A Smart Mobile Health Tool Versus a Paper Action Plan to Support Self-Management of Chronic Obstructive Pulmonary Disease Exacerbations: Randomized Controlled Trial

Background Many patients with chronic obstructive pulmonary disease (COPD) suffer from exacerbations, a worsening of their respiratory symptoms that warrants medical treatment. Exacerbations are often poorly recognized or managed by patients, leading to increased disease burden and health care costs. Objective This study aimed to examine the effects of a smart mobile health (mHealth) tool that supports COPD patients in the self-management of exacerbations by providing predictions of early exacerbation onset and timely treatment advice without the interference of health care professionals. Methods In a multicenter, 2-arm randomized controlled trial with 12-months follow-up, patients with COPD used the smart mHealth tool (intervention group) or a paper action plan (control group) when they experienced worsening of respiratory symptoms. For our primary outcome exacerbation-free time, expressed as weeks without exacerbation, we used an automated telephone questionnaire system to measure weekly respiratory symptoms and treatment actions. Secondary outcomes were health status, self-efficacy, self-management behavior, health care utilization, and usability. For our analyses, we used negative binomial regression, multilevel logistic regression, and generalized estimating equation regression models. Results Of the 87 patients with COPD recruited from primary and secondary care centers, 43 were randomized to the intervention group. We found no statistically significant differences between the intervention group and the control group in exacerbation-free weeks (mean 30.6, SD 13.3 vs mean 28.0, SD 14.8 weeks, respectively; rate ratio 1.21; 95% CI 0.77-1.91) or in health status, self-efficacy, self-management behavior, and health care utilization. Patients using the mHealth tool valued it as a more supportive tool than patients using the paper action plan. Patients considered the usability of the mHealth tool as good. Conclusions This study did not show beneficial effects of a smart mHealth tool on exacerbation-free time, health status, self-efficacy, self-management behavior, and health care utilization in patients with COPD compared with the use of a paper action plan. Participants were positive about the supportive function and the usability of the mHealth tool. mHealth may be a valuable alternative for COPD patients who prefer a digital tool instead of a paper action plan. Trial Registration ClinicalTrials.gov NCT02553096; https://clinicaltrials.gov/ct2/show/NCT02553096.

1b) ABSTRACT: Structured summary of trial design, methods, results, and conclusions NPT extension: Description of experimental treatment, comparator, care providers, centers, and blinding status. 1a) Does your paper address CONSORT item 1a? * 1a-i) Identify the mode of delivery in the title Does your paper address subitem 1a-i? * "smart mHealth tool" 1a-ii) Non-web-based components or important co-interventions in title Does your paper address subitem 1a-ii? subitem not relevant, subitem 1a-i covers the mode of delivery 1a-iii) Primary condition or target group in the title Does your paper address subitem 1a-iii? * "to support self-management of COPD exacerbations" INTRODUCTION 2a) In INTRODUCTION: Scientific background and explanation of rationale Does your paper address subitem 1b-iii? "Of the 87 patients with COPD recruited from primary and secondary care, 43 were randomized to the intervention group. " 1b-iv) RESULTS section in abstract must contain use data Does your paper address subitem 1b-iv? "Patients using the mHealth tool valued it as a more supportive tool than patients using the paper action plan. Patients considered the usability of the mHealth tool as good." 1b-v) CONCLUSIONS/DISCUSSION in abstract for negative trials Does your paper address subitem 1b-v? This is a negative trial. The abstract only concludes about the results, the discussion section in the main paper dwells about the primary outcome and the uptake.
2a-i) Problem and the type of system/solution Does your paper address subitem 2a-i? * "Telemonitoring, in which patients record and send information on symptoms and/or physiological measurements to a supervising clinician, may be an alternative approach to self-management strategies to reduce the impact of COPD exacerbations. Beneficial effects have been reported on number of hospital admissions,[13] emergency visits, [13] and quality of life in some studies, [14,15] but not in all. [16] There is much heterogeneity between telemonitoring interventions regarding devices and clinical content, and the amount of additional support that patients receive. However, in contrast with selfmanagement, telemonitoring strongly depends on the judgement of the clinician and the patient is not expected to interpret his or her own symptoms and signs. Therefore, we have developed [17] and validated [18] an innovative mHealth tool, called the Adaptive Computerised COPD Exacerbation Self-management Support (ACCESS) system. This tool aims to tailor self-management support more efficiently and continuously than with a written action plan, but without heavily increasing the involvement of healthcare professionals to monitor input as is the case with telemonitoring. The mHealth tool integrates information on symptom changes and physiological measurements (i.e., pulse oximetry, spirometry and measurement of body temperature) in an easy-to-use application by means of a smartphone.
