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Decentralized clinical trials involving the use of digital tools to facilitate remote research are gaining momentum. Rapid advancements in digital technologies have supported the adoption of these trials. These innovations facilitate virtual interactions between clinical trial teams and participants by making it easier to collect, transfer and store electronic data. While some studies have demonstrated the potential for these approaches to reduce barriers to clinical trial participation, they are associated with several challenges that may create or worsen existing health inequalities and limit the generalizability of trial results. Here we review the potential for digitally enabled and decentralized clinical trials to enhance clinical trial participation in an equitable manner. We describe the key barriers individuals from underserved groups may face, and provide recommendations to promote equity, diversity and inclusion., Competing Interests: Competing interests O.L.A. receives funding from the NIHR Birmingham Biomedical Research Centre (BRC), NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, NIHR Applied Research Collaboration (ARC) West Midlands, UK Research and Innovation (UKRI), LifeArc, Health Foundation, Merck, Gilead, Anthony Nolan, Sarcoma UK and GSK. O.L.A. declares personal fees from Gilead Sciences, Merck and GSK outside the submitted work. S.C.R. receives funding from UK SPINE and Merck, and declares personal fees from Merck. M.J.C. is director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, director of the Centre for the Centre for Patient Reported Outcomes Research and an NIHR Senior Investigator. M.J.C. receives funding from the NIHR, UKRI, NIHR Birmingham BRC, the NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, LifeArc, UK SPINE, European Regional Development Fund—Demand Hub and Health Data Research UK at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, Janssen, GSK and Gilead. M.C. has received personal fees from Astellas, Aparito, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK, Pfizer, the Patient-Centered Outcomes Research Institute and Vertex outside the submitted work. In addition, a family member owns shares in GSK. N.A. is an NIHR Senior Research Leader and receives funding from the NIHR, NIHR ARC West Midlands and NIHR Birmingham BRC. S.E.H. receives funding from the NIHR, NIHR BTRU in Precision Transplant and Cellular Therapeutics, NIHR Birmingham BRC, NIHR (ARC) West Midlands, UKRI and UK SPINE. S.E.H. declares personal fees from Cochlear, Pfizer, Rinri Therapeutics, Astra Zeneca, Aparito and CIS Oncology outside the submitted work. K.K. has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Bayer, Novo Nordisk, Sanofi-Aventis, Servier, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi Sankyo, Applied Therapeutics, Embecta and Nestle Health Science. K.K. is supported by the NIHR Applied Research Collaboration East Midlands (ARC EM), the NIHR Leicester BRC and the British Heart Foundation (BHF) Centre of Excellence. D.K. reports grants from the NIHR (CDF-2015-08-074 RATE-AF, NIHR130280 DaRe2THINK, NIHR132974 D2T-NeuroVascular, NIHR203326 Biomedical Research Centre), the BHF (PG/17/55/33087, AA/18/2/34218 and FS/CDRF/21/21032), the EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074), EU Horizon and UKRI (HYPERMARKER 101095480), UK National Health Service—Data for R&D-Subnational Secure Data Environment programme, UK Department for Business, Energy & Industrial Strategy Regulators Pioneer Fund, the Cook & Wolstenholme Charitable Trust and the European Society of Cardiology supported by educational grants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre and BHF/University of Birmingham Accelerator Award (STEEER-AF); in addition, D.K. has received research grants and advisory board fees from Bayer, Amomed and Protherics Medicines Development; all are outside the submitted work. C.M. receives funding from NIHR Surgical Reconstruction and Microbiology Research Centre, UKRI, NIHR, NIHR BTRU in Precision Transplant and Cellular Therapeutics and declares personal fees from Aparito outside the submitted work. A.D. is deputy director of the Birmingham Health Partners Centre for Regulatory Science and Innovation and is an NIHR Senior Investigator. A.D. receives funding from the NIHR, UKRI and NIHR Birmingham BRC. J.M. is chief editor at Nature Medicine and has excused himself from the peer review and editorial process of this article. P.M. is director of the Clinical Practice Research Datalink, a UK government real-world data research service that also provides clinical trial recruitment services. R.H. receives funding from the Leverhulme Trust., (© 2024. Springer Nature America, Inc.)

Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation., Competing Interests: C.Y. has received consulting fees from Faron Pharmaceuticals and an honoraria from Bayer. O.L.A. reported receiving grants from the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research center, NIHR Applied Research Collaboration West Midlands, NIHR Blood Transplant Research Unit (BRTU), UK Research and Innovation (UKRI), Health Foundation, Gilead, Anthony Nolan, GlaxoSmithKline, Merck, and Sarcoma UK. OLA declares personal fees from Gilead Sciences Ltd, Merck, and GlaxoSmithKline, Innovate UK outside the submitted work. E.B. has received payments as a scientific advisor for Navigating Cancer, AstraZeneca, Resilience, N-Power Medicine, and Verily. J.B. is an employee of AstraZeneca, with ownership interest in AstraZeneca and is engaged by Evinova, a separate healthtech business within the AstraZeneca group. A.H. has Research funding (paid to institution): Advancell, BMS, MSD, Macrogenics, Tyra Biosciences, Janssen, Seagen, Aveo, Roche/Genetech; Consulting (paid personally): MSD, Pfizer, Eisai, Astellas, Bayer. P.K. has shares in Merck Healthcare KgaA and is a Full-time employee of Merck Healthcare KgA. B.K.K. has grants paid direct to organisation from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Jazz Pharma, Genentech, Eli Lilly, Janssen, Takeda, Dachii Sankyo, Blueprint, Medicines, Janssen, Amgen, Seagen, Manta Cares and personal consultancy fees from Eli Lilly, BMS, AbbVie, Shionogi. H.M.K. has received grants unrelated to the work from the American Heart Association to Jansson; Agency for Healthcare Research and Quality to Kenvue; National Institutes of Health to Novartis; Centers for Medicare & Medicaid Services to Pfizer and Centers for Disease Control and Prevention. These grants and contracts are unrelated to the work above and are through Yale University or Yale New Haven Hospital. Received consulting fees from Massachusetts Medical Society (to Co-Editor, Journal Watch Cardiology); UpToDate (as Section Editor) and Ensight (unpaid advisor). Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events would have received occasional travel expenses and/or honoraria to speak at various educational/academic venues. Received travel expenses and/or honoraria to speak at various educational/academic venues. Stocks in Element Science and Identifeye. A.M. has served on advisory boards for Janssen Pharmaceuticals, GSK, Merck Pharmaceuticals, Takeda Pharmaceuticals, MSD Pharmaceuticals, Faron Pharmaceuticals, Pfizer Pharmaceuticals, AZ, Genmab Pharmaceuticals and Immutep Pharmaceuticals. Has received honoraria from Chugai Pharmaceuticals, Faron Pharmaceuticals, Merck Pharmaceuticals, GSK, Seagen, Takeda Pharmaceuticals and Janssen Pharmaceuticals. Has travel support from Amgen Pharmaceuticals and Janssen Pharmaceuticals. Has received research funding from Astex Pharmaceutical, Merck Pharmaceuticals and MSD. J.P. is a Patient representative on CCTG. S.R. Research grants with Medical Research Council, NIH/NEI, NIHR outside permitted work. A.R. reported receiving grants from National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC) paid to University of Birmingham and has funding outside the submitted work from NIHR, Birmingham City Council, ACCELERATE, Office of Health Disparity and Inequality. Support for attending meetings from Outsourcing in Clinical Trials UK/Ireland as invited speaker. Honoraria from Wellcome Sanger Institute Representative Research Strategy Advisory Group and ACCELERATE (Innovations for Children and Adolescents with Cancer) International Patient-Reported Outcomes Working Group—Core Group Member and Work-package Lead (unpaid). S.R. is employed by Veloxis Pharmaceuticals, Inc. Stock in the following companies: Bristol Myers-Squibb, Gilead Sciences, IGM Biosciences, Merck & Co, Pfizer. L.I.W. has received consulting fees from Celgene/Bristol Myers Squibb; Connect Multiple Myeloma registry, member Scientific Steering Committee. L.K.S. reports funding to institution from AZ, Bayer, Roche, GSK, Treadwell, REPARE, Novartis, Janssen, MERCK. Shares: AZ. H.A.W. is employed by Pfizer AG, Switzerland and owns non-voting shares of Roche Ltd. M.J.C. is the Director of Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient Reported Outcomes Research and a National Institute for Health and Care Research (NIHR) senior investigator; has received funding from Anthony Nolan, European Regional Development Fund-Demand Hub and Health Data Research UK, Gilead, GSK, Janssen, Macmillan Cancer Support, Merck, NIHR, NIHR ARC WM, NIHR Birmingham BRC, NIHR BTRU Precision and Cellular Therapeutics, UCB Pharma, UKRI, and UK SPINE; and has received consultancy fees from Aparito, Astellas, Boehringer Ingelheim, CIS Oncology, Daiichi Sankyo, Gilead, Glaukos, GSK, Halfloop, Merck, Patient-Centered Outcomes Research Institute, Pfizer, Takeda, and Vertex Pharmaceuticals Incorporated, outside of the submitted work. The views and opinions expressed in this publication are those of the individual co-authors and may not be understood or quoted as being made on behalf of or reflecting the position of any organisation, committee, working party or group with which the co-authors are affiliated., (© 2024 The Author(s).)

