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

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 matching 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 FDA and EMA 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. We will share the study findings (in particular, highlighting any lack of concordance between COS and regulatory guidance overall or for particular disease areas) and will invite feedback from FDA and EMA; we 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.

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

HRB Open Research ◽

10.12688/hrbopenres.13139.1 ◽

2021 ◽

Vol 4 ◽

pp. 45

Author(s):

Susanna Dodd ◽

Rebecca Fish ◽

Sarah Gorst ◽

Deborah Hall ◽

Pamela Jacobsen ◽

...

Keyword(s):

Patient Involvement ◽

European Medicines Agency ◽

Core Outcome ◽

Core Outcome Sets ◽

Regulatory Guidance ◽

The Core ◽

Key Stakeholders ◽

Regulatory Guidelines ◽

Core Outcomes ◽

Guidance Documents

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.

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

HRB Open Research ◽

10.12688/hrbopenres.13139.2 ◽

2021 ◽

Vol 4 ◽

pp. 45

Author(s):

Susanna Dodd ◽

Rebecca Fish ◽

Sarah Gorst ◽

Deborah Hall ◽

Pamela Jacobsen ◽

...

Keyword(s):

Patient Involvement ◽

European Medicines Agency ◽

Core Outcome ◽

Core Outcome Sets ◽

Regulatory Guidance ◽

The Core ◽

Key Stakeholders ◽

Regulatory Guidelines ◽

Core Outcomes ◽

Guidance Documents

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Core Outcome Sets in Miscarriage Trials (COSMisT) study: a study protocol

BMJ Open ◽

10.1136/bmjopen-2017-018535 ◽

2017 ◽

Vol 7 (11) ◽

pp. e018535

Author(s):

Paul Smith ◽

Natalie Cooper ◽

Rima Dhillon-Smith ◽

Emily O’Toole ◽

T Justin Clark ◽

...

Keyword(s):

Delphi Survey ◽

Core Outcome ◽

Potential Core ◽

Core Outcome Sets ◽

Face To Face ◽

The Core ◽

Modified Delphi ◽

Key Stakeholders ◽

Core Set ◽

Core Outcomes

Introduction‘Core outcome sets’ are an agreed, standardised set of outcomes based on what key stakeholders (clinicians, patients, their partners, researchers, service developers, funding organisations and so on) consider the important outcomes in the management or prevention of a condition. This paper describes the rationale and design for the development of Core Outcome Sets for Miscarriage Trials.Methods and analysisSystematic reviews, interviews and focus groups with patients and their partners will be conducted to identify potential core outcomes that will be introduced into a modified Delphi survey. To ensure all key stakeholders are included, patients, partners, clinicians, charities and researchers will be invited to take part in the modified Delphi survey. There will be three rounds of scoring and rescoring during the Delphi survey to reach consensus regarding outcomes to be included in the core set, which will be subsequently refined through face-to-face consensus discussions.Ethics and disseminationThe use of core outcome sets allows results from different studies to be compared and combined, thereby reducing inconsistency and aiding interpretation of study findings. It also means research is more likely to report relevant outcomes and so can reduce reporting bias. Understanding which outcomes are important to patients has the potential to act as a driver to improve both the quality and cost-effectiveness of miscarriage services.

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Protocol for the development of Core Outcome Sets for Early intervention trials to Prevent Obesity in CHildren (COS-EPOCH)

BMJ Open ◽

10.1136/bmjopen-2020-048104 ◽

2021 ◽

Vol 11 (7) ◽

pp. e048104

Author(s):

Vicki Brown ◽

Marj Moodie ◽

Huong Ngoc Quynh Tran ◽

Marufa Sultana ◽

Kylie Elizabeth Hunter ◽

...

