PURPOSE:Proximal femoral (hip) fracture is common, serious, and costly. Increasing the amount and quality of rehabilitation post-hip fracture potentially improves patient outcomes. Process evaluation examined implementation, mechanisms, and context of the FEMuR intervention, a community rehabilitation programme. Despite patient-reported benefits, RCT found no improvement in quantitatively measured outcomes compared with usual rehabilitation care. MATERIALS AND METHODS:Intervention was delivered across 13 sites. Embedded mixed methods evaluation using realist frameworks. Thematic analysis of semi-structured interviews (patients n = 39: intervention n = 20, control n = 19), carers (n = 2), therapists (n = 10), and recruiting staff (n = 7), plus descriptive analysis of workbooks, goal-setting diaries, and therapy records. RESULTS:Additional therapy sessions were valued by patients and staff; patients appreciated tailored, person-centred support. Therapists appreciated time to work holistically. However, there were disparities in intervention delivery. COVID-19 necessitated remote delivery, impacting therapist feedback and risk assessment. Impacting context and mechanism factors included patient motivation, therapist expertise, variable usual care, poor service integration, and pandemic restrictions limiting activities. CONCLUSIONS:Despite high levels of acceptability, intervention implementation and fidelity were compromised. Process evaluation revealed important lessons for future rehabilitation research. Capturing patient-centred intangible benefits, accounting for implementation variations, and considering outcomes beyond standard measures are necessary to fully understand effectiveness.

Background Patient Information Leaflets (PILs) provide potential participants with the information needed to make an informed decision about joining a randomised controlled trial (RCT). The growing use of healthcare systems data (HSD) adds complexity to documents already under pressure to remain concise. While regulatory requirements exist for transparency about data use, no specific guidance prescribes the level of detail or wording required to describe HSD in PILs. This study examined how PILs from NIHR-funded RCTs communicate HSD use to potential participants. Methods A document analysis was conducted using a cohort of RCTs. Eligibility was determined by NIHR-HTA funding, active trial status in 2022, and planned use of HSD, resulting in 51 eligible RCTs. PILs were obtained through online searches and direct contact with trial teams. Data were extracted using a form based on HRA data protection disclosure requirements. Questions examined, data access, linkage, confidentiality and regulatory compliance. PILs were assessed against trial protocols to evaluate completeness of HSD source disclosure. A three-category scale (Vague, Clear, Detailed) captured variation in level of detail. Informed consent forms (ICFs) were reviewed where available. Results PILs were obtained for 43 of the 51 trials (84%). 33(77%) mentioned at least one HSD source, but of these only 22(67%) mentioned all sources planned in the protocol[GC1] . Only 7(16%) PILs described what specific data would be accessed from HSD. Three ICFs requested consent for HSD use not previously explained in the PIL, raising concerns about informed consent adequacy. HSD detail varied across PILs, from vague references of medical records to detailed descriptions of data linkage and access procedures. Most PILs were in a paper format, referencing additional websites through links. Seven (16%) were presented using a multimedia format, allowing for dynamic explanations of the trial. Conclusion Patients have identified data explanation as a high-priority feature of PILs, yet the level of detail provided about HSD is often insufficient to support informed decision-making. There is an absence of guidance for HSD-specific PIL content. The introduction of ICH E6(R3), which strengthens patient rights and data governance related to external data sources, highlights the need to address this gap and support trialists and patients.

Background Plasma concentrations of procollagen type-I C-terminal pro-peptide (PICP) and collagen type-I C-terminal telopeptide (CITP) may reflect collagen turnover and systemic fibrosis. We investigated the effect of pirfenidone, an anti-fibrotic agent, on PICP and CITP, and their association with myocardial fibrosis, using cardiovascular magnetic resonance to measure extracellular volume (ECV).Methods In the trial (Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction), PICP, CITP and PICP:CITP ratio were measured at baseline and follow-up in patients with ECV≥27% randomised (n=94) to pirfenidone or placebo, and at baseline only in patients who were not randomised because of ECV<27% (n=13).Results There was no association between baseline myocardial ECV and baseline log PICP, log CITP and log PICP:CITP ratio (p=0.19, p=0.13, p=0.60, respectively). Treatment with pirfenidone did not alter PICP, but reduced CITP and increased PICP:CITP ratio at 13 and 26 weeks (all p<0.05) but not at 52 weeks. After multivariable adjustment, there was a weak relationship between change in myocardial ECV and change in log PICP (R2 0.16, p=0.01) and log CITP (R2 0.12, p=0.04), but not log PICP:CITP ratio (p=0.56).Conclusions In patients with stable heart failure with preserved ejection fraction, pirfenidone treatment had no sustained effect on plasma levels of PICP and CITP at 52 weeks. Changes in ECV during treatment with pirfenidone are associated with changes in plasma PICP and CITP, suggesting a weak association between changes in collagen volume/mass and plasma markers of collagen turnover.