Introduction: Aortic stenosis (AS) is common affecting >13% of adults over the age of 75 years. In people who develop symptoms, without valve replacement, prognosis is dismal with mortality as high as 50% at 1 year. In asymptomatic patients, the timing of valve intervention is less well defined and a strategy of watchful waiting is recommended. Many, however, may develop symptoms and attribute this to age related decline, rather than worsening AS. Timely intervention in asymptomatic severe AS is critical, since delayed intervention often results in poor outcomes. Proactive surveillance of symptoms, quality of life and functional capacity should enable timely identification of people who will benefit from aortic valve replacement. There are no data however, to support the clinical and cost effectiveness of such an approach in a healthcare setting in the UK. The aim of this pilot trial is to test the feasibility of a full-scale randomised controlled trial (RCT) to determine the utility of proactive surveillance in people with asymptomatic severe AS to guide the timing of intervention., Methods and Analysis: APRAISE-AS is a multi-centre, non-blinded, two-arm, parallel group randomised controlled trial of up to 66 participants aged >18 years with asymptomatic severe AS. Participants will be randomised to either standard care or standard care supplemented with the APRAISE-AS intervention. Primary outcomes will capture; adherence to and participant acceptability of the intervention, recruitment and retention rates, and completeness of data collection. The findings will be used to inform the sample size and most appropriate outcome measure(s) for a full-scale RCT and health economic evaluation., Ethics and Dissemination: Ethical approval was granted by the Black Country REC, reference: 22/WM/0214. Results will be submitted for publication in peer-reviewed journals and disseminated at local, regional and national meetings where appropriate., Trial Registration Number: ISRCTN19413194 registered on 14.07.2023., Competing Interests: Competing interests: LF reports grants from the BHF (AA/18/2/34218), EU Horizon 2020 CATCH ME (grant agreement number 633196), MAESTRIA (grant agreement number 965286), AFFECT-EU (grant agreement number 847770, NIHR award 1002898 (APRAISE-AS) at University of Birmingham, and German Center for Cardiovascular Research (DZHK). LF has also received institutional research grants from governmental funding agencies, charities and companies in biomedical research. LF is part of the scientific advisory board of a patient initiative. DK reports grants from the NIHR and Kidney Research UK outside the submitted work. NK reports grants from the NIHR., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2024 The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Konrad Maruszczyk reports financial support was provided by GSK plc. Melanie Calvert reports financial support was provided by GSK plc. Christel McMullan reports financial support was provided by GSK plc. Olalekan Lee Aiyegbusi reports financial support was provided by GSK plc. Melanie Calvert reports a relationship with NIHR Birmingham Biomedical Research Centre that includes: funding grants. Melanie Calvert reports a relationship with Health Data Research UK that includes: funding grants. Melanie Calvert reports a relationship with Innovate UK that includes: funding grants. Melanie Calvert reports a relationship with Macmillan Cancer Support that includes: funding grants. Melanie Calvert reports a relationship with GSK plc that includes: consulting or advisory and funding grants. Melanie Calvert reports a relationship with UCB Pharma SA that includes: funding grants. Melanie Calvert reports a relationship with Research England that includes: funding grants. Melanie Calvert reports a relationship with European Commission and EFPIA that includes: funding grants. Melanie Calvert reports a relationship with Brain Tumor Charity that includes: funding grants. Melanie Calvert reports a relationship with Gilead Sciences Inc that includes: funding grants. Melanie Calvert reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants. Melanie Calvert reports a relationship with National Institute for Health and Care Research that includes: funding grants. Melanie Calvert reports a relationship with UK Research and Innovation that includes: funding grants. Melanie Calvert reports a relationship with Aparito that includes: consulting or advisory. Melanie Calvert reports a relationship with CIS Oncology that includes: consulting or advisory. Melanie Calvert reports a relationship with Takeda UK Ltd that includes: consulting or advisory. Melanie Calvert reports a relationship with Merck & Co Inc that includes: consulting or advisory. Melanie Calvert reports a relationship with Daiichi Sankyo Inc that includes: consulting or advisory. Melanie Calvert reports a relationship with Glaukos Corporation that includes: consulting or advisory. Melanie Calvert reports a relationship with Patient-Centered Outcomes Research Institute that includes: consulting or advisory. Melanie Calvert reports a relationship with Genentech that includes: consulting or advisory. Melanie Calvert reports a relationship with Vertex that includes: consulting or advisory. Melanie Calvert reports a relationship with Icon plc that includes: consulting or advisory. Melanie Calvert reports a relationship with University of Maastricht that includes: speaking and lecture fees. Melanie Calvert reports a relationship with Cochrane Portugal that includes: speaking and lecture fees. Melanie Calvert reports a relationship with South-Eastern Norway Regional Health Authority that includes: paid expert testimony. Melanie Calvert reports a relationship with Singapore National Medical Research Council that includes: paid expert testimony. Melanie Calvert reports a relationship with PROTEUS Consortium that includes: board membership. Catherine Bottomley reports a relationship with Vitaccess Limited that includes: employment. Olalekan Lee Aiyegbusi reports a relationship with GSK plc that includes: consulting or advisory and funding grants. Olalekan Lee Aiyegbusi1 reports a relationship with Merck & Co Inc that includes: consulting or advisory. Christel McMullan reports a relationship with National Institute for Health and Care Research that includes: funding grants. Christel McMullan reports a relationship with CIS Oncology that includes: funding grants. Christel McMullan reports a relationship with Aparito that includes: consulting or advisory. Thomas Keeley reports a relationship with GSK plc that includes: employment and equity or stocks., (© 2023 The Authors.)

Background: The lack of standardised outcome assessments during hospitalisation and follow-up for acute COPD exacerbations has hampered scientific progress and clinical proficiency. The objective of the present study was to evaluate patients' acceptance of selected outcome and experience measurements during hospitalisations for COPD exacerbations and follow-up., Methods: An online survey was held amongst COPD patients in France, Belgium, The Netherlands, Germany and the UK. The European Lung Foundation COPD Patient Advisory Group was involved in the conceptualisation, development and dissemination of the survey. The survey was complementary to a previously obtained expert consensus. We assessed patients' views and acceptance of selected patient-reported outcomes or experiences and corresponding measurement instruments (for dyspnoea, frequent productive cough, health status and hospitalisation experience), and of selected clinical investigations (blood draw, pulmonary function test, 6-min walk test, chest computed tomography, echocardiography)., Findings: 200 patients completed the survey. All selected outcomes and experiences were deemed important, and acceptance of their methods of assessment was high. The modified Medical Research Council scale and a numerical rating scale to address dyspnoea, the COPD Assessment Test for quality of life and frequent productive cough, and the Hospital Consumer Assessment of Healthcare Providers and Systems for hospital experiences were the instruments preferred by patients. Consensus on importance of blood draw and spirometry was higher compared with the other investigations., Interpretation: The survey results endorse the use of the selected outcome and experience measurements during hospitalisations for COPD exacerbations. They can be used to optimise standardised and patient-centred care and facilitate multicentric data collection., Competing Interests: Conflicts of interest: An ICMJE Conflict of Interest form has been collected from all authors. I. Gyselinck reports grants from Research Foundation Flanders (FWO). S. Ramakrishnan reports grants from the National Institute of Health Research UK and AstraZeneca paid to his institution; and honoraria for speaker's fees from AstraZeneca. C. Coleman reports funding from the CICERO CRC budget for coordinating patient involvement in the project paid to the ERS; and is an employee of the European Lung Foundation. T. Greulich reports grants from Grifols paid to his institution; consulting fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma, Novartis and Takeda; honoraria for speaker's fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma and Takeda; travel support from AstraZeneca, Berlin-Chemie, Chiesi, CSL-Behring, Grifols, GSK and Takeda; DSMB and/or advisory board participation for AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma, Novartis, Takeda; and membership of Alpha-1-Deutschland. F. Franssen reports grants from AstraZeneca; consulting fees from MSD; honoraria for speaker's fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Chiesi and Novartis; and travel support from Chiesi. P.R. Burgel reports grants from GSK and Vertex paid to his institution; consulting fees from AstraZeneca, Chiesi, Insmed, Viatris, Vertex, Zambon and Boehringer Ingelheim; travel support from Chiesi and Zambon. M. Bafadhel reports grants from AstraZeneca and Roche paid to her institution; honoraria for speaker's fees from AstraZeneca, Chiesi, Cipla, GlaxoSmithKline and Boehringer Ingelheim, paid to her institution; travel support from Boehringer Ingelheim; DSMB and/or advisory board participation for AstraZeneca, Sanofi/Regeneron, GlaxoSmithKline, Albus Health and ProAxsis; unpaid leadership roles in the BTS research and scientific faculty and NIHR TRC. W. Janssens reports grants from FWO, AstraZeneca and Chiesi, paid to the institution; honoraria for speaker's fees from AstraZeneca, Chiesi and GlaxoSmithKline; and nonfinancial support from ArtiQ. K. Vermeersch, A. Halner, H. Pott, F. Dobbels, P. Collis and H. Watz report no conflicts of interest., (Copyright ©The authors 2023.)