Keyword(s):

Physical Activity ◽

Early Childhood ◽

Childhood Obesity ◽

Obesity Prevention ◽

Core Outcome ◽

Core Outcome Sets ◽

Key Stakeholders ◽

Core Outcomes ◽

Prevention Interventions ◽

Early Childhood Obesity

IntroductionChildhood overweight and obesity is prevalent in the first 5 years of life, and can result in significant health and economic consequences over the lifetime. The outcomes currently measured and reported in randomised controlled trials of early childhood obesity prevention interventions to reduce this burden of obesity are heterogeneous, and measured in a variety of ways. This variability limits the comparability of findings between studies, and contributes to research waste. This protocol presents the methodology for the development of two core outcome sets (COS) for obesity prevention interventions in children aged from 1 to 5 years from a singular development process: (1) a COS for interventions targeting physical activity and sedentary behaviour and (2) a COS for interventions targeting child feeding and dietary intake. Core outcomes related to physical activity and sedentary behaviour in children aged ≤1 year will also be identified to complement an existing COS for early feeding interventions, and provide a broader set of core outcomes in this age range. This will result in a suite of COS useful for measuring and reporting outcomes in early childhood obesity prevention studies, including multicomponent interventions.Methods and analysisDevelopment of the COS will follow international best practice guidelines. A scoping review of trial registries will identify commonly reported outcomes and associated measurement instruments. Key stakeholders involved in obesity prevention, including policy-makers/funders, parents, researchers, health practitioners and community and organisational stakeholders will participate in an e-Delphi study and consensus meeting regarding inclusion of outcomes in the COS. Finally, recommended outcome measure instruments will be identified through literature review and group consensus.Ethics and disseminationDeakin University Human Research Ethics Committee (HEAG-H 231_2020). The COS will be disseminated through peer-reviewed publications and engagement with key stakeholders.

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Core outcome set for three ophthalmic conditions: a healthcare professional and patient consensus on core outcome sets for amblyopia, ocular motility and strabismus (COSAMS Study)

BMJ Open ◽

10.1136/bmjopen-2020-042403 ◽

2021 ◽

Vol 11 (5) ◽

pp. e042403

Author(s):

Samiya Al-Jabri ◽

Fiona J Rowe ◽

Jamie J Kirkham

Keyword(s):

Healthcare Professionals ◽

Core Outcome Set ◽

Routine Clinical Practice ◽

Ocular Motility ◽

Core Outcome ◽

Core Outcome Sets ◽

The Core ◽

Outcome Set ◽

Core Outcomes

ObjectivesAmblyopia, strabismus and ocular motility disorders are common conditions with significant impact on visual function, appearance and quality of life. We aimed to establish a core set of outcomes for each of the three conditions for use in clinical trials and routine clinical practice.DesignA comprehensive databank of outcomes was developed from a systematic review of the literature and a series of focus groups with healthcare professionals, researchers, patients and carers. The databank of outcomes was scored in a two-round Delphi Survey completed by two stakeholder groups: healthcare professionals/researchers and patients/carers. Results of the online Delphi were discussed at a face-to-face consensus meeting where the core outcome sets were finalised.SettingUK-wide consultation.ParticipantsResearchers, clinicians, patients and carers.Outcome measuresCore outcome sets.ResultsFor amblyopia, strabismus and ocular motility, 40/42/33 participants contributed to both rounds of the Delphi; six/nine/seven members attended consensus meetings, respectively. Consensus was reached on ten core outcomes for both amblyopia and ocular motility and nine for strabismus. All three conditions shared the core outcomes: adverse events, cost, vision-related quality of life and ocular alignment. The strabismus and ocular motility disorder core sets included, in addition, measuring the deviation, binocular vision, ocular movement, patient satisfaction and symptoms. The amblyopia set, distinct from the sets for the other two conditions, included best corrected distance and near visual acuity, spherical and cylindrical refraction, compliance and treatment-related and functionality/long-term impacts.ConclusionsThe study used robust consensus methods to develop a core outcome set for three ophthalmic conditions. Implementation of these core outcome sets in clinical trials and routine clinical practice will ensure that the outcomes being measured and reported are relevant to all stakeholders. This will enhance the relevance of study findings and enable comparison of results from different studies.