BACKGROUND AND AIMS:Pathophysiological features of hypertrophic cardiomyopathy include left ventricular hypertrophy, myocardial fibrosis, and myocardial energy deficiency. Depletion of cardiomyocyte copper I ions leads to impaired mitochondrial function, a state associated with left ventricular hypertrophy. Unbound or loosely bound copper II ions activate profibrotic pathways. Trientine dihydrochloride improves intracellular copper I ion trafficking and availability, and chelates copper II ions. In preclinical studies, trientine improved myocardial mitochondrial function and reduced left ventricular hypertrophy and fibrosis. The efficacy and safety of trientine in persons with hypertrophic cardiomyopathy are unknown. METHODS:In this multicentre, placebo-controlled phase 2 trial, adults with hypertrophic cardiomyopathy, a left ventricular wall thickness of 15 mm or greater, and who were in New York Heart Association class I to III were randomly assigned to receive trientine 400 mg twice daily or placebo for 52 weeks. Patients with any left ventricular outflow tract (LVOT) gradient were eligible. The primary endpoint was the change in left ventricular mass indexed to body surface area measured using cardiovascular magnetic resonance. RESULTS:A total of 154 patients underwent randomization. The mean age was 53.4 years, median maximum left ventricular wall thickness was 20.0 mm, median maximum LVOT gradient was 6.0 mmHg, 18.6% of patients had a resting LVOT gradient ≥30 mmHg, and 61.7% were in New York Heart Association class I. At 52 weeks, the mean change in the left ventricular mass indexed to body surface area was -4.4 ± 7.7 g/m2 in the trientine group and -1.5 ± 6.1 g/m2 in the placebo group (between-group difference -3.2 g/m2; 95% confidence interval -5.6 to -0.8; P = .009). The efficacy of trientine increased at higher levels of baseline left ventricular mass (baseline left ventricular mass indexed to body surface area by treatment allocation interaction P = .015). The effect of trientine was mediated via a reduction in myocardial cellular mass (average causal mediated effect -3.9 g/m2; 95% confidence interval -6.8 to -0.9). The incidence of adverse events was similar in the two groups. CONCLUSIONS:Among patients with hypertrophic cardiomyopathy, treatment with trientine resulted in a significantly greater reduction in left ventricular mass indexed to body surface area than placebo. (Funded by NIHR; TEMPEST ClinicalTrials.gov number, NCT04706429).

OBJECTIVES:Identify the key challenges and opportunities researchers face when accessing healthcare systems data (HSD) for randomised controlled trials (RCTs) and develop a consolidated set of recommended improvements. METHODS:Multidisciplinary researchers with expertize in RCTs were invited to participate in online focus groups and individual interviews to share their experiences of accessing HSD. Data were analyzed using directed content analysis guided by themes identified in prior research. RESULTS:Three distinct stages of the HSD access process were identified, covering preparation, submission of a data access application to a provider, and working with the received data, each presenting specific challenges and opportunities for improvement. In the preapplication stage, participants highlighted limited awareness and experience with HSD and emphasized the need for clearer guidance. During the data access application stage, researchers described difficulties related to the mismatch between application requirements and the needs of RCTs, as well as delays in progression. In the postapplication stage, challenges in receiving and working with the data were reported, alongside recognition of the tangible benefits that HSD can provide for trial delivery and quality. CONCLUSION:Identifying challenges across the HSD access process can help trial teams anticipate potential obstacles and plan more effectively. Given that the current application process does not fully meet the needs of RCTs, the recommendations derived from this work highlight key areas for improvement that providers could implement to reduce barriers and better support the use of HSD in trials.

