline populations, interventions, comparators and outcome (PICO) statement. ResultsWe found 38 guidelines that contained 170 PICO statements matching the scope of the ten COS and of sufficient quality to allow data extraction. None of the guidelines reviewed explicitly mentioned or referenced the relevant COS. The median (range) of the proportion of core outcomes covered either specifically or generally by the guideline PICO was 30% (0%–100%). ConclusionThere is no evidence that COS are being used routinely to inform the guideline development process, and concordance between outcomes in published guidelines and those in COS is limited. Further work is warranted to explore barriers and facilitators in the use of COS when developing clinical guidelines.

Induction of labor via Foley balloon catheter placement for 6 vs 12 hours in women with 1 previous cesarean delivery and unfavorable cervices: a randomized controlled trial

Induction of labor in women with 1 previous cesarean delivery and unripe cervices is a high-risk process, carrying an increased risk of uterine rupture and the need for cesarean delivery. Balloon ripening is often chosen as prostaglandin use is associated with an appreciable risk of uterine rupture in vaginal birth after cesarean delivery. A shorter duration of placement of the balloon typically expedites delivery; however, this has not been evaluated in induction of labor after 1 previous cesarean delivery. This study aimed to compare Foley balloon catheter placement for 6 vs 12 hours in induction of labor after 1 previous cesarean delivery. A randomized controlled trial was conducted in a university hospital in Malaysia from January 2022 to February 2023. Eligible women with 1 previous cesarean delivery admitted for induction of labor were enrolled. Participants were randomized after balloon catheter insertion for 6 or 12 hours of passive ripening before balloon deflation and removal to check cervical status for amniotomy. The primary outcome was the induction of labor to delivery interval. The secondary outcomes were largely derived from the core outcome set for trials on induction of labor (Core Outcomes in Women's and Newborn Health [CROWN]). The Student t test, Mann-Whitney U test, chi-square test, and Fisher exact test were used as appropriate for the data. Overall, 126 women were randomized, 63 to each intervention. The mean induction of labor to delivery intervals were 23.0 (standard deviation, ±8.9) in the 6-hour arm and 26.6 (standard deviation, ±7.1) in the 12-hour arm (mean difference, -3.5 hours; 95% confidence interval, -6.4 to -0.7; P=.02). The median induction of labor (Foley balloon catheter insertion) to Foley balloon catheter removal intervals were 6.0 hours (interquartile range, 6.0-6.3) in the 6-hour arm and 12.0 hours (interquartile range, 12.0-12.5) in the 12-hour arm (P<.001). The median induction of labor to amniotomy intervals were 14.1 hours (interquartile range, 9.3-21.8) in the 6-hour arm and 19.0 hours (interquartile range, 15.9-22.0) in the 12-hour arm (P=.02). The usage rates of epidural analgesia in labor were 46.0% (29/63) in the 6-hour arm and 65.1% (41/63) in the 12-hour arm (relative risk, 0.71; 95% confidence interval, 0.51-0.98; P=.03). Spontaneous balloon catheter expulsion rates were 22.2% (14/63) in the 6-hour arm and 17.5% (11/63) in the 12-hour arm (relative risk, 1.27; 95% confidence interval, 0.63-2.58; P=.50), and additional ripening use rates (Foley reinsertion) were 46.0% (29/63) in the 6-hour arm and 31.7% (20/63) in the 12-hour arm (relative risk, 1.45; 95% confidence interval, 0.92-2.27; P=.10). The results were not different. Moreover, maternal satisfaction scores (0-10 numerical rating scale) of 9 (range, 8-10) in the 6-hour arm and 9 (range, 8-10) in the 12-hour arm (P=.41) were not different. Other secondary maternal and neonatal outcomes were not significantly different either. Foley balloon catheter placement for 6 hours hastened birth and reduced epidural analgesia use in labor without a change in maternal satisfaction.