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The Core Outcome DEvelopment for Carrier Screening (CODECS) study: protocol for development of a core outcome set

Trials ◽

10.1186/s13063-021-05439-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ebony Richardson ◽

Alison McEwen ◽

Toby Newton-John ◽

Karine Manera ◽

Chris Jacobs

Keyword(s):

Systematic Review ◽

Genetic Testing ◽

Core Outcome Set ◽

Carrier Screening ◽

Core Outcome ◽

The Core ◽

Key Stakeholders ◽

Outcome Set ◽

Methods Of Measurement ◽

Genetic Carrier Screening

Abstract Background Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for ‘what to measure’ in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention. Objectives The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice. Methods In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: (i) a systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement; (ii) a systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes; (iii) semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them; (iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps; and (v) a virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting. Discussion This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET core outcome set registration http://www.comet-initiative.org/Studies/Details/1381.

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A protocol for developing a core outcome set for ectopic pregnancy

Trials ◽

10.1186/s13063-021-05772-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Krystle Y. Chong ◽

Sarah Solangon ◽

James Kemper ◽

Kurt Barnhart ◽

Pamela Causa Andrieu ◽

...

Keyword(s):

Ectopic Pregnancy ◽

Randomised Controlled Trials ◽

Core Outcome Set ◽

Future Research ◽

Controlled Trials ◽

Core Outcome ◽

Key Stakeholders ◽

Outcome Set ◽

Core Outcomes ◽

Randomised Controlled

Abstract Background Randomised controlled trials (RCTs) evaluating ectopic pregnancy have reported many different outcomes, which are themselves often defined and measured in distinct ways. This level of variation results in an inability to compare results of individual RCTs. The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. Study aim To develop and implement a core outcome set to guide future research in ectopic pregnancy. Methods and analysis We have established an international steering group of key stakeholders, including healthcare professionals, researchers, and individuals with lived experience of ectopic pregnancy. We will identify potential outcomes from ectopic pregnancy from a comprehensive literature review of published randomised controlled trials. We will then utilise a modified Delphi method to prioritise outcomes. Subsequently, key stakeholders will be invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes. We will also establish standardised definitions and recommend high-quality measurements for individual core outcomes. Trial registration COMET 1492. Registered in November 2019.

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A protocol for the Development of Core Outcome Sets for Endodontic Treatment modalities (COSET): an international consensus process

10.21203/rs.3.rs-610497/v1 ◽

2021 ◽

Author(s):

Ikhlas El karim ◽

Henry F Duncan ◽

Siobhan Cushley ◽

Venkatesh Nagendrababu ◽

Lise-Lotte Kirkevang ◽

...

Keyword(s):

