F1000Research 2021, 9:120 Last updated: 13 DEC 2021 STUDY PROTOCOL The perspectives of patients and their caregivers on self-management interventions for chronic conditions: a protocol for a mixed-methods overview [version 2; peer review: 2 approved] Ena Niño de Guzmán 1,2, Laura Martínez García 1,3, Ana I. González4,5, Monique Heijmans6, Jorge Huaringa7, Kaisa Immonen8, Lyudmil Ninov8, Carola Orrego-Villagrán2,4,5, Javier Pérez-Bracchiglione9, Karla Salas-Gama10, Andrés Viteri-García 11,12, Pablo Alonso-Coello1,3 1Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, 08025, Spain 2Universitat Autònoma de Barcelona, Barcelona, Spain 3CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain 4Avedis Donabedian Research Institute (FAD), Barcelona, 08037, Spain 5Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Madrid, Spain 6Netherlands institute for health services research (Nivel), Utrecht, 3513, The Netherlands 7Hospital Arzobispo Loayza, Lima, Lima 15082, Peru 8European Patients’ Forum, Brussels, 1040, Belgium 9Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Valparaíso, 2520000, Chile 10Hospital Santa Creu i Sant Pau, Barcelona, 08025, Spain 11Universidad UTE, Quito, 170527, Ecuador 12Cochrane Ecuador, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC), Quito, 170527, Ecuador v2 First published: 18 Feb 2020, 9:120 Open Peer Review https://doi.org/10.12688/f1000research.22125.1 Latest published: 29 Nov 2021, 9:120 https://doi.org/10.12688/f1000research.22125.2 Reviewer Status Invited Reviewers Abstract Introduction: Self-management (SM) interventions are complex 1 2 interventions and one of the main components of high-quality chronic disease care for which the incorporation of the perspectives of version 2 patients and their informal caregivers is crucial. We aim to identify, (revision) report appraise and synthesise the evidence exploring patients’ and 29 Nov 2021 caregivers’ perspectives on SM interventions. More precisely, we aim to 1) describe how they value the importance of outcomes of SM version 1 interventions, and 2) identify the factors that might impact on report report 18 Feb 2020 acceptability and feasibility of SM interventions based on their preferences and experiences. Methods and analysis: We will conduct four mixed-methods 1. Milena Vainieri, Sant'Anna School of overviews as part of COMPAR-EU, a European Union (EU) funded Advanced Studies of Pisa, Pisa, Italy project aimed to identify the most effective and cost-effective SM interventions for chronic obstructive pulmonary disease (COPD), heart failure (HF), obesity, and type 2 diabetes mellitus (T2DM). We will Page 1 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 search in MEDLINE, CINAHL, and PsycINFO for systematic reviews of studies addressing patients’ preferences on outcomes, or their 2. Edward Zimbudzi , Monash University, experiences with SM alongside their disease trajectory or with SM Melbourne, Australia interventions, published in English. Selection of studies and data extraction will be conducted in pairs. We will assess the overlap of Any reports and responses or comments on the studies and methodological quality. We will follow a three-step article can be found at the end of the article. synthesis process: 1) narrative synthesis for quantitative evidence, 2) thematic synthesis for qualitative evidence, and 3) integration of findings in the interpretation phase. Additionally, we will consult on the relevance of findings with patients and their caregivers. Systematic review registration: PROSPERO CRD42019117867 Keywords Systematic Review, Self-Management, Chronic Diseases, Mixed- Methods Research, Patient Preferences, Outcomes Corresponding author: Ena Niño de Guzmán (ena.ninodeguzman@gmail.com) Author roles: Niño de Guzmán E: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing; Martínez García L: Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing; González AI: Methodology, Writing – Review & Editing; Heijmans M: Methodology, Writing – Review & Editing; Huaringa J: Methodology, Writing – Review & Editing; Immonen K: Methodology, Resources, Writing – Review & Editing; Ninov L: Resources, Writing – Review & Editing; Orrego-Villagrán C: Funding Acquisition, Methodology, Resources, Writing – Review & Editing; Pérez-Bracchiglione J: Methodology, Writing – Review & Editing; Salas-Gama K: Methodology, Writing – Review & Editing; Viteri-García A: Methodology, Writing – Review & Editing; Alonso-Coello P: Conceptualization, Funding Acquisition, Methodology, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests: No competing interests were disclosed. Grant information: This work is supported by the European Union’s Horizon 2020 research and innovation programme [754936]. ENDG is a PhD candidate at the Universidad Autònoma de Barcelona and will include this publication and related overviews in her PhD thesis project. She is funded by a Rio Hortega contract from the Instituto de Salud Carlos III [CM17/00199]. LMG is funded by a Miguel Servet contract from the Instituto de Salud Carlos III [CP18/00007]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2021 Niño de Guzmán E et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Niño de Guzmán E, Martínez García L, González AI et al. The perspectives of patients and their caregivers on self-management interventions for chronic conditions: a protocol for a mixed-methods overview [version 2; peer review: 2 approved] F1000Research 2021, 9:120 https://doi.org/10.12688/f1000research.22125.2 First published: 18 Feb 2020, 9:120 https://doi.org/10.12688/f1000research.22125.1 Page 2 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 for or against intervention is an implicit result of the relative REVISED Amendments from Version 1 importance of the health outcomes an individual connects to the We thank reviewers for their comments on our manuscript. In intervention14. The patient’s preference is also implicitly related this new version, we have included only minor amendments to to other aspects such as attitudes, expectations and beliefs. the text. These aspects often fall within two other EtD criteria: accept- Any further responses from the reviewers can be found at ability, whether interventions are acceptable for patients; and the end of the article feasibility, whether interventions are feasible to implement from the patient’s point of view13–15. However, the methods to identify, collect and integrate this body of evidence in healthcare decision-making is still an evolving research area10 which Introduction requires more practical guidance16,17. The global burden of chronic conditions constitutes a significant public health challenge that undermines social and economic One method to find out the perspectives of patients and their development, accounting for