Six vs 12 hours of Foley catheter balloon placement in the labor induction of multiparas with unfavorable cervixes: a randomized controlled trial

Planned 6- vs 12-hour placement of the double-balloon catheter for cervical ripening in labor induction hastens delivery. The Foley catheter is low-priced and typically performs at least as well as the proprietary double-balloon devices in labor induction. Maternal satisfaction with labor induction is usually inversely related to the speed of the process. This study aimed to compare Foley balloon placement for 6 vs 12 hours in the labor induction of multiparas with unfavorable cervixes. A randomized controlled trial was conducted in a university hospital in Malaysia from January to October of 2022. Eligible multiparous women admitted for induction of labor for various indications were enrolled. Participant inclusion criteria were multiparity (at least 1 previous vaginal delivery of ≥24 weeks' gestation), age ≥18 years, term pregnancy >37 weeks' gestation, singleton pregnancy, cephalic presentation, intact membranes, normal fetal heart rate tracing, no significant contractions (< 2 in 10 minutes), and unfavorable cervix (Bishop score < 6). Participants were randomized after successful Foley balloon insertion for the balloon to be left in place for 6 or 12 hours of passive ripening before removal to check cervical suitability for amniotomy. The primary outcomes were the induction-to-delivery interval and maternal satisfaction with the allocated intervention assessed using a visual numerical rating scale (0-10). Secondary outcomes were derived in part from the core outcome set for trials on induction of labor (Core Outcomes in Women's and Newborn Health [CROWN]). Maternal outcomes were change in first Bishop score after intervention, use of additional method for cervical ripening, time to delivery after balloon removal, mode of delivery, indication for cesarean delivery, duration of oxytocin infusion, blood loss during delivery, presence of third- or fourth-degree perineal tear, maternal infection, use of regional analgesia in labor, length of hospital stay, intensive care unit (ICU) admission, cardiorespiratory arrest, and need for hysterectomy. The secondary neonatal outcomes were Apgar score at 1 and 5 minutes, neonatal intensive care unit (NICU) admission, cord blood pH, neonatal sepsis, birthweight, birth trauma, hypoxic-ischemic encephalopathy, or need for therapeutic hypothermia. Analyses were conducted with the t-test, Mann-Whitney U test, chi-square test, and Fisher exact test, as appropriate. A total of 220 women were randomized (110 to each intervention). Regarding the 2 primary outcomes, the induction-to-delivery intervals were a median (interquartile range) of 15.9 (12.0-24.0) and 21.6 (17.3-26.0) hours (P<.001), and maternal satisfaction scores were 7 (6-8) and 7 (6-8) (P=.734) for 6- and 12-hour placement, respectively. The following rates were observed for 6- and 12-hour placement, respectively: sequential use of additional cervical ripening agent (Foley reinsertion)-29 per 110 (26.4%) and 13 per 110 (11.8%) (relative risk, 2.23; 95% confidence interval, 1.23-4.10; P=.006); spontaneous balloon expulsion-22 per 110 (20.0%) and 37 per 110 (33.6%) (relative risk, 0.60; 95% confidence interval, 0.38-0.94; P=.022); and recommendation of the allocated intervention to a friend-61 per 110 (73.6%) and 87 per 110 (79.1%) (relative risk, 0.90; 95% confidence interval, 0.80-1.08; P=.341). Other secondary outcomes, including cesarean delivery, were not significantly different. Foley balloon placement for 6 hours for cervical ripening in parous women hastens birth but does not increase maternal satisfaction relative to 12-hour placement. Foley reinsertion for additional ripening was more frequent in the 6-hour group.

443 Selection of Outcome Measurement Instruments for a Core Outcome Set for trials aimed at improving appropriate polypharmacy in older people in primary care