Clinical Studies ◽

Endodontic Treatment ◽

Treatment Modalities ◽

Core Outcome ◽

Consensus Process ◽

International Consensus ◽

Core Outcome Sets ◽

Key Stakeholders ◽

Dental Practitioners ◽

Patient Reported

Abstract BackgroundThe outcome of endodontic treatment is generally assessed using a range of patient and clinician-centred, non-standardised clinical and radiographic outcome measures. This makes it difficult to synthesise evidence for systematic analysis of the literature and the development of clinical guidelines. Core outcome sets (COS) represent a standardised list of outcomes that should be measured and reported in all clinical studies in a particular field. Recently, clinical researchers and guideline developers have focussed on the need for integration of a patient-reported COS with clinician-centred measures. This study aims to develop a COS that includes both patient reported outcomes and clinician centred measures for various endodontic treatment modalities to be used in clinical research and practice.MethodsTo identify reported outcomes (including when and how they are measured), systematic reviews and their included clinical studies, which focus on the outcome of endodontic treatment and were published between 1990 and 2020 will be screened. The COSs will be defined by a consensus process involving key stakeholders using semi-structured interviews and an online Delphi methodology followed by an interactive virtual consensus meeting. A heterogeneous group of key ‘stakeholders’ including patients, general dental practitioners, endodontists, endodontic teachers, clinical researchers, students and policy-makers will be invited to participate. Patients will establish, via interactive interviews, which outcomes they value and feel should be included in a COS. In the Delphi process, other stakeholders will be asked to prioritise outcomes identified from the literature and patients interviews, and will have the opportunity at the end of the first round to add outcomes that are not included, but which they consider relevant. Feedback will be provided in the second round, when participants will be asked to prioritise the list again. If consensus is reached, the remaining outcomes will be discussed at an online meeting and agreement established via defined consensus rules of outcome inclusion. If consensus is not reached after the second round, a third round will be conducted with feedback, followed by the online meeting. Following identification of a COS, we will proceed to identify how and when these outcomes are measured.DiscussionUsing a rigorous methodology, the proposed consensus process aims to develop a COS for endodontic treatment that will be relevant to stakeholders. The results of the study will be shared with participants and COS users. To increase COS uptake, it will also be actively shared with clinical guideline developers, research funders and the editors of general dental and endodontology journals.Study registrationThe study is registered in COMET (https://comet-initiative.org/Studies/Details/1879)

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Implementing Community-Based Systems of Services for Children and Youths With Special Health Care Needs: How Well Are We Doing?

PEDIATRICS ◽

10.1542/peds.113.s4.1538 ◽

2004 ◽

Vol 113 (Supplement_4) ◽

pp. 1538-1544 ◽

Cited By ~ 22

Author(s):

Merle McPherson ◽

Gloria Weissman ◽

Bonnie B. Strickland ◽

Peter C. van Dyck ◽

Stephen J. Blumberg ◽

...

Keyword(s):

Health Care ◽

Transition To Adulthood ◽

Special Health Care Needs ◽

Core Outcome ◽

Health Care Needs ◽

Care Needs ◽

Special Health Care ◽

The Core ◽

Core Outcomes ◽

Special Health

Objective. To provide a baseline measure of the proportion of US children who meet the Maternal and Child Health Bureau's core outcomes for children with special health care needs (CSHCN). Those core outcomes include the following: 1) families of CSHCN will partner in decision making and will be satisfied with the services that they receive; 2) CSHCN will receive coordinated, ongoing comprehensive care within a medical home; 3) families of CSHCN will have adequate private and/or public insurance to pay for the services that they need; 4) children will be screened early and continuously for special health care needs; 5) community-based service systems will be organized so that families can use them easily; and 6) youths with special health care needs will receive the services necessary to make transitions to adult life, including adult health care, work, and independence. Methods. A national household survey was conducted using telephone interviews. We analyzed data on 38 866 CSHCN included in the 2001 National Survey of CSHCN and 13 579 children included in the 2001 National Health Interview Survey. We assessed the proportion of US children who met each of the 6 core outcomes for CSHCN using data from 2 surveys. Results. Success rates ranged from 6% (the core outcome on successful transition to adulthood) to 74% (the core outcome on organization of the service system). For 5 of the 6 core outcomes, success rates exceeded 50%. Conclusion. Our results indicate that, for the most part, the United States is well positioned to meet the 6 core outcomes. However, much more work lies ahead before success can be claimed. This is especially true for the core outcome on transition to adulthood, for which only 6% of children in the target population are now meeting this goal.

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

Trials ◽

10.1186/s13063-022-06000-w ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Olalekan Lee Aiyegbusi ◽

Lavinia Ferrante di Ruffano ◽

Ameeta Retzer ◽

Philip N. Newsome ◽

Christopher D. Buckley ◽

...

Keyword(s):

Systematic Review ◽

Inflammatory Diseases ◽

Core Outcome ◽

Core Outcome Sets ◽

Regulatory Guidance ◽

Immune Mediated ◽

Outcome Selection ◽

Similarities And Differences ◽

Selection For

Abstract 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.

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