Self-management interventions for adults living with Chronic Obstructive Pulmonary Disease (COPD): The development of a Core Outcome Set for COMPAR-EU project

Background A large body of evidence suggests that self-management interventions (SMIs) may improve outcomes in chronic obstructive pulmonary disease (COPD). However, accurate comparisons of the relative effectiveness of SMIs are challenging, partly due to heterogeneity of outcomes across trials and uncertainty about the importance of these outcomes for patients. We aimed to develop a core set of patient-relevant outcomes (COS) for SMIs trials to enhance comparability of interventions and ensure person-centred care. Methods We undertook an innovative approach consisting of four interlinked stages: i) Development of an initial catalogue of outcomes from previous EU-funded projects and/or published studies, ii) Scoping review of reviews on patients and caregivers’ perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with patients and patient representatives to rate the importance of outcomes, and iv) Face-to-face consensus workshop with patients, patient representatives, health professionals and researchers to develop the COS. Results From an initial list of 79 potential outcomes, 16 were included in the COS plus one supplementary outcome relevant to all participants. These were related to patient and caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, caregiver quality of life, activities of daily living, coping with the disease, participation and decision-making, emergency room visits/admissions and cost effectiveness. Conclusion The development of the COPD COS for the evaluation of SMIs will increase consistency in the measurement and reporting of outcomes across trials. It will also contribute to more personalized health care and more informed health decisions in clinical practice as patients’ preferences regarding COPD outcomes are more systematically included.


Unfunded studies
Enter: The author(s) received no specific funding for this work.

Competing Interests
Use the instructions below to enter a The authors have declared that no competing interests exist. We undertook an innovative approach consisting of four interlinked stages: i) 97 Development of an initial catalogue of outcomes from previous EU-funded projects 98 and/or published studies, ii) Scoping review of reviews on patients and caregivers' 99 perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with 100 patients and patient representatives to rate the importance of outcomes, and iv) Face-101 to-face consensus workshop with patients, patient representatives, health 102 professionals and researches to develop the COS. 103

104
From an initial list of 79 potential outcomes, 16 were included in the COS plus one 105 supplementary outcome relevant to all participants. These were related to patient and 106 caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, 107 adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, 108 caregiver quality of life, activities of daily living, coping with the disease, participation 109 and decision-making, emergency room visits/admissions and cost effectiveness. 110

Conclusion 111
The development of the COPD COS for the evaluation of SMIs will increase consistency 112 in the measurement and reporting of outcomes across trials. It will also contribute to 113 more personalized health care and more informed health decisions in clinical practice 114 as patients' preferences regarding COPD outcomes are more systematically included. Two recent studies, the COMET (10) and the PIC-COPD (11) showed the potential of 131 SMIs for reducing exacerbations and mortality in integrated case management, as well 132 as for increasing physical activity. However, synthesizing the evidence on the relative 133 effectiveness of SMIs for COPD is challenging due to heterogeneity of interventions, 134 lack of clear definitions of self-management components, and variability in the 135 outcomes reported. Moreover, systematic reviews on SMI effectiveness have found 136 insufficient data for some outcomes, which may be suggestive of selective reporting 137 (9,12,13). 138 SMIs can only be compared across studies when they share some common outcomes. 139 In addition, it is important to create consensus about what outcomes are especially 140 relevant to assess the effects of SMI and how they should be measured. By reaching 141 consensus of a standardized set of outcomes that should be minimally measured and 142 reported in future COPD clinical trials, we will ensure the comparativeness of results 143 and synthesis of the evidence across studies (14). This outcome set should be relevant 144 for all stakeholders, but especially for patients, as they are the ones primarily 145 responsible for the daily management of their disease. In this study we propose a  Health Measurement] (19). 168

Study selection 169
We included systematic reviews and individual studies that reported outcomes on 170 SMIs for patients with COPD. We excluded systematic reviews that did not report a 171 final list of outcomes or individual studies where the final list of outcomes was not 172 developed considering patients' input, experiences or values and preferences. 173 We screened title and abstracts and assessed eligible full-text articles independently. 174 In case of disagreement, reviewers reached consensus or consulted with a referee. 175 Reviewers checked references from included studies to identify other potentially 176 eligible studies. 177