Abstract Introduction Different outcome measurement instruments (OMIs) have been used to measure similar outcomes in intervention studies focusing on improving appropriate polypharmacy in older people (1). It is crucial to reach consensus on which OMIs should be used for each outcome in a core outcome set (COS) to promote synthesis of trial findings and help identify effective interventions. A polypharmacy COS was previously developed, consisting of seven outcomes, including serious adverse drug reactions (ADRs), medication appropriateness, falls, medication regimen complexity, quality of life, mortality and medication side effects (1). To date, there has been no consensus as to which OMIs should be used for these outcomes. Aim To select OMIs for the seven outcomes in the COS developed to improve appropriate polypharmacy in older people in primary care. Methods This study followed the COSMIN (Consensus-based Standards for the selection of health Measurement Instruments) initiative’s guidelines for selecting OMIs for a COS (2), which include finding existing OMIs from a systematic review, conducting a quality assessment of the OMIs, selecting one OMI for each outcome in the COS, and running a Delphi consensus survey (two rounds) on OMIs for each outcome. For the Delphi exercise, researchers focusing on care of older people or clinicians who had experience in prescribing for this population in primary care, together with public advocates for older people were invited by email to participate. Following provision of consent, a questionnaire was developed and distributed by the SoGoSurvey® platform on two occasions. The two rounds were distributed on June 21st 2022 and July 11th 2022, respectively. Each round remained open for 14 days to allow participants to take part in the study. The questionnaire comprised a list of seven OMIs along with their definitions and illustrative examples. Stakeholders were asked to choose one option (‘agree’, ‘disagree’ or ‘unsure’) for every OMI. Response rate and distribution of scores for the seven OMIs were calculated following each round. Consensus for the inclusion of an OMI in the COS was reached if 70% or more participants selected ‘agree’ and 15% or less participants selected ‘disagree’. Results One hundred and eighty-eight emails were sent to relevant stakeholders (176 researchers or clinicians, 12 public representatives) inviting them to take part in the study. Fifty-seven (30.32%) stakeholders (56 researchers and one public representative) agreed to participate. Fifty (87.72%; all participants were researchers or clinicians) completed Rounds 1 and 2 of the Delphi survey. Following Rounds 1 and 2, consensus (≥70% participants agreed) was reached for three OMIs – ‘the number of ADRs’ (98%), ‘the number of deaths’ (76%) and ‘the number of patients who fell’ (70%) – to measure the ‘serious ADRs’, ‘mortality’ and ‘falls’ outcomes, respectively. Consensus was not reached for the remaining four OMIs. Conclusion This study led to the selection of OMIs for outcomes in a COS aimed at improving appropriate polypharmacy in older people. Although this study planned to include public participants, none agreed to participate. Future work should determine the most appropriate OMIs for the other four outcomes in the COS.

A core outcome set for trials in miscarriage management and prevention: An international consensus development study.

To develop core outcome sets (COS) for miscarriage management and prevention. Modified Delphi survey combined with a consensus development meeting. International. Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. Modified Delphi method and modified nominal group technique. The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks' gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage.

Development of Core Outcome Sets for trials on the management of Atrial fiBrillAtion in Critically Unwell patientS (COS-ABACUS): a protocol

IntroductionAtrial fibrillation (AF) is the most common cardiac arrhythmia in critically unwell patients. New-onset AF (NOAF) affects 5%–11% of all admissions and up to 46% admitted with septic shock. NOAF...

A Core Outcome Set for Trials in Glomerular Disease: A Report of the Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) Stakeholder Workshops.

Outcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outcomes of critical importance to patients, care partners, and clinicians are consistently reported. We convened two 1.5-hour workshops in Melbourne, Australia, and Washington, DC, United States. Attendees were identified purposively with 50 patients/care partners and 88 health professionals from 19 countries; 51% were female. Patients and care partners were from the United States, Australia, and Canada, and had experience of a glomerular disease with systemic features (n=9), kidney-limited nephrotic disease (n=9), or other kidney-limited glomerular disease (n=8). Attendees reviewed the results of the SONG-GD Delphi survey and aims of the workshop and then discussed potential core outcomes and their implementation in trials among moderated breakout groups of eight to 12 people from diverse backgrounds. Transcripts of discussions were analyzed thematically. Three themes were identified that supported the proposed core outcomes: limiting disease progression, stability and control, and ensuring universal relevance (i.e., applicable across diverse populations and settings). The fourth theme, preparedness for implementation, included engaging with funders and regulators, establishing reliable and validated measures, and leveraging existing endorsements for patient-reported outcomes. Workshop themes demonstrated support for kidney function, disease activity, death, life participation, and cardiovascular disease, and these were established as the core outcomes for trials in adults with glomerular disease. Future work is needed to establish the core measures for each domain, with funders and regulators central to the uptake of the core outcome set in trials.

The Development of a Core Outcome Set for Trials and Evaluative Studies in Adult Social Care

<strong>Context:</strong> Core outcome sets that help to harmonise results across studies have had a major impact on clinical research and policymaking. However, it is less developed in social care research. <strong>Objectives:</strong> We aimed to explore feasibility and identify a set of domains that would comprise a core outcome set for adult social care research and specific measures to assess these domains. <strong>Methods:</strong> We identified core domains through a scoping review. A panel was recruited to participate in two surveys. In the first survey, participants scrutinised the approach and the proposed domains; based on which, domains were refined. Outcome measures were then identified for each domain. In the second survey, the panel provided their views on domains and measures. <strong>Findings:</strong> Of 30 individuals approached, 25 participated in the first survey and 19 in the second. The first survey revealed that the majority (20/25) were supportive of the overall approach. Of seven domains proposed initially, six (well-being, health-related quality of life, functional ability, experience with services, service use and costs, and carers’ perspectives) were retained and one (psychological well-being) was merged with the well-being domain. Based on available evidence, we recommended specific measures for four domains and highlighted potentially relevant resources for the other two domains. In the second survey, majority of the panel (i.e. over 70%) agreed with the domains and recommendations on measures. <strong>Implications:</strong> This study has shown that it is feasible to progress the idea of a core outcome set that might inform and guide future social care research.

Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC): a modified Delphi process to develop a core outcome set for trials in perioperative care and anaesthesia

BackgroundOutcome selection underpins clinical trial interpretation. Inconsistency in outcome selection and reporting hinders comparison of different trials' results, reducing the utility of research findings. MethodsWe conducted an iterative consensus process to develop a set of Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC), following the established Core Outcome Measures for Effectiveness Trials (COMET) methodology. First, we undertook a systematic review of RCTs in high-impact journals to describe current outcome reporting trends. We then surveyed patients, carers, researchers, and perioperative clinicians about important outcomes after surgery. Finally, a purposive stakeholder sample participated in a modified Delphi process to develop a core outcome set for perioperative and anaesthesia trials. ResultsOur systematic review revealed widespread inconsistency in outcome reporting, with variable or absent definitions, levels of detail, and temporal criteria. In the survey, almost all patients, carers, and clinicians rated clinical outcome measures critically important, but clinicians rated patient-centred outcomes less highly than patients and carers. The final core outcome set was: (i) mortality/survival (postoperative mortality, long-term survival); (ii) perioperative complications (major postoperative complications/adverse events; complications/adverse events causing permanent harm); (iii) resource use (length of hospital stay, unplanned readmission within 30 days); (iv) short-term recovery (discharge destination, level of dependence, or both); and (v) longer-term recovery (overall health-related quality of life). ConclusionsThis core set, incorporating important outcomes for both clinicians and patients, should guide outcome selection in future perioperative medicine or anaesthesia trials. Mapping these alongside standardised endpoint definitions will yield a comprehensive perioperative outcome framework.

CoreSCD: multi-stakeholder consensus on core outcomes for sickle cell disease clinical trials

BackgroundWith the dramatic increase in the pipeline for new sickle cell disease (SCD) therapies in recent years, the time is ripe to ensure a robust body of evidence is available for decision making by regulators, payers, clinicians, and patients. Harmonization of the outcomes selected across interventional trials enables optimal post-trial appraisal and decision making through valid pooled analyses and indirect comparisons. We employed a structured, multi-stakeholder consensus process to develop core outcome sets (COS) for use in clinical trials of SCD interventions.MethodsCoreSCD utilized a modified Delphi method adapted from the standards recommended by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. An initial list of candidate outcomes was developed through a targeted literature review and input from an 11-member advisory committee. A 44-member multi-stakeholder Delphi Panel was established and included patients and family members, advocates, clinicians, researchers, payers, health technology assessors, representatives from government agencies, and industry representatives. Patients/advocates comprised 25% of the Delphi Panel and orientation and training was provided prior to the consensus process to ensure all were prepared to participate meaningfully. Panelists completed three rounds of an online survey to rate the importance of candidate outcomes for inclusion in the COS. Summary data was provided between each voting round and an in-person consensus meeting was held between the second and third round of voting. Consensus rules were applied following each round of voting to eliminate outcomes that did not meet predetermined criteria for retention.ResultsConsensus was reached for two core outcome sets. The final COS for trials of disease-modifying therapies includes ten outcomes and the COS for trials of acute interventions includes six outcomes. Both core sets include clinical outcomes as well as outcomes related to functioning/quality of life, resource utilization, and survival/mortality.ConclusionsUse of the COS in clinical development programs for SCD will help to ensure that relevant, consistent outcomes are available for decision making across the product lifecycle.