Background: Real-world evidence (RWE) plays an increasingly important role within global regulatory and reimbursement processes. RWE generation can be enhanced by collecting and using patient-reported outcomes (PROs), which can provide valuable information on the effectiveness, safety, and tolerability of health interventions from the patient perspective. This analysis aims to examine and summarise the utilisation of patient-reported outcomes measures (PROMs) in real-world studies., Methods: Descriptions of phase IV trials were downloaded on July 22, 2021 from the Clinicaltrials.gov database since its inception. An automated algorithm was built to detect trials utilising PROMs and composite measures including patient-reported components. Search terms were developed based on the PROQOLID database., Results: Of 27,976 phase IV clinical trials posted on Clinicaltrials.gov between 1999 and July 2021, 21% and 4% used PROMs and composite measures, respectively. Recent years demonstrated a steady increase in the utilisation of PROMs in phase IV trials., Conclusions: The use of PROMs in phase IV trials seems to be lower than its use in earlier phases of clinical research. Increased uptake of PROMs in RWE studies can be facilitated in a number of ways including the development of standards for their collection, analysis and use., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient-Reported Outcomes Research and is a National Institute for Health and Care Research (NIHR) Senior Investigator. She receives funding from the NIHR Birmingham Biomedical Research Centre, the NIHR Surgical Reconstruction and Microbiology Research Centre and NIHR Applied Research Collaboration (ARC) West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Health Data Research UK, Innovate UK (part of UK Research and Innovation), Macmillan Cancer Support, UCB and GSK. MC has received personal fees from Astellas, Takeda, Merck, Daiichi Sankyo, Glaukos, CIS Oncology, Aparito Ltd, GSK, Genentech and the Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. OLA receives funding from the NIHR Birmingham Biomedical Research Centre (BRC), NIHR Applied Research Collaboration (ARC) West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation, Innovate UK (part of UK Research and Innovation), Gilead Sciences Ltd, Janssen Pharmaceuticals, Inc., and Sarcoma UK. OLA declares personal fees from Gilead Sciences Ltd, GSK and Merck outside the submitted work. TK is an employee and shareholder of GSK Ltd. KM is the holder of the GSK PhD grant. Other authors declare no competing interests. The views expressed in this article are those of the authors and not necessarily those of the NIHR, or the Department of Health and Social Care., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Real-world evidence (RWE) plays an increasingly important role within global regulatory and reimbursement processes. RWE generation can be enhanced by the collection and use of patient-reported outcomes (PROs), which can provide valuable information on the effectiveness, safety, and tolerability of health interventions from the patient perspective. This systematic review aims to examine and summarise the available PRO-specific recommendations and guidance for RWE generation., Methods and Findings: Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and websites of selected organisations were systematically searched to identify relevant publications. 1,249 articles were screened of which 7 papers met the eligibility criteria and were included in the review. The included publications provided PRO-specific recommendations to facilitate the use of PROs for RWE generation and these were extracted and grouped into eight major categories. These included: (1) instrument selection, (2) participation and engagement, (3) burden to health care professionals and patients, (4) stakeholder collaboration, (5) education and training, (6) PRO implementation process, (7) data collection and management, and (8) data analysis and presentation of results. The main limitation of the study was the potential exclusion of relevant publications, due to poor indexing of the databases and websites searched., Conclusions: PROs may provide valuable and crucial patient input in RWE generation. Whilst valuable insights can be gained from guidance for use of PROs in clinical care, there is a lack of international guidance specific to RWE generation in the context of use for regulatory decision-making, reimbursement, and health policy. Clear and appropriate evidence-based guidance is required to maximise the potential benefits of implementing PROs for RWE generation. Unique aspects between PRO guidance for clinical care and other purposes should be differentiated. The needs of various stakeholder groups (including patients, health care professionals, regulators, payers, and industry) should be considered when developing future guidelines., (© 2022. The Author(s).)

