Understanding how traumatic brain injury-related changes in fluid biomarkers affect quality of life outcomes in veterans: a prospective observational trial protocol (UNTANGLE).

INTRODUCTION: Traumatic brain injury (TBI) is a major cause of disability, with annual global incidence estimated as 69 million people. Survivors can experience long-term visual changes, altered mental state, neurological deficits and long-term effects that may be associated with mental illness. TBI is prevalent in military personnel due to gunshot wounds, and blast injury. This study aims to evaluate the relationship between evolving visual, biochemical and mental health changes in both military veterans and civilians, suffering from TBI, and detect preliminary indicators of prognosis for TBI recovery, and quality-of-life outcomes. METHODS AND ANALYSIS: UNTANGLE is a 24-month prospective observational pilot study recruiting three patient groups: civilians with acute moderate-severe TBI, military veterans with diagnosis of a previous TBI and a control group of civilians or veterans with no history of a previous TBI. Patients will undergo visual, biochemical and mental health assessments, as well as patient-reported quality of life outcome measures over the course of a 1-year follow-up period. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales with a REC reference number of 23/NW/0203. The results of the study will be presented at scientific meetings and published in peer-reviewed journals, including both civilian and military-related publications. We will also present our findings at national and international meetings of learnt neuroscience and neuropsychiatry and military societies. We anticipate that our pilot study will inform a larger study on the long-term outcomes of TBI and quality of life, specific to military veterans, such that potential interventions may be accessed as quickly as possible. TRIAL REGISTRATION NUMBER: ISRCTN13276511.

Development of a quality of life measure for left ventricular assist device recipients using a mixed methods approach.

BACKGROUND: Left ventricular assist device (LVAD) recipients report symptom improvement but find adjusting to life with the LVAD challenging. These challenges are unique, and existing patient-reported outcome measures (PROMs) do not reflect their experiences. This study aimed to develop a culturally relevant quality of life PROM for use with LVAD recipients in future research, design evolutions and clinical practice. METHODS: A three-stage mixed-methods approach was used to develop a PROM: stage 1 included group concept mapping (GCM); stage 2 semi-structured qualitative interviews were conducted with 11 LVAD recipients and 10 clinicians, and a questionnaire was developed using a conceptual framework; and stage 3 used exploratory psychometric analysis of the PROM data using Rasch measurement theory. This paper presents stages 2 and 3. RESULTS: The conceptual framework consisted of four key concepts, including general health, life with the LVAD, equipment and clothing and emotional impact. Statements from interviews and GCM were used to create items for the LVAD quality of life (LVAD-QoL). Cognitive interviews tested face validity and participant comprehension. Forty-nine participants were recruited from three UK transplant centres. PROM data were collected and analysed using Rasch analysis. Four items displayed misfit; dependency between item sets was the biggest issue (57/485 pairwise differences). After restructuring and dealing with item misfit, the LVAD-QoL conformed to the Rasch model, supporting the psychometric properties and quality of the LVAD-QoL. CONCLUSIONS: Using a mixed-methods approach ensured the development of a robust and psychometrically sound tool for research, design evolution and clinical practice with LVAD recipients.

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.

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.

Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.

BACKGROUND: Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies. METHODS: An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system. RESULTS: Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials. CONCLUSION: By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development. TRIAL REGISTRATION: ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.

More and more patients tell clinicians how they feel by completing questionnaires electronically. Therefore, it is important to assess how easy it is for patients to do this. In this study, we describe how we developed an electronic platform for patients to report their symptoms and how we tested the usability of this platform with patient partners and research nurses. Once the electronic platform was developed, quality of life and symptoms questionnaires were programmed onto it. Alerts were sent to the clinical team if specific scores were obtained on the symptoms questionnaires. Although two patient partners were not able to finish the testing session because of technical issues, the ones who completed the session liked its simplicity and responsiveness. The research nurses also liked the system and only suggested minor modifications. Following this testing, we refined the electronic platform to test it further in a larger study which investigates the safety and use of a drug. We hope that thanks to this electronic platform, we will obtain useful information on the safety and efficacy of treatment.

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).

Clinician survey of current global practice for sarcoma surveillance following resection of primary retroperitoneal, abdominal, and pelvic sarcoma.

