ArticleLiterature Review

Review finds core outcome set uptake in new studies and systematic reviews needs improvement

June 2022
Journal of Clinical Epidemiology 150(2)

DOI:10.1016/j.jclinepi.2022.06.016

License
CC BY 4.0

Authors:

Paula Williamson

University of Liverpool

Jane M Blazeby

University of Bristol

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Objective: To review evidence about the uptake of core outcome sets (COS). A COS is an agreed standardized set of outcomes that should be measured and reported, as a minimum, in all clinical trials in a specific area of health or health care. Study design and setting: This article provides an analysis of what is known about the uptake of COS in research. Similarities between COS and outcomes recommended by stakeholders in the evidence ecosystem is reviewed, and actions taken by them to facilitate COS uptake described. Results: COS uptake is low in most research areas. Common facilitators relate to trialist awareness and understanding. Common barriers were not including in the development process all specialties who might use the COS, and the lack of recommendations for how to measure the outcomes. Increasingly, COS developers are considering strategies for promoting uptake earlier in the process, including actions beyond traditional dissemination approaches. Overlap between COS and outcomes in regulatory documents and health technology assessments is good. An increasing number and variety of organisations are recommending COS be considered. Conclusion: We suggest actions for various stakeholders for improving COS uptake. Research is needed to assess the impact of these actions to identify effective evidence-based strategies.

Assessing the uptake of infertility core outcome set in IVF randomized controlled trials

Article

Full-text available

Dec 2024
HUM REPROD

STUDY QUESTION Do the infertility core outcome set and standardized definitions affect the outcome selection for randomized controlled trials, and what aspects should be further improved in the future? SUMMARY ANSWER Intrauterine pregnancy demonstrated the highest uptake level, whereas others were low, especially in neonatal outcomes; as time progresses, the target sample size increases, and with prospective registration, the consistency between outcomes reported in registrations and infertility core outcome set improves significantly. WHAT IS KNOWN ALREADY The infertility core outcome set, published on 30 November 2020, aims to standardize outcome reporting and prevent selective reporting bias; however, there is a paucity of research evaluating its actual adoption, which is crucial for the timely promotion of transparency, standardization, adjustment of development strategies, and efficient resource utilization. STUDY DESIGN, SIZE, DURATION This cross-sectional study included 1673 eligible randomized controlled trial registrations for infertility in 18 registries from March 2004 to July 2024 based on registry entries. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 4625 infertility-related studies from 1 November 1999 to 26 July 2024 were retrieved in the World Health Organization International Clinical Trials Registry Platform. Finally, 1673 randomized controlled trial registrations were selected and divided into four period groups. Period, target sample size, prospective registration, blinding, support, and countries/regions were potential influencing factors. The consistency of outcomes, definitions, and standardized denominators of randomized controlled trial registry entries with the recommendations of the infertility core outcome set were the main outcomes. Independent retrieval, screening, data extraction, and consistency evaluations by two assessors and expert consultations were conducted to assess the uptake and potential influencing factors of the infertility core outcome set in randomized controlled trials involving infertile patients undergoing in vitro fertilization. MAIN RESULTS AND THE ROLE OF CHANCE Results reveal that the reporting level in the pregnancy domain was significantly higher than that in the neonatal domain (13.6% vs 5.7%). Intrauterine pregnancy (66.9%), live birth (27.6%), and miscarriage (26.5%) had relatively high uptake levels. The uptake of most core outcomes and domains, as well as the total number of reported core outcomes, showed statistically significant differences based on period, target sample size, and prospective registration. Multivariable analyses supported the above finding. Reasons responsible for the results may be attributed to the lack of effective promotional measures, as well as the limited researcher awareness regarding this core outcome set. LIMITATIONS, REASONS FOR CAUTION Some results in this study may have been influenced by the subjective judgment of the evaluators due to the complexity of the information in registries. WIDER IMPLICATIONS OF THE FINDINGS Uptake of most core outcomes or domains is increasing but is not yet ideal. Moreover, the upward trend cannot be solely attributed to the publication of the infertility core outcome set. The key to promoting uptake is to thoroughly explore and recognize the factors that both facilitate and hinder the uptake of the infertility core outcome set, further expand and publicize the core outcome set, and foster multidisciplinary or multiple stakeholder cooperation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Capital’s Funds for Health Improvement and Research (CFH 2024-2G-4097), as well as the special fund of Beijing Key Clinical Specialty Construction Project. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER http://www.comet-initiative.org/Studies/Details/3184

Harmonising outcome measurement for child focused domestic abuse interventions. Reflections on the development and implementation of a core outcome set

Article

Full-text available

Mar 2024

There is appetite in the UK to better measure the impact of domestic violence and abuse (DVA) interventions on children. The spread of outcomes-based commissioning means outcome measurement is no longer just the territory of academic researchers but is now firmly within the purview of practitioners and policy makers. However, outcomes measured in trials only partially represent the views of those delivering and using services with respect to how success should be defined and captured. Even within trials there is huge inconsistency in the definition and measurement of important endpoints. This yields a body of evidence that is difficult to make sense of, defeating the ends for which it was produced – to improve the response to children and families who have experienced abuse. Development of Core Outcome Sets (COS) is seen as a solution to this problem, by establishing consensus across key stakeholder groups regarding a minimum standard for outcome measurement in trials, and increasingly in service delivery contexts. To date COS development has addressed outcomes relating to health conditions or interventions, with limited application to public health challenges. We reflect on our efforts to develop a COS to evaluate psychosocial interventions for children and families experiencing DVA. We highlight the value of COS development as a mechanism for improving evidence quality and the response to families experiencing abuse. Finally, we make recommendations to researchers and COS guideline developers to support this broader application of COS methodology.

European Glaucoma Society – A guide on surgical innovation for glaucoma

Article

Full-text available

Dec 2023

Prologue Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the “advent” of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us “bring benefit, not harm” and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an ‘add-on’ to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS’s Vision and Mission. Fotis Topouzis EGS President Contributors All contributors have provided the appropriate COI visible in detail at www.eugs.org/pages/guidesurgical/ This manuscript reflects the work and thoughts of the list of individuals recognized above, but importantly, it reflects EGS views on the subject matter. Its strength originates from a team effort, where a cohesive group of authors and reviewers have worked towards a common goal and now stand behind the text in its entirety. The EGS nevertheless wishes to thank the following external contributors for their additional expertise, which was particularly valuable to the development of this Surgical Guide: Amanda Bicket, Jonathan Bonnar, Catey Bunce, Kuan Hu, Sheffinea Koshy, Jimmy Le, Tianjing Li, Francisco Otarola, Riaz Qureshi, Anupa Shah, Richard Stead and Marta Toth. A particular appreciation goes to Ian Saldanha for drafting the introductory overview on Core Outcomes on chapter 8. Finally, EGS would like to acknowledge Augusto Azuara Blanco, Chair of the Scientific and Guidelines Committee, for his expertise and advisory role throughout the entire process. Luis Abegao Pinto Editor Gordana Sunaric Mégevand Editor Ingeborg Stalmans Editor Luis Abegao Pinto , Centro Hospitalar Universitário Lisboa Norte Hana Abouzeid , Clinical Eye Research Centre Adolph de Rothschild, AZ Ophthalmologie Eleftherios Anastasopoulos , Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece Augusto Azuara Blanco , Centre for Public Health, Queen’s University Belfast Luca Bagnasco , Clinica Oculistica, DiNOGMI University of Genoa Alessandro Bagnis , Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Joao Barbosa Breda , Faculty of Medicine of the University of Porto, Porto, Portugal. Centro Hospitalar e Universitário São João, Porto, Portugal. KULeuven, Belgium Keith Barton , University College London, Moorfields Eye Hospital Amanda Bicket , University of Michigan (Ann Arbor, MI, USA) Jonathan Bonnar , Belfast Health and Social Care Trust Chiara Bonzano , Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Rupert Bourne , Cambridge University Hospital Alain Bron , University Hospital Dijon Catey Bunce , King’s College London Carlo Cutolo , Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Barbara Cvenkel , University Medical Centre Ljubljana Faculty of Medicine, University of Ljubljana Antonio Fea , University of Turin Theodoros Filippopoulos , Athens Vision Eye Institute Panayiota Founti , Moorfields Eye Hospital NHS Foundation Trust Stefano Gandolfi , U.O.C. Oculistica, University of Parma Julian Garcia Feijoo , Hospital Clinico San Carlos, Universidad Complutense, Madrid Gerhard Garhoefer , Medical University of Vienna, Austria David Garway Heath , Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Gus Gazzard , Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Stylianos Georgoulas , Addenbrooke’s, Cambridge University Hospitals Dimitrios Giannoulis , Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece Franz Grehn , University Hospitals Wuerzburg Kuang Hu , NIHR Moorfields Biomedical Research Centre, London – Institute of Ophthalmology – University College London Michele Iester , Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Hari Jayaram , Moorfields Eye Hospital Gauti Johannesson , Umea University Stylianos Kandarakis , National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens, Greece. Efthymios Karmiris , Hellenic Air Force General Hospital & National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens Alan Kastner , Clinica Oftalmologica Pasteur, Santiago, Chile Andreas Katsanos , University of Ioannina, Greece Christina Keskini , Aristotle University of Thessaloniki, AHEPA Hospital Anthony Khawaja , Moorfields Eye Hospital and UCL Institute of Ophthalmology Anthony King , Nottingham University Hospitals NHS Trust James Kirwan , Portsmouth hospitals university NHS trust Miriam Kolko , University of Copenhagen, Copenhagen University Hospital Rigshospitalet Sheffinea Koshy , University of Galway Antoine Labbe , Quinze-Vingts National Ophthalmology Hospital Jimmy Le , Johns Hopkins Bloomberg School of Public Health, Baltimore Sanna Leinonen , Tays Eye Centre, Tampere University Hospital Sophie Lemmens , University Hospitals UZ Leuven Tianjing Li , School of Medicine, University of Colorado Anschutz Medical Campus Giorgio Marchini , Clinica Oculistica, University Hospital, AOUI, Verona, Italy José Martinez De La Casa , Hospital Clinico San Carlos. Universidad Complutense Andy McNaught , Gloucestershire Eye Unit Frances Meier Gibbons , Eye Center Rapperswil, Switzerland Karl Mercieca , University Hospitals Eye Clinic, Bonn, Germany Manuele Michelessi , IRCCS – Fondazione Bietti Stefano Miglior , University of Milan Bicocca Eleni Nikita , Moorfields Eye Hospital NHS Foundation Trust Francesco Oddone , IRCCS Fondazione Bietti Francisco Otarola , Universidad de La Frontera Marta Pazos , Institute of Ophthalmology. Hospital Clínic Barcelona. Researcher at Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Norbert Pfeiffer , Mainz University Medical Center Verena Prokosh , University of Cologne, Center for ophthalmology. Riaz Qureshi , Johns Hopkins Medicine, Baltimore Gokulan Ratnarajan , Queen Victoria Hospital, East Grinstead, UK Herbert Reitsamer , University Clinic Salzburg / SALK Luca Rossetti , University of Milan, ASST Santi Paolo e Carlo, Milano, Italy Ian Saldanha , Johns Hopkins Bloomberg School of Public Health, Baltimore Cedric Schweitzer , CHU Bordeaux, Univ. Bordeaux, ISPED, INSERM, U1219 – Bordeaux Population Health Research Centre, France Andrew Scott , Moorfields Eye Hospital London Riccardo Scotto , Clinica Oculistica, DiNOGMI University of Genoa Anupa Shah , Queen’s University Belfast George Spaeth , Wills Eye Hospital/Sidney Kimmel Medical College/Thomas Jefferson University Ingeborg Stalmans , University Hospitals UZ Leuven, Catholic University KU Leuven Richard Stead, Nottingham University Hospitals NHS Trust Francesco Stringa , University Hospital Southampton NHS FT Gordana Sunaric , Centre Ophtalmologique de Florissant, Centre de Recherche Clinique en Ophtalmologie Mémorial Adolphe de Rothschild Andrew Tatham , University of Edinburgh, Princess Alexandra Eye Pavilion Mark Toeteberg , University Hospital Zurich Fotis Topouzis , Aristotle University of Thessaloniki, AHEPA Hospital Marta Toth , Moorfields Eye Hospital NHS Foundation Trust Carlo Traverso , Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Anja Tuulonen , Tays Eye Centre, Tampere University Hospital Clemens Vass , Medical University of Vienna Ananth Viswanathan , Moorfields Eye Hospital NHSFT and UCL Institute of Ophthalmology Richard Wormald , UCL Institute of Ophthalmology External Reviewers American Glaucoma Society Asia-Pacific Glaucoma Society Middle East Africa Glaucoma Society World Glaucoma Society www.eugs.org/pages/externalreviewers The team of Clinica Oculistica of the University of Genoa for medical editing and illustration Luca Bagnasco Alessandro Bagnis Chiara Bonzano Carlo Cutolo Michele Iester Riccardo Scotto Carlo Traverso

Irish funder guidance increased searching for, and uptake of, Core Outcome Sets

Article

Full-text available

Mar 2023
J CLIN EPIDEMIOL

Objective: Assess the impact of the Health Research Board (HRB) Ireland guidance on the uptake of core outcome sets (COS). Study design and setting: 1. Information on COS use, searching of the Core Outcome Measures in Effectiveness Trials (COMET) database and rationale for outcome selection were extracted from HRB funding applications 2. COMET was searched for relevant COS availability at the time of application or developed since 3. PI choices were explored through online surveys. Results: Out of 187 funding applications, 44% (n=82) searched the COMET database, and 13% (n=11) of those found a relevant COS to inform their outcomes. Four applicants proposed COS development. However, 84% (n=156) of applications had no relevant COS available at the time of submission, as identified by subsequent author COMET search. Among 84 Principal Investigators who participated in the surveys, 10 (12%) found and used a COS and 19 (42%) of the 45 respondents who did not reference COMET had searched the COMET database. A new question in the application form prompted a rise in those reporting a search of the COMET database from 6% to 99%. Conclusion: The study found low COS uptake in funding applications, but a new application question prompted an increase in reporting searches of the COMET database. Funder guidance promoted COS awareness and use, but more efforts are needed to facilitate COS development and adoption in clinical research.