Importance: Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use., Objective: To develop international, consensus-based, PRO-specific ethical guidelines for clinical research., Evidence Review: The PRO ethics guidelines were developed following the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network's guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched from inception until March 2020. The keywords patient reported outcome* and ethic* were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a 2-round international Delphi process (n = 96 participants; May and August 2021) and a consensus meeting (n = 25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance., Findings: Twenty-three items were considered in the first round of the Delphi process: 6 relevant candidate items from the systematic review and 17 additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and 12 additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n = 25 participants). The final wording of the PRO ethical guidelines was agreed on by consensus meeting participants with input from 6 additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination plans., Conclusions and Relevance: The PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimizing participant risk, burden, and harm and protecting participant and researcher welfare.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives., Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance., Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors., Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patient-reported outcomes (PROs) are measures of a person's own views of their health, functioning and quality of life. They are typically assessed using validated, self-completed questionnaires known as patient-reported outcome measures (PROMs). PROMs are used in healthcare settings to support care planning, clinical decision-making, patient-practitioner communication and quality improvement. PROMs have a potential role in the delivery of social care where people often have multiple and complex long-term health conditions. However, the use of PROMs in this context is currently unclear. The objective of this scoping review is to explore the evidence relating to the use of PROMs in adult social care., Methods and Analyses: The electronic databases Medline (Ovid), PsychInfo (Ovid), ASSIA (ProQuest), Social Care Online (SCIE), Web of Science and EMBASE (Ovid) were searched on 29 September 2020 to identify eligible studies and other publically available documents published since 2010. A grey literature search and hand searching of citations and reference lists of the included studies will also be undertaken. No restrictions on study design or language of publication will be applied. Screening and data extraction will be completed independently by two reviewers. Quality appraisal of the included documents will use the Critical Appraisal Skills Programme and AACODS (Authority, Accuracy, Coverage, Objectivity, Date, Significance) checklists. A customised data charting table will be used for data extraction, with analysis of qualitative data using the framework method. The review findings will be presented as tables and in a narrative summary., Ethics and Dissemination: Ethical review is not required as scoping reviews are a form of secondary data analysis that synthesise data from publically available sources. Review findings will be shared with service users and other relevant stakeholders and disseminated through a peer-reviewed publication and conference presentations. This protocol is registered on the Open Science Framework (www.osf.io)., Competing Interests: Competing interests: SEH is supported by the National Institute of Health Research (NIHR) Applied Research Centre (ARC), West Midlands. SH is company director of Narra Consulting Limited and undertakes consultancy work for Cochlear Ltd. MC is a National Institute for Health Research (NIHR) Senior Investigator and receives funding from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the NIHR Surgical Reconstruction and Microbiology Research Centre and NIHR ARC West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Health Data Research UK, Innovate UK (part of UK Research and Innovation), Macmillan Cancer Support, UCB Pharma MC has received personal fees from Astellas, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. OLA is supported by the National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Birmingham, West Midlands. OLA also receives funding from the Health Foundation and has received personal fees from Gilead Sciences. DL is supported by the NIHR ARC West Midlands and the NIHR Community Healthcare MedTech and IVD Cooperative, hosted by Oxford Health NHS Foundation Trust. JG is a non-executive director of University Hospitals Birmingham, adjunct professor at Curtin University, member of the leadership team for an ESRC large grant on sustainable adult social care, and member of the expert advisory group for West Midlands ARC. PC, GT, SCR, and CM have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Quadriceps