INTRODUCTION: - Postoperative surveillance following resection of primary retroperitoneal, abdominal, and pelvic sarcoma (RPS) is standard of care in international sarcoma centres and has rapidly evolved without an evidence base to become highly intensive and prolonged. This clinician survey aims to capture a global, contemporary snapshot of international guidelines used to inform sarcoma surveillance following resection of primary RPS. MATERIALS AND METHODS: - Between July 2022 and March 2023, an online, anonymous, clinician survey to assess the current duration, imaging intervals and imaging modalities used for postoperative surveillance following resection of primary RPS was distributed among clinicians working at centres which are members of the TransAtlantic Australasian Retroperitoneal Working Group (TARPSWG). RESULTS: - Responses were received from 58 different TARPSWG centres. The majority of centres use institutional guidelines to guide surveillance intensity (n = 43, 74%) and the surveillance imaging modality (n = 39, 67%) used. For surveillance intensity and imaging modality, institutional guidelines are partially or entirely based on international guidelines in 81% (n = 47) and 78% (n = 45) of centres, respectively. Commonly used imaging modalities are contrast-enhanced CT abdomen-pelvis (n = 51, 88%) for abdominal surveillance and non-contrast enhanced CT (n = 25, 43%) for chest surveillance. Imaging intervals, timing of de-escalation of imaging frequency and total duration of surveillance for low-grade and high-grade RPS are reported. CONCLUSION: - This global survey among TARPSWG members demonstrates the heterogeneity in sarcoma surveillance strategies worldwide and emphasises the need for a randomised controlled trial to provide an evidence base for the optimal surveillance schedule following primary resection of RPS.

Global use of electronic patient-reported outcome systems in nephrology: a mixed methods study.

OBJECTIVES: The use of electronic patient-reported outcome (ePRO) systems to support the management of patients with chronic kidney disease is increasing. This mixed-methods study aimed to comprehensively identify existing and developing ePRO systems, used in nephrology settings globally, ascertaining key characteristics and factors for successful implementation. STUDY DESIGN: ePRO systems and developers were identified through a scoping review of the literature and contact with field experts. Developers were invited to participate in a structured survey, to summarise key system characteristics including: (1) system objectives, (2) population, (3) PRO measures used, (4) level of automation, (5) reporting, (6) integration into workflow and (7) links to electronic health records/national registries. Subsequent semistructured interviews were conducted to explore responses. SETTING AND PARTICIPANTS: Eligible systems included those being developed or used in nephrology settings to assess ePROs and summarise results to care providers. System developers included those with a key responsibility for aspects of the design, development or implementation of an eligible system. ANALYTICAL APPROACH: Structured survey data were summarised using descriptive statistics. Interview transcripts were analysed using Codebook Thematic Analysis using domains from the Consolidated Framework for Implementation Research. RESULTS: Fifteen unique ePRO systems were identified across seven countries; 10 system developers completed the structured survey and 7 participated in semistructured interviews. Despite system heterogeneity, reported features required for effective implementation included early and sustained patient involvement, clinician champions and expanding existing electronic platforms to integrate ePROs. Systems demonstrated several common features, with the majority being implemented within research settings, thereby affecting system implementation readiness for real-world application. CONCLUSIONS: There has been considerable research investment in ePRO systems. The findings of this study outline key system features and factors to support the successful implementation of ePROs in routine kidney care.Cite Now.

Considerations for patient and public involvement and engagement in health research.

Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.

Usability testing of an electronic patient-reported outcome system linked to an electronic chemotherapy prescribing and patient management system for patients with cancer.

Background: People affected by cancer experience a wide range of symptoms which have a major impact on their functioning and health-related quality of life (HRQoL). One way to measure the impact of cancer symptoms is through the use of patient-reported outcomes. Methods: An electronic patient-reported outcome (ePRO) application (ChemoPRO®) was designed to be used by cancer patients to report their symptoms and communicate with their clinical team. Usability testing sessions were conducted with people with lived experience of cancer to understand how real users interact with the ChemoPRO® system. One-to-one testing sessions were conducted to assess use of the system and identify areas for further refinement. User satisfaction was assessed using a brief satisfaction questionnaire previously used by Aiyegbusi et al. (date). Results: Ten people with lived experience of cancer took part in the usability study. Symptoms and HRQoL measures, including the Euroqol EQ5D5L and the PRO-CTCAE™ were included in the ePRO system. Participants: had a mean age of 62.3 years. Three critical errors and 21 non-critical errors were reported. All participants were enthusiastic about the app. Participants liked the simplicity and responsiveness of the patient-facing app and highlighted the potential for communicating with their clinical team. The overall usability and satisfaction score was 4.5 (sd = 0.09). Conclusion: This usability study suggests that people with lived experience of cancer found the ChemoPRO® app acceptable and easy to use. One of the key features of this particular ePRO system that should be developed further is system functionality to facilitate communication between patients and clinicians. Future testing should include testing in a clinical setting and testing with people from ethnic minorities.

Experiences of patients and their relatives of postoperative radiological surveillance and surveillance intensity following primary resection of a soft tissue sarcoma and its impact on their quality of life: a systematic review protocol.