almost 86% of deaths and 77% caregivers is the development of a systematic review (SR) of the disease burden in the WHO European Region. The of studies exploring how they value the importance of out- increasing healthcare demands of chronic conditions lead to comes or the features of the interventions that might affect the development of integrated healthcare models based on their benefit-risk perceptions. This information can be obtained patient-centred care1. from quantitative and qualitative evidence reported as utility or non-utility measures (Table 1)9,14,18. Utility meas- Self-management (SM) interventions are critical components ures reflect how a respondent values or feels about a state of of high-quality patient-centred care in chronic conditions1–3. health19. Non-utility measures inform about patients’ (or their SM can be defined as what individuals, families, and communi- informal caregivers’) preferences and experiences with the ties do to promote, maintain, or restore health and to cope with intervention of interest derived from quantitative, qualitative or the disease or disability with or without the support of health mixed methods studies14. professionals. It includes, but is not limited to, self-prevention, self-diagnosis, self-medication, and daily management of the Since 2010, there has been an increasing number of qualita- disease and its disabilities4. Ideally, SM interventions support tive evidence synthesis (QES) published exploring patients’ patients taking their individual needs and their specific context and their caregivers’ experiences and perceptions regarding into account5. SM interventions are complex and multifaceted living with a chronic condition, some of these explicitly and may contain multiple topics, formats, and components addressing the process of self-care20. There are also some SRs (e.g. participants, family, facilitators, or technology) that interact of studies exploring patients’ preferences quantitatively for with each other. Different outcomes can be defined to measure different health states20. their impact based on the specific scope (e.g. behavioural, psychosocial, physiological, or utilisation outcomes) of the However, summarising this body of evidence in a complete intervention5,6. and comprehensible way for stakeholders might be chal- lenging. In this context, the development of overviews might An increasing body of evidence suggests that SM interventions represent the most suitable option to summarise this broad and have beneficial effects for patients with chronic conditions in complex phenomenon. Previously published overviews address- terms of knowledge, the performance of SM behaviours, self- ing this research area were very diverse in the length and depth efficacy, health status7 and quality of life8. However, what might of scope21–25. However, some focused more on SM interven- be beneficial for some patients might be less beneficial for oth- tions and included only qualitative evidence for some specific ers; for that reason, it is necessary to identify which elements conditions, such as stroke24, rheumatic diseases, cancer and of SM interventions are effective and under what circum- fibromyalgia21. Others explored the experience of living stances. Especially, it is important to consider the perspectives with a chronic condition using a quantitative22 or qualitative of patients and their caregivers to get insight into their values approaches23. Moreover, some were focused on some specific and preferences on specific healthcare alternatives9–11. symptoms (e.g. chronic non-malignant pain25). Even though previous research had enhanced knowledge on the perspec- Preference is conceived as the result of cognition, experience tives of patients and their caregivers on chronic conditions and reflection. Moreover, a specific preference is the conse- and SM, we consider it is required to move towards a more quence of what a person values12. In healthcare, patients’ prefer- comprehensive approach, applying a mixed-methods approach26 ences can be defined as the qualitative or quantitative assessments including quantitative and qualitative sources of evidence, through of the relative desirability or acceptability to patients of speci- developing overviews of systematic reviews. fied alternatives or choices among outcomes or other attributes that differ among alternative health interventions13. Objectives This study protocol is part of a large multi-method and multi-step The GRADE Evidence to Decision (EtD) framework is a deci- project: “Comparing the cost-effectiveness of self-management sion-making tool that integrates the perspective of patients interventions in four high priority chronic diseases in Europe: under the term values, defined as the relative importance of out- COMPAR-EU”. This is a European Union-funded project comes or health states of interest14. The patient’s preference aiming to identify the most effective and cost-effective Page 3 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 Table 1. Methods to ascertain values and preferences. Source /type Measures Method of data Health utilities Matching -  Allocation game -  Standard gamble - Time trade-off -  Visual analogue scale -  Willingness to pay Direct Conjoint analysis -  Best-worst choice experiment -  Binary choice experiments -  Conjoint analysis -  Full ranking exercise -  Multinomial choice experiment -  Probability trade-off Multi-attribute utility instruments -  EuroQoL-5D -  Health Utilities Index 2S -  Short-form-6D Indirect -  PROMIS-29 Quality of life tools -  EQ5D utility estimates from St. George Respiratory Questionnaire -  Others Non-utilities (preferences -  Adaptive questioning and experiences) -  Direct choice Quantitative -  Ranking -  Rating (e.g. numerical rating scales) -  Survey -  Focus groups Qualitative -  Interviews Adapted from Zhang et al.14 SM interventions for patients living with chronic obstructive Methods and analysis pulmonary disease (COPD), heart failure (HF), obesity or type 2 We will conduct four mixed-methods overviews of SRs accord- diabetes mellitus (T2DM). ing to the most updated methodological guidance from the Cochrane Collaboration27–29, the Joanna Briggs Institute (JBI)30 Our main objective is to identify, appraise, and analyse the and key methodological references31–34. We adhere to the appli- perspectives of patients and their caregivers on outcomes of SM cable items of the Preferred Reporting Items for Systematic interventions for the selected chronic conditions. To provide reviews and Meta-Analyses Protocols (PRISMA-P) statement35. a more detailed assessment, we will conduct four overviews We registered this protocol in the PROSPERO registry: (one per chronic condition). Our specific objectives are 1) to CRD42019117867. Any amendment to the