Background A Core Outcome Set (COS), defined as the agreed minimum set of outcomes to be measured and reported in all clinical trials for a particular condition, could help address outcome heterogeneity across studies and lack of consideration of what matters to patients. This study aimed to identify all COS developed for research relevant to physiotherapy interventions, evaluate whether their development met minimum standards, and classify the recommended outcomes to provide a reference point for future comparisons. Methods The COMET database was searched to identify relevant published and ongoing COS related to physiotherapy interventions. Two investigators independently screened the articles for inclusion, followed by independent data extraction of included COS and evaluation of the COS according to the Core Outcome Set-STAndards for Development (COS-STAD). For each included COS, the core outcomes were categorised using the COMET taxonomy. Results The scope of the COS was specified in all the included studies (N = 31), with most COS applicable to rheumatological conditions and physical rehabilitation interventions. Around 40% (n = 13) were developed with participation from more than one region of the world. Patients participated in the development process in two thirds of COS studies (n = 21, 68%) with health care professionals participating in almost all included studies (n = 30, 97%). Aspects of the consensus process were decided a priori in 26% (n = 8, for consensus definition and criteria for including, dropping or adding outcomes) and 32% (n = 10, for scoring process) of studies. All COS included at least one life impact outcome, and emotional functioning outcomes were more prominent in COS that included patient input. Conclusion This review highlights the need for improvement in the development of COS, particularly in relation to increasing global involvement, patient participation, and reporting of the consensus process during COS development. Systematic review registration number: PROSPERO CRD42025620018

Background Novel collagen-derived circulating peptides, such as endotrophin, have been proposed as biomarkers of myocardial fibrosis. Objectives We aimed to determine the effect of pirfenidone, an antifibrotic agent, on circulating levels of these peptides, and their association with cardiovascular magnetic resonance extracellular volume (ECV). Methods In the PIROUETTE (Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, novel collagen-derived circulating peptides (PRO-C3, C3M, CTX-III, endotrophin, PRO-C6, and C6M) were measured at baseline and at prespecified time points in patients with ECV ≥27% randomized (n = 94) to pirfenidone or placebo. Baseline peptide levels were also measured in patients with ECV <27% who were not randomized (n = 13). Results Treatment with pirfenidone was associated with a significant reduction in log endotrophin (P = 0.034), with a treatment effect seen from 13 weeks. After multivariable adjustment there were significant albeit modest associations between change in myocardial ECV and change in log endotrophin (R2: 0.14; P = 0.031), and baseline ECV and baseline log endotrophin (R2: 0.30; P = 0.022). Pirfenidone had no effect on the levels of other collagen-derived circulating peptides, and there were no associations between their levels and change in myocardial ECV or baseline ECV. Conclusions In patients with heart failure with preserved ejection fraction, treatment with pirfenidone was associated with a sustained reduction in circulating levels of endotrophin from 13 weeks. Circulating endotrophin was also independently associated with both baseline myocardial ECV and change in myocardial ECV. Endotrophin shows high potential as a circulating biomarker reflective of myocardial fibrosis burden and sensitive to change in myocardial fibrosis over time.