Core outcome sets in cancer clinical trials: current status and future opportunities—an EORTC perspective

Article

Full-text available

Apr 2025
TRIALS

Background Inconsistent, varied and selective outcome reporting is problematic in clinical trials. Core outcome sets (COS) standardise the outcomes that should be measured and reported in all trials in a specific area of health or health care. We reviewed available cancer COS and assessed their uptake in cancer clinical trials through surveying members of the European Organisation for Research and Treatment of Cancer (EORTC). Methods This study employs an exploratory cross-sectional design across two phases. The Core Outcome Measures in Effectiveness Trials (COMET) Initiative database was searched for cancer-specific COS on June 1st, 2023. Awareness and use of COS amongst EORTC trialists was assessed in November 2023 via an online survey. Results We identified a total of 85 cancer-related COS on the COMET database. Of these, 69 related to the tumour types as categorised by the EORTC and their disease orientated groups. A total of 710 EORTC members responded, of whom half (50%) stated they were unfamiliar with COS. Relevant COS were available to over a quarter of respondents, with a tenth utilising available COS. Those who chose not to use an available COS cited volume of outcomes, lack of time and infrastructure for implementation as key barriers. Conclusions While COS are becoming increasingly available to, and acknowledged by, cancer clinical trialists, their implementation is currently still limited. Our findings indicate that further development of COS to fill gaps for missing tumour types, greater involvement of trialists in the COS development process, and increased awareness and understanding of COS amongst trialists are all required to ensure widespread implementation of COS in cancer clinical trials.

Uptake of core outcome sets in paediatric clinical trials: a protocol

Article

Full-text available

Mar 2025

Introduction A growing number of paediatric core outcome sets (COS) have been developed in the past 20 years. Previous studies have provided many useful insights into the uptake of COS. In addition to the awareness of COS among clinical trialists, the COS development process (especially patient participation) and the actions of the developers can promote COS uptake. However, the uptake of COS in paediatric clinical trials needs to be further explored. The aim of this study is to provide information on the rationale and use of paediatric COS in clinical trials, and to analyse in depth the awareness and views of COS developers and clinical trialists about the development and use of COS. Methods and analysis We will include all paediatric COS identified in our previous systematic review and those subsequently included in the Core Outcome Measures in Effectiveness Trials (COMET) database. We will extract the target condition, population, intervention, list of core outcomes and the details of patient involvement. Next, we will search the Clinicaltrials.gov and WHO International Clinical Trials Registry Platform for trials on health conditions addressed by the identified COS. We will assess the comparability of the scopes in each COS-trial pair and determine for the outcomes in each clinical trial if they match exactly or generally, or if they do not match, with the outcomes of their respective COS. Finally, we will conduct a survey and semistructured interviews among COS developers and clinical trialists to examine their views. Ethics and dissemination Ethical approval for the study has been granted by the ethics committee of the Institute of Health Data Science, Lanzhou University (No. HDS-202405–01). This study was registered on COMET ( https://www.comet-initiative.org/Studies/Details/3122 ).

Assessing the Uptake of Core Outcome Sets in Randomized Controlled Trials for Inflammatory Bowel Disease: A Cross-Sectional Study

Article

Full-text available

Dec 2024

Background Increasing prevalence and significant medical expenses associated with Inflammatory Bowel Disease (IBD) necessitate high-quality clinical research to evaluate treatment effectiveness. Randomized control trials (RCTs) provide robust evidence, but the diversity of outcomes used in these trials poses challenges in summarizing outcomes for systematic reviews. Core Outcome Sets (COS) were established to improve the comparability of outcomes across studies. The aim of this study is to examine the uptake of the COS for IBD within clinical trials. Methods This cross-sectional analysis involved screening ClinicalTrials.gov for RCTs evaluating outcomes in patients with IBD. We extracted information on the four outcome domains — (1) symptoms, function, and quality of life; (2) disutility of care; (3) healthcare utilization; and (4) survival and disease control — and trial characteristics. Extraction was performed in a masked, duplicate manner. Results The initial search identified 3,205 trials from ClinicalTrials.gov, and after exclusions, the final sample included 177 clinical trials for analysis. The uptake of COS over time was not statistically significant. The most frequently reported outcomes were change in bowel symptoms (88.1%, 156/177) and pain or discomfort (83.1%, 147/177). In contrast, no trial reported on colorectal cancer, only 1% (2/177) reported overall survival, and 8% (15/177) reported cause of death. Conclusion Our study revealed no increase in adherence to COS in IBD clinical trials, before or after the publication of the IBD COS. We recommend that trialists make efforts to implement COS in clinical trials to improve the standardization across studies in the field of IBD.

Uptake of core outcome sets in pediatric clinical trials: a protocol

Preprint

Full-text available

May 2024

Introduction A growing number of pediatric core outcome sets (COS) have been developed in the past 20 years. Previous studies have provided many useful insights into the uptake of COS. In addition to the awareness of COS among clinical trialists, some methodology of COS development (especially patient involvement) can promote COS uptake. However, the uptake of COS in pediatric clinical trials needs to be further explored. The aim of this study is to provide information on the rationale and use of pediatric COS in clinical trials, and to analyze in depth the awareness and views of COS developers and clinical trialists about the development and use of COS. Methods and analysis We will include all pediatric COS identified in our previous systematic review and those subsequently included in the COMET database. We will extract the data including the target condition, population, intervention, list of core outcomes, and the details of patient involvement. Next, we will search Clinicaltrials.gov for trials on health conditions addressed by the identified COS. The comparability of the scopes in each COS-trial pair and for the outcomes in each clinical trial that are exact matches, general matches, and non-matches with outcomes in each relevant COS will be assessed. Finally, we will conduct a survey and semi-structured interviews among COS developers and clinical trialists to examine their views. Ethics and dissemination Ethical approval for the study has been granted by the ethics committee of the Lanzhou University. Strengths and limitations of the proposed study The uptake of pediatric COS will be presented and analyzed in a comprehensive manner through comparative analysis of the literature and a combination of quantitative and qualitative methods. There will be language restrictions in the selection of the studies, and the survey and interview sample will include only subjects speaking English or Chinese. Both restrictions may limit the generalizability of our results.

Representation of published core outcome sets in practice guidelines

Article

Full-text available

Feb 2024
J CLIN EPIDEMIOL

Objective A Core Outcome Set (COS) is an agreed standardised 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 healthcare 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 setting We searched for clinical guidelines relevant to ten high-quality COS (with focus on UK, Germany, China, India, Canada, Denmark, USA and WHO). 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 PICO statement. Results We 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% to 100%). Conclusion There 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.

Using behavioral science to increase core outcome set use in trials

Article

Feb 2024
J CLIN EPIDEMIOL

The Uptake of the Core Outcome Set for Non-Specific Low Back Pain Clinical Trials is Poor: A Meta-Epidemiological Study of Trial Registrations

Article

Aug 2023
J PAIN

We conducted a meta-epidemiological study on all NSLBP trial registrations on the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. We aimed to: (1) assess the uptake of the core outcome set (COS) for non-specific low back pain (NSLBP) in clinical trials; (2) assess the uptake of the core outcome measurement set (COMS) for NSLBP in clinical trials; and (3) determine whether specific study characteristics are associated with the COS uptake. After applying the relevant filters for the condition, study type, and the phase of the trial, 240 registry entries were included in this study. Only 50 (20.8%) entries showed a full COS uptake, and this rate did not increase over time. Most registry entries that planned to measure physical functioning (n = 152) used the Roland Morris Disability Questionnaire (n = 74; 48.7%); a small percentage used the Numeric Rating Scale (n = 60; 27.3%) or Short Form-12 (n = 5; 8.3%) if they planned to measure pain intensity (n = 220) or health-related quality of life (n = 60), respectively. Only the planned sample size (OR = 1.02; 95% CI = 1.01, 1.03.) showed a significant but small association with COS uptake. The uptake of the COS for NSLBP is poor. Only 21% of randomised controlled trials aimed to measure all COS domains in their study registration, and COS uptake is not increasing over time. Great heterogeneity in measurement instruments was also observed, revealing poor COMS uptake. PERSPECTIVE: The Core Outcome Set (COS) for non-specific low back pain was published more than 20 years ago. We evaluated whether trial registrations are using this set of outcomes when testing interventions for low back pain. Full uptake was found only in 21% of the sample, and this is not increasing over time. Researchers should use the COS to ensure that trials measure relevant outcomes consistently.

The Harmonising Outcome Measures for Eczema (HOME) implementation roadmap

Article

Full-text available

Aug 2023
BRIT J DERMATOL

Background: Core outcome sets (COS) are consensus-driven sets of minimum outcomes that should be measured and reported in all clinical trials. COS aim to reduce heterogeneity in outcome measurement and reporting, and selective outcome reporting. Implementing COS into clinical trials is challenging. Guidance to improve COS uptake in dermatology is lacking. Objective: To develop a structured practical guide to COS implementation. Methods: Members of the Harmonising Outcome Measurement for Eczema (HOME) executive committee developed an expert-opinion based roadmap founded on a combination of a review of COS implementation literature, the Core Outcome Measures in Effectiveness Trials (COMET) initiative resources, input from HOME members, and experience in COS development and clinical trials. Results: The data review and input from HOME members was synthesized into themes which guided roadmap development: a. barriers and facilitators to COS uptake based on stakeholder awareness/engagement and COS features; b. key implementation science principles: assessment-driven, data-centered, priority-based, and context-sensitive.The HOME implementation roadmap follows 3 stages. First, the COS uptake scope and goals need to be defined. Second, during COS development, preparation for future implementation is supported by establishing the COS as a credible evidence-informed consensus by applying robust COS development methodology, engaging multiple stakeholders, fostering sustained and global engagement, emphasizing COS ease-of-use and universal applicability, and providing recommendations on COS use. Third, incorporating completed COS into primary (trials) and secondary (reviews) research is an iterative process starting with mapping COS uptake and stakeholders' attitudes, followed by designing and carrying out targeted implementation projects. Main themes for implementation projects identified at HOME are stakeholder awareness/engagement; universal applicability for different populations; and improving ease-of-use by reducing administrative and study burden. Formal implementation frameworks can be utilized to identify implementation barriers/facilitators and to design implementation strategies. The effect of these strategies on uptake should be evaluated, and implementation plans adjusted accordingly. Conclusion: COS can improve the quality and applicability of research and so clinical practice but can only succeed if used and reported consistently. The HOME implementation roadmap is an extension of the original HOME roadmap for COS development and provides a pragmatic framework to develop COS implementation strategies.

Developing a core outcome set for interventions in people with mild cognitive impairment: study protocol

Article

Full-text available

Jan 2025

Introduction There is no standardised national guidance on clinical management for people living with mild cognitive impairment (MCI), and therapeutic interventions are limited. Understanding what outcomes are important and meaningful to people living with MCI and developing a core outcome set (COS) for research and clinical practice will improve the impact of clinical research and contribute towards developing effective care pathways for MCI. This study aims to develop a COS for adults living with MCI intended for use in interventional and clinical settings. Methods and analysis The COS will be developed using a five-stage study design: (1) systematic literature search, (2) qualitative interviews, (3) evidence synthesis from stages 1 and 2, (4) two-round Delphi survey and (5) consensus meeting(s). First, we will conduct an umbrella review of existing MCI interventional studies and extract a list of outcomes. Qualitative interviews will be held with key stakeholders including individuals living with MCI, friends and family, and relevant professionals to identify further outcomes considered important. Outcomes from the review and interviews will be synthesised into a ‘long list’ of outcomes for potential inclusion in the COS. Two rounds of Delphi surveys followed by a consensus meeting will be used to reach stakeholder consensus on which outcomes should be included in the final COS. Ethics and dissemination We have received ethical approval from the London—Queen Square Research Ethics Committee (23/PR/1580). Patient and public involvement and engagement are central to developing the COS. The results will be disseminated via conferences, peer-reviewed publications, briefing notes to key agencies, to the public via social media and blog posts and directly to stakeholders who participate in the project. Trial registration number Core Outcome Measures in Effectiveness Trials Initiative 2117; PROSPERO registration: CRD42023452514.

Editorial: The relevance of core outcome sets to clinical guideline development

Article

Full-text available

Aug 2024

Uptake of core outcome sets by clinical trialists in China: a protocol

Article

Jul 2024

Background The concept of core outcome sets (COS) has been introduced in China for about 10 years. In recent years, some Chinese researchers also committed to developing COS, though the majority of COS are ongoing. However, there were more than 500 published COS for research in the COMET database by 2020. The extent of availability of COS for the top 25 diseases with the highest burden in China is unknown. In addition, the uptake of COS in clinical trials for these diseases is unknown, along with the knowledge, perceptions, and views of the clinical trialist community in China on the use of COS in relation to choosing outcomes for their research. Methods The main burden of disease in China will be identified. Then we will search the COMET database to identify if there are ongoing or completed relevant COS research A COS published since 2012 would be preferred to one published before 2012 for the analysis of COS uptake if one meets the eligibility criteria. We will extract scopes of published eligible COS, including condition, population, interventions, and core outcomes. Then we will search the Chinese Clinical Trial Registry using disease names for each disease that has a published COS. We will assess the overlap in scope between clinical trials and COS. Then we will conduct an online survey and semi-structured interviews to identify the knowledge and perceptions of COS among primary investigators of included clinical trials. Discussion This research will fill in gaps between COS and the burden of disease in China. Understanding clinical trialists’knowledge and perceptions of COS may help dissemination and application of COS in the future. Trial registration This research is registered in Core Outcome Measures in Effectiveness: https://www.comet-initiative.org/Studies/Details/2563.

Developing a core outcome set for interventions in people with mild cognitive impairment: study protocol

Preprint

Full-text available

Jul 2024

Introduction There is no standardised national guidance on clinical management for people living with mild cognitive impairment (MCI) and therapeutic interventions are limited. Understanding what outcomes are important and meaningful to people living with MCI and developing a core outcome set for research and clinical practice will improve the impact of clinical research and contribute towards developing effective care pathways for MCI. This study aims to develop a core outcome set (COS) for adults living with MCI intended for use in interventional and clinical settings. Methods and analysis The COS will be developed using a five-stage study design: (1) systematic literature search; (2) qualitative interviews; (3) evidence synthesis from stage 1 and 2; (4) two-round Delphi survey; (5) consensus meetings. First, we will conduct an umbrella review of existing MCI interventional studies and extract a list of outcomes. Qualitative interviews will be held with key stakeholders including individuals living with MCI, friends and family, and relevant professionals to identify further outcomes considered important. Outcomes from the review and interviews will be synthesised into a long list of outcomes for potential inclusion in the COS. Two rounds of a Delphi surveys followed by a consensus meeting will be used to reach stakeholder consensus on which outcomes should be included in the final COS. Ethics and dissemination We have received ethical approval from London - Queen Square Research Ethics Committee (23/PR/1580). Patient and public involvement and engagement are central to developing the COS. The results will be disseminated via conferences, peer-reviewed publications, briefing notes to key agencies, to the public via social media and blog posts, and directly to stakeholders who participate in the project. Trial registration number Core Outcome Measures in Effectiveness Trials (COMET) Initiative 2117; PROSPERO registration: CRD42023452514.