protocol and the explore how patients with one of the four chronic conditions, supporting rationale will be reported. and their caregivers, value the importance of different outcomes of SM interventions, and 2) to identify the factors that might Eligibility criteria impact the acceptability and feasibility of SM interventions Type of reviews. We will consider for inclusion: 1) quan- based on their preferences and experiences with SM through the titative SRs 2) qualitative evidence syntheses QES; and 3) disease trajectory and when taking part in SM interventions. mixed methods research synthesis (MMRS). To be eligible for Page 4 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 inclusion, the SRs should report as a minimum: 1) the search importance of different outcomes. Utilities are measures strategy for at least one database; 2) the list of included studies; of the value ascribed to states of health, most often scaled and 3) the methods applied for synthesis36. from “0”, representing death, to “1”, representing perfect health; they reflect the health-related quality of life of Context/setting. We will include SRs of studies without geo- the individual at a particular point in time40. Methods to graphical restriction and will include all settings, except obtain utilities can be: a) direct methods such as match- those confined to inpatient care. ing methods (i.e. standard gamble, time trade-off, or rating scales), or conjoint analysis (i.e. discrete choice Population/perspectives. We will limit inclusion to SRs of stud- experiments, contingent valuation and willingness to ies conducted in adult patients (18 or older) with one or more pay, probability trade-off, paired comparison); or b) indi- of the chronic conditions of interest (COPD, HF, obesity and rect methods with multi-attribute instruments like the T2DM), without restricting by disease severity. We will consider EuroQual-5-dimension (EQ-5D), the Short Form-6- SRs assessing multiple chronic conditions (e.g., patients with Dimension (SF-6D), Health Utilities Index (HUI-3)14, more than one of the chronic conditions of interest or patients the Patient-Reported Outcomes Measurement Informa- with chronic conditions of interest plus other chronic condi- tion System (PROMIS-29)41, among other quality of tions) We will exclude SRs focused on patients with the chronic life tools which transform results across several domains conditions of interest and cancer comorbidity or severe mental into utilities (Table 1). disorders. We will include SRs exploring the perspectives of • N  on-utility measures for outcomes of SM interventions, patients or their informal caregivers. We will include SRs assess- which are the result of the assessment of preferences ing both perspectives if these are reported separately. We will and experiences of patients and their caregivers with exclude SRs addressing only healthcare providers’ or healthy SM in the disease trajectory or with SM interventions population perspectives. through quantitative (e.g. surveys), qualitative (e.g. interviews, focus groups), or mixed methods studies14 The phenomenon of interest/intervention. We will include (Table 1). SRs aimed at exploring the perspectives of patients and their caregivers on the importance of outcomes of SM interven- Information sources and search strategy tions. Their perspectives are based on their values, preferences We will design and execute a literature search strategy in and experiences. As described by Zhang et al.14, preferences MEDLINE (accessed through PubMed), the Cumulative Index for or against intervention are implicitly related to the relative of Nursing and Allied Health Literature (CINAHL), and Psy- importance people place (or value) on the expected or definite cINFO. The leading search concepts will be: 1) the perspective health outcomes connected to a specific intervention. We define of patients, for which we will include a sensitive content search SM intervention as supportive interventions systematically strategy previously published42; and 2) specific terms for each provided by healthcare staff, peers or laypersons to increase chronic condition. We will apply methodological filters lim- patients’ skills and confidence in their ability to manage a chronic iting to SRs, retrieving references using the filters available condition. SM interventions aim to prepare patients (and, where in each database, and to qualitative research, synthesis using appropriate, informal caregivers37) to actively participate in the non-controlled terms. We will consider English-language stud- management of their disease37,38. ies for inclusion without restriction on publication date. We will hand-search the reference list of overviews identified through We will apply the COMPAR-EU taxonomy for the domain of our search strategy and conduct a forward citation search outcomes of SM interventions, with 35 elements categorised of the included studies in Scopus43. We will establish regu- in seven subdomains39: 1) empowerment, 2) level of fulfil- lar search update alerts. Studies identified through these alerts ment of the expected SM behaviours, 3) clinical outcomes and meeting the eligibility criteria will be incorporated until the (progression of disease, complications, adverse events, and mor- stakeholders’ consultation starts. tality), 4) quality of life of patients and caregivers, 5) perceptions and satisfaction with care, 6) health care use, and 7) cost. Selection of studies We will not exclude SRs addressing other outcomes not We will manage references with Endnote X9. Pairs of authors listed in the COMPAR-EU taxonomy. Instead, these will be will conduct the screening of references and selection of stud- incorporated as a new category if applicable. ies. After initial calibration with 10% of retrieved references, one author will independently select references to be included, Comparison. While not addressed as an objective in these and a second author will check the final list of included and overviews, if reported, we will consider usual care as the excluded studies with reasons. Disagreements will be solved by comparison. discussion or with the help of a third author. Outcomes. We will include SRs evaluating studies reporting Data collection any of the following outcomes: We will extract data using Nvivo 12 Pro44. We will design and pilot-test one form for each type of SR (quantitative, qualitative • U  tility measures for outcomes of SM interventions; or mixed methods). After initial calibration between pairs defined as how patients or their caregivers value the of authors, one author will extract data from the included Page 5 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 reviews, and a second author will check the data against the full • I ntervention characteristics: target population/s, sup- text for accuracy. We will solve disagreements by consen- port technique/s, support delivery method/s, and expected sus or with the help of a third author. We will collect the patient (or caregiver) self-management behaviours. following information from each type of SR: • T  hemes or findings related to outcomes of SM inter- • G  eneral characteristics: country of contacting author, year ventions: 1) quantitative data, including health utility of publication, aim or phenomenon of interest, search measures (mean, standard deviation, confidence inter- databases, search timeframe, the number of included val) and the methods applied to obtain them; and studies, and the number of participants. 