[17] Based on a decision tree built by a clinical expert panel and a Bayesian prediction model, the tool provides automated, tailored self-management advices to the patient without the involvement of the healthcare professional.
[18] Patients can use the tool at their own initiative to monitor symptom changes at any time of day or night, and receive ad hoc, tailored advice. " 2a-ii) Scientific background, rationale: What is known about the (type of) system 2b) In INTRODUCTION: Specific objectives or hypotheses METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons Does your paper address subitem 2a-ii? * "Telemonitoring, in which patients record and send information on symptoms and/or physiological measurements to a supervising clinician, may be an alternative approach to self-management strategies to reduce the impact of COPD exacerbations. Beneficial effects have been reported on number of hospital admissions,[13] emergency visits, [13] and quality of life in some studies, [14,15] but not in all. [16] There is much heterogeneity between telemonitoring interventions regarding devices and clinical content, and the amount of additional support that patients receive. However, in contrast with selfmanagement, telemonitoring strongly depends on the judgement of the clinician and the patient is not expected to interpret his or her own symptoms and signs. Therefore, we have developed [17] and validated [18] an innovative mHealth tool, called the Adaptive Computerised COPD Exacerbation Self-management Support (ACCESS) system. This tool aims to tailor self-management support more efficiently and continuously than with a written action plan, but without heavily increasing the involvement of healthcare professionals to monitor input as is the case with telemonitoring. The mHealth tool integrates information on symptom changes and physiological measurements (i.e., pulse oximetry, spirometry and measurement of body temperature) in an easy-to-use application by means of a smartphone.
[17] Based on a decision tree built by a clinical expert panel and a Bayesian prediction model, the tool provides automated, tailored self-management advices to the patient without the involvement of the healthcare professional.
[18] Patients can use the tool at their own initiative to monitor symptom changes at any time of day or night, and receive ad hoc, tailored advice. " Does your paper address CONSORT subitem 2b? * "In this study, we examined the clinical effectiveness of the mHealth tool. We hypothesised that in patients with COPD the use of the tool would lead to more weeks without exacerbations, improvement in health status, self-efficacy, and self-management behaviour, and a reduction in healthcare utilization, compared to the use of a paper exacerbation action plan. We also evaluated how patients valued the tool's supportive function and usability. " Does your paper address CONSORT subitem 3a? * "This study was a multicenter, parallel, two-arm, randomized controlled trial (RCT) with a follow-up of 12 months per patient. " 4a) Eligibility criteria for participants Does your paper address CONSORT subitem 3b? * not applicable 3b-i) Bug fixes, Downtimes, Content Changes Does your paper address subitem 3b-i? not applicable Does your paper address CONSORT subitem 4a? * "Patients were eligible for participation if they (i) were at least 40 years of age, (ii) had a spirometry-confirmed diagnosis of COPD (post-bronchodilator forced expiratory volume in one second / forced vital capacity (FEV1/FVC) < 0.7), and (iii) had experienced two or more symptom-based exacerbations in the previous "Our primary outcome was the difference in number of exacerbation-free weeks between the intervention and control groups. An exacerbation-free week was defined as a week in which there had not been episodes of two or more consecutive days with worsening of two major symptoms (i.e. dyspnoea, sputum purulence, sputum amount) or one major and one or more minor symptoms (i.e. colds, wheeze, sore throat, and cough).
[21] Symptom changes were assessed by means of the Telephonic Exacerbation Assessment System (TEXAS), an automated telephone call system that contacted participants weekly on the day and time of their preference.
[22] TEXAS consisted of closed questions regarding changes in respiratory symptoms, use of healthcare resources and use of respiratory medication in the week prior to the call and its validity has been demonstrated previously. [22] Due to discontinuation of the contract with the provider of TEXAS, the last 19 participants in the trial received a weekly online questionnaire containing the same questions as with TEXAS. These participants used both measuring tools during two weeks before stopping with TEXAS, which enabled us to compare data entry from TEXAS with the online survey tool. We found no differences in data entry. Secondary outcomes included: • Exacerbation-related outcomes, i.e. the number of unscheduled healthcare contacts, the number of exacerbations treated with antibiotics and/or prednisolone, and the number of exacerbation-related hospital admissions, all retrieved from patients' medical records, and the number of symptom-based exacerbations as assessed with TEXAS.