Experiences of core outcome set developers on including stakeholders from low- and middle-income countries: An online survey

Article

Full-text available

Jun 2024

Core outcome set (COS) development and use enhances comparability of research findings. It may also enhance the translation of research into practice and reduce research waste. However, there is limited involvement of stakeholders from low- and middle-income countries (LMICs) in COS development and use. In this study, we explored the experiences of researchers in COS development projects who included stakeholders from LMICs. Online survey conducted in English of 70 COS developers from HICs who had included LMIC stakeholders in the process of developing a COS, published before the end of 2019. Respondents were identified from the COMET database and sent a link to the survey via a personalised email. Quantitative data were analysed using simple descriptive statistics. Qualitative data analysis was based on qualitative content analysis. There were 37 respondents yielding a 53% overall response rate. Analysis was limited to the responses related to 29 COS developed in the years 2015 to 2019, to reduce the potential for recall bias for earlier COS. Most respondents 20/29 (69%) were researchers. Determining ‘what to measure’ was reported as the most common stage of inclusion of LMIC stakeholders. Respondents cited (24/29, 83%) their ongoing collaborations with LMIC stakeholders such as clinicians or researchers as their main rationale for including LMICs stakeholders and reported that translation of the Delphi into languages other than English may be useful to enhance wider stakeholder participation. Involvement of LMIC stakeholders only in the later stages of COS development, lack of adequate resources to support their involvement, and lack of networks and contacts were thought to limit fuller participation of stakeholders from LMICs. To improve the involvement of LMIC stakeholders in COS development and use, COS developers need to raise awareness on the utility of COS. The need for and feasibility of translation into multiple languages warrants further discussion.

Factors influencing use and choice of Core Outcome Sets and outcome measurement instruments in trials of interventions to prevent childhood obesity: A survey protocol

Article

Full-text available

May 2024

Background Two core outcome sets for childhood obesity prevention have been developed; standardised sets of outcome measurement instruments for these core outcome sets are currently being developed. Core outcome sets and standardised measurement sets can reduce heterogeneity and improve evidence syntheses for trials of interventions to prevent childhood obesity and/or interventions to improve child health behaviours related to childhood obesity. Such benefits are only realised if core outcome sets and standardised measurement sets are used in trials. The aims of this study are 1) to examine trialists’ awareness and attitudes towards the two existing core outcome sets and factors influencing their use; 2) to explore the characteristics of outcome measurement instruments that trialists currently use; and 3) to better understand how trialists choose outcome measurement instruments and the factors that influence those choices. Methods A cross-sectional online survey will be conducted with researchers involved in the design and/or conduct of trials of interventions to prevent childhood obesity and/or to improve child health behaviours related to childhood obesity, in children aged 0 to 5 years (trialists). Trialists will be recruited using purposive sampling, and will complete a 22-item survey examining trialist characteristics, awareness of the existing core outcome sets, factors influencing use of the existing core outcome sets, characteristics of measurement instruments, how trialists choose measurement instruments, and factors influencing choice of measurement instrument. Quantitative data will be analysed descriptively; responses to open-ended questions will be analysed using qualitative content analysis. Conclusions Findings from this study will inform approaches to maximising use of core outcome sets and standardised measurement sets for childhood obesity prevention. Use of standardised approaches to what and how outcomes are measured in this area will reduce heterogeneity and research waste and enhance evidence syntheses to better determine intervention effects.

Which outcomes should be included in a Core Outcome Set for capturing and measuring doctor well-being? A Delphi study

Preprint

Full-text available

Apr 2024

Objectives To develop a core outcome set (COS) to capture and measure the well-being of doctors working in the NHS. Design An online Delphi study. Setting United Kingdom National Health Service. Participants Participants from four stakeholder groups: i) those who might use the COS in research, ii) organisations that measure/capture NHS staff wellbeing, iii) professionals with experience managing NHS staff wellbeing, and iv) NHS doctors, were identified through authorship of relevant publications, attendee lists of doctor well-being conferences and meetings, professional bodies, participation in a previous study and recommendations from others. They were recruited via email. Method A two-stage process: 1) creating a list of 43 wellbeing outcomes informed by a systematic review of wellbeing measurement instruments, a survey of UK doctors and 2 doctor engagement workshops, and 2) an online modified Delphi study (with two rounds) to reach consensus. Outcomes were rated on a 9-point Likert scale; ‘consensus’ was reached when < 75% agreed that an outcome was critical for inclusion in the COS. Results Fifty-two participants completed both Delphi rounds. Seven wellbeing outcomes met the threshold for inclusion in the COS: General wellbeing, Health, Personal safety, Job satisfaction, Morale, Life work balance, and Good clinical practice. Conclusion Use of the COS has the potential to reduce heterogeneity and standardise the capture and measurement of doctor well-being and ensure outcomes important to all stakeholders are reported. Trial registration This study was prospectively registered with the COMET initiative www.comet-initiative.org (Registration: 1577)

Uptake of core outcome sets by clinical trialists in China: a protocol

Article

Mar 2024

Individual and organizational interventions to promote staff health and well-being in residential long-term care: a systematic review of randomized controlled trials over the past 20 years

Article

Full-text available

Mar 2024
BMC Nurs

Background Staff in residential long-term care (RLTC) experience significant physical and mental work demands. However, research on specific interventions to promote staff health and well-being in RLTC facilities is limited. This systematic review aimed to synthesize the current evidence on health promotion interventions among RLTC staff. Methods A comprehensive systematic literature review was conducted on studies published between January 2000 and April 2023. Four electronic databases were searched, including PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and PsychArticles via EBSCO. The review followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The methodological quality of the included studies was assessed using the Risk of Bias Assessment tool (RoB 2). Results A total of 26 publications, referring to 23 different interventions with a randomized controlled design were included. Among these interventions, ten used training/educational approaches, six used behavioral approaches, and seven employed a multimodal approach. Significant improvements in health and well-being outcomes were found in four interventions using a training/educational approach, three interventions using a behavioral approach, and four interventions using a multimodal approach. Within the interventions studied, twelve specifically targeted the reduction of job demands, while only one intervention exclusively addressed job resources among RLTC staff. Furthermore, ten interventions addressed primary outcomes that encompassed both job demands and job resources. Conclusion Current evidence for health promotion interventions among RLTC staff is still limited, but research suggests that there is potential to improve certain outcomes related to RLTC staff health and well-being. Future research is recommended to contemplate a tailored intervention design that encompasses both individual-level and organizational-level approaches, and gender-specific physiological and sociological characteristics of RLTC staff. Moreover, detailed reporting of the development process, and research on the interaction between job demands and resources of RLTC staff are also recommended.

Comparing risk-adjusted inpatient fall rates internationally: validation of a risk-adjustment model using multicentre cross-sectional data from hospitals in Switzerland and Austria

Article

Full-text available

Mar 2024
BMC HEALTH SERV RES

Background Inpatient falls in hospitals are an acknowledged indicator of quality of care. International comparisons could highlight quality improvement potential and enable cross-national learning. Key to fair cross-national comparison is the availability of a risk adjustment model validated in an international context. This study aimed to 1) ascertain that the variables of the inpatient fall risk adjustment model do not interact with country and thus can be used for risk adjustment, 2) compare the risk of falling in hospitals between Switzerland and Austria after risk adjustment. Methods The data on inpatient falls from Swiss and Austrian acute care hospitals were collected on a single measurement day in 2017, 2018 and 2019 as part of an international multicentre cross-sectional study. Multilevel logistic regression models were used to screen for interaction effects between the patient-related fall risk factors and the countries. The risks of falling in hospital in Switzerland and in Austria were compared after applying the risk-adjustment model. Results Data from 176 hospitals and 43,984 patients revealed an inpatient fall rate of 3.4% in Switzerland and 3.9% in Austria. Two of 15 patient-related fall risk variables showed an interaction effect with country: Patients who had fallen in the last 12 months (OR 1.49, 95% CI 1.10–2.01, p = 0.009) or had taken sedatives/psychotropic medication (OR 1.40, 95% CI 1.05–1.87, p = 0.022) had higher odds of falling in Austrian hospitals. Significantly higher odds of falling were observed in Austrian (OR 1.38, 95% CI 1.13–1.68, p = 0.002) compared to Swiss hospitals after applying the risk-adjustment model. Conclusions Almost all patient-related fall risk factors in the model are suitable for a risk-adjusted cross-country comparison, as they do not interact with the countries. Further model validation with additional countries is warranted, particularly to assess the interaction of risk factors “fall in the last 12 months” and “sedatives/psychotropic medication intake” with country variable. The study underscores the crucial role of an appropriate risk-adjustment model in ensuring fair international comparisons of inpatient falls, as the risk-adjusted, as opposed to the non-risk-adjusted country comparison, indicated significantly higher odds of falling in Austrian compared to Swiss hospitals.

Brain health measurement: a scoping review

Article

Full-text available

Feb 2024

Objectives Preservation of brain health is an urgent priority for the world’s ageing population. The evidence base for brain health optimisation strategies is rapidly expanding, but clear recommendations have been limited by heterogeneity in measurement of brain health outcomes. We performed a scoping review to systematically evaluate brain health measurement in the scientific literature to date, informing development of a core outcome set. Design Scoping review. Data sources Medline, APA PsycArticles and Embase were searched through until 25 January 2023. Eligibility criteria for selecting studies Studies were included if they described brain health evaluation methods in sufficient detail in human adults and were in English language. Data extraction and synthesis Two reviewers independently screened titles, abstracts and full texts for inclusion and extracted data using Covidence software. Results From 6987 articles identified by the search, 727 studies met inclusion criteria. Study publication increased by 22 times in the last decade. Cohort study was the most common study design (n=609, 84%). 479 unique methods of measuring brain health were identified, comprising imaging, cognitive, mental health, biological and clinical categories. Seven of the top 10 most frequently used brain health measurement methods were imaging based, including structural imaging of grey matter and hippocampal volumes and white matter hyperintensities. Cognitive tests such as the trail making test accounted for 286 (59.7%) of all brain health measurement methods. Conclusions The scientific literature surrounding brain health has increased exponentially, yet measurement methods are highly heterogeneous across studies which may explain the lack of clinical translation. Future studies should aim to develop a selected group of measures that should be included in all brain health studies to aid interstudy comparison (core outcome set), and broaden from the current focus on neuroimaging outcomes to include a range of outcomes.

Core Outcome Measurement Set for Shared Decision Making in Rheumatic and Musculoskeletal Conditions: A Scoping Review to Identify Candidate Instruments

Article

Dec 2023
SEMIN ARTHRITIS RHEU

Awareness and experiences on core outcome set development and use amongst stakeholders from low- and middle- income countries: An online survey

Article

Full-text available

Dec 2023

Harmonization of outcomes to be measured in clinical trials can reduce research waste and enhance research translation. One of the ways to standardize measurement is through development and use of core outcome sets (COS). There is limited involvement of low- and middle-income country (LMIC) stakeholders in COS development and use. This study explores the level of awareness and experiences of LMIC stakeholders in the development and use of COS. We conducted an online survey of LMIC stakeholders. Three existing COS (pre-eclampsia, COVID-19, palliative care) were presented as case scenarios, and respondents asked to state (with reason(s)) if they would or would not use the COS if they were working in that area. Quantitative data were analyzed descriptively while qualitative data were analyzed thematically. Of 81 respondents, 26 had COS experience, 9 of whom had been involved in COS development. Personal research interests and prevalence of disease are key drivers for initiation/participation in a given COS project. Most respondents would use the COS for pre-eclampsia (18/26) and COVID-19 (19/26) since the development process included key stakeholders. More than half of the respondents were not sure or would not use the palliative care COS as they felt stakeholder engagement was limited and it was developed for a different resource setting. Respondents reported that use of COS can be limited by (i) feasibility of measuring the outcomes in the COS, (ii) knowledge on the usefulness and availability of COS and (iii) lack of wide stakeholder engagement in the COS development process including having patients and carers in the development process. To ensure the development and use of COS in LMICs, collaborations are essential in awareness raising on COS utility, training, and COS development. The COS also needs to be made accessible in locally understandable languages and feasible to measure in LMICs.

Common measures or common metrics? the value of IRT-based common metrics

Article

Full-text available

Nov 2023

Caroline B Terwee

There is a clear need to harmonize outcome measurement. Some authors propose to express scores as T scores to facilitate interpretation of PROM results in clinical practice. While this is a step in the right direction, there are important limitations to the acceptance of the T score metric as a common metric when T scores are based on raw sum scores of ordinal items: Such T scores of different instruments are not exactly comparable because they are not interval scaled; T scores of different measures are only on the same scale if exactly the same reference group is used; and the T sore metric cannot be maintained because it is reference population-dependent and needs to be updated regularly. These limitations can be overcome by using an item response theory (IRT)-based metric. Items from different measures can be placed on the same IRT metric to make scores comparable on an interval scale. The PROMIS initiative used IRT to develop item banks for measuring various health outcomes. Other PROMs have been linked to the PROMIS metric. Although PROMIS uses a T-score metric for practical reasons, the underlying PROMIS metric is actually an IRT metric. An IRT approach also enables further development of an item bank while preserving the underlying metric. Therefore, IRT-based metrics should be considered as common metrics for the future.

Core outcome set for pulmonary rehabilitation of patients with COPD: results of a modified Delphi survey

Article

Sep 2023

Introduction There is high heterogeneity of outcomes and measures reported in pulmonary rehabilitation (PR) trials of people with chronic obstructive pulmonary disease (COPD). This hinders study comparability and benchmarking of PR. We have developed a core outcome set (COS) to overcome these challenges. Methods This study was informed by a systematic review and two qualitative studies and had patient involvement since its inception. A two-round Delphi survey was available in seven languages. Outcomes (n=63) scored 7–9 (crucial) by ≥70% of the participants and 1–3 (not that important) by ≤15% of participants from both groups in the Likert scale were automatically included in the COS, while outcomes that were considered crucial by only one of the groups were further discussed by the authors in a meeting. Results A total of 299 people (n=229 healthcare professionals/researchers/policy-makers; n=70 people with COPD and informal caregivers) participated in the survey (83% retention), which covered 29 countries/five continents. After the second round, six outcomes were included and three were added in the meeting. The final COS contains dyspnoea, fatigue, functional exercise capacity, health-related quality of life, health behaviours/lifestyle, knowledge about the disease, lower limb muscle function, personal goals and problematic activities of daily living. Conclusion A COS for PR of people with COPD is now available and can be used by different stakeholders to improve consistency and comparability of studies, benchmark PR and improve the quality of care provided. Future research should establish the core measures and investigate the uptake of this COS.