2) qualitative data extraction, this process overlaps with • M  ethodological characteristics: the type of SR, the the first stage of thematic synthesis (Figure 1). method of synthesis, methods of primary studies, the quality assessment tool, the certainty of the evidence In the extraction process, we will record the extent of relevant assessment tool, and their findings. information not reported (e.g. information about age), but we will not take additional steps to get further information from • S  ettings: location/s (countries) of primary studies, and the primary studies29,45. For discrepant data (two or more SRs report- context of included studies. ing different data for the same primary study), we will extract • P  articipants’ main characteristics: type of respondent, the data from the SR with the highest methodological quality, and severity of the disease, demographic characteristics, and if similar methodological quality, from the review with the most comorbidities. updated search45. For discrepant methodological quality assess- Figure 1. Thematic synthesis stages and levels of interpretation. Levels of interpretation: adapted from Pierce et al.24, thematic synthesis stages based on Thomas and Newman46. Page 6 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 ment (two or more SRs using different tools or reporting different respondents’ characteristics (sample size, the severity of results for the same primary study), we will report both disease), and methods used. We will perform statistical results. analyses using STATA software V.1453. Assessment of overlapping primary studies Step 2: Qualitative evidence. We will analyse and synthe- We will assess the overlapping primary studies (studies appear- sise qualitative data using a thematic synthesis46 approach ing in more than one review) using a citation matrix47. We using NVivo 12 Pro44. The levels of analysis will comprise sec- will extract the references of the primary studies answering ond-order (primary studies) and third-order SRs constructs24,54 our research question within all selected reviews, calculate (Figure 1). We will not specify any a priori theme. the “corrected covered area” (CCA), and describe the extent of overlap (slight [0 to 5], moderate [6 to 10], high [11 to 15], The synthesis process will follow the three stages of thematic or very high [over 15])48. We will include all SRs that meet the synthesis46, the first two taking place concurrently: 1) text eligibility criteria regardless of overlap49. We will conduct coding - line-by-line coding of the text of each SR; 2) develop- this assessment using Excel files. ing descriptive themes; 3) re-interpretation and synthesis of this newly organised information, to produce analytical themes that For duplicated data (two or more SRs reporting the same data go beyond the findings of the SRs authors (overview of SRs) from the same primary study or with over 25% of overlap within (Figure 1). For this step, we will conduct a collaborative primary studies), we will include data only once, selecting the analysis with at least three review authors to consider alter- one with the most complete and detailed data49. native interpretations and ensure that fourth-order constructs remain grounded in the primary studies. Assessment of methodological quality of included systematic reviews Step 3: Integration of qualitative and quantitative evidence. We will use the JBI Critical Appraisal Checklist for System- We will integrate the results of these two sources of evidence in atic Reviews and Research Syntheses to test the quality of the the interpretation phase of results55. For findings informing out- included reviews30. The JBI Checklist, which comprises 11 items, comes, we will organise them according to the COMPAR-EU is a tool to assess the methodological quality of both quantitative taxonomy (or to additional outcomes, if applicable)39. For emerg- SRs and QES30. After initial calibration, one author will inde- ing themes informing about feasibility and acceptability of pendently apply this checklist, and a second author will check SM interventions, we will develop a framework, according to results to validate scores. We will solve disagreements through the classification of analytical themes. The goal of the inte- consensus or with the help of a third author. We will adopt a gration phase is to categorise the importance of outcomes previously published scoring method50 that allocates “one point” and provide a framework to identify the factors that influ- to positive responses and “zero points” to negative or unclear ence acceptability and feasibility of SM interventions, always responses, and we will calculate the percentage of positive from the perspectives of patients and their caregivers. We will responses for each review (sum of positive responses divided by present findings using tabular formats, which will inform total items tested). The quality of each SR will be ranked based the development of decision-making tools for the interactive on the following criteria: 0–33% of criteria met (low quality), platform of the COMPAR-EU project. 