Data extraction 178
Pairs of authors independently extracted the following data from eligible studies: i) 179 study database, ii) type of publication (i.e., published COS, literature review or 180 systematic review), iii) age groups, and iv) list of outcomes. 181

Data synthesis 182
We tabulated and classified the identified outcomes into the following seven terms specific for COPD. We used review filters available in each database. 204

Study selection 205
We included reviews of quantitative, qualitative or mixed-methods studies that 206 explored the perspectives, experiences, values and preferences of patients and 207 caregivers on SMIs for COPD. 208

Data extraction 209
In a previously pilot-tested data extraction form, we collected the general 210 characteristics and main findings of each review. 211

Data synthesis 212
We conducted a descriptive thematic synthesis including the identification of codes, 213 descriptive themes and main themes relevant to outcomes of SMI for COPD. We 214 paired main emerging themes with the subdomains of the COMPAR-EU taxonomy (20)  215 and mapped the correspondence between themes and the initial catalogue of 216 outcomes. We developed infographics illustrating themes to be used as aid materials 217 during the consensus workshop. 218

Stage 3. Delphi survey (Round I and II) 219
To prioritize the outcomes identified, we administered two-round modified Delphi 220 online surveys to a convenience sample. Our sample included patients and patients' 221 representatives to ensure that we address outcomes that matter to patients as well as 222 to other stakeholders. 223

Study population and eligibility criteria 224
We included adults diagnosed with COPD and patients' representatives who were able 225 to understand and speak English and provided informed consent to participate 226 through the web platform hosting the Delphi rounds. participants received an online survey with the outcomes and definitions. They also 235 received weekly reminders and were able to return to the questionnaire within a 3-236 week period. Some of the participants were supported by their local organizations 237 when completing it. Participants were asked "How important do you think the 238 following outcomes are to measure the success of self-management in people with 239 COPD?". COPD outcomes for SMIs were prioritized during the two-round Delphi 240 process using a 1 to 9 Likert scale (1 being the least and 9 being the most important for 241 the self-management of COPD). 242 During the second round, participants were able to see ratings (average score) from 243 the first round and thus, adjust, confirm or rethink their answers. This process enabled 244 participants to rate the most relevant SMIs outcomes for COPD according to their 245 perspective. 246

Data synthesis and analysis 247
All outcomes were categorized into three groups based on the level of agreement of 248 ratings from the two-round Delphi online surveys as follows (Table 1) The additional search in COMET (10), ICHOM (19) and through snowballing yielded 23 283 articles. After full-text appraisal, we included five studies (46-50); one study was 284 excluded because it did not report the list of outcomes (51). 285

Study characteristics 286
The five included studies reported: i) a summary of outcomes for COPD 287 pharmacological trials from lung function to biomarkers created by the American 288 Thoracic Society / European Respiratory Society Task Force (46), ii) a review of 289 instruments used to measure symptom response in pharmacological trials (47), iii) a 290 review of articles determining themes identified as most important by COPD patients 291 for any aspect of care of COPD (48), iv) a review assessing clinical outcomes in COPD 292 mainly used on current published data (50), and v) a study addressing patient 293 preferences regarding the expectations related to treatment of COPD. 294

List of outcomes and outcomes classification 295
We identified 79 outcomes for the initial list of outcomes. We classified outcomes into 296 seven predefined subdomains based on a taxonomy for SMIs (20).