Uptake of core outcome sets by clinical trialists in China: a protocol

Article

Aug 2023

Background: The concept of core outcome sets (COS) has been introduced in China for about 10 years. In recent years, some Chinese researchers also committed to developing COS, though the majority of COS are ongoing. However, there were more than 500 published COS for research in the COMET database by 2020. Whether the disease category of ongoing and completed COS include the burden of disease in China is unclear. In addition, whether the published COS are used by clinical trialists is also unclear. In this research, we would like to investigate if COS are applicable to the burden of disease in China, and to ascertain whether completed COS are used by clinical trialists in China. Methods: The main burden of disease in China will be identified. Then we will search the COMET database to identify if there are ongoing or completed relevant COS research since 2012. Only COS for clinical trials or clinical research will be included. We will extract scopes of published eligible COS, including condition, population, interventions, and core outcomes. Then we will search the Chinese Clinical Trial Registry using disease names for each disease that has a published COS. We will assess the overlap in scope between clinical trials and COS. Then we will conduct an online survey and semi-structured interviews to identify the knowledge and perceptions of COS among primary investigators of included clinical trials. Discussion: This research will fill in gaps between COS and the burden of disease in China. Understanding clinical trialists’ knowledge and perceptions of COS may help dissemination and application of COS in the future. Trial registration: This research is registered in Core Outcome Measures in Effectiveness: https://www.comet-initiative.org/Studies/Details/2563.

Improvement studies for building capacity at Bali State Poly-technic

Article

Full-text available

Jul 2023

Bali State Polytechnic has 6 majors, with 32 study programs. As many prospective students are interested in studying at the Bali State Polytechnic, it is not in line with the addition of classrooms. Until the 2021, PNB ideally needs 214 classrooms, while the number of available rooms is 142 classrooms. Thus PNB in 2021 still has a shortage of 72 learning rooms. In this study, a case study was taken in a Civil Engineering lecture building with a study of increasing space capacity through adding floors to existing buildings. The research was conducted by analyzing the strength of the building in terms of structure. The methods used are field studies and data analysis. Field studies are carried out through testing on the strength of existing structures, then from the results of field studies continued by analyzing additional designs. The capacity of the lecture building at the Bali State Polytechnic can be increased because the strength of the existing lecture building structure is able to bear the load due to the addition of space capacity from 2 floors to 3 floors.

Updating the ATS/ERS Task Force Report on Outcomes for COPD Pharmacological Trials

Article

May 2023

Background: In 2008, a dedicated American Thoracic Society (ATS)/European Respiratory Society (ERS) task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in COPD patients. Since then our scientific understanding of COPD has increased considerably since then, there has been a progressive shift from a one-size-fits-all diagnostic/therapeutic approach to a personalized approach, and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Results: Endpoints, outcomes and biomarkers have been revisited. The limitations of some of those reported in the ERS/ATS task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Since the 'label-free' treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, which will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help identify better the right patient to be treated with the new drugs.

Development of core outcome sets for both research and care

Article

Full-text available

May 2023
ACTA OBSTET GYN SCAN

Measures for the Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS)

Article

Full-text available

Apr 2023

Unlabelled: To gain consensus on measurement methods for outcomes (delirium occurrence, severity, time to resolution, mortality, health-related quality of life [HrQoL], emotional distress including anxiety, depression, acute stress, and post-traumatic stress disorder, and cognition) of our Core Outcome Set (COS) for trials of interventions to prevent and/or treat delirium in critically ill adults. Design: International consensus process. Setting: Three virtual meetings (April 2021). Patients/subjects: Critical illness survivors/family, clinicians, and researchers from six Countries. Interventions: None. Measurements and main results: Measures (selected based on instrument validity, existing recommendations, and feasibility) and measurement time horizons were discussed. Participants voted on instruments and measurement timing (a priori consensus threshold ≥ 70%). Eighteen stakeholders (28% ICU survivors/family members) participated. We achieved consensus on the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist to measure delirium occurrence and delirium resolution (100%), Hospital Anxiety and Depression Scale for emotional distress (71%), and Montreal Cognitive Assessment-Blind for cognition (83%). We did not achieve consensus on EQ-5D five-level for HrQoL (69%) or its measurement at 6 months. We also did not achieve consensus on the Impact of Event Scale (IES)-Revised or IES-6 for post-traumatic stress (65%) or on measurement instruments for delirium severity incorporating delirium-related emotional distress. We were unable to gain consensus on when to commence and when to discontinue assessing for delirium occurrence and time to resolution, when to determine mortality. We gained consensus that emotional distress and cognition should be measured up to 12 months from hospital discharge. Conclusions: Consensus was reached on measurement instruments for four of seven outcomes in the COS for delirium prevention or treatment trials for critically ill adults. Further work is required to validate instruments for delirium severity that include delirium-related emotional distress.

Lessons learned from the INTEGRATE-Pain Delphi process to develop core outcome sets (COS) across the pain continuum

Article

Feb 2025
PAIN MED

A Core Outcome Set for Trials in CKD: Report of the Standardized Outcomes in Nephrology–Chronic Kidney Disease (SONG-CKD) Stakeholder Workshops

Article

Jan 2025

Leptomeningeal metastatic disease: new frontiers and future directions

Article

Dec 2024
NAT REV CLIN ONCOL

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients. Underdiagnosis and misdiagnosis are common, response assessment remains challenging, and the prognosis associated with this disease of whole neuroaxis remains extremely poor. The dearth of effective therapies is further challenged by the difficulties in studying this dynamic disease state. In this Review, a multidisciplinary group of experts describe the emerging evidence and areas of active investigation in LMD and provide directed recommendations for future research. Drawing upon paradigm-changing advances in mechanistic science, computational approaches, and trial design, the authors discuss domain-specific and cross-disciplinary strategies for optimizing the clinical and translational research landscape for LMD. Advances in diagnostics, multi-agent intrathecal therapies, cell-based therapies, immunotherapies, proton craniospinal irradiation and ongoing clinical trials offer hope for improving outcomes for patients with LMD.

Core Patient-Reported Outcomes for Trials in Nephrology

Article

Sep 2024
SEMIN NEPHROL

Core outcome set for intervention research on snakebite envenomation in South Asia

Article

Full-text available

Sep 2024

Background The 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden. Methods We used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori. Results Overall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part. Conclusion The COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.

Supporting meaningful participation of older people in core outcome set development

Article

Sep 2024
J AM GERIATR SOC

Developing a core outcome set for evaluating medication adherence interventions for adults prescribed long-term medication in primary care

Article

Apr 2024
RES SOC ADMIN PHARM

Increasing Uptake through Collaboration in the Development of Core Outcome Sets: Lessons Learned at OMERACT 2023

Article

Mar 2024
SEMIN ARTHRITIS RHEU

Study found increasing use of core outcome sets in Cochrane systematic reviews and identified facilitators and barriers

Article

Feb 2024

Core outcome set developers should consider and specify the level of granularity of outcome domains

Article

Feb 2024
J CLIN EPIDEMIOL

How to use the HOME Core Outcome Set for atopic dermatitis trials – a users’ guide

Article

Full-text available

Dec 2023

The Harmonizing Outcome Measures for Eczema (HOME) initiative has agreed upon the core outcome set for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximise uptake of the core set. This article provides answers to some of the commonly asked questions about using the HOME core outcome set. It also provides data to aid interpretation of trial results and to support sample size calculations for future trials. By encouraging adoption of the core outcome set and facilitating consistent reporting of outcome data, we hope that results of eczema trials will be more comprehensive and readily combined in meta-analyses and patient care will be improved.

Prognostic value of neurofilament light in blood in patients with polyneuropathy: A systematic review

Article

Dec 2023
J PERIPHER NERV SYST

Background and Aims Neurofilament light protein (NfL) is a part of the neuronal skeleton, primarily expressed in axons and is released when nerves are damage. NfL has been found to be a potential diagnostic biomarker in different types of polyneuropathies. However, whether NfL levels can be used as a predictor for the risk of disease progression is currently less understood. Methods We searched MEDLINE (PubMed), Embase, Cochrane Library, and Web of Science Searches and included longitudinal studies with a baseline and follow‐up examination of adult patients with polyneuropathy and NfL measured in blood. Results Twenty studies investigating NfL as a predictor of disease progression were identified, examining eight polyneuropathy subtypes. The results from studies in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients were divergent, with two out of five studies finding a statistically significant association between NfL levels and clinical outcome. Meta‐analysis of the three Guillian‐Barré Syndrome (GBS) studies found higher odds for the inability to run after one year in patients with high levels of NfL (OR 2.18, 95% CI 1.04‐4.56). Results from studies examining other subacute or chronic polyneuropathies like Charcot‐Marie‐Tooth (CMT) varied in study design and results. Interpretation Our findings suggest NfL can be used as a predictor of disease progression, particularly in polyneuropathies as CIDP and GBS. However, NfL may not serve as a reliable and cost‐effective biomarker for slowly progressive polyneuropathies like CMT. Future standardized studies considering NfL as a prognostic blood biomarker in patients with different types of polyneuropathies are warranted.

Using behavioural science to enhance use of core outcome sets in trials: protocol

Article

Nov 2023

Background Core outcome sets (COS) represent agreed-upon sets of outcomes, which are the minimum that should be measured and reported in all trials in specific health areas. Use of COS can reduce outcome heterogeneity, selective outcome reporting, and research waste, and can facilitate evidence syntheses. Despite benefits of using COS, current use of COS in trials is low. COS use can be understood as a behaviour, in that it is something trialists do, or not do, adequately. The aim of this study is to identify strategies, informed by behaviour change theory, to increase COS use in trials. Methods The project will be conducted in two stages, informed by the behaviour change wheel (BCW). The BCW is a theoretically based framework that can be used to classify, identify, and develop behaviour change strategies. In Stage 1, barriers and enablers to COS use will be extracted from published studies that examined trialist’s use of COS. Barriers and facilitators will be mapped to the components of COM-B model (capability, opportunity, and motivation), which forms part of the BCW framework. Stage 2 will build on Stage 1 findings to identify and select intervention functions and behaviour change techniques to enhance COS use in trials. Discussion The findings of this study will provide an understanding of the behavioural factors that influence COS use in trials and what strategies might be used to target these factors to increase COS use in trials.

Current trends, barriers, and facilitators of use of core outcome sets in Cochrane systematic reviews: Protocol

Article

Sep 2023

Background : Core outcome sets (COS) represent agreed-upon minimum outcomes that should be reported in all studies in a given topic area. Cochrane reviews are considered among the most rigorously conducted systematic reviews (SRs). In 2019, seven of the first 100 published Cochrane SRs (7%) cited a COS in relation to choosing outcomes. A relevant COS existed but was not mentioned (or cited) for 27 of the remaining 93 SRs (29%). Among Cochrane Review Group editors surveyed in 2019, 86% felt that COS should definitely/possibly be used in Cochrane SRs. As of September 2019, the Cochrane Handbook recommends that SR teams consult resources that host relevant COS when choosing outcomes for the SR. Objectives : (1) Examine the extent to which authors are currently considering COS to inform outcome choice in Cochrane protocols and completed SRs. (2) Understand author barriers and facilitators of using COS in Cochrane protocols and completed SRs. Methods: We will examine the extent to which all Cochrane SRs published in the last 3 months of 2022 and all Cochrane protocols published in 2022: (a) cited a COS, (b) searched for COS, and (c) reported outcome inconsistency among included studies and/or noted the need for COS. One investigator will extract information from SRs and protocols; a second extractor will verify all information, discussing discrepancies to achieve consensus. Using Jisc Online Surveys ® , we will conduct an online survey of authors of all the included completed SRs and protocols to assess author awareness of COS and identify barriers and facilitators of using COS to inform outcome choice. Discussion: This study will provide key information regarding uptake of COS by Cochrane SR authors and the barriers and facilitators that they experience. Our findings will inform approaches to increasing awareness and uptake of COS in future SRs, both within and beyond Cochrane.

Assessment highlights need for improvement in standards of development for rare genetic diseases core outcome sets

Article

Jul 2023
J CLIN EPIDEMIOL

Objective: A rare disease is classified as such if it affects less than 1 persons in 2,000. The Core Outcome Set STandards for Development (COS-STAD) is a set of standards that represent the minimum recommendations to be considered in the process of COS development. The aim of this study was to provide a baseline assessment of COS development standards for rare genetic diseases. Study design and setting: Core Outcome Measures in Effectiveness Trials (COMET) database contains 447 published COS studies. Studies focusing on COS development for rare genetic diseases were eligible for inclusion and were assessed by two independent evaluators. Results: Nine COS studies were included in the analysis. Eight different rare genetic diseases were investigated. None of the studies met all standards for development. The number of standards met ranged from 6 to 10 and the median was 7. Conclusion: This study is the first assessment of COS-STAD for rare genetic diseases COS studies and it highlights a great need for improvement. First in terms of numbers of rare diseases considered for COS developments, second in methodology, particularly regarding the consensus process and third in reporting of the COS development studies.

Current trends, barriers, and facilitators of use of core outcome sets in Cochrane systematic reviews: Protocol

Article

Jun 2023

Background : Core outcome sets (COS) represent agreed-upon minimum outcomes that should be reported in all studies in a given topic area. Cochrane reviews are considered among the most rigorously conducted systematic reviews (SRs). In 2019, seven of the first 100 published Cochrane SRs (7%) cited a COS in relation to choosing outcomes. A relevant COS existed but was not mentioned (or cited) for 27 of the remaining 93 SRs (29%). Among Cochrane Review Group editors surveyed in 2019, 86% felt that COS should definitely/possibly be used in Cochrane SRs. As of September 2019, the Cochrane Handbook recommends that SR teams consult resources that host relevant COS when choosing outcomes for the SR. Objectives : (1) Examine the extent to which authors are currently considering COS to inform outcome choice in Cochrane protocols and completed SRs. (2) Understand author barriers and facilitators of using COS in Cochrane protocols and completed SRs. Methods: We will examine the extent to which all Cochrane SRs published in the last 3 months of 2022 and all Cochrane protocols published in 2022: (a) cited a COS, (b) searched for COS, and (c) reported outcome inconsistency among included studies and/or noted the need for COS. One investigator will extract information from SRs and protocols; a second extractor will verify all information, discussing discrepancies to achieve consensus. Using Jisc Online Surveys®, we will conduct an online anonymous survey of authors of all the included completed SRs and protocols to assess author awareness of COS and identify barriers and facilitators of using COS to inform outcome choice. Discussion: This study will provide key information regarding uptake of COS by Cochrane SR authors and the barriers and facilitators that they experience. Our findings will inform approaches to increasing awareness and uptake of COS in future SRs, both with and beyond Cochrane.