34–66% of criteria met (medium quality), and 67% or more of criteria met (high quality)50. We will not exclude SRs based on Sub-group analysis. For quantitative evidence and depending their quality scores. on the sufficiency of SRs, we plan to analyse the primary out- comes according to the patient population (e.g. age, the sever- Data synthesis and reporting ity of the disease, number and types of chronic conditions, and To synthesise findings from selected SRs, we will use a mixed- type of respondent), intervention (e.g.,. type of SM interven- methods three-step approach, with a convergent parallel tion) and setting (e.g., country). For qualitative evidence, it is analysis of quantitative and qualitative evidence51. not possible to specify the groups in advance, due to the nature of this synthesis. Step 1: Quantitative evidence. To analyse and synthesise quantitative findings (utility and non-utility data), we will use Sensitivity analysis. If applicable, we will conduct a sen- narrative synthesis52. We will calculate descriptive statistics sitivity analysis exploring the impact of the quality of the (mean, SD for variables with a normal distribution and the included SRs (low, medium and high) in the final synthesis of median, interquartile range, for other distributions). findings. For reporting, we will present results in summarised tables Patient’s and caregiver’s involvement (grouping by relevant categories of outcomes). We will plot After the integration of quantitative and qualitative findings, reported results, e.g. mean values, 95% confidence intervals we will conduct an online survey with patients’ and caregivers’ and I2 statistic for heterogeneity (if pooled), or the range of representatives from each chronic condition. We will ask for mean values or other measures (if not pooled) across SRs, the their feedback on the draft of summaries of perspectives of number of studies and the number of respondents for each out- patients and their caregivers derived from the SRs. We will come. Where possible we will present results by country of design a tabular format for the seven subdomains of outcomes study, location, type of respondent (patient or caregiver), with close and open-ended questions assessing: 1) to what Page 7 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 extent the overview findings resound with their preferences mixed-methods approach26. We will follow the most updated and experiences; and 2) the relevance of findings for healthcare methodological guidance for overviews27–34. decision-making on SM interventions from their point of view. Each overview will provide new knowledge in a summarised For the recruitment of participants, we will invite patients’ and format about the perspectives of patients living with the four caregivers’ representatives through the patient’s networks col- selected chronic conditions and their caregivers on SM inter- laborating in the COMPAR-EU project. We aim to include at ventions. This evidence will be readily available to inform least five patients with different profiles of gender, age group, decision-making tools (i.e. EtD frameworks and decisions and severity of disease and one informal caregiver for each aids) where, in addition to effectiveness and cost-effectiveness condition. After giving their informed consent, patients will findings, the COMPAR-EU project will develop recommen- receive the link to complete the survey. Their responses will dations for SM interventions. More precisely, we will inform be analysed based on frequencies, and thematic analysis for about the importance of outcomes of SM interventions, the open-ended questions. After discussion within the review acceptability and feasibility considerations, through quantitative working group, we will include their perspectives in the and qualitative data. discussion section of each chronic condition manuscript. Although patients vary greatly in their preferences10, this Ethics and dissemination approach will help to identify subgroups of patients (and car- Ethical approval was obtained by the Clinical Research Ethics egivers) that might find an acceptable risk-benefit balance for Committee of the Avedis Donabedian Research Institute, SM interventions. We will also inform about acceptability the coordinator partner of the COMPAR-EU Project (EU and feasibility considerations for implementation concerns of 754936), the University Institute for Primary Care Research these interventions. Our findings will be incorporated into the (IDIAP Jordi Gol) and was signed on March 2018. We will COMPAR-EU Project final product: an interactive platform that disseminate our findings as conference abstracts, peer-review will be designed and adapted to different profiles of end- manuscripts, and social community media. Patients’ and car- users, including patients, caregivers, healthcare providers, egivers’ representatives participating in the draft summaries policymakers, researchers and industry representatives. assessment will receive feedback based on their responses. Our results will inform the development of decision-making Some limitations include that our findings will represent a sam- tools for the COMPAR-EU Project. ple of primary studies published in English already included in SRs. Because of time constraints, we do not plan to update Study status them32, so we may miss the most recent studies. Further- Since we planned to conduct the overviews of reviews for the more, we are not using a specific tool to assess the quality of four conditions consecutively, we are in different points on each reporting. Instead, we will describe this aspect as an overall one: 1) we conducted the searches in the selected databases assessment32. Finally, the overall assessment of the certainty and selected the initial list of included reviews for the four of the evidence is out of our scope, since there is still scarce conditions on March 2019; 2) we finalised the extraction of guidance on how to assess this aspect within an the quantitative data of SRs reporting health utilities for the overview32. four conditions on September 2019, updated until November 2020; 3) we started the extraction of qualitative data, and the- Our findings will help to characterise better the perspec- matic synthesis for reviews of T2DM on November 2019 and tive of patients with chronic conditions and their caregivers this process is still in progress; 4) in the upcoming months we on SM interventions, identifying challenges patients face in will follow with obesity, HF and COPD. Finally, we plan to their daily life, which may inform and help healthcare provid- publish results also in a consecutive manner, one manuscript ers to get a deeper understanding the patients’ experiences and per condition, during the second semester of 2021 and the first what is important for them. In this way, they will be able to of 2022. provide support to patients that better fits their needs. For Discussion policy and decision-makers, being aware of the perspec- Our study will collect the perspectives of patients and their car- tive of patients will help to design patient-centred strategies to egivers on SM interventions for four high priority chronic implement SM interventions. conditions. We will synthesise and integrate quantitative and qualitative findings describing how patients and their caregiv- We expect our findings will provide valuable insights to be con- ers value the importance of outcomes of SM interventions, and sidered in the design and conduct of future studies of SM inter- the factors that might affect acceptability and feasibility of ventions for patients living with any of these or similar chronic conducting these SM interventions, based on their preferences conditions. These overviews