Outcomes used in trials regarding the prevention and treatment of orthodontically induced white spot lesions: A scoping review

The objective was to identify and summarize the outcomes and evaluation methods used in clinical trials regarding the prevention and treatment of orthodontically induced white spot lesions (WSLs). Three electronic databases were searched to identify studies that were (1) clinical trials on prevention and/or treatment of orthodontically induced WSLs, (2) reported in English, and (3) published between January2010 and October 2019. At least 2 authors assessed the eligibility and extracted the characteristics, outcomes, and evaluation methods from included studies. All disagreements were resolved through discussion. Among 1328 studies identified, 51 were eligible and included. A total of 48 different outcomes and 11 different evaluation methods were used in these studies. The most frequently used outcomes were WSLs clinical visual examination scores (n=22, 43.1%), DIAGNOdentvalues (n=14; 27.5%), fluorescence loss measured with quantitative light-induced fluorescence (QLF) (n=10; 19.6%), and lesion area measured with QLF (n=10; 19.6%). The most frequently used evaluation methods were clinical examination (n=25; 49.0%), visual inspection by photographs (n=15; 29.4%), DIAGNOdent (n=14; 27.5%), and QLF (n=10; 19.6%). None of the included studies reported data on quality of life. Substantial outcome heterogeneity exists among studies regarding the prevention and treatment of orthodontically induced WSLs. Most of the identified outcomes are aimed to assess morphologic changes of WSLs and may not reflect patient perspectives. The Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) project was registered in the COMET Initiative database (No. 1399).

Protocol for the development of a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL)

BackgroundEnamel white spot lesions (WSLs), characterized by an opaque, matt, and chalky white appearance of enamel, are a sign of incipient caries. WSLs are common in orthodontic practice and can affect both the oral health and dental aesthetics of patients. Extensive studies have been conducted to evaluate the effectiveness of prevention or treatment for orthodontically induced enamel WSLs. However, substantial heterogeneity has been found in the outcomes used for the prevention and treatment of WSLs in literature, which prevents researchers from comparing and combining the results of different studies to draw more decisive conclusions. Therefore, we aim to develop a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL).MethodsThe development of COS-OWSL comprises four phases: (1) a scoping review to identify and summarize all existing outcomes that have been used in trials on the prevention or treatment of orthodontically induced WSLs; (2) qualitative interviews with orthodontic patients without (for prevention) and with WSL-affected teeth (for treatment) and relevant dental professionals to identify additional outcomes relevant to them; (3) Delphi surveys to collect opinions from key stakeholders including patients, dental professionals, and researchers and to reach a preliminary consensus; and (4) a consensus meeting to develop the final COS-OWSL.DiscussionThe COS-OWSL will be developed to facilitate the synthesis of evidence regarding the prevention and treatment of orthodontically induced WSLs and to promote the consistent use of relevant patient-important outcomes among future studies in this field.Trial registrationCore Outcome Measures in Effectiveness Trials (COMET) initiative (the COS-WSL project) 1399

Clinimetrics: Core Outcome Set for trials with Coronavirus disease 2019 (COVID-19-COS).

Clinimetrics: Core Outcome Set for trials with Coronavirus disease 2019 (COVID-19-COS).

Development of a core outcome set for interventions to prevent stillbirth.

To develop a core outcome set for trials investigating interventions to prevent stillbirth. Outcomes identified from a systematic literature review and semi-structured interviews with parents in Australia and the UK were entered into a two-round online Delphi survey and focus group/consensus meetings. A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher-level neonatal care length of stay. Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.

Evidence and clinical trials in Endourology: where are we going.

There is an ongoing explosion in the amount and quality, of research in the field of Endourology. From a solid basis of systematic reviews and small, single centre trials it has been possible to design large randomised controlled trials in the UK and in the USA. This review will describe some of the more recent trials (small and large) that are helping to provide a solid evidence base for our practice in Endourology. Randomised controlled trial (RCTs) include: The Therapeutic Interventions for Stones in the Ureter (TISU), the Percutaneous nephrolithotomy, flexible Ureterorenoscopy and extracorporeal Shockwave lithotripsy for lower pole kidney stones (PURE RCTs) and the Prevention of Urinary Stones with Hydration (PUSH). Quality of life (QoL) measures and studies include: the Wisconsin Stone QoL Questionnaire, the Cambridge Renal Stone PROM, the Cambridge Ureteral Stone PROM, the Urinary stone and Intervention QoL questionnaire and the Study to Enhance Understanding of sTent-associated Symptoms (STENTS). The Core Outcome Set in Trials on treatments for Renal and UreteriC sTones (COSTRUCT) study aims to define a core outcome set to be used in future trials. On-going studies will provide higher quality evidence on the treatment of ureteric and renal stones to inform treatment decision making and guideline recommendations. They will also guide decisions relating to prevention and recurrence and give insight into the true impact of urinary stones and endourological interventions on patients' quality of life. Future studies will incorporate big data and artificial intelligence.