tendon (QT) autograft ACL reconstruction was hypothesized to possess less anterior knee laxity, pivot shift laxity, and lower failure rates than hamstring tendon (HT) autografts., Methods: Terms "hamstring tendon autograft" and "ACL reconstruction" or "quadriceps tendon autograft" and "ACL reconstruction" were searched in Embase and PubMed. Inclusion criteria required that studies included patients treated for primary ACL injury with reconstruction using either a QT autograft (Group 1) or a HT autograft (Group 2) and instrumented anterior knee laxity assessment. Extracted information included surgical fixation method, graft type, graft thickness or diameter, single vs. double bundle surgical method, publication year, time between the index knee injury and surgery, % women, initial and final subject number, subject age, follow-up length, side-to-side anterior knee laxity difference, Lysholm Score, Subjective IKDC score, anterior knee laxity side-to-side difference grade, ipsilateral pivot shift laxity grade, and failure rate. The Methodological Index for Nonrandomized Studies was used to evaluate study methodological quality., Results: The QT group (Group 1) had 17 studies and the HT group (Group 2) had 61 studies. Overall, Group 2 had greater pivot shift laxity (OR 1.29, 95% CI 1.05-1.59, p = 0.005). Group 2 suspensory femoral fixation had greater pivot shift laxity (OR 1.26, 95% CI 1.01-1.58, p = 0.02) than Group 1 compression femoral fixation. Group 2 compression femoral fixation also had more anterior knee laxity (OR 1.25, 95% CI 1.03-1.52, p = 0.01) than Group 1 compression femoral fixation and higher failure rates based on initial (OR 1.69, 95% CI 1.18-2.4, p = 0.002) and final (OR 1.89, 95% CI 1.32-2.71, p = 0.0003) subject number. Failure rate for HT compression femoral fixation was greater than suspensory femoral fixation based on initial (OR 2.08, 95% CI 1.52-2.84, p < 0.0001) and final (OR 2.26, 95% CI 1.63-3.16, p < 0.0001) subject number., Conclusions: Overall, QT autografts had less pivot shift laxity and lower failure rates based on final subject number than HT autografts. Compression QT autograft femoral fixation had lower pivot shift laxity than suspensory HT autograft femoral fixation. Compression QT autograft femoral fixation had less anterior knee laxity and lower failure rates than compression HT autograft femoral fixation. Suspensory HT autograft femoral fixation had lower failure rates than compression HT autograft femoral fixation. Greater knee laxity and failure rates may be related to a combination of HT autograft diameter and configuration (tissue quality and dimensions, strands, bundles, and suturing method) variability and fixation mode., Level of Evidence: Level IV.

Background: The purpose of this study is to compare liposomal bupivacaine to a modified (Ranawat) local injection for total knee arthroplasty (TKA)., Methods: This is a prospective, randomized study of 105 consecutive patients undergoing primary TKA. Group A patients received a periarticular injection with liposomal bupivacaine and group B with a mixture of ropivacaine, epinephrine, ketorolac, and clonidine. There were 54 patients in the group A (liposomal bupivacaine) and 51 in group B., Results: There were no differences in the groups with respect to age, sex, and preoperative knee scores. There were no differences with respect to postoperative narcotic usage and knee range of motion., Conclusion: Liposomal bupivacaine as a periarticular injection after TKA demonstrated similar pain levels, narcotic usage, and range of motion compared to a modified Ranawat suspension but improved walking distance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Diagnosis is crucial in early-stage lumbar spondylolysis, as osseous healing can occur with conservative treatment. Single-photon emission computed tomography (SPECT) traditionally has been the most sensitive modality for diagnosing active (early) spondylolysis. More recently, high signal change (HSC) in the pedicle or pars interarticularis on fluid-specific (T2) magnetic resonance imaging (MRI) has been shown to be important in the diagnosis of early spondylolysis. We conducted a study to determine the clinical and radiographic characteristics associated with the diagnosis of early or active spondylolysis. Fifty-seven patients with a total of 108 pars defects and a mean age of 14.6 years were retrospectively identified. Defects with a positive SPECT or HSC on T2 MRI were classified as active. There were 49 active and 59 inactive defects. The active and inactive groups did not differ in age, body mass index, symptom duration, lumbar lordosis, pelvic incidence, slip percentage, or laterality. There was a difference in sex (35 vs 19 males; P < .0001) and presence of listhesis (16 vs 35; P = .006). Active or early juvenile spondylolysis appears to be associated with male patients and the absence of listhesis, which may be important in identifying patients with a higher potential to experience osseous healing with nonoperative treatment.