will help to identify gaps in and experiences about SM, through the disease trajectory research in this field and areas of potentially redundant research, and with SM interventions. reducing waste and streamlining the use of limited resources. To our knowledge, these will be the first overview of the Data availability perspectives of patients and their caregivers on SM inter- Underlying data ventions for any of these four chronic conditions using a No underlying data are associated with this article. Page 8 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 Extended data Data are available under the terms of the Creative Commons OSF: The perspectives of patients and their caregivers on Attribution 4.0 International license (CC-BY 4.0). self-management interventions for chronic conditions. https://doi. org/10.17605/OSF.IO/GFSA556 Acknowledgements We would like to thank Ivan Solà (Iberoamerican Cochrane Reporting guidelines Centre) for his invaluable help in the design of the search strat- OSF: The perspectives of patients and their caregivers on egy. We would also like to thank Dr Rosa Suñol (Avedis self-management interventions for chronic conditions. https://doi. Donabedian Research Institute) for her advice and feedback for the org/10.17605/OSF.IO/GFSA556. earlier version of this protocol. References 1. Epping-Jordan JE, Pruitt SD, Bengoa R, et al.: Improving the quality of health guideline development: a systematic review of guidance documents. J Clin care for chronic conditions. Qual Saf Health Care. 2004; 13(4): 299–305. Epidemiol. 2017; 88: 102–12. PubMed Abstract | Publisher Full Text | Free Full Text PubMed Abstract | Publisher Full Text 2. Bodenheimer T, Lorig K, Holman H, et al.: Patient self-management of 18. Zhang Y, Coello PA, Brożek J, et al.: Using patient values and preferences chronic disease in primary care. JAMA. 2002; 288(19): 2469–75. to inform the importance of health outcomes in practice guideline PubMed Abstract | Publisher Full Text development following the GRADE approach. Health Qual Life Outcomes. 3. Grady PA, Gough LL: Self-management: a comprehensive approach to 2017; 15(1): 52. management of chronic conditions. Am J Public Health. 2014; 104(8): e25–31. PubMed Abstract | Publisher Full Text | Free Full Text PubMed Abstract | Publisher Full Text | Free Full Text 19. Hunink MGM, Weinstein MC, Wittenberg E, et al.: Decision Making in Health 4. Pilot project on the promotion of self-care systems in the European Union. and Medicine: Integrating Evidence and Values. 2nd ed. Cambridge: European Union; 2018. Cambridge University Press; 2014. Reference Source Reference Source 5. Craig P, Dieppe P, Macintyre S, et al.: Developing and evaluating complex 20. Niño de Guzmán EP, Martínez-García L, Pérez-Bracchiglione J, et al.: What do interventions: the new Medical Research Council guidance. BMJ. 2008; 337: patients and their caregivers value on self-management interventions a1655. for chronic conditions? A scoping review of systematic reviews for the PubMed Abstract | Publisher Full Text | Free Full Text COMPAR-EU project. Cochrane Colloquium. 2019. Reference Source 6. Taylor SJC, Pinnock H, Epiphaniou E, et al.: A rapid synthesis of the evidence on interventions supporting self-management for people with long-term 21. Dwarswaard J, Bakker EJ, van Staa A, et al.: Self-management support from conditions: PRISMS - Practical systematic Review of Self-Management the perspective of patients with a chronic condition: a thematic synthesis Support for long-term conditions. Health Serv Deliv. Southampton (UK), 2014; of qualitative studies. Health Expect. 2016; 19(2): 194–208. 2(53). PubMed Abstract | Publisher Full Text | Free Full Text PubMed Abstract | Publisher Full Text 22. Earle CC, Chapman RH, Baker CS, et al.: Systematic overview of cost-utility 7. Barlow J, Wright C, Sheasby J, et al.: Self-management approaches for people assessments in oncology. J Clin Oncol. 2000; 18(18): 3302–17. with chronic conditions: a review. Patient Educ Couns. 2002; 48(2): 177–87. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text 23. May CR, Cummings A, Myall M, et al.: Experiences of long-term life-limiting 8. Murphy LA, Harrington P, Taylor SJ, et al.: Clinical-effectiveness of self- conditions among patients and carers: what can we learn from a meta- management interventions in chronic obstructive pulmonary disease: An review of systematic reviews of qualitative studies of chronic heart failure, overview of reviews. Chron Respir Dis. 2017; 14(3): 276–88. chronic obstructive pulmonary disease and chronic kidney disease? BMJ PubMed Abstract | Publisher Full Text | Free Full Text Open. 2016; 6(10): e011694. PubMed Abstract | Publisher Full Text | Free Full Text 9. Andrews J, Guyatt G, Oxman AD, et al.: GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of 24. Pearce G, Pinnock H, Epiphaniou E, et al.: Experiences of Self-Management recommendations. J Clin Epidemiol. 2013; 66(7): 719–25. Support Following a Stroke: A Meta-Review of Qualitative Systematic PubMed Abstract | Publisher Full Text Reviews. PLoS One. 2015; 10(12): e0141803. PubMed Abstract | Publisher Full Text | Free Full Text 10. Ho M, Saha A, McCleary KK, et al.: A Framework for Incorporating Patient Preferences Regarding Benefits and Risks into Regulatory Assessment of 25. Toye F, Seers K, Hannink E, et al.: A mega-ethnography of eleven qualitative Medical Technologies. Value Health. 2016; 19(6): 746–50. evidence syntheses exploring the experience of living with chronic non- PubMed Abstract | Publisher Full Text malignant pain. BMC Med Res Methodol. 2017; 17(1): 116. PubMed Abstract | Publisher Full Text | Free Full Text 11. Schünemann HJ, Wiercioch W, Etxeandia I, et al.: Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline 26. Pluye P, Hong QN: Combining the power of stories and the power of enterprise. CMAJ. 2014; 186(3): E123–42. numbers: mixed methods research and mixed studies reviews. Annu Rev PubMed Abstract | Publisher Full Text | Free Full Text Public Health. 2014; 35: 29–45. PubMed Abstract | Publisher Full Text 12. Brennan PF, Strombom I: Improving health care by understanding patient preferences: the role of computer technology. J Am Med Inform Assoc. 1998; 27. Harris JL, Booth A, Cargo M, et al.: Cochrane Qualitative and Implementation 5(3): 257–62. Methods Group guidance series-paper 2: methods for question PubMed Abstract | Publisher Full Text | Free Full Text formulation, searching, and protocol development for qualitative evidence synthesis. J Clin Epidemiol. 2018; 97: 39–48. 13. FDA Guidance Patient Preference Information – Voluntary Submission, PubMed Abstract | Publisher Full Text Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision 28. Noyes J, Booth A, Cargo M, et al.: Cochrane Qualitative and Implementation Summaries and Device Labeling. FDA; 2016. Methods Group guidance series-paper 1: introduction. J Clin Epidemiol. 