Study selection 302
Among the 1,031 unique screened references, 27 reviews were included comprising 303 more than 800 studies. 304

Main themes related to SMI outcomes for COPD 314
We identified 21 main themes, which are presented in Table 3. These themes were 315 classified under i) empowerment components, ii) adherence to the expected self-316 management behaviours, iii) clinical-related outcomes, iv) quality of life of patients 317 and caregivers, v) perceptions and/or satisfaction with care, vi) health care use, vii) 318 costs. Table 3 presents the subdomains of the COMPAR-EU taxonomy and the related 319 identified themes for COPD. 320 [Insert here: Table 3 on Main themes related to COPD outcomes according to the 321 subdomains from the COMPAR-EU taxonomy]. 322

Mapping of themes 323
Of the 79 outcomes from the initial catalogue of outcomes, 45 were covered in the 324 thematic synthesis (57%). All outcomes of the subdomain "empowerment 325 components" were informed by the scoping review findings (n=4, 100%), while the 326 subdomain "costs" was the least informed subdomain (n=1, 20%).  Table 1). 350

Stage 4. Consensus workshop and final COPD core outcome set 351
Five of the nine patients or patients' representatives that participated in the Delphi 352 online survey and five health professionals and researchers participated in the face-to-353 face consensus meeting. Five members of the COMPAR-EU research team participated 354 as facilitators (Supplementary files 3 and 4). They could represent very motivated individuals or well-informed patients with high 414 education or digital skills. However, and given the resources available, it would not 415 have been feasible to adopt methodology different from electronic surveys (e.g., in-416 person interviews or surveys) to reach out to participants that are more diverse. 417

Implications for practice and research 418
The identified COS will inform a series of systematic reviews and network meta-419 analysis (NMA) about the effectiveness of SMIs as part of the COMPAR-EU project. We 420 are confident that the COPD COS reflects the preferences of all key stakeholders and 421 that it might be applicable with context adaptation to wide range of settings across 422 Europe and the world. Future research evaluating SMIs for COPD should, as a 423 minimum, include the outcomes in the proposed COS. Further work is needed to 424 identify and provide guidance on the most appropriate measures for each outcome. 425 426 CONCLUSIONS 427 We have developed the first COS for SMIs in COPD. This COS will increase consistency 428 in the reporting of results that are relevant to patients across trials evaluating SMIs for 429 COPD. This COS will enhance evidence synthesis of COPD patient-relevant outcomes 430 and will decisively support research and overall field development. It will improve 431 informed health-decision making in clinical practice and will increase the certainty of 432 evidence to guide policy-making and clinical practice regarding SMI in COPD patients.   Relates to knowledge about COPD in general and COPD self-management, or the way care for COPD is organized and this both for patients and their social network. Caregiver knowledge and competence That the caregiver has competences and knowledge of the disease and its management.

Self-efficacy
A person's belief that s/he is capable of doing something, often related to a specific goal s/he wants to achieve; feeling of confidence and of being in control.

Patient activation
The knowledge, skills and confidence a person has on managing their own health and healthcare, including a feeling of being responsible for taking care of their own health.

Self-monitoring
The extent to which a patient (regularly) monitors themselves as agreed with her/his healthcare professionals, for example her/his symptoms or weight. Taking medication or other treatment as advised (adherence) and adherence to regular visits The extent to which a patient follows the prescribed treatment, such as taking medication as advised and following life-style advice, and extent of attending scheduled visits.

Smoking cessation
Stopping smoking (and/or smoking less). COPD symptoms (short term) Extent of Symptoms relief (in the short-term, including cough; breathlessness, among others).

Physical activity -muscle strength
Referral/participation in a Pulmonary Rehabilitation program: Physical activity, Physical activities, Muscle strength linked with exercise capacity plus an overall support.

Sleep quality
Sleep quality contains interrupted sleep, sleep problems, sleep quality (as overall) and sleepiness.

Exacerbation
Increased breathlessness, mucus/phlegm/sputum production, and change in color of sputum and Feeling out of breath. Caregiver quality of life (including burden) Caregiver quality of life and the burden that he/she feels from the caregiver's tasks. Activities of daily living: including sex life, social activities and work (usual activities) Being able to do usual activities, such as personal hygiene, housework, sex, managing finances, social activities and work.
Coping with the disease, including depression and anxiety How well a person feels able to cope/manage with stress or other difficulties caused by the disease, including depression and anxiety. Participation and decision making Feeling able to participate actively in her/his own care (as much as s/he wishes).

Number of emergency room
Number of visits to emergency department visits and hospital admissions. visits and admissions Cost effectiveness and resources use It includes value for money of the self-management intervention and the use of resources.