Background: Seasonal interpandemic influenza causes >200,000 annual hospitalizations in the United States. Optimal antiviral treatment in hospitalized patients is not established., Methods: During three interpandemic influenza seasons, 137 patients hospitalized with suspected acute influenza were randomized to 5-day treatment with intravenous peramivir 400 mg or 200 mg once daily or oral oseltamivir 75 mg twice daily. Time to clinical stability and quantitative changes in viral titres from nasopharyngeal specimens were primary and key secondary end points, respectively., Results: Infection was confirmed in 122 patients with influenza A (H1N1), influenza A (H3N2) or influenza B. Median times (95% CI) to clinical stability were 37.0 h (22.0, 48.7) with peramivir 400 mg, 23.7 h (16.0, 38.9) with peramivir 200 mg and 28.1 h (22.0, 37.0) with oseltamivir (P=0.306). Patients (n=97) who were clinically unstable at enrolment had median times (95% CI) to clinical stability of 24.3 h (21.2, 47.5) with peramivir 400 mg, 31.0 h (17.2, 47.7) with peramivir 200 mg and 35.5 h (23.3, 37.9) with oseltamivir (P=0.541). Titres of influenza A viruses in nasopharyngeal specimens decreased similarly across treatments, but more rapid decreases in titres of influenza B occurred with peramivir treatment. There were no deaths among patients with confirmed influenza and the incidence of adverse events was low and generally similar among treatment groups., Conclusions: Treatment of acute seasonal influenza in hospitalized adults with either peramivir or oseltamivir resulted in generally similar clinical outcomes. Treatment with peramivir was generally safe and well tolerated and could be of benefit in this population.

Background: Breast reconstruction techniques have focused increasingly on using autologous tissue, with emphasis being placed on employing muscle sparing adipocutaneous flaps to reduce abdominal wall complications such as hernias, bulges, weakness, and length of hospital stay. The result has been the emergence of the deep inferior epigastric perforator (DIEP) flap for breast reconstruction. Isolating perforator vessels challenges most surgeons. We describe surface anatomical landmarks to predict the location of the deep inferior epigastric artery (DIEA) and its perforators to aid in the efficient elevation of this flap., Methods: Ten fresh hemi-abdomens were dissected with loupe magnification. The DIEA and its perforators were identified, and measurements in relation to the rectus muscle, xiphoid, umbilicus, and pubis were taken. Statistical analysis was undertaken to determine distance ratios to account for variance in patient size., Results: Average distance from the xiphoid to umbilicus was 18.2 +/- 1.27 cm. The distance from the umbilicus to pubis was 14.9 +/- 2.3 cm. The vertical distance from the umbilicus to the DRJ (DIEA rtctus junction) was 10.45 +/- 1.58 cm, and the vertical distance from the level of the umbilicus to where the first DIEA perforator traverses the RAM was 7.4 +/- 1.64 cm. The distance between the umbilicus and the DRJ is approximately 0.7 times the distance between the umbilicus and the pubic symphysis. The distance between the umbilicus and the first perforator is approximately 0.5 times the distance between the umbilicus and the pubic symphysis., Conclusions: Knowledge of anatomical landmarks can aid the surgeon in more efficiently harvesting the DIEP flap. Surface landmarks along the abdominal midline coupled with normalizing ratios can aid surgeons in predicting the location of the DIEA and its first perforator. The DIEA crosses the rectus at approximately two thirds of the distance between the umbilicus and pubis, and the first perforator can reliably be located at one half of this distance.