2018; Reference Source 97: 35–8. PubMed Abstract | Publisher Full Text 14. Zhang Y, Alonso-Coello P, Guyatt GH, et al.: GRADE Guidelines: 19. Assessing the certainty of evidence in the importance of outcomes or values and 29. Pollock MFR, Becker LA, Pieper D, et al.: Overviews of Reviews. In: Cochrane preferences-Risk of bias and indirectness. J Clin Epidemiol. 2019; 111: 94–104. Handbook for Systematic reviews of Interventions. 2019. PubMed Abstract | Publisher Full Text Reference Source 15. Alonso-Coello P, Oxman AD, Moberg J, et al.: [GRADE Evidence to Decision 30. Aromataris E, Fernandez R, Godfrey CM, et al.: Summarizing systematic (EtD) frameworks: a systematic and transparent approach to making well reviews: methodological development, conduct and reporting of an informed healthcare choices. 2: Clinical practice guidelines]. Gac Sanit. umbrella review approach. Int J Evid Based Healthc. 2015; 13(3): 132–40. 2018; 32(2): 167.e1–167.e10. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text 31. Hunt H, Pollock A, Campbell P, et al.: An introduction to overviews of reviews: 16. Selva A, Sanabria AJ, Niño de Guzman E, et al.: Colorectal cancer guidelines planning a relevant research question and objective for an overview. Syst seldom include the patient perspective. J Clin Epidemiol. 2019; 116: 84–97. Rev. 2018; 7(1): 39. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text 17. Selva A, Sanabria AJ, Pequeño S, et al.: Incorporating patients’ views in 32. Lunny C, Brennan SE, McDonald S, et al.: Toward a comprehensive evidence Page 9 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 map of overview of systematic review methods: paper 2-risk of bias 45. Becker L, Oxman A: Overviews of reviews. In: Handbook for Systematic Reviews assessment; synthesis, presentation and summary of the findings; and of Interventions. London: The Cochrane Collaboration. Version 5.1.0. 2008. assessment of the certainty of the evidence. Syst Rev. 2018; 7(1): 159. Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text 46. Thomas JH, Newman M: Synthesis: Combining results systematically and 33. Lunny C, Brennan SE, McDonald S, et al.: Toward a comprehensive evidence appropriately. In: Gough D, Oliver S, Thomas J, editor. An Introduction to map of overview of systematic review methods: paper 1-purpose, Systematic Reviews. London: Sage Publications Ltd. 2012.179–227. eligibility, search and data extraction. Syst Rev. 2017; 6(1): 231. Reference Source PubMed Abstract | Publisher Full Text | Free Full Text 47. Pieper D, Antoine SL, Neugebauer EA, et al.: Up-to-dateness of reviews is 34. Lunny C, Brennan SE, McDonald S, et al.: Evidence map of studies evaluating often neglected in overviews: a systematic review. J Clin Epidemiol. 2014; methods for conducting, interpreting and reporting overviews of systematic 67(12): 1302–8. reviews of interventions: rationale and design. Syst Rev. 2016; 5: 4. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text 48. Pieper D, Antoine SL, Mathes T, et al.: Systematic review finds overlapping 35. Moher D, Shamseer L, Clarke M, et al.: Preferred reporting items for reviews were not mentioned in every other overview. J Clin Epidemiol. 2014; systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. 67(4): 368–75. Syst Rev. 2015; 4: 1. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text 49. Cooper H, Koenka AC: The overview of reviews: unique challenges and 36. Barnett-Page E, Thomas J: Methods for the synthesis of qualitative research: opportunities when research syntheses are the principal elements of new a critical review. BMC Med Res Methodol. 2009; 9: 59. integrative scholarship. Am Psychol. 2012; 67(6): 446–62. PubMed Abstract | Publisher Full Text | Free Full Text PubMed Abstract | Publisher Full Text 37. Reinhard SC, Given B, Petlick NH, et al.: Supporting Family Caregivers in Providing Care. In: Patient Safety and Quality: An Evidence-Based Handbook 50. Jadczak AD, Makwana N, Luscombe-Marsh N, et al.: Effectiveness of exercise for Nurses. Rockville Agency for Healthcare Research and Quality (US). 2008. interventions on physical function in community-dwelling frail older Reference Source people: an umbrella review of systematic reviews. JBI Database System Rev Implement Rep. 2018; 16(3): 752–75. 38. Tattersall RL: The expert patient: a new approach to chronic disease PubMed Abstract | Publisher Full Text management for the twenty-first century. Clin Med (Lond). 2002; 2(3): 227–9. PubMed Abstract | Publisher Full Text | Free Full Text 51. Hong QN, Pluye P, Bujold M, et al.: Convergent and sequential synthesis designs: implications for conducting and reporting systematic reviews of 39. Orrego C, Ballester M, Pacheco-Barrios K, et al.: Development and qualitative and quantitative evidence. Syst Rev. 2017; 6(1): 61. external validation of a comprehensive Taxonomy of Self-Management PubMed Abstract | Publisher Full Text | Free Full Text Interventions in chronic conditions: the COMPAR-EU taxonomy. G-I-N & JBI Conference; October/November 2019; Adelaide, Australia. 2019. 52. Rodgers M, Sowden A, Petticrew M, et al.: Testing Methodological Guidance Reference Source on the Conduct of Narrative Synthesis in Systematic Reviews: Effectiveness 40. Torrance GW: Utility approach to measuring health-related quality of life. of Interventions to Promote Smoke Alarm Ownership and Function. J Chronic Dis. 1987; 40(6): 593–603. Evaluation. 2009; 15(1): 49–73. PubMed Abstract | Publisher Full Text Publisher Full Text 41. Hartman JD, Craig BM: Comparing and transforming PROMIS utility values 53. StataCorp: Stata Statistical Software. Release 14 ed. College Station, TX: to the EQ-5D. Qual Life Res. 2018; 27(3): 725–33. StataCorp LP. 2015. PubMed Abstract | Publisher Full Text 54. Campbell R, Pound P, Morgan M, et al.: Evaluating meta-ethnography: 42. Selva A, Solà I, Zhang Y, et al.: Development and use of a content search systematic analysis and synthesis of qualitative research. Health Technol strategy for retrieving studies on patients’ views and preferences. Health Assess. 2011; 15(43): 1–164. Qual Life Outcomes. 2017; 15(1): 126. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text 55. Caffery LJ, Martin-Khan M, Wade V: Mixed methods for telehealth research. 43. Greenhalgh T, Peacock R: Effectiveness and efficiency of search methods J Telemed Telecare. 2017; 23(9): 764–9. in systematic reviews of complex evidence: audit of primary sources. BMJ. PubMed Abstract | Publisher Full Text 2005; 331(7524): 1064–5. 56. Niño de Guzmán E: The Perspectives of Patients and Their Caregivers on PubMed Abstract | Publisher Full Text | Free Full Text Self-Management Interventions for Chronic Conditions. 