Background: Selection of second-line therapy in Crohn’s disease (CD) patients after failure of first-line TNFα-inhibitor (TNFi) therapy to optimise outcomes remains challenging in real-world clinical practice. Objectives: This study aimed to provide real-world outcomes of CD patients who failed first-line TNFi therapy and switched to either another TNFi or to a biologic with a different mechanism of action. Patients were stratified as to whether they switched because of primary non-response or secondary loss of response to initial TNFi. Design: Retrospective cohort study. Methods: CD patients whose first biologic therapy was a TNFi and switched to another biologic therapy between 26 August 2015 and 31 March 2021 were identified in records held by the UK IBD Registry. Patients were enrolled at study sites, and data were validated by clinical teams. Patients were grouped as within-class switchers (WCS) if their second-line (index) biologic therapy was another TNFi, or out-of-class switchers (OCS) if their index therapy was vedolizumab or ustekinumab. Patients were followed up for at least 1 year. Time to drug discontinuation and outcomes at 1 year after index therapy start were analysed using Cox regression and binary logistic regression models, before and after baseline covariate adjustment through inverse probability of treatment weighting. Results: A total of 180 adult CD patients were included in the study. OCS were less likely to discontinue index therapy in both unweighted analysis (hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.42–0.96, p = 0.03) and weighted analysis (HR: 0.58, 95% CI: 0.38–0.90, p = 0.01), and more likely to show index drug persistence at 1 year in both unweighted analysis (adjusted odds ratio (aOR): 3.66, 95% CI: 1.81–7.67, p < 0.001) and weighted analysis (aOR: 3.95, 95% CI: 2.04–7.89, p < 0.001). These findings were consistent across all secondary endpoints of steroid-free and/or surgery-free index drug survival at 1 year. Conclusion: Patients switching from a TNFi to either vedolizumab or ustekinumab exhibited significantly higher rates of drug persistence compared to those switching to another TNFi, particularly among those experiencing primary non-response to the initial TNFi.

OBJECTIVES:The annual systematic review update of published core outcome sets (COSs) by the Core Outcome Measures in Effectiveness Trials Initiative allows assessment of adherence to development standards. The objectives of this study were to assess the quality of COS development and the approach to the inclusion of adverse event outcomes. STUDY DESIGN AND SETTING:Studies reporting the development of a COS, published or indexed in 2022 and 2023, were identified using systematic review methods previously applied. Adherence to internationally agreed consensus-based standards for COS development was assessed. An existing outcome taxonomy was used to classify the core outcomes from all studies. The approach to consideration and inclusion of adverse event outcomes was examined. RESULTS:Fifty-eight COS development studies were included in the 2022 update and a further 40 studies in the 2023 update. Scope specification standards were fully met in all studies. Stakeholder inclusion standards were fully met in 38 (66%) and 34 (85%) of the 2022 and 2023 studies, respectively; the proportion meeting all four standards for the consensus process was lower, 13 (22%) and 13 (33%), respectively. The consideration of adverse events in the COS development process varied. Around half (54, 49%) of 2022-2023 COS included either the adverse events domain or specifically named adverse events as core outcomes. CONCLUSION:Continued improvement in adherence to recognized standards, including patient participation, is evident; however, further improvement is needed in relation to the consensus process standards. COS developers should be explicit about and explain the rationale for their approach to consideration of adverse events.

OBJECTIVE:Deficiencies have been highlighted in acute hospital care for alcohol-related liver disease (ARLD). Such problems may be worse at weekends (WEs). Increased 30-day mortality for WE admissions has been reported for several acute conditions, but data for ARLD are limited. We aimed to compare patient and pathway characteristics between WE and weekday (WD) admissions and investigate the 'weekend effect' on mortality. METHODS:Retrospective cohort study (2008-2018) using linked electronic databases (Hospital Episode Statistics-Clinical Practice Research Datalink and death registration) including 17 575 first emergency admissions identified using the Liverpool ARLD algorithm. EXPOSURE:WE admission (Saturday or Sunday). MAIN OUTCOME:all-cause death within 30 days. Covariates included socio-demographic characteristics, pathway characteristics (pre-admission contacts and admission method) and markers of severity (recorded stage of liver disease, ascites and varices, comorbidity). Alternative risk-adjustment methods were used, including standard regression and propensity-weighted analysis (Inverse Probability of Treatment Weighting). RESULTS:3249 admissions (18.5%) were at WE. Unadjusted 30-day mortality was significantly higher for WE versus WD (17.1% vs 15.5%, p=0.018). All models demonstrated increased odds of death for WE admissions with adjusted ORs ranging from 1.15 to 1.23 (relative risk of 1.12-1.19). Causes of death did not vary by admission day and effect was consistent across subgroups. Findings were robust to sensitivity analyses restricting the cohort to patients admitted directly from Accident and Emergency department (A&E), or cirrhosis or ascites but not varices. CONCLUSION:First ARLD admissions at the WE experienced a 12-19% increase in 30-day mortality risk compared with WD. Although residual confounding cannot be excluded, this suggests the possibility of avoidable mortality among those hospitalised at WEs. Services should be alert to risks of WE effects when planning care.