INTRODUCTION: Postoperative radiological surveillance following primary resection of a soft tissue sarcoma (sarcoma of the retroperitoneum, abdomen, pelvis, trunk or extremities) is standard of care in all international high-volume sarcoma centres in the world. The intensity of postoperative surveillance imaging is highly varied and knowledge of the impact of surveillance and surveillance intensity on patients' quality of life is limited. The aim of this systematic review is to summarise the experiences of patients and their relatives/caregivers of postoperative radiological surveillance following resection of a primary soft tissue sarcoma and its impact on their quality of life. METHODS AND ANALYSIS: We will systematically search MEDLINE, EMBASE, PsycINFO, CINAHL Plus and Epistemonikos. Hand searching of reference lists of included studies will be conducted. Further searches will be performed via Google Scholar, to reveal further studies within unpublished 'grey' literature. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. After retrieval of the full text of the selected studies, the methodological quality will be appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research and the Center for Evidence-Based Management checklist for Critical Appraisal of a Cross-Sectional Study. Data on the study population, relevant themes and conclusions will be extracted from the selected papers, and a narrative synthesis will be conducted. ETHICS AND DISSEMINATION: The systematic review does not require ethics approval. The findings of the proposed work will be published in a peer-reviewed journal and disseminated widely to patients, clinicians and allied health professionals through the Sarcoma UK website, the Sarcoma Patient Advocacy Global Network and the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group. In addition, the outcomes of this research will be presented at national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42022375118.

Co-production of a feasibility trial of pacing interventions for Long COVID.

BACKGROUND: The high incidence of COVID-19 globally has led to a large prevalence of Long COVID but there is a lack of evidence-based treatments. There is a need to evaluate existing treatments for symptoms associated with Long COVID. However, there is first a need to evaluate the feasibility of undertaking randomised controlled trials of interventions for the condition. We aimed to co-produce a feasibility study of non-pharmacological interventions to support people with Long COVID. METHODS: A consensus workshop on research prioritisation was conducted with patients and other stakeholders. This was followed by the co-production of the feasibility trial with a group of patient partners, which included the design of the study, the selection of interventions, and the production of dissemination strategies. RESULTS: The consensus workshop was attended by 23 stakeholders, including six patients. The consensus from the workshop was to develop a clinical trial platform that focused on testing different pacing interventions and resources. For the co-production of the feasibility trial, patient partners selected three pacing resources to evaluate (video, mobile application, and book) and co-designed feasibility study processes, study materials and undertook usability testing of the digital trial platform. CONCLUSION: In conclusion, this paper reports the principles and process used to co-produce a feasibility study of pacing interventions for Long COVID. Co-production was effective and influenced important aspects of the study.

The World Health Organisation defines Long COVID as a condition which impacts people 3 months after they first had COVID-19. Some of the symptoms that characterise Long COVID symptoms include fatigue, breathlessness and brain fog. These symptoms have a major impact on people's health and quality of life. Today, over 2 million people in the United Kingdom suffer from Long COVID and there is a lack of drugs and non-drugs treatment. However, some non-drugs treatments which aim to manage fatigue in other conditions, such as pacing, could be used with people with Long COVID. In this paper, we report how we co-produced a study which tested whether or not it is feasible for people who have Long COVID to use a pacing resource and report their symptoms using an electronic platform. After a meeting to review existing non-drugs treatments, the research team and a group of patient partners agreed on co-developing a clinical trial platform to test different pacing resources. The research team then met with the patient partners twice a week to co-design the study during which people with Long COVID will use the pacing resources and report their symptoms. They also co-designed the study documents and how to report its results. Co-producing a study with patient partners was effective and influenced important aspects of the study.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Peer support for carers and patients with inflammatory bowel disease: a systematic review.

BACKGROUND: The support provided by people with the same condition, including inflammatory bowel diseases (IBD), has the potential to improve a range of psychosocial outcomes by allowing people with the disease to receive emotional support as well as to learn coping strategies from more experienced peers. The aim of this systematic review was to summarise the evidence on peer support interventions and their effectiveness on people with IBD. METHODS: Bibliographic databases, conference proceedings, grey literature, and clinical trial registers were searched from inception to November 2021. Comparative and single-arm studies that evaluated interventions that were solely or contained in part peer support, for people with IBD and/or their carers of any age and in any setting were included. Effectiveness was evaluated using outcomes relating to physical and psychosocial function, disease control and healthcare utilisation. Data for each outcome were tabulated and presented in a narrative synthesis. Study design specific tools were used to assess risk of bias. Study selection and risk of bias assessment were undertaken by two reviewers independently. RESULTS: Fourteen completed studies and five ongoing studies met the inclusion criteria. Substantial heterogeneity was observed in the studies in relation to the intervention type and peer support was usually part of a wider intervention. All but one study analysed the total effect of the intervention, so it was not possible to fully isolate the effect of the peer support alone. The appropriateness of outcomes and outcome measurement tools for the assessment of effects was a further key issue. As such, overall, no significant evidence of beneficial effects of peer support interventions on quality of life and other psychosocial outcomes was found. CONCLUSIONS: New randomised controlled trials designed to isolate the effects of peer support are needed to evaluate the (net) effects of peer support only. Agreement on the outcomes to be targeted, and the choice of reliable and validated measurement tools for standalone peer support interventions would provide a focus for further intervention design and evaluation. SYSTEMATIC REVIEW REGISTRATION: The protocol was accepted in the international prospective register of systematic reviews (PROSPERO CRD42020168817).