Involving people with lived experience in developing a core outcome set for implant dentistry research. The Implant Dentistry-Core Outcomes Sets and Measures (ID-COSM) project

Article

May 2023
CLIN ORAL IMPLAN RES

Aims: The aims of this project were to establish the outcomes for dental implant research that are important to people with lived experience (PWLE) and to achieve consensus with those developed by dental professionals (DPs) for a core outcome set (COS). This paper reports the process, outcomes and experiences of involving PWLE in developing a COS for dental implant research: the Implant Dentistry Core Outcome Sets and Measures project. Materials and methods: Overall methods were guided by the Core Outcome Set Measures in Effectiveness Trials (COMET) initiative. Initial outcome identification was achieved from focus groups with PWLE employing calibrated methods across two low-middle-income countries (China and Malaysia) and two high-income countries (Spain and the United Kingdom). Following consolidation of the results, the outcomes were incorporated into a three-stage Delphi process with PWLE participation. Finally, consensus between PWLE and DPs was achieved using a mixed live and recorded platform. The experiences of PWLE involvement in the process was also evaluated. Results: Thirty-one PWLE participated in four focus groups. Thirty-four outcomes were suggested across the focus groups. Evaluation of the focus groups revealed a high level of satisfaction with the engagement process and some new learning. Seventeen PWLE contributed to the first 2 Delphi rounds and 7 to the third round. The final consensus included 17 PWLE (47%) and 19 DPs (53%). Out of the total of 11 final consensus outcomes considered essential by both PWLE and health professionals, 7 (64%) outcomes mapped across to ones that PWLE initially identified, broadening their definition. One outcome (PWLE effort required for treatment and maintenance) was entirely novel. Conclusions: We conclude that engaging PWLE in COS development can be achieved across widely different communities. Furthermore, the process both broadened and enriched overall outcome consensus, yielding important and novel perspectives for health-related research.

Involving people with lived experience in developing a core outcome set for implant dentistry research. The Impant Dentistry-Core Outcomes Sets and Measures (ID-COSM) project

Article

May 2023
J CLIN PERIODONTOL

A pilot study assessing the similarity between core outcome sets and outcomes included in health technology assessments

Article

Full-text available

May 2022

Objective: Core outcome sets (COS) are an agreed standardised collection of outcomes created with representation from all key stakeholders (such as patients, clinicians, researchers), which should be reported as a minimum for all trials in that corresponding clinical area. There has been little research investigating the use of core outcomes in Health technology assessments (HTAs) and none in non-oncology HTAs. This study aimed to assess the similarity between COS and HTA outcomes. Methods: Ten COS published between 2015 and 2019 were selected, with patient participation taken as a proxy measure for a high quality COS. The INAHTA database was used as a source to identify relevant HTAs, which were accessed through the hyperlinks provided. Outcomes selected for these assessments were categorised as either a specific, partial or no match compared to the COS. An additional cohort of non-oncology HTAs published between 2019 and 2021 were identified from the NICE website and compared against a relevant COS. Results: Six hundred and fifty-one HTAs were matched to the ten COS areas, of which 119 were reviewed. Of a possible 1318 core outcome matches, there were 562 (43%) matches, 413 (31%) specific and 149 (11%) partial. NICE HTA matches against corresponding COS ranged from 44% to 100%, with a total of 78% (73/94) matches, 57 (61%) specific and 16 (17%) partial. Conclusion: Further work is required to promote the awareness and implementation of COS within HTAs. The degree of matching between COS and NICE HTA outcomes is encouraging, demonstrating acceptance of COS by HTA producers.

Enhancing patient and public contribution in health outcome selection during clinical guideline development: an ethnographic study

Article

Full-text available

Mar 2022
BMC HEALTH SERV RES

Background Patient and public involvement (PPI) is a cornerstone in enhancing healthcare research and delivery, including clinical guideline development. Health outcomes concern changes in the health status of an individual or population that are attributable to an intervention. Discussion of relevant health outcomes impacts the resulting clinical guidelines for practice. This study explores how the input of PPI contributors at the National Institute of Health and Care Excellence (NICE) is integrated into guideline development, particularly in relation to health outcome selection. Methods The study used an ethnographic methodological approach. Data comprised: observations of committee meetings, scoping workshops and training sessions, and in-depth interviews with PPI contributors, health professionals and chairs from clinical guideline development committees. Data were analysed thematically. Results PPI contributors’ input in the guideline development process was often of limited scope, particularly in selecting health outcomes. Key constraints on their input included: the technical content and language of guidelines, assumed differences in the health-related priorities between PPI contributors and health professionals, and the linear timeline of the guideline development process. However, PPI contributors can influence clinical guideline development including the selection of relevant health outcomes. This was achieved through several factors and highlights the important role of the committee chair, the importance of training and support for all committee members, the use of plain language and the opportunity for all committee members to engage. Conclusions Lay member input during the outcome selection phase of clinical guideline development is achievable, but there are challenges to overcome. Study findings identify ways that future guideline developers can support meaningful lay involvement in guideline development and health outcome selection.

Outcome selection for tissue-agnostic drug trials for immune-mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance

Article

Full-text available

Jan 2022
TRIALS

Background Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to: Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies. Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration Not registered.

Usefulness of Cochrane Reviews in Clinical Guideline Development-A Survey of 585 Recommendations

Article

Full-text available

Jan 2022
Int J Environ Res Publ Health

The Danish Health Authority develops clinical practice guidelines to support clinical decision-making based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and prioritizes using Cochrane reviews. The objective of this study was to explore the usefulness of Cochrane reviews as a source of evidence in the development of clinical recommendations. Evidence-based recommendations in guidelines published by the Danish Health Authority between 2014 and 2021 were reviewed. For each recommendation, it was noted if and how Cochrane reviews were utilized. In total, 374 evidence-based recommendations and 211 expert consensus recommendations were published between 2014 and 2021. Of the 374 evidence-based recommendations, 106 included evidence from Cochrane reviews. In 28 recommendations, all critical and important outcomes included evidence from Cochrane reviews. In 36 recommendations, a minimum of all critical outcomes included evidence from Cochrane reviews, but not all important outcomes. In 33 recommendations, some but not all critical outcomes included evidence from Cochrane reviews. Finally, in nine recommendations, some of the important outcomes included evidence from Cochrane reviews. In almost one-third of the evidence-based recommendations, Cochrane reviews were used to inform clinical recommendations. This evaluation should inform future evaluations of Cochrane review uptake in clinical practice guidelines concerning outcomes important for clinical decision-making.

Bridging health technology assessment and healthcare quality improvement using international consortium of health outcomes measurement standard sets

Article

Full-text available

Jan 2022

Objective Although health technology assessment (HTA) and healthcare quality improvement are distinct processes, a greater level of alignment in outcome measures used may increase the quality and efficiency of data collection. This study evaluates the agreement in outcome measures used in oncology for healthcare quality improvement and HTAs, and how these align to the International Consortium for Health Outcomes Measurement (ICHOM) standard sets. Methods We conducted a cross-sectional comparative analysis of ICHOM sets focusing on oncological indications and publicly available measures for healthcare quality and HTA reports published by the National Health Care Institute from the Netherlands and the National Institute for Health and Care Excellence from the United Kingdom. Results All ICHOM sets and HTAs used overall survival, whereas quality improvement used different survival estimates. Different progression estimates for cancer were used in HTAs, ICHOM sets, and quality improvement. Data on health-related quality of life (HRQoL) was recommended in all ICHOM sets and all HTAs, but selectively for quality improvement. In HTAs, generic HRQoL questionnaires were preferred, whereas, in quality improvement and ICHOM sets, disease-specific questionnaires were recommended. Unfavorable outcomes were included in all HTAs and all ICHOM sets, but not always for quality improvement. Conclusions Although HTA and quality improvement use outcome measures from the same domains, a greater level of alignment seems possible. ICHOM may provide input on standardized outcome measures to support this alignment. However, residual discrepancies will remain due to the different objectives of HTA and quality improvement.

A survey of knowledge, perceptions and use of core outcome sets among clinical trialists

Article

Full-text available

Dec 2021
TRIALS

Background Core outcome sets (COS) are standardised sets of outcomes, which represent the minimum outcomes that should be measured and reported in clinical trials. COS can enhance comparability across health trials by reducing heterogeneity of outcome measurement and reporting and potentially minimising selective outcome reporting. Examining what researchers involved in trials know and think about COS is essential to increase awareness and promote COS uptake. The aim of this study is therefore to examine clinical trialists’ knowledge, perceptions and experiences of COS. Methods An online survey design was used. Participants were clinical trialists, operationalised for the current study as researchers named as the contact person on a trial registered on the International Standard Randomised Controlled Trial Number (ISRCTN) Trial repository between 1 January 2019 and 21 July 2020. Survey items assessed clinical trialists’ familiarity with and understanding of COS, along with experiences of COS use and development. Results Of 1913 clinical trialists contacted to participate, 62 (3%) completed the survey. Forty (65%) participants were familiar with COS and, of those familiar with COS, 21 (55%) had been involved in a trial that used a COS. Of clinical trialists who used COS in a trial(s), less than half ( n = 9, 41%) reported that all COS outcomes were used. The main barriers to using COS are poor knowledge about COS ( n = 43, 69%) and difficulties identifying relevant COS ( n = 42, 68%). Clinical trialists also reported perceptions of COS as restrictive and often containing too many outcomes. The main enablers to using COS are clear understanding ( n = 51, 82%) and perceived importance of COS ( n = 44, 71%). Conclusions Enhancing clinical trialists’ use of all COS outcomes is needed to reduce outcome heterogeneity and enhance comparability across trial findings. Enhancing awareness of COS importance among researchers and funders is needed to ensure that COS are developed and used by clinical trialists. Education and training may further promote awareness and understanding of COS.

Outcomes assessed in therapeutic randomized controlled trials in hospitalized patients with COVID-19: is the meta Core Outcome Set (meta-COS) adopted?

Article

Full-text available

Nov 2021
CLIN MICROBIOL INFEC

ERS Statement: A core outcome set for clinical trials evaluating the management of chronic obstructive pulmonary disease (COPD) exacerbations

Article

Full-text available

Oct 2021

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritized for inclusion in the core outcome set through a two-round Delphi survey that was completed by 1,063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in 5 continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to (i) finalize the core outcome set and (ii) prioritize a single measurement instrument to be used for evaluating each of the prioritized outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for in all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, need for higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimize some of the selected measurement instruments. The panel did not consider the prioritized set of outcomes and associated measurement instruments burdensome for patients and health professionals to use.

More than half of systematic reviews have relevant core outcome sets

Article

Full-text available

May 2021
J CLIN EPIDEMIOL

Objectives Using recent systematic reviews (SRs), our objectives were to: (1) develop a framework to assess whether a given COS is relevant to the scope of a SR; (2) examine the proportion of SRs for which relevant COS exist; and (3) for SRs for which COS exist, examine the extent to which outcomes in the COS and outcomes in the SR match. Study Design and Setting We included a sample of SRs published by the Agency for Healthcare Research and Quality Evidence-based Practice Center Program between January 1, 2018 and October 12, 2020. We searched for potentially relevant COS from the Core Outcome Measures for Effectiveness Trials (COMET) database. We assessed the matching between outcomes recommended by COS and those included in corresponding SRs. When outcomes were matched, we considered matches to be specific (i.e., exact) or general (i.e., non-specific). Results Sixty-seven SRs met criteria. We found relevant COS for 36/67 SRs (54%). Our framework for comparing the scope of a SR and a COS describes 16 scenarios arising when the breadth of the populations and the interventions are considered. The framework guides systematic reviewers to determine whether a COS is very likely to be relevant, may be relevant, or unlikely to be relevant. Sixty-two percent of outcomes in COS (interquartile range, 40% to 80%) were either specific or general matches to outcomes in SRs. Conclusion We found a COS with relevant scope for more than half of the SRs in our sample, with almost two-thirds of the recommended core outcomes matched to outcomes chosen for the SRs. Consideration of COS appears relevant for SR planning and our framework for assessing relevance of a given COS may help with this process.

Realising the full potential of data-enabled trials in the UK: A call for action

Article

Full-text available

May 2021

Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Representation of published core outcome sets for research in regulatory guidance: protocol

Article

Full-text available

May 2021

Background: The COMET Initiative promotes the development and use of ‘core outcome sets’ (COS), agreed standardised sets of outcomes that should be measured and reported in all studies in a particular clinical condition. COS are determined by consensus amongst key stakeholders, including health professionals, policymakers and patients, ensuring that the priorities and expertise of these representatives inform the choice of the most important outcomes to measure for a given condition. There is increased recognition of the need to integrate COS across the healthcare system and with existing regulatory apparatus, to ensure that outcomes being recorded are those of key relevance to important stakeholders. The aim of this study is to assess the degree of concordance between outcomes recommended in COS for research and in guidance provided by two key regulators: US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Methods: COS for research published during 2015-2019 with patient involvement and covering drug or device interventions will be compared against relevant regulatory guidelines, matched by condition. Guidance documents which match in scope (relating to intervention and population) to a COS for research will be scrutinised to identify all suggested outcomes for comparison against the core outcomes in the corresponding COS. Discussion: This study will identify variation between outcomes suggested in EMA and FDA regulatory guidance relative to outcomes included in published COS for research, thus demonstrating the degree of representation of COS in regulatory guidance and vice versa. If the findings of this study reveal a lack of concordance between COS and regulatory guidance overall or for particular disease areas, we will invite feedback from FDA and EMA and will seek to highlight where findings support the recommendations towards using well-developed COS or will make recommendations to COS developers on outcomes of importance to these key regulators.

Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review

Article

Full-text available

Dec 2020

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies.

A systematic review finds Core Outcome Set uptake varies widely across different areas of health

Article

Full-text available

Sep 2020

Objective: The aim of our review was to bring together studies that had assessed the uptake of core outcome sets (COS) to explore the level of uptake across different COS and areas of health. Study design and setting: We examined the citations of 337 COS reports to identify studies that had assessed the uptake of a particular COS in randomised controlled trials (RCTs) or systematic reviews (SRs). Results: We identified 24 studies that had assessed uptake in RCTs and two studies that has assessed uptake in SRs. The studies covered a total of 17/337 (5%) COS. Uptake rates reported for RCTs varied from 0% of RCTs (gout) to 82% RCTs (rheumatoid arthritis) measuring the full COS. Studies that assessed uptake of individual core outcomes showed wide variation in uptake between the outcomes. Suggested barriers to uptake included lack of validated measures, lack of patient and other key stakeholder involvement in COS development and lack of awareness of the COS. Conclusions: Few studies have been undertaken to assess the uptake of COS in RCTs and SRs. Further studies are needed to assess whether COS have been implemented across a wider range of disease categories and to explore the barriers and facilitators to COS uptake.