• Exacerbation-related self-management behaviour, measured with TEXAS or the online questionnaire, and defined as taken one or more of the following three actions during symptom-based exacerbations: (i) contacting the healthcare professional , (ii) starting a course of prednisolone and/or antibiotics, or (iii) maximising bronchodilator use. We also assessed the time between the date of exacerbation onset and the date of one of these three actions, defining actions taken within 3 days of exacerbation onset as adherence to the instructions. based on weighted scores on mobility, self-care, usual activities, pain/discomfort and anxiety/depression, as well as a vertical VAS scale varying between 0 and 100. At the start and at 12 months, data were gathered on exacerbation history, selfefficacy and health status. CCQ and EQ-5d were also completed at three, six, and nine months follow-up.
At 12 months, information on healthcare utilization, lung function, respiratory medication use, and comorbid conditions were extracted from the participants' medical records. Also, all participants were asked to evaluate the supportive function of either the mHealth tool or the paper action plan and participants of the intervention group were asked to complete the System Usability Scale (SUS).
[25] The SUS contains 10 questions on system usability, which are calculated into one total score between 0 and 100. SUS scores < 68 are considered as low, ≥ 68 and ≤ 80.3 as good, and > 80.3 as excellent. " Does your paper address subitem 5-ii?
"in the manuscript we refer to previous studies in which we report on development and validation of our tool"

5-iii) Revisions and updating
Does your paper address subitem 5-iii?
not applicable yet 5-iv) Quality assurance methods Does your paper address subitem 5-iv?
"in the manuscript we refer to previous studies in which we report on development and validation of our tool" 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Does your paper address subitem 5-v?
in the main paper we refer to previous work in which algorithms are presented.

5-vi) Digital preservation webcitation.org
Does your paper address subitem 5-vi? not applicable

5-vii) Access
Does your paper address subitem 5-vii? * " Before the trial started participants in the intervention group were instructed to use the system daily for two weeks in order to get familiarised with the application, smartphone, spirometer, pulse-oximeter, and forehead thermometer. Data were sent to a secured web-based interface and were monitored by the research team to make sure participants practiced sufficiently. After this 2-week run-in period, the nurses evaluated patients' use of the system, including the physiological measurements. Reference values for each patient's FEV1 and peripheral oxygen saturation were set. Then, the 12month follow-up period started. Patients were instructed to use the tool every time they experienced or had any doubts about any change in symptoms or disease burden. At three months follow-up, patients were invited by their nurse to evaluate the use of the mHealth tool. Only then the nurses received from the research team the patients' entries to enable tailoring of feedback on selfmanagement behaviour. " 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework Before the trial started participants in the intervention group were instructed to use the system daily for two weeks in order to get familiarised with the application, smartphone, spirometer, pulse-oximeter, and forehead thermometer. Data were sent to a secured web-based interface and were monitored by the research team to make sure participants practiced sufficiently. After this 2-week run-in period, the nurses evaluated patients' use of the system, including the physiological measurements. Reference values for each patient's FEV1 and peripheral oxygen saturation were set. Then, the 12month follow-up period started. Patients were instructed to use the tool every time they experienced or had any doubts about any change in symptoms or disease burden. At three months follow-up, patients were invited by their nurse to evaluate the use of the mHealth tool. Only then the nurses received from the research team the patients' entries to enable tailoring of feedback on selfmanagement behaviour. "

5-xi) Report any prompts/reminders used
Does your paper address subitem 5-xi? * "At three months follow-up, patients were invited by their nurse to evaluate the use of the mHealth tool. Only then the nurses received from the research team the patients' entries to enable tailoring of feedback on self-management behaviour. " 6a) Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 5-xii) Describe any co-interventions (incl. training/support) Does your paper address subitem 5-xii? * "Prior to randomization and after signing written informed consent participants received a 20-minute educational session based on the Dutch version of the Living Well with COPD self-management program provided by the nurse in groups of 4 to 10 participants, to establish a homogeneous baseline in exacerbation self-management knowledge.