Randomisation controlled trial are the gold standard for causal inference, however the rapidly increasing development of new treatments and the movement towards personalised medicine mean there is a need to measure efficacy outside of the costly and time-consuming RCT. Here we propose a method of estimating treatment effects using parametric models to act as control against which to compare data from an experimental arm. This allows for treatment effects to be estimated where data are only available from an experimental arm and can be a tool useful in the analysis of observational cohorts or for the design and analysis of RCTs. We develop this approach using Bayesian estimation procedures and compare this approach against other casual inference tools. We then demonstrate how this may be used to estimate the efficacy between two treatment in different RCTs for the analysis of Pancreatic Cancer. It is proposed that with reasonable assumptions, this approach can produce a reliable estimate of efficacy and can have applications in both evaluating currently available data and in the efficient design of future trials.

OBJECTIVE:To determine whether an enhanced community rehabilitation intervention (the Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR) intervention) was more effective than usual National Health Service care, following surgical repair of hip fracture, in terms of the recovery of activities of daily living (ADLs). DESIGN:Definitive, pragmatic, multisite, parallel-group, two-armed, superiority randomised controlled trial with 1:1 allocation ratio. SETTING:Participant recruitment in 13 hospitals across England and Wales, with the FEMuR intervention delivered in the community. PARTICIPANTS:Patients aged over 60 years, with mental capacity, recovering from surgical treatment for hip fracture and living in their own home prior to fracture. INTERVENTIONS:Usual rehabilitation care (control) was compared with usual rehabilitation care plus the FEMuR intervention, which comprised a patient-held workbook and goal-setting diary to improve self-efficacy, and six additional therapy sessions delivered in-person in the community, or remotely during COVID-19 restrictions (intervention), to increase the practice of exercise and ADL. PRIMARY AND SECONDARY OUTCOME MEASURES:Primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) scale at 12 months. Secondary outcomes included: Hospital Anxiety and Depression Scale, Falls Self-Efficacy-International scale, hip pain intensity, fear of falling, grip strength and Short Physical Performance Battery. Outcomes were collected by research assistants in participants' homes, whenever possible, but had to be collected remotely during COVID-19 restrictions. RESULTS:In total, 205 participants were randomised (n=104 experimental; n=101 control). Trial processes were adversely affected by the COVID-19 pandemic. There were 20 deaths, 34 withdrawals and three lost to follow-up. At 52 weeks, there was no significant difference in NEADL score between the FEMuR intervention and control groups. Joint modelling analysis testing for difference in longitudinal outcome adjusted for missing values also found no significant difference with a mean difference of 0.1 (95% CI -1.1, 1.3). There were no significant between-group differences in secondary outcomes. Sensitivity analyses, examining the impact of COVID-19 restrictions, produced similar results. A median of 4.5 extra rehabilitation sessions were delivered to the FEMuR intervention group, with a median of two sessions delivered in-person. Instrumental variable regression did not find any effect of the amount of rehabilitation on the main outcome. There were 53 unrelated serious adverse events (SAEs) including 11 deaths in the control group: 41 SAEs including nine deaths in the FEMuR intervention group. CONCLUSIONS:The FEMuR intervention was not more effective than usual rehabilitation care. The trial was severely impacted by COVID-19. Possible reasons for lack of effect included limited intervention fidelity (fewer sessions than planned and remote delivery), lack of usual levels of support from health professionals and families, and change in recovery beliefs and behaviours during the pandemic. TRIAL REGISTRATION NUMBER:ISRCTN28376407.

Consistent outcome assessment in surgical research, from early phase studies (during introduction and refinement of new procedures) to late phase studies (to establish comparative effectiveness) needs improvement to ensure efficient and safe surgical care. This study explored the potential continuity of outcome domain assessment throughout the evaluation lifecycle of surgical interventions. Core outcome sets (COS) for late phase studies of surgical interventions were identified through COMET database searches. Core outcomes/outcome domains were extracted and mapped to core domains of a COS developed specifically for evaluating surgical innovation (COHESIVE COS). Outcomes/domains were categorised as “definite match” (clear similarity), “possible match” (potential similarity) and “no match” (no similarity) COHESIVE domain based on similarity in wording or meaning. A total of 54 COS studies were included, yielding 573 core outcomes/domains. Most late phase core outcomes/domains (N = 519, 91

Background:Proximal femoral (hip) fracture is common, serious and costly. An enhanced community rehabilitation intervention (Fracture in the Elderly Multidisciplinary Rehabilitation) was codeveloped with patients, carers and therapists. Trial methods have been tested previously in a feasibility study. Objective:To determine the effectiveness and cost-effectiveness of the Fracture in the Elderly Multidisciplinary Rehabilitation intervention compared with usual NHS rehabilitation care. To determine the mechanisms and processes that explain the implementation and impacts of the Fracture in the Elderly Multidisciplinary Rehabilitation intervention. Design and methods:Definitive, pragmatic, multisite, parallel-group, two-armed, superiority randomised controlled trial with 1 : 1 allocation ratio. Concurrent economic and process evaluations. Setting:Participant recruitment in 13 hospitals across England and Wales, with the Fracture in the Elderly Multidisciplinary Rehabilitation intervention delivered in the community. Participants:Patients aged over 60 years, with mental capacity, recovering from surgical treatment for proximal femoral fracture, and living in their own home prior to fracture. Interventions:Usual rehabilitation care (control) was compared with usual rehabilitation care plus the Fracture in the Elderly Multidisciplinary Rehabilitation intervention, which comprised a patient-held workbook and goal-setting diary aimed at improving self-efficacy, and six additional therapy sessions delivered in the community (intervention), to increase the practice of exercise and activities of daily living. Primary and secondary outcome measures:Primary effectiveness outcome was the Nottingham Extended Activities of Daily Living scale at 12 months. Secondary outcomes included: Hospital Anxiety and Depression Scale, Falls Self-Efficacy - International scale, hip pain intensity, fear of falling, grip strength and Short Physical Performance Battery. Economic outcomes were EuroQol EQ-5D-3L and Client Service Receipt Inventory. Results:In total, 205 participants were randomised (n = 104 experimental; n = 101 control). Trial processes were adversely affected by the coronavirus disease discovered in 2019 pandemic and the target sample of 446 was not met. By 52 weeks, the intervention group had worse Nottingham Extended Activities of Daily Living scores than the control group (mean difference: -1.9; 95% confidence interval: -3.7 to -0.1), which was not clinically important. Joint modelling analysis testing for difference in longitudinal outcome adjusted for missing values, removed the apparent inferiority of the Fracture in the Elderly Multidisciplinary Rehabilitation intervention with a mean difference of 0.1 (95% confidence interval: -1.1 to 1.3). There was no statistical or clinically significant difference in secondary outcomes between groups. A median of 4.5 extra rehabilitation sessions were delivered to the intervention group, with a median of two sessions delivered in-person. Instrumental variable regression did not find any effect of the amount of rehabilitation on the main outcome. There were 53 unrelated serious adverse events including 11 deaths in the control group: 41 serious adverse events including nine deaths in the intervention group. The mean cost of delivering the Fracture in the Elderly Multidisciplinary Rehabilitation intervention was £444 per participant. The intervention group gained 0.02 (95% confidence interval: -0.036 to 0.076) more quality-adjusted life-years than the control group. This was not clinically or statistically significant. Mean health service use costs were higher in the intervention group. Limitations:The trial was severely impacted by coronavirus disease discovered in 2019. Possible reasons for lack of detected effect included limited intervention fidelity (number and remote mode of delivery), lack of usual levels of support from health professionals and families, and change in recovery beliefs and behaviours during the pandemic. Conclusion:The Fracture in the Elderly Multidisciplinary Rehabilitation intervention was not more effective and had higher costs than usual rehabilitation care. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/167/09.