Assessing the relevance and uptake of core outcome sets (an agreed minimum collection of outcomes to measure in research studies) in Cochrane systematic reviews: A review

Article

Full-text available

Sep 2020

Objectives: A core outcome set (COS) is an agreed standardised minimum collection of outcomes that should be measured and reported in research in a specific area of health. Cochrane systematic reviews ('reviews') are rigorous reviews on health-related topics conducted under the auspices of Cochrane. This study examines the use of existing COS to inform the choice of outcomes in Cochrane systematic reviews ('reviews') and investigates the views of the coordinating editors of Cochrane Review Groups (CRGs) on this topic. Methods: A cohort of 100 recently published or updated Cochrane reviews were assessed for reference to a COS being used to inform the choice of outcomes for the review. Existing COS, published 2 or more years before the review publication, were then identified to assess how often a reviewer could have used a relevant COS if it was available. We asked 52 CRG coordinating editors about their involvement in COS development, how outcomes are selected for reviews in their CRG and their views of the advantages and challenges surrounding the standardisation of outcomes within their CRG. Results: In the cohort of reviews from 2019, 40% (40/100) of reviewers noted problems due to outcome inconsistency across the included studies. In 7% (7/100) of reviews, a COS was referenced in relation to the choice of outcomes for the review. Relevant existing COS could be considered for a review update in 35% of the others (33/93). Most editors who responded (31/36, 86%) thought that COS should definitely or possibly be used to inform the choice of outcomes in a review. Conclusions: Systematic reviewers are continuing to note outcome heterogeneity but are starting to use COS to inform their reviews. There is potential for greater uptake of COS in Cochrane reviews.

Core outcome sets through the healthcare ecosystem: the case of type 2 diabetes mellitus

Article

Full-text available

Dec 2020
TRIALS

Background: It is increasingly accepted that insufficient attention has been given to the patient health outcomes that are important to measure in comparative effectiveness research that will inform decision-making. The relationship between outcomes chosen for comparative effectiveness research, outcomes used in decision-making in routine care, and outcome data recorded in electronic health records (EHR) is also poorly understood. The COMET Initiative (http://www.comet-initiative.org/. Accessed 3 Apr 2020) supports and encourages the development and use of 'core outcome sets' (COS), which represent the minimum set of patient health outcomes that should be measured and reported for a specific condition. There is growing interest in identifying how COS might fit into the different stages of the healthcare research and delivery ecosystem, and whether inclusion in the EHR might facilitate this. Methods: We sought to determine the degree of overlap between outcomes within COS for research and routine care, EMA, FDA and NICE guidelines, NICE quality statements/indicators, EHR and a point-of-care randomised clinical trial, using type 2 diabetes (T2D) as a case study. Results: There is substantial agreement about important patient outcomes for T2D for research and healthcare, with associated coverage within the UK general practice EHR. Conclusions: This case study has demonstrated the potential for efficient research and value-based healthcare when the EHR can include COS for both research and care, where the COS comprises outcomes of importance to all relevant stakeholders. However, this concordance may not hold more generally, as the focus on patient-centred outcomes may well be greater in T2D than in other conditions. Work is ongoing to examine other clinical areas, in order to highlight any current inefficiencies when health outcomes in research and healthcare do not agree with core outcomes identified by patients, clinicians and other key stakeholders.

Methods used in the selection of instruments for outcomes included in Core Outcome Sets have improved since the publication of the COSMIN/COMET guideline

Article

Full-text available

May 2020
J CLIN EPIDEMIOL

Objectives Once a core outcome set (COS) has been defined, it is important to achieve consensus on how these outcomes should be measured. The aim of this systematic review is to gain insight into the methods used to select outcome measurement instruments and determine whether methods have improved following the COSMIN/COMET guideline publication. Study Design and Setting Eligible articles, which were identified from the annual COMET systematic review, concerned any COS development studies that provided a recommendation on how to measure the outcomes included in the COS. Data was extracted on the methods used to select outcome measurement instruments in accordance with the COSMIN/COMET guideline. Results Of the 118 studies included in the review, 48% used more than one source of information when finding outcome measurement instruments and 74% performed some form of quality assessment of the measurement instruments. Twenty-three studies recommended one single instrument for each core outcome included in the COS. Clinical experts and public representatives were involved in selecting instruments in 62% and 28% of studies, respectively. Conclusion Methods used to select outcome measurement instruments have improved since the publication of the COSMIN/COMET guideline. Going forward COS developers should ensure that recommended outcome measurement instruments have sufficient content validity. In addition, COS developers should recommend one instrument for each core outcome to contribute to the overarching goal of uniformity in outcome reporting.

A scoping review of core outcome sets and their ‘mapping’ onto real-world data using prostate cancer as a case study

Article

Full-text available

Feb 2020
BMC MED RES METHODOL

Background: A Core Outcomes Set (COS) is an agreed minimum set of outcomes that should be reported in all clinical studies related to a specific condition. Using prostate cancer as a case study, we identified, summarized, and critically appraised published COS development studies and assessed the degree of overlap between them and selected real-world data (RWD) sources. Methods: We conducted a scoping review of the Core Outcome Measures in Effectiveness Trials (COMET) Initiative database to identify all COS studies developed for prostate cancer. Several characteristics (i.e., study type, methods for consensus, type of participants, outcomes included in COS and corresponding measurement instruments, timing, and sources) were extracted from the studies; outcomes were classified according to a predefined 38-item taxonomy. The study methodology was assessed based on the recent COS-STAndards for Development (COS-STAD) recommendations. A 'mapping' exercise was conducted between the COS identified and RWD routinely collected in selected European countries. Results: Eleven COS development studies published between 1995 and 2017 were retrieved, of which 8 were classified as 'COS for clinical trials and clinical research', 2 as 'COS for practice' and 1 as 'COS patient reported outcomes'. Recommended outcomes were mainly categorized into 'mortality and survival' (17%), 'outcomes related to neoplasm' (18%), and 'renal and urinary outcomes' (13%) with no relevant differences among COS study types. The studies generally fulfilled the criteria for the COS-STAD 'scope specification' domain but not the 'stakeholders involved' and 'consensus process' domains. About 72% overlap existed between COS and linked administrative data sources, with important gaps. Linking with patient registries improved coverage (85%), but was sometimes limited to smaller follow-up patient groups. Conclusions: This scoping review identified few COS development studies in prostate cancer, some quite dated and with a growing level of methodological quality over time. This study revealed promising overlap between COS and RWD sources, though with important limitations; linking established, national patient registries to administrative data provide the best means to additionally capture patient-reported and some clinical outcomes over time. Thus, increasing the combination of different data sources and the interoperability of systems to follow larger patient groups in RWD is required.

Assessing the impact of a research funder’s recommendation to consider core outcome sets

Article

Full-text available

Sep 2019
PLOS ONE

Background Core outcome sets (COS) have the potential to reduce waste in research by improving the consistency of outcomes measured in trials of the same health condition. However, this reduction in waste will only be realised through the uptake of COS by clinical trialists. Without uptake, the continued development of COS that are not implemented may add to waste in research. Funders of clinical trials have the potential to have an impact on COS uptake by recommending their use to those applying for funding. The aim of our study was to assess the extent to which applicants followed the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme’s recommendation to search for a COS to include in their clinical trial. Methods and findings We examined the outcomes section and detailed project descriptions of all 95 researcher-led primary research applications submitted to the NIHR HTA between January 2012, when the recommendation to search for a COS was included in the guidance for applicants, and December 2015 for evidence that a search for a COS had taken place and rationale for outcome choice in the absence of COS. A survey of applicants was conducted to further explore their use of COS and choice of outcomes with a response rate of 49%. Nine out of 95 applicants (10%) stated in their application that they had searched the COMET (Core Outcome Measures for Effectiveness Trials) Initiative database for a COS and another nine referred to searching for a COS using another method, e.g. a review of the literature. Of the 77 (81%) applicants that did not mention COMET or COS in their application, eight stated in the survey that they had searched the COMET database and ten carried out a search using another method. Some applicants who did not search for a COS gave reasons for their choice of outcomes including taking advice from patients and the public and choosing outcomes used in previous trials. Conclusion A funding body can have an impact on COS uptake by encouraging trialists to search for a COS. Funders could take further steps by putting processes in place to prompt applicants to be explicit about searching for COS in their application and notifying the funding board if a search has not taken place. The sources of information used by trialists to make decisions about outcomes in the absence of COS may suggest methods of dissemination for COS.

World Workshop in Oral Medicine VII: Reporting of IMMPACT‐recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review

Article

Full-text available

Jun 2019

Objectives To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). Methods This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. Results A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. Conclusions The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

Improving outcome reporting in clinical trial reports and protocols: Study protocol for the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT)

Article

Full-text available

Mar 2019
TRIALS

Background Inadequate and poor quality outcome reporting in clinical trials is a well-documented problem that impedes the ability of researchers to evaluate, replicate, synthesize, and build upon study findings and impacts evidence-based decision-making by patients, clinicians, and policy-makers. To facilitate harmonized and transparent reporting of outcomes in trial protocols and published reports, the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT) is being developed. The final product will provide unique InsPECT extensions to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines. Methods The InsPECT SPIRIT and CONSORT extensions will be developed in accordance with the methodological framework created by the EQUATOR (Enhancing the Quality and Transparency of Health Research Quality) Network for reporting guideline development. Development will consist of (1) the creation of an initial list of candidate outcome reporting items synthesized from expert consultations and a scoping review of existing guidance for reporting outcomes in trial protocols and reports; (2) a three-round international Delphi study to identify additional candidate items and assess candidate item importance on a 9-point Likert scale, completed by stakeholders such as trial report and protocol authors, systematic review authors, biostatisticians and epidemiologists, reporting guideline developers, clinicians, journal editors, and research ethics board representatives; and (3) an in-person expert consensus meeting to finalize the set of essential outcome reporting items for trial protocols and reports, respectively. The consensus meeting discussions will be independently facilitated and informed by the empirical evidence identified in the primary literature and through the opinions (aggregate rankings and comments) collected via the Delphi study. An integrated knowledge translation approach will be used throughout InsPECT development to facilitate implementation and dissemination, in addition to standard post-development activities. Discussion InsPECT will provide evidence-informed and consensus-based standards focused on outcome reporting in clinical trials that can be applied across diverse disease areas, study populations, and outcomes. InsPECT will support the standardization of trial outcome reporting, which will maximize trial usability, reduce bias, foster trial replication, improve trial design and execution, and ultimately reduce research waste and help improve patient outcomes. Electronic supplementary material The online version of this article (10.1186/s13063-019-3248-0) contains supplementary material, which is available to authorized users.

Core Outcome Set-STAndardised Protocol Items: the COS-STAP Statement

Article

Full-text available

Feb 2019
TRIALS

Background Several hundred core outcome set (COS) projects have been systematically identified to date which, if adopted, ensure that researchers measure and report those outcomes that are most likely to be relevant to users of their research. The uptake of a COS by COS users will depend in part on the transparency and robustness of the methods used in the COS development study, which would be increased by the use of a standardised protocol. This article describes the development of the COS-STAP (Core Outcome Set-STAndardised Protocol Items) Statement for the content of a COS development study protocol. Methods The COS-STAP Statement was developed following the Enhancing the Quality and Transparency Of Health Research (EQUATOR) Network’s methodological framework for guideline development. This included an initial item generation stage, a two-round Delphi survey involving more than 150 participants representing three stakeholder groups (COS developers, journal editors and patient and public involvement researchers interested in COS development), followed by a consensus meeting with eight voting participants. Results The COS-STAP Statement consists of a checklist of 13 items considered essential documentation in a protocol, outlining the scope of the COS, stakeholder involvement, COS development plans and consensus processes. Conclusions Journal editors and peer reviewers can use the guidance to assess the completeness of a COS development study protocol submitted for publication. By providing guidance for key content, the COS-STAP Statement will enhance the drafting of high-quality protocols and determine how the COS development study will be carried out. Electronic supplementary material The online version of this article (10.1186/s13063-019-3230-x) contains supplementary material, which is available to authorized users.

Implementing core outcomes in kidney disease: report of the Standardized Outcomes in Nephrology (SONG) implementation workshop

Article

Full-text available

Oct 2018
KIDNEY INT

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.

Core Outcome Set-STAndards for Development: The COS-STAD recommendations

Article

Full-text available

Nov 2017
PLOS MED

Background The use of core outcome sets (COS) ensures that researchers measure and report those outcomes that are most likely to be relevant to users of their research. Several hundred COS projects have been systematically identified to date, but there has been no formal quality assessment of these studies. The Core Outcome Set-STAndards for Development (COS-STAD) project aimed to identify minimum standards for the design of a COS study agreed upon by an international group, while other specific guidance exists for the final reporting of COS development studies (Core Outcome Set-STAndards for Reporting [COS-STAR]). Methods and findings An international group of experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives produced the COS-STAD recommendations to help improve the quality of COS development and support the assessment of whether a COS had been developed using a reasonable approach. An open survey of experts generated an initial list of items, which was refined by a 2-round Delphi survey involving nearly 250 participants representing key stakeholder groups. Participants assigned importance ratings for each item using a 1–9 scale. Consensus that an item should be included in the set of minimum standards was defined as at least 70% of the voting participants from each stakeholder group providing a score between 7 and 9. The Delphi survey was followed by a consensus discussion with the study management group representing multiple stakeholder groups. COS-STAD contains 11 minimum standards that are the minimum design recommendations for all COS development projects. The recommendations focus on 3 key domains: the scope, the stakeholders, and the consensus process. Conclusions The COS-STAD project has established 11 minimum standards to be followed by COS developers when planning their projects and by users when deciding whether a COS has been developed using reasonable methods.

The COMET Handbook: version 1.0

Article

Full-text available

Jun 2017
TRIALS

The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1978-4) contains supplementary material, which is available to authorized users.

Clinical trials and systematic reviews addressing similar interventions for the same condition do not consider similar outcomes to be important: A case study in HIV/AIDS

Article

Full-text available

Feb 2017
J CLIN EPIDEMIOL

Background: The usefulness of clinical trials and systematic reviews is compromised when they report different outcomes. We compared outcomes in reviews of HIV/AIDS and the trials included in the reviews. Study design and setting: We examined all Cochrane reviews of HIV/AIDS (as of June 2013) that included ≥1 trial, and the trials that the reviews included. We compared outcomes within subgroups defined by type of intervention: clinical management, biomedical prevention, behavioral prevention, and health services. Results: We included 84 reviews that encompassed 524 trials. Although the median number of outcomes per trial (8) and per review (7.5) was similar, the trials reported a considerably greater number of unique outcomes than the reviews (779 vs. 218), ranging from 2.3 times greater (clinical management) to 5.4 times greater (behavioral prevention). High proportions of trial outcomes were not in any review: 68% (clinical management) to 83% (behavioral prevention). Lower proportions of review outcomes were not in any trial: 11% (clinical management) to 39% (health services). Conclusion: Outcomes in trials and reviews are not well aligned for appropriate inclusion of trial results in reviews and meta-analyses. Differences in perspectives, goals, and constraints between trialists and reviewers may explain differences in outcomes they consider important.