21st November ed. 44. NVivo qualitative data analysis software. Version 12 ed: QSR International OSF. 2019. Pty Ltd. 2018. http://www.doi.org/10.17605/OSF.IO/GFSA5 Page 10 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 Open Peer Review Current Peer Review Status: Version 2 Reviewer Report 01 December 2021 https://doi.org/10.5256/f1000research.79074.r101464 © 2021 Zimbudzi E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Edward Zimbudzi Monash Centre for Health Research and Implementation, Monash University, Melbourne, Australia The authors have addressed my comments. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Chronic kidney disease; self-management; patient activation; health related quality of life; dialysis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Version 1 Reviewer Report 02 June 2021 https://doi.org/10.5256/f1000research.24400.r84691 © 2021 Zimbudzi E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Edward Zimbudzi Monash Centre for Health Research and Implementation, Monash University, Melbourne, Australia In this protocol, the authors seek to identify, appraise and synthesise evidence regarding patients' and caregivers' perspectives on self-management interventions. To do this, the authors will conduct four mixed-methods overviews specific to patients with chronic obstructive pulmonary Page 11 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 disease (COPD), heart failure (HF), obesity and type 2 diabetes mellitus. Appropriate databases will be searched for systematic reviews that meet preidentified criteria followed by well described data extraction and analysis process. Here are my comments/remarks that require clarification; ○ The authors may need to make it clear from the onset that they will include patients with only one of the four conditions (if that is the case). It is important to clarify this because a number of patients have more than one condition. ○ In line with the point above, patients may also have a chronic condition of interest plus other chronic diseases which are not part of this study. Are they going to be excluded? ○ The stage of the disease does affect how patients self-manage as well as outcomes. Authors may need to provide a rationale regarding why they are not considering the stage of the disease as a variable. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Chronic kidney disease; self-management; patient activation; health related quality of life; dialysis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Author Response 02 Nov 2021 Ena Niño de Guzman, Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain Eligibility criteria We will include SRs that included studies in patients with chronic conditions of interest (COPD, HF, obesity and T2DM) and without restricting by 1) disease severity, 2) the number of conditions of interest (e.g., > 1 of the chronic conditions of interest), or 3) the number of chronic conditions (e.g., ≥ 1 of the chronic conditions of interest plus ≥ 1 of other Page 12 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 chronic conditions, except cancer or severe mental disorders). We will collect and analyse data considering these criteria if data is available. We will collect and analyse data considering disease severity and the number and types of chronic conditions if data is available. If SRs included more than one of the chronic conditions of interest, we will collect and analyse data of each condition in the corresponding overview. We have modified the text in the "Methods and analysis - Eligibility criteria - Population/perspectives" section to clarify the reviewer's concern. The text reads: "We will limit inclusion to SRs of studies conducted in adult patients (18 or older) with one or more of the chronic conditions of interest (COPD, HF, obesity and T2DM), without restricting by the severity of the disease. We will consider SRs assessing multiple chronic conditions (e.g., patients with more than one of the chronic conditions of interest or patients with chronic conditions of interest plus other chronic conditions). We will exclude SRs focused on patients with the chronic conditions of interest and cancer comorbidity or severe mental disorders." We have modified the text in the "Methods and analysis - Data synthesis and reporting - Sub-group analysis" section to clarify the reviewer's concern. The text reads: "For quantitative evidence and depending on the sufficiency of SRs, we plan to analyse the primary outcomes according to the patient population (e.g., age, the severity of the disease, number and types of chronic conditions, and type of respondent), intervention (e.g., type of SM intervention) and setting (e.g., country)". Competing Interests: No conflicts of interest Reviewer Report 24 August 2020 https://doi.org/10.5256/f1000research.24400.r66199 © 2020 Vainieri M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Milena Vainieri Management and Health Laboratory, Sant'Anna School of Advanced Studies of Pisa, Pisa, Italy The article presents the study protocol for a systematic review of the reviews dealing with 4 main chronic diseases. The methods that this group of authors intend to apply are innovative and comprehensive. The only minor suggestions regard the language proofreading (for instance see the use of connects as a noun) and if the authors expect to publish a review per disease or a unique Page 13 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 comprehensive review also comparing the 4 (potentially overlapping) diseases. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Health service research, healthcare management I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Author Response 02 Nov 2021 Ena Niño de Guzman, Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain Comment 1: Language proofreading and publication plan Response 1 We have reviewed English grammar correctness and made some minor edits. We plan to publish one overview per disease. We have modified the text in the " Study status" section to clarify the reviewer's concern. The text reads: “... Finally, we plan to publish results also in a consecutive manner, one manuscript per condition, during the second semester of 2021 and the first of 2022.” Competing Interests: No conflicts of interest Page 14 of 15 F1000Research 2021, 9:120 Last updated: 13 DEC 2021 The benefits of publishing with F1000Research: • Your article is published within days, with no editorial bias • You can publish traditional articles, null/negative results, case reports, data notes and more • The peer review process is transparent and collaborative • Your article is indexed in PubMed after passing peer review • Dedicated customer support at every stage For pre-submission enquiries, contact research@f1000.com Page 15 of 15