[12] " "Before the trial started participants in the intervention group were instructed to use the system daily for two weeks in order to get familiarised with the application, smartphone, spirometer, pulse-oximeter, and forehead thermometer. " Does your paper address CONSORT subitem 6a? * "Outcomes and follow-up Our primary outcome was the difference in number of exacerbation-free weeks between the intervention and control groups. An exacerbation-free week was defined as a week in which there had not been episodes of two or more consecutive days with worsening of two major symptoms (i.e. dyspnoea, sputum purulence, sputum amount) or one major and one or more minor symptoms (i.e. colds, wheeze, sore throat, and cough).
[21] Symptom changes were assessed by means of the Telephonic Exacerbation Assessment System (TEXAS), an automated telephone call system that contacted participants weekly on the day and time of their preference.
[22] TEXAS consisted of closed questions regarding changes in respiratory symptoms, use of healthcare resources and use of respiratory medication in the week prior to the call and its validity has been demonstrated previously.
[22] Due to discontinuation of the contract with the provider of TEXAS, the last 19 participants in the trial received a weekly online questionnaire containing the same questions as with TEXAS. These participants used both measuring tools during two weeks before stopping with TEXAS, which enabled us to compare data entry from TEXAS with the online survey tool. We found no differences in data entry. Secondary outcomes included: based on weighted scores on mobility, self-care, usual activities, pain/discomfort and anxiety/depression, as well as a vertical VAS scale varying between 0 and 100. At the start and at 12 months, data were gathered on exacerbation history, selfefficacy and health status. CCQ and EQ-5d were also completed at three, six, and nine months follow-up.
At 12 months, information on healthcare utilization, lung function, respiratory medication use, and comorbid conditions were extracted from the participants' medical records. Also, all participants were asked to evaluate the supportive function of either the mHealth tool or the paper action plan and participants of the intervention group were asked to complete the System Usability Scale (SUS).
[25] The SUS contains 10 questions on system usability, which are calculated into one total score between 0 and 100. SUS scores < 68 are considered as low, ≥ 68 and ≤ 80.3 as good, and > 80.3 as excellent. " 6b) Any changes to trial outcomes after the trial commenced, with reasons 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed Does your paper address subitem 6a-i? not relevant 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored Does your paper address subitem 6a-ii?
"Also, all participants were asked to evaluate the supportive function of either the mHealth tool or the paper action plan and participants of the intervention group were asked to complete the System Usability Scale (SUS).
[25] The SUS contains 10 questions on system usability, which are calculated into one total score between 0 and 100. SUS scores < 68 are considered as low, ≥ 68 and ≤ 80.3 as good, and > 80.3 as excellent. " 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Does your paper address subitem 6a-iii?
"Also, all participants were asked to evaluate the supportive function of either the mHealth tool or the paper action plan and participants of the intervention group were asked to complete the System Usability Scale (SUS).
[25] The SUS contains 10 questions on system usability, which are calculated into one total score between 0 and 100. SUS scores < 68 are considered as low, ≥ 68 and ≤ 80.3 as good, and > 80.3 as excellent. " Does your paper address CONSORT subitem 6b? * not applicable 7a) How sample size was determined NPT: When applicable, details of whether and how the clustering by care provides or centers was addressed 7b) When applicable, explanation of any interim analyses and stopping guidelines 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group 8b) Type of randomisation; details of any restriction (such as blocking and block size) 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size Does your paper address subitem 7a-i? "Sample size calculation using analysis of variance showed that we needed 43 participants in each group for 80% power (α=0.05, two sided) to detect an increase of six exacerbation-free weeks per year and anticipating a drop-out rate of 20%. " Does your paper address CONSORT subitem 7b? * not applicable Does your paper address CONSORT subitem 8a? * "We used a computer generated two-block randomization procedure, stratifying for healthcare centre. Allocation order was determined by the order in which eligible patients responded to our invitation to participate (kept by the research assistant). Participants were assigned to one of the groups after signing informed consent, during the group meeting by the researcher (LB). " Does your paper address CONSORT subitem 8b? * "We used a computer generated two-block randomization procedure, stratifying for healthcare centre. Allocation order was determined by the order in which eligible patients responded to our invitation to participate (kept by the research assistant). Participants were assigned to one of the groups after signing informed consent, during the group meeting by the researcher (LB). " 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment Does your paper address CONSORT subitem 9? * " We used a computer generated two-block randomization procedure, stratifying for healthcare centre. Allocation order was determined by the order in which eligible patients responded to our invitation to participate (kept by the research assistant). Participants were assigned to one of the groups after signing informed consent, during the group meeting by the researcher (LB). " Does your paper address CONSORT subitