Methodological quality of 100 recent systematic reviews of health-related outcome measurement instruments: an overview of reviews.

PURPOSE: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards. METHODS: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies' findings. RESULTS: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use. CONCLUSION: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic reviews of OMIs meet current scientific standards, more consistent conduct and reporting of systematic reviews of OMIs is needed.

Guideline for reporting systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN for OMIs 2024.

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

Guideline for reporting systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN for OMIs 2024.

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

Guideline for reporting systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN for OMIs 2024.

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

Guideline for reporting systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN for OMIs 2024.

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

Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging, with several innovative clinical trials in progress. Despite these advancements, there is considerable heterogeneity in the outcomes studied, with lack of consensus as to what outcomes to measure, when to measure and how to measure. Furthermore, there has been a paradigm shift in PSC treatment targets over recent years, moving from biochemistry-based endpoints to histological assessment of liver fibrosis, imaging-based biomarkers and patient-reported outcome measures. The abundance of new interventional trials and evolving endpoints pose opportunities for all stakeholders involved in evaluating novel therapies. To this effect, there is a need to harmonise measures used in clinical trials through the development of a core outcome set (COS). METHODS AND ANALYSIS: Synthesis of a PSC-specific COS will be conducted in four stages. Initially, a systematic literature review will be performed to identify outcomes previously used in PSC trials, followed by semistructured qualitative interviews conducted with key stakeholders. The latter may include patients, clinicians, researchers, pharmaceutical industry representatives and healthcare payers and regulatory agencies, to identify additional outcomes of importance. Using the outcomes generated from the literature review and stakeholder interviews, an international two-round Delphi survey will be conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting will be convened to ratify the COS and disseminate findings for application in future PSC trials. ETHICS AND DISSEMINATION: Ethical approval has been granted by the East Midlands-Leicester Central Research Ethics Committee (Ref: 24/EM/0126) for this study. The COS from this study will be widely disseminated including publication in peer-reviewed journals, international conferences, promotion through patient-support groups and made available on the Core Outcomes Measurement in Effectiveness Trials (COMET) database. TRIAL REGISTRATION NUMBER: 1239.

Patient and public involvement and engagement in the development of innovative patient-centric early phase dose-finding trial designs.

BACKGROUND: In light of the FDA's Project Optimus initiative, there is fresh interest in leveraging Patient-reported Outcome (PRO) data to enhance the assessment of tolerability for investigational therapies within early phase dose-finding oncology trials. Typically, dose escalation in most trial designs is solely reliant on clinician assessed adverse events. Research has shown a disparity between patients and clinicians when assessing whether an investigational therapy is tolerable, leading to the recommendation of potentially intolerable doses for further investigation in subsequent trials. It is also increasingly recognized that patient and public involvement and engagement (PPIE) plays a pivotal role in enriching trial design and conduct. However, to our knowledge, no PPIE has explored the optimal integration of PROs in the development of advanced statistical trial designs within early phase dose-finding oncology trials. METHODS: A virtual PPIE session was held with nine participants on 18th October 2023 to discuss the incorporation of PROs within a dose-finding trial design. This cross disciplinary session was developed and led by a team of statisticians, clinical specialists, qualitative experts, and trial methodologists. Following the session, in-depth perspectives were provided by two patient advocates who actively engaged in the PPIE session. We discuss the importance of PPIE in shaping advanced dose-finding trial designs, share insights from patients on integrating PROs to inform treatment tolerability, and present a template for meaningful patient involvement in trial design development. RESULTS: Participants generally supported the introduction of PROs within dose-finding trials but showed some apprehensiveness as to how PROs may reduce the size of the recommended dose (and potentially efficacious effect). Some participants shared that they may be reluctant to record the real severity of their symptoms via PROs if it would mean that they would have to discontinue treatment. They discussed that PROs could be used to assess tolerability rather than toxicity of a dose. CONCLUSIONS: Amplifying patient voice in the development of patient-centric dose-finding trial designs is now essential. This paper offers an exemplary illustration of how trialists and methodologists can effectively incorporate patient voice in the future development of advanced dose-finding trial designs.

The aim of dose-finding oncology trials is to make sure a treatment is safe, understand its side effects, and recommend the right dose (or doses) for future clinical trials. Traditionally, a patient's tolerance to treatment is assessed by doctors who evaluate toxicities (side-effects) using established grading guidelines. Research has shown that doctors might not identify all the side effects that patients actually experience during a trial.There is growing interest in the introduction of patient-reported outcomes (PROs) within dose-finding trials. PROs are reports of a patient's health and well-being experiences which come directly from the patient themselves, usually assessed using a questionnaire.In a dose-finding trial, we start with a low dose of a drug and increase it until too many patients have severe side effects. The highest safe dose is then investigated in a later phase trial.   We are suggesting a new way to do these trials. We want to look at both what doctors see as severe side effects and what patients say. This enables us to recommend a dose that balances both perspectives. We would also like to ask patients what level of risk they are comfortable with regarding severe side effects.In this paper, we highlight the importance of involving patients in creating advanced dose-finding trial designs, particularly with PROs to help decide whether a dose is tolerable for patients. We also share findings of a patient and public involvement and engagement session and provide a guide for meaningful patient involvement in developing trial designs.

Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care. METHODS AND ANALYSIS: Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system. ETHICS AND DISSEMINATION: Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups. TRIAL REGISTRATION NUMBER: ISCTRN11232653.

Patient-reported outcomes in integrated health and social care: A scoping review.

Background: Patient-reported outcomes (PROs) have potential to support integrated health and social care research and practice; however, evidence of their utilisation has not been synthesised. Objective: To identify PRO measures utilised in integrated care and adult social care research and practice and to chart the evidence of implementation factors influencing their uptake. Design: Scoping review of peer-reviewed literature. Data sources: Six databases (01 January 2010 to 19 May 2023). Study selection: Articles reporting PRO use with adults (18+ years) in integrated care or social care settings. Review methods: We screened articles against pre-specified eligibility criteria; 36 studies (23%) were extracted in duplicate for verification. We summarised the data using thematic analysis and descriptive statistics. Results: We identified 159 articles reporting on 216 PRO measures deployed in a social care or integrated care setting. Most articles used PRO measures as research tools. Eight (5.0%) articles used PRO measures as an intervention. Articles focused on community-dwelling participants (35.8%) or long-term care home residents (23.9%), with three articles (1.9%) focussing on integrated care settings. Stakeholders viewed PROs as feasible and acceptable, with benefits for care planning, health and wellbeing monitoring as well as quality assurance. Patient-reported outcome measure selection, administration and PRO data management were perceived implementation barriers. Conclusion: This scoping review showed increasing utilisation of PROs in adult social care and integrated care. Further research is needed to optimise PROs for care planning, design effective training resources and develop policies and service delivery models that prioritise secure, ethical management of PRO data.

Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Background: Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. Method: The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Results: Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, ß -0.037, 95% CI -0.058 to -0.016, P = .001), HADS depression score ≥8 (ß -0.159, -0.182 to -0.137, P < .001), anxiety score ≥8 (ß -0.090, -0.110 to -0.069, P < .001), taking ≥10 medications (ß -0.065, -0.085 to -0.046, P < .001), sarcopenia (ß -0.062, -0.080 to -0.043, P < .001) haemoglobin <100 g/L (ß -0.047, -0.085 to -0.010, P = .012) and pain (ß -0.134, -0.152 to -0.117, P < .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Conclusion: Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Recommendations to address respondent burden associated with patient-reported outcome assessment.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden.

Factors that influence the selection of conservative management for end-stage renal disease - a systematic review.