Objective If clinical trials measure and report the outcomes included in core outcome sets (COS) for a given condition/disease as a minimum, this has the potential to improve comparability between trials and prevent research waste. Until now, the uptake of the Bronchiectasis and Hidradenitis Suppurativa (HS) COS has not been assessed.This study assessed the uptake of Bronchiectasis and HS COS using a review of trial registries, with entries taken from ClinicalTrials.gov and the WHO International Clinical Trial Registry Platform. This uptake assessment provides valuable information to inform COS refinement and uncover areas lacking uptake to inform further dissemination requirements.Methods For each trial, the outcomes included in the trial registry entry were extracted and compared with those included in the corresponding Bronchiectasis or HS COS. The Bronchiectasis COS consists of 18 outcomes, and the HS COS, 6.Results Of the trials registered after both COS were developed in 2018, 63% (12/19) of HS trials planned to measure the full COS, whereas for Bronchiectasis, 0% (0/24) of trials planned to measure the full COS. However, of the five priority outcomes to be measured for Bronchiectasis, 4% (1/24) of trials planned to measure all five outcomes.Both COS publications’ focus was to reach consensus on what outcomes should be measured. Despite both publications referring to the Core outcome Measures for Effectiveness Trials (COMET) Handbook, which discusses the importance of COS dissemination, implementation plans were not included in either publication.Conclusions The results suggest that uptake of the HS COS is relatively good, despite yearly fluctuations, whereas for Bronchiectasis, COS uptake is limited. Further research into standardised measurement tools for HS is expected to increase uptake. The focus for Bronchiectasis, however, will be to refine the COS for feasible application in clinical trials. Future COS development publications should use all resources from the COMET initiative to ensure feasible dissemination of the COS.

Objectives To support the use of the Core Outcome Measures in Effectiveness Trials taxonomy for health outcomes, its suitability and applicability must be assessed more broadly beyond that of its early piloting phases. Demonstration of its suitability in practice would provide further support for its use in aiding the development of core outcome sets (COS), systematic reviews, and searching in online resources, thereby aiding knowledge dissemination. Study Design and Setting A citation analysis identified published studies where the taxonomy had been applied. Analysis of these publications aimed to understand the type of publication, clinical area, reason for taxonomy use or adaptation, and any comments made by researchers who had applied the taxonomy. Results Of 315 papers identified, 200 were sampled and 193 publications relating to 184 projects were analyzed. Nearly one-third (58, 30%) of publications were related to the development of COS and half (98, 51%) were related to the development of reviews (systematic, scoping, and literature). In two-thirds (123, 67%) of the projects the taxonomy was applied for the classification of health outcomes and the vast majority (117, 95%) of these did so without making any changes. Conclusion This research confirms the taxonomy is sufficiently comprehensive and granular for the classification of all patient outcomes in health research. Its application can highlight a lack of attention being paid toward outcomes most important to patients. We encourage the adoption of this classification system to facilitate evidence searching. Plain Language Summary Patient health outcomes measure things that happen to patients relating to their health. These outcomes include clinical measures (such as blood pressure), life impact measures (such as effects on physical functioning), use of resources (such as number of hospital appointments), survival (such as how long someone survives after surgery), and harms (such as adverse events following treatment). In 2018, we developed a classification system (called a taxonomy) to help researchers organize the types of outcomes that they are collecting (perhaps when carrying out a clinical trial) or reporting (eg, when combining results from many studies in a systematic review). This taxonomy was designed to help researchers to more clearly present their results, as well as to allow them to search for outcomes online in a more organized manner. We used outcomes taken from many trials and reviews when developing the taxonomy, to make sure that all types of outcomes were covered, but we wanted to make sure that researchers found the taxonomy helpful in practice. This study has been carried out to understand the opinions of researchers who mentioned the taxonomy in their publications, to find out whether they thought any types of outcomes were missing. The study found that researchers found the taxonomy useful, either to classify their research outcomes or because they found our definitions of the different types of outcomes useful. Sometimes researchers wanted to be able to classify “who” reported the outcomes (such as patients) or wanted more specific definitions of the different types of outcomes included. We would encourage them to create subcategories within our taxonomy categories to cover these outcome features. A few researchers felt that they needed to add some extra outcome types, but this was because they did not realize that these outcomes would fit within one of the existing taxonomy groups. In summary, this study found that the taxonomy is useful to researchers to classify “what” patient health outcomes are recorded in their studies, and researchers are very welcome to contact us if they have any questions about how to use it or how to classify particular outcomes.