Towards evidence based research

Article

Full-text available

Oct 2016
Br Med J

To avoid waste of research, no new studies should be done without a systematic review of existing evidence, argue Hans Lund and colleagues Whether or not today’s medical researchers, like Isaac Newton, see themselves as “standing on the shoulders of giants,” they might still be expected to build systematically on previous research when planning new studies. Even though this issue was highlighted as early as 2005,1 2 numerous studies indicate that researchers do not use a systematic methodology to identify and refer to earlier research when justifying, designing, or discussing new research.3 4 5 6 7 8 9 10 11 This is true, even in high quality clinical studies published in the most prestigious medical journals.4 5 8 12 Rather, medical researchers select studies to cite based primarily on preferences and strategic considerations.13 14 15 16 17 18 The term “evidence based research” was coined in 2009 to indicate the approach that is needed to reduce this practice, which is an important source of research waste19 and risks unnecessary harm for patients and study participants. In view of the easy access to both electronic research databases and high quality systematic reviews—spearheaded by groups such as the Cochrane Collaboration, and numerous evidence synthesis centres worldwide—there is little excuse for researchers failing to refer to current systematic assessments of previous research. Nevertheless, authors seem to get away with being very selective,13 14 preferentially citing studies with results that support the intervention they are evaluating.15 16 17 18 Some research funders have already taken action. For example, the National Institute for Health Research in England now requires that applicants for primary research funding justify any proposed research by referencing a current systematic review of relevant existing research to show that they have taken account of the …

GRADE Evidence to Decision (EtD) frameworks: A systematic and transparent approach to making well informed healthcare choices. 1: Introduction

Article

Full-text available

Jun 2016
Br Med J

#### Summary points Healthcare decision making is complex. Decision-making processes and the factors (criteria) that decision makers should consider vary for different types of decisions, including clinical recommendations, coverage decisions, and health system or public health recommendations or decisions.1 2 3 4 However, some criteria are relevant for all of these decisions, including the anticipated effects of the options being considered, the certainty of the evidence for those effects (also referred to as quality of evidence or confidence in effect estimates), and the costs and feasibility of the options. Decision makers must make judgments about each relevant factor, informed by the best evidence that is available to them. Often, the processes that decision makers use, the criteria that they consider and the evidence that they …

Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms

Article

Full-text available

Jan 2016

Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess a drug's efficacy. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges with relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts-- symptomatic adverse events, physical function and disease- related symptoms-- that are key contributors to a therapy's effect on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials.

The Core Outcomes in Women's Health (CROWN) Initiative: Journal Editors Invite Researchers to Develop Core Outcomes in Women's Health

Article

Full-text available

Jun 2014

Khalid Saeed Khan

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes -a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative.

The Quality of Registration of Clinical Trials: Still a Problem

Article

Full-text available

Jan 2014
PLOS ONE

The benefits of clinical trials registration include improved transparency on clinical trials for healthcare workers and patients, increased accountability of trialists, the potential to address publication bias and selective reporting, and possibilities for research collaboration and prioritization. However, poor quality of information in registered records of trials has been found to undermine these benefits in the past. Trialists' increasing experience with trial registration and recent developments in registration systems may have positively affected data quality. This study was conducted to investigate whether the quality of registration has improved. METHODS We repeated a study from 2009, using the same methods and the same research team. A random sample of 400 records of clinical trials that were registered between 01/01/2012 and 01/01/2013 was taken from the International Clinical Trials Registry Platform (ICTRP) and assessed for the quality of information on 1) contact details, 2) interventions and 3) primary outcomes. Results were compared to the equivalent assessments from our previous study. RESULTS There was a small and not statistically significant increase from 81.0% to 85.5% in the percentage of records that provided a name of a contact person. There was a significant increase from 68.7% to 74.9% in the number of records that provided either an email address or a telephone number. There was a significant increase from 44.2% to 51.9% in the number of intervention arms that were complete in registering intervention specifics. There was a significant increase from 38.2% to 57.6% in the number of primary outcomes that were specific measures with a meaningful timeframe. Approximately half of all trials continued to be retrospectively registered. DISCUSSION There have been small but significant improvements in the quality of registration since 2009. Important problems with quality remain and continue to constitute an impediment to the meaningful utilization of registered trial information.

SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials

Article

Full-text available

Jan 2013
Br Med J

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

Article

Full-text available

Jan 2013
ANN INTERN MED

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items:Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Bias in meta-analysis with variable selection within studies

Article

Full-text available

Feb 2000
J R STAT SOC C-APPL

Although bias in meta-analysis arising from selective publication has been studied, within-study selection has received little attention. Chronic diseases often have several possible outcome variables. Methods based on the size of the effect allow results from studies with different outcomes to be combined. However, the possibility of selective reporting of outcomes must be considered. The effect of selective reporting on estimates of the size of the effect and significance levels is presented, and sensitivity analyses are suggested. Substantial publication bias could arise from multiple testing of outcomes in a study, followed by selective reporting. Two meta-analyses, on anthelminth therapy and a treatment for incontinence, are reassessed allowing for within-study selection, as it is clear that more outcomes had been measured than were reported. The sensitivity analyses show that the robustness of the anthelminth results is dependent on what assumption one makes about the reporting strategy for the largest trial. The possible influence of correlation between within-child measurements was such that the conclusions could easily be reversed. The effect of a mild assumption on within-trial selection alone could alter general recommendations about the treatment for incontinence.

In-depth qualitative interviews identified barriers and facilitators that influenced chief investigators’ use of core outcome sets in randomised controlled trials

Article

Dec 2021
J CLIN EPIDEMIOL

Objective : This study aimed to investigate barriers and facilitators to core outcome set (COS) uptake in randomised controlled trials to inform the first steps in developing interventions to improve the uptake of COS. Study Design and Setting : Semi-structured qualitative interviews with a purposive sample of UK chief investigators were audio-recorded, transcribed and analysed thematically. Where appropriate, barriers and facilitators were mapped to components of behaviour informed by the COM-B model of behaviour. Results : Thirteen chief investigators were interviewed. Facilitators to uptake included: the behaviour of investigators, for example, their awareness and understanding of COS; and the wider research system, for example, recommendations to use COS from funders and journals. Barriers to uptake included: the perceived characteristics of COS, for example, increasing patient burden and recommendations becoming outdated; and the COS development process, for example, not including all specialties who will use the COS. Conclusions : Based on the barriers and facilitators identified, recommendations to improve COS uptake include ensuring engagement with the research community who will use the COS, involving patients in the development of COS and ensuring COS remain up to date.

Use of Core Outcome Sets was Low in Clinical Trials Published in Major Medical Journals

Article

Oct 2021
J CLIN EPIDEMIOL

Objectives To examine current practices in late-phase trials published in major medical journals and examine trialists’ views about core outcome set (COS) use. Design and Setting A sequential multi-methods study was conducted. We examined late-phase trials published between October 2019 and March 2020 in JAMA, NEJM, The Lancet, BMJ, and Annals of Internal Medicine. The COMET database was searched for COS potentially relevant to trials not reporting using a COS; overlap of trial and COS outcomes was examined. An online survey examined awareness of, and decisions to search for and use a COS. Results Ninety-five trials were examined; 93 (98%) did not report using a COS. Relevant COS were identified for 31 trials (33%). Core outcomes were measured in 9 (23%) studies; all trials measured at least one core outcome. Thirty-one trialists (33%) completed our survey. The most common barrier to COS use was trialist's own outcome preferences and choice (68%). The most common perceived facilitator was awareness and knowledge about COS (90%). Conclusion COS use in this cohort of trials was low, even when relevant COS were available. Increased use of COS in clinical trials can improve evaluation of intervention effects and evidence synthesis and reduce research waste.

Producing and using timely comparative evidence on drugs: Lessons from clinical trials for covid-19

Article

Oct 2020
Br Med J

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff

Article

Apr 2020

Background: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. Objectives: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. Search methods: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. Selection criteria: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. Data collection and analysis: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. Main results: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. Authors' conclusions: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

Industry funding was associated with increased use of core outcome sets

Article

Jul 2019
J CLIN EPIDEMIOL

Objectives: The objective of this study was to assess the uptake of the rheumatoid arthritis core outcome set (RA-COS) using data from multiple data providers, and to investigate factors that may influence this uptake. Study design and setting: An observational review was carried out on all clinical trials of rheumatoid arthritis that were indexed on the World Health Organization-International Clinical Trials Registry Platform (WHO-ICTRP). Various measures of COS uptake were calculated from information presented in the trial registries and trial publications. Logistic regression was conducted to investigate factors thought to be associated with planned COS uptake. Results: A total of 341 trials were eligible for the evaluation of RA-COS uptake. In the decade leading up to 2019, the assessment of uptake based on published results was maintained at just over 80%. Trials that were not commercially funded were much less likely to plan to measure the RA-COS than those with industry funding (60% vs. 80%; adjusted OR 0.18, 95% CI 0.11 to 0.32; P < 0.001). Conclusion: This study has demonstrated that the use of the WHO-ICTRP can identify a large and geographically diverse range of trials to include in the evaluation of COS uptake.

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff

Article

Jul 2019

Background: In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or Severe Acute Respiratory Syndrome (SARS), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCW use PPE as instructed. Objectives: To evaluate which type of full body PPE and which method of donning or doffing PPE have the least risk of self-contamination or infection for HCW, and which training methods increase compliance with PPE protocols. Search methods: We searched MEDLINE (PubMed up to 15 July 2018), Cochrane Central Register of Trials (CENTRAL up to 18 June 2019), Scopus (Scopus 18 June 2019), CINAHL (EBSCOhost 31 July 2018), and OSH-Update (up to 31 December 2018). We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. Selection criteria: We included all controlled studies that compared the effects of PPE used by HCW exposed to highly infectious diseases with serious consequences, such as Ebola or SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that used simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training in PPE use on the same outcomes. Data collection and analysis: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We planned to perform meta-analyses but did not find sufficiently similar studies to combine their results. Main results: We included 17 studies with 1950 participants evaluating 21 interventions. Ten studies are Randomised Controlled Trials (RCTs), one is a quasi RCT and six have a non-randomised controlled design. Two studies are awaiting assessment.Ten studies compared types of PPE but only six of these reported sufficient data. Six studies compared different types of donning and doffing and three studies evaluated different types of training. Fifteen studies used simulated exposure with fluorescent markers or harmless viruses. In simulation studies, contamination rates varied from 10% to 100% of participants for all types of PPE. In one study HCW were exposed to Ebola and in another to SARS.Evidence for all outcomes is based on single studies and is very low quality.Different types of PPEPPE made of more breathable material may not lead to more contamination spots on the trunk (Mean Difference (MD) 1.60 (95% Confidence Interval (CI) -0.15 to 3.35) than more water repellent material but may have greater user satisfaction (MD -0.46; 95% CI -0.84 to -0.08, scale of 1 to 5).Gowns may protect better against contamination than aprons (MD large patches -1.36 95% CI -1.78 to -0.94).The use of a powered air-purifying respirator may protect better than a simple ensemble of PPE without such respirator (Relative Risk (RR) 0.27; 95% CI 0.17 to 0.43).Five different PPE ensembles (such as gown vs. coverall, boots with or without covers, hood vs. cap, length and number of gloves) were evaluated in one study, but there were no event data available for compared groups.Alterations to PPE design may lead to less contamination such as added tabs to grab masks (RR 0.33; 95% CI 0.14 to 0.80) or gloves (RR 0.22 95% CI 0.15 to 0.31), a sealed gown and glove combination (RR 0.27; 95% CI 0.09 to 0.78), or a better fitting gown around the neck, wrists and hands (RR 0.08; 95% CI 0.01 to 0.55) compared to standard PPE.Different methods of donning and doffing proceduresDouble gloving may lead to less contamination compared to single gloving (RR 0.36; 95% CI 0.16 to 0.78).Following CDC recommendations for doffing may lead to less contamination compared to no guidance (MD small patches -5.44; 95% CI -7.43 to -3.45).Alcohol-based hand rub used during the doffing process may not lead to less contamination than the use of a hypochlorite based solution (MD 4.00; 95% CI 0.47 to 34.24).Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4).Different types of trainingThe use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7).A video lecture on donning PPE may lead to better skills scores (MD 30.70; 95% CI 20.14,41.26) than a traditional lecture.Face to face instruction may reduce noncompliance with doffing guidance more (OR 0.45; 95% CI 0.21 to 0.98) than providing folders or videos only.There were no studies on effects of training in the long term or on resource use.The quality of the evidence is very low for all comparisons because of high risk of bias in all studies, indirectness of evidence, and small numbers of participants. Authors' conclusions: We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. Alterations to PPE, such as tabs to grab may decrease contamination. Double gloving, following CDC doffing guidance, and spoken instructions during doffing may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than video or folder based training. Because data come from single small studies with high risk of bias, we are uncertain about the estimates of effects.We still need randomised controlled trials to find out which training works best in the long term. We need better simulation studies conducted with several dozen participants to find out which PPE protects best, and what is the safest way to remove PPE. Consensus on the best way to conduct simulation of exposure and assessment of outcome is urgently needed. HCW exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection in the field.

The increasing complexity of the core outcomes landscape

Article

May 2019
J CLIN EPIDEMIOL

In this project, we set out to identify ways to increase the uptake of core outcome sets in clinical research. In doing so, we uncovered a growing recognition, across many different health care sectors, of the need for common, relevant outcomes to improve the quality of decision-making. This has led to a plethora of projects, initiatives, and new organizations all intended to develop standardized outcomes and outcome measures for their particular fields. However, the standardized outcome sets developed across siloed initiatives do not carry over to other sectors, such as from research to quality of care. This trend has the potential to lead to confusion and unintended redundancies, as well as wasteful use of both financial and intellectual resources. Better communication and collaboration among different initiatives, and more deliberate alignments of initiative scopes, are needed to ensure a future paradigm in which standards align across contexts where possible and differ for understandable and transparent reasons.

Outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain in children and adolescents

Article

Sep 2018

Background We analyzed outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain management in children and adolescents, and compared them to the core outcome set recommended by the Pediatric Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (PedIMMPACT). Methods Systematic literature search was conducted in MEDLINE, CDSR, DARE, CINAHL and PsycINFO up to January 31, 2017. One author extracted data and second verified the extraction. Outcome domains and pain outcome measures were analyzed and compared with the PedIMMPACT core outcome set. Results We included 337 trials. Median number of reported outcomes was five (range 1 to 11) for the included trials and two (range 0 to 6) for PedIMMPACT. The most commonly analyzed PedIMMPACT outcome domains were pain intensity (93%) and ‘symptoms and adverse events’ (83%). The remaining four PedIMMPACT outcomes were present in under 30% of included randomized controlled trials. Proportion of PedIMMPACT outcome domains did not change after the PedIMMPACT was published in 2008. Of the 312 trials that reported pain intensity, 303 (97%) also specified pain assessment tools, in which the most common was the visual analogue scale (24%) followed by the Children's Hospital of Eastern Ontario Pain Scale (18%). Conclusion Analyzed trials about interventions for pediatric postoperative pain insufficiently used the recommended core outcome set for acute pain in children. Relevance of the PedIMMPACT core outcome set, as well as the reasons behind its limited uptake, need to be further evaluated. This article is protected by copyright. All rights reserved.