Background: Most patients with end-stage renal disease (ESRD) are managed with dialysis and less commonly kidney transplantation. However, not all are suitable for or desire either of these renal replacement therapies. Conservative management (CM) is an option. However, the selection of CM is often not easy for patients and clinicians. The aim of this systematic review is to identify the key factors that influence the selection of CM for ESRD. Methods: Medline, Embase, PsychINFO, and CINAHL Plus were systematically searched from inception to 10 September 2021. Titles/abstracts and full texts were independently screened by two reviewers. Reference lists of included articles were searched. An update search via PubMed was conducted on 10 August 2023. A narrative synthesis of review findings was conducted. Results: At the end of the screening process, 15 qualitative and 8 survey articles were selected. Reference checking yielded no additional relevant studies. Main themes were: (i) Patient-specific factors; (ii) Clinician-specific factors; (iii) Organisational factors; and (iv) National and international factors. Patient-specific factors were awareness and perceptions of CM and dialysis, beliefs about survival, preferred treatment outcomes and influence of family/caregivers and clinicians. Clinician-specific factors included perceptions of CM as 'non-intervention', perceptions of clinician role in the decision-making process, and confidence and ability to initiate sensitive treatment discussions. Relationships with and involvement of other healthcare professionals, time constraints, and limited clinical guidance were also important factors. Conclusions: An improvement in the provision of education regarding CM for patients, caregivers, and clinicians is essential. Robust studies are required to generate crucial evidence for the development of stronger recommendations and guidance for clinicians.

Patient-Reported Outcome Measures for Patients With CKD: The Case for Patient-Reported Outcomes Measurement Information System (PROMIS) Tools.

Chronic kidney disease (CKD), kidney failure, and kidney replacement therapies are associated with high symptom burden and impaired health-related quality of life (HRQOL). Symptoms change with disease progression or transition between treatment modalities and frequently go unreported and unmanaged. Tools that reliably monitor symptoms may improve the management of patients with CKD. Patient-reported outcome measures (PROMs) assess symptom severity; physical, psychological, social, and cognitive functioning; treatment-related side effects; and HRQOL. Systematic use of PROMs can improve patient-provider communication, patient satisfaction, clinical outcomes, and HRQOL. Potential barriers to their use include a lack of engagement, response burden, and limited guidance about PROM collection, score interpretation, and workflow integration. Well-defined, acceptable, and effective clinical response pathways are essential for implementing PROMs. PROMs developed by the Patient-Reported Outcomes Measurement Information System (PROMIS) address some challenges and may be suitable for clinical use among patients with CKD. PROMIS tools assess multiple patient-valued, clinically actionable symptoms and functions. They can be administered as fixed-length, customized short forms or computer adaptive tests, offering precise measurement across a range of symptom severities or function levels, tailored questions to individuals, and reduced question burden. Here we provide an overview of the potential use of PROMs in CKD care, with a focus on PROMIS.

Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review.

Background: Traditionally, within dose-finding clinical trials, treatment toxicity and tolerability are assessed by clinicians. Research has shown that clinician reporting may have inadequate inter-rater reliability, poor correlation with patient reported outcomes, and under capture the true toxicity burden. The introduction of patient-reported outcomes (PROs), where the patient can assess their own symptomatic adverse events or quality of life, has potential to complement current practice to aid dose optimisation. There are no international recommendations offering guidance for the inclusion of PROs in dose-finding trial design and analysis. Our review aimed to identify and describe current statistical methods and data visualisation techniques employed to analyse and visualise PRO data in published early phase dose-finding oncology trials (DFOTs). Methods: DFOTs published from June 2016-December 2022, which presented PRO analysis methods, were included in this methodological review. We extracted 35 eligible papers indexed in PubMed. Study characteristics extracted included: PRO objectives, PRO measures, statistical analysis and visualisation techniques, and whether the PRO was involved in interim and final dose selection decisions. Findings: Most papers (30, 85.7%) did not include clear PRO objectives. 20 (57.1%) papers used inferential statistical techniques to analyse PROs, including survival analysis and mixed-effect models. One trial used PROs to classify a clinicians' assessed dose-limiting toxicities (DLTs). Three (8.6%) trials used PROs to confirm the tolerability of the recommended dose. 25 trial reports visually presented PRO data within a figure or table within their publication, of which 12 papers presented PRO score longitudinally. Interpretation: This review highlighted that the statistical methods and reporting of PRO analysis in DFOTs are often poorly described and inconsistent. Many trials had PRO objectives which were not clearly described, making it challenging to evaluate the appropriateness of the statistical techniques used. Drawing conclusions based on DFOTs which are not powered for PROs may be misleading. With no guidance and standardisation of analysis methods for PROs in early phase DFOTs, it is challenging to compare study findings across trials. Therefore, there is a crucial need to establish international guidance to enhance statistical methods and graphical presentation for PRO analysis in the dose-finding setting. Funding: EA has been supported to undertake this work as part of a PhD studentship from the Institute of Cancer Research within the MRC/NIHR Trials Methodology Research Partnership. AM is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust, the Institute of Cancer Research and Imperial College.

COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management.

PURPOSE OF REVIEW: This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome. RECENT FINDINGS: Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed. SUMMARY: The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.

The effect of disease modifying therapies on fatigue in multiple sclerosis.

INTRODUCTION: Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS). We conducted a systematic review to 1) understand whether fatigue is included as an outcome in MS trials of DMTs; 2) determine the effects on fatigue of treating MS with DMTs and 3) assess the quality of MS trials including fatigue as an outcome. METHODS: Two independent researchers systematically searched MEDLINE, EMBASE and ClinicalTrials.gov from 1993 to January 2023 for RCTs that measured fatigue as an outcome. Adherence to reporting standards was assessed with the Consolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO), while the risk of bias (RoB) was assessed with the RoB 2 tool by the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review protocol was registered in PROSPERO (CRD42022383321). RESULTS: The search strategy identified 130 RCTs of DMTs of which 7 (5%) assessed fatigue as an outcome. Of the 7 trials, only two presented statistically significant results. In addition, the reporting of fatigue among RCTs was suboptimal with a mean adherence to the CONSORT-PRO Statement of 36% across all trials. Of the 7 trials included, four were assessed as 'high' RoB.. CONCLUSIONS: Fatigue has a major impact on PwMS yet there is limited trial-based evidence on the impact of DMTs on fatigue. Assessment of fatigue as an outcome is underrepresented in trials of DMTs and the reporting of PRO trial data is suboptimal. Thus, it is imperative that MS researchers conduct RCTs that include fatigue as an outcome, to support clinicians and people with MS (PwMS) to consider the impact of the different DMTs on fatigue.

Paving the way for patient centricity in real-world evidence (RWE): Qualitative interviews to identify considerations for wider implementation of patient-reported outcomes in RWE generation.

Objectives: Real-world evidence (RWE) generation can be enhanced by including patient-reported outcomes (PROs). Methods for collecting and using PRO data in the real-world setting are currently underdeveloped and there is no international guidance specific to its use in this context. This study explored stakeholders' perspectives and needs for using PROs in RWE generation. Barriers, facilitators, and opportunities for wider use of PROs in real-world studies were also investigated. Methods: Online semi-structured interviews were conducted with international stakeholders: patients, patient advocates, regulators, payers, clinicians, academic researchers, and industry experts. Interviews were recorded, transcribed verbatim and analysed using NVivo 20. Thematic analysis was conducted based on the updated Consolidated Framework for Implementation Research (CFIR). Results: Twenty-three interviews were conducted. Participants confirmed that the use of PROs in RWE generation is not yet well established. Participants expressed a mixed level of confidence in the value of PROs collected in a real-world setting. Operational challenges associated with collecting routine PRO data to inform care delivery at the individual level (e.g., setting up infrastructure) need to be addressed. Methodological and other challenges (e.g., financing research) associated with collecting prospective de novo data in a real-world setting should be considered to facilitate PRO utilisation in real-world studies. Conclusions: Several opportunities and challenges were identified regarding the broader use of PROs in RWE research. Joint efforts from different stakeholders are needed to maximise PRO implementation, with consideration given to each stakeholders' specific needs (e.g., by developing good practices).