Core outcome set for gene therapy in haemophilia: Results of the coreHEM multistakeholder project

Article

May 2018

Background Gene therapy trial results show potential to cure haemophilia A and haemophilia B. Securing broad access to a cure for a lifelong chronic disease is anticipated to face barriers at the individual and healthcare system levels, which can be partly mitigated by harmonized planning of clinical research studies. The aim of the coreHEM project was to determine the set of outcome measures required to evaluate efficacy, safety, comparative effectiveness and value of gene therapy for haemophilia. Methods Modified Delphi consensus process, based on methods adapted from the COMET Initiative. Results Forty‐nine participants (five patients, five clinicians, five researchers, four regulators, three research agencies, six health technology assessors, nine payers and 12 drug developers) took part in the study, with over 90% participation. The frequency of bleeds, factor activity level, duration of expression, chronic pain, healthcare resource use and mental health were identified as the core outcomes to be measured in addition to regulatory‐mandated adverse effects. Conclusions For the first time in haemophilia, a core outcome set has been developed, with the involvement of representatives of all relevant stakeholder groups. The core set has been expanded to include outcomes supporting assessment of comparative effectiveness and value, with the goal of streamlining regulatory approval, health technology assessment and market access decisions. Patient involvement ensures that outcomes are meaningful and relevant to those living with haemophilia. Active dialogue among drug developers, regulators and payers throughout the process is expected to facilitate broad uptake of the core outcomes in forthcoming clinical trials.

Efficacy and Safety Outcomes in Systematic Reviews of Interventions for Postoperative Pain in Children: Comparison Against the Recommended Core Outcome Set

Article

Oct 2017
PAIN MED

Objective: To investigate the range of efficacy and safety outcomes used in systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions for postoperative pain in children and compare them with outcome domains recommended in the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (PedIMMPACT). Methods: Five electronic databases were searched: MEDLINE, Cochrane Database of Systematic Reviews, DARE, CINAHL, and PsycINFO. Two review authors extracted outcome data independently. Efficacy and safety outcomes were extracted and categorized. The type and number of outcomes were analyzed and compared against the outcomes recommended by PedIMMPACT. The study protocol was registered in PROSPERO (CRD42015029654). Results: We included 50 systematic reviews with data from 866 trials. The median number of all outcomes was 4, while the median number of the PedIMMPACT core outcomes was three out of six. The most commonly reported outcome of the PedIMMPACT Core Outcome set (COS) was "symptoms and adverse events," followed by pain intensity, which was reported in 75% of the included SRs. Just over half of the SRs that included a pain intensity outcome also indicated the specific pain assessment tool used in the methods section. Conclusions: Systematic reviews in the field of pediatric pain do not use the recommended COS. Nor do they consistently include pain as an outcome. This makes comparisons of efficacy and safety across interventions very difficult. Future studies should explore whether the authors are aware of the COS and whether the recommended COS is appropriate.

Comparison of Clinical Trial and Systematic Review Outcomes for the 4 Most Prevalent Eye Diseases

Article

Aug 2017

Importance Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies. Objectives To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews. Design, Setting, and Participants This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease. Main Outcomes and Measures Proportion of review outcomes also reported in trials and vice versa. Results This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews. Conclusions and Relevance Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

Engaging Stakeholders and Promoting Uptake of OMERACT Core Outcome Instrument Sets

Article

Aug 2017

Objective: While there has been substantial progress in the development of core outcomes sets, the degree to which these are used by researchers is variable. We convened a special workshop on knowledge translation at the Outcome Measures in Rheumatology (OMERACT) 2016 with 2 main goals. The first focused on the development of a formal knowledge translation framework and the second on promoting uptake of recommended core outcome domain and instrument sets. Methods: We invited all 189 OMERACT 2016 attendees to the workshop; 86 attended, representing patient research partners (n = 15), healthcare providers/clinician researchers (n = 52), industry (n = 4), regulatory agencies (n = 4), and OMERACT fellows (n = 11). Participants were given an introduction to knowledge translation and were asked to propose and discuss recommendations for the OMERACT community to (1) strengthen stakeholder involvement in the core outcome instrument set development process, and (2) promote uptake of core outcome sets with a specific focus on the potential role of post-regulatory decision makers. Results: We developed the novel "OMERACT integrated knowledge translation" framework, which formalizes OMERACT's knowledge translation strategies. We produced strategies to improve stakeholder engagement throughout the process of core outcome set development and created a list of creative and innovative ways to promote the uptake of OMERACT's core outcome sets. Conclusion: The guidance provided in this paper is preliminary and is based on the views of the participants. Future work will engage OMERACT groups, "post-regulatory decision makers," and a broad range of different stakeholders to identify and evaluate the most useful methods and processes, and to revise guidance accordingly.

“How aligned are the perspectives of the eu regulator and the hta bodies? A comparative analysis of regulatory- hta parallel scientific advice”.: A comparative analysis of regulatory-HTA parallel scientific advice

Article

Jun 2016
BRIT J CLIN PHARMACO

Background: In 2010 the European Medicines Agency (EMA) initiated a pilot project on parallel scientific advice with Health Technology Assessment bodies (HTABs) that allows manufacturers to receive simultaneous feedback from both the EU Regulator and HTABs on their development plans for medicines. Aims: This retrospective qualitative analysis aims to explore how the parallel scientific advice system is working and levels of commonality between the EU Regulator and HTABs, and among HTABs, when Applicants obtain parallel scientific advice from both a regulatory and a HTA perspective. Methods: We analysed the minutes of discussion meetings held at the European Medicines Agency between 2010, when parallel advice was launched, and 1 May 2015, when the cut-off date for data extraction was set. The analysis was based on predefined criteria and conducted at two different levels of comparison: HTABs' answers versus the Regulator's and in-between the participating HTA agencies' answers. Results: The analysis was based on 31 procedures of parallel scientific advice. The level of full agreements was highest for questions on patient population (77%), while disagreements reached a peak for questions on study comparator (30%). With regard to comparisons among HTABs, there was a high level of agreement for all domains. Conclusions: Commonality, in terms of evidence requirements between the EU Regulator and participating HTABs as well as among HTABs, on most aspects of clinical development is evident. Indeed, regardless of the question content, the analysis showed that a high level of overall agreement was reached through the process of parallel scientific advice.

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff

Article

Jan 2016

Background: In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or SARS, healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCWs use PPE as instructed. Objectives: To evaluate which type or component of full-body PPE and which method of donning or removing (doffing) PPE have the least risk of self-contamination or infection for HCWs, and which training methods most increase compliance with PPE protocols. Search methods: We searched MEDLINE (PubMed up to 8 January 2016), Cochrane Central Register of Trials (CENTRAL up to 20 January 2016), EMBASE (embase.com up to 8 January 2016), CINAHL (EBSCOhost up to 20 January 2016), and OSH-Update up to 8 January 2016. We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. Selection criteria: We included all eligible controlled studies that compared the effect of types or components of PPE in HCWs exposed to highly infectious diseases with serious consequences, such as EVD and SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that simulated contamination with fluorescent markers or a non-pathogenic virus. We also included studies that compared the effect of various ways of donning or removing PPE, and the effects of various types of training in PPE use on the same outcomes. Data collection and analysis: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We intended to perform meta-analyses but we did not find sufficiently similar studies to combine their results. Main results: We included nine studies with 1200 participants evaluating ten interventions. Of these, eight trials simulated the exposure with a fluorescent marker or virus or bacteria containing fluids. Five studies evaluated different types of PPE against each other but two did not report sufficient data. Another two studies compared different types of donning and doffing and three studies evaluated the effect of different types of training. None of the included studies reported a standardised classification of the protective properties against viral penetration of the PPE, and only one reported the brand of PPE used. None of the studies were conducted with HCWs exposed to EVD but in one study participants were exposed to SARS. Different types of PPE versus each other In simulation studies, contamination rates varied from 25% to 100% of participants for all types of PPE. In one study, PPE made of more breathable material did not lead to a statistically significantly different number of spots with contamination but did have greater user satisfaction (Mean Difference (MD) -0.46 (95% Confidence Interval (CI) -0.84 to -0.08, range 1 to 5, very low quality evidence). In another study, gowns protected better than aprons. In yet another study, the use of a powered air-purifying respirator protected better than a now outdated form of PPE. There were no studies on goggles versus face shields, on long- versus short-sleeved gloves, or on the use of taping PPE parts together. Different methods of donning and doffing procedures versus each other Two cross-over simulation studies (one RCT, one CCT) compared different methods for donning and doffing against each other. Double gloving led to less contamination compared to single gloving (Relative Risk (RR) 0.36; 95% CI 0.16 to 0.78, very low quality evidence) in one simulation study, but not to more noncompliance with guidance (RR 1.08; 95% CI 0.70 to 1.67, very low quality evidence). Following CDC recommendations for doffing led to less contamination in another study (very low quality evidence). There were no studies on the use of disinfectants while doffing. Different types of training versus each other In one study, the use of additional computer simulation led to less errors in doffing (MD -1.2, 95% CI -1.6 to -0.7) and in another study additional spoken instruction led to less errors (MD -0.9, 95% CI -1.4 to -0.4). One retrospective cohort study assessed the effect of active training - defined as face-to-face instruction - versus passive training - defined as folders or videos - on noncompliance with PPE use and on noncompliance with doffing guidance. Active training did not considerably reduce noncompliance in PPE use (Odds Ratio (OR) 0.63; 95% CI 0.31 to 1.30) but reduced noncompliance with doffing procedures (OR 0.45; 95% CI 0.21 to 0.98, very low quality evidence). There were no studies on how to retain the results of training in the long term or on resource use. The quality of the evidence was very low for all comparisons because of high risk of bias in studies, indirectness of evidence, and small numbers of participants. This means that it is likely that the true effect can be substantially different from the one reported here. Authors' conclusions: We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. We also found very low quality evidence that double gloving and CDC doffing guidance appear to decrease the risk of contamination and that more active training in PPE use may reduce PPE and doffing errors more than passive training. However, the data all come from single studies with high risk of bias and we are uncertain about the estimates of effects. We need simulation studies conducted with several dozens of participants, preferably using a non-pathogenic virus, to find out which type and combination of PPE protects best, and what is the best way to remove PPE. We also need randomised controlled studies of the effects of one type of training versus another to find out which training works best in the long term. HCWs exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Improving the relevance and consistency of outcomes in comparative effectiveness research

Article

Mar 2016

Policy makers have clearly indicated - through heavy investment in the Patient Centered Outcomes Research Institute - that reporting outcomes that are meaningful to patients is crucial for improvement in healthcare delivery and cost reduction. Better interpretation and generalizability of clinical research results that incorporate patient-centered outcomes research can be achieved by accelerating the development and uptake of core outcome sets (COS). COS provide a standardized minimum set of the outcomes that should be measured and reported in all clinical trials of a specific condition. The level of activity around COS has increased significantly over the past decade, with substantial progress in several clinical domains. However, there are many important clinical conditions for which high-quality COS have not been developed and there are limited resources and capacity with which to develop them. We believe that meaningful progress toward the goals behind the significant investments in patient-centered outcomes research and comparative effectiveness research will depend on a serious effort to address these issues.

Clinical outcomes in psoriatic arthritis: A systematic literature review

Article

Mar 2012

Many outcomes have been proposed in the assessment of psoriatic arthritis (PsA). The Outcome Measures in Rheumatology (OMERACT) core set for PsA evaluation comprises 6 domains: joints, skin, function, pain, patient's global assessment, and quality of life. The objective of this work was to assess reporting of outcomes in PsA, including patient-reported outcomes (PROs) in recent publications. A systematic literature search of clinical trials related to PsA and reporting at least 1 clinical outcome between 2006 and 2010 was performed in PubMed, i.e., just before to just after publication of the OMERACT core set. All clinical outcomes were noted and subdivided into domains of health. Data analysis was descriptive. Fifty-eight articles (12,405 patients) were included in the analysis: 17 (29%) were randomized clinical trials; the patients' mean ± SD age was 48.2 ± 5.4 years and the mean ± SD disease duration was 9.0 ± 3.1 years. Eighty-four different outcomes were reported, with a mean ± SD of 6.9 ± 4.3 per study. Patients were mainly assessed using the 6 core set domains, reported in 37.9% (quality of life) to 55.2% (skin) of articles; however, the core set was rarely completely reported since only 10.3% of the studies reported all 6 core domains. PROs were heterogeneous and in particular there was no consensus regarding the number of joints to assess and instruments for dactylitis and enthesitis. PROs were assessed in more than 75% of publications using 28 different instruments. There is great heterogeneity in PsA assessment, even since publication of the OMERACT core set. Better consensus on instruments to assess each domain of health and better insight into which outcomes are important for patients is needed.

What is Value in Health Care?

Article

Dec 2010
NEW ENGL J MED

Michael E. Porter

Benjamin F. Byrd, Theodore P. Abraham, Denis B. Buxton, Anthony V. Coletta, James H.S. Cooper, Pamela S. Douglas, Linda D. Gillam, Steven A. Goldstein, Thomas R. Graf, Kenneth D. Horton, Alexis A. Isenberg, Allan L. Klein, Joseph Kreeger, Randolph P. Martin, Susan M. Nedza, Amol Navathe, Patricia A. Pellikka, Michael H. Picard, John C. Pilotte, Thomas J. Ryan, Jack Rychik, Partho P. Sengupta, James D. Thomas, Leslie Tucker, William Wallace, R. Parker Ward, Neil J. Weissman, David H. Wiener, Sarah Woodruff. (2015) A Summary of the American Society of Echocardiography Foundation Value-Based Healthcare: Summit 2014. Journal of the American Society of Echocardiography 28, 755-769 CrossRef Neil E. Martin, Laura Massey, Caleb Stowell, Chris Bangma, Alberto Briganti, Anna Bill-Axelson, Michael Blute, James Catto, Ronald C. Chen, Anthony V. D’Amico, Günter Feick, John M. Fitzpatrick, Steven J. Frank, Michael Froehner, Mark Frydenberg, Adam Glaser, Markus Graefen, Daniel Hamstra, Adam Kibel, Nancy Mendenhall, Kim Moretti, Jacob Ramon, Ian Roos, Howard Sandler, Francis J. Sullivan, David Swanson, Ashutosh Tewari, Andrew Vickers, Thomas Wiegel, Hartwig Huland. (2015) Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer. European Urology 67, 460-467 CrossRef

Review finds core outcome set uptake in new studies and systematic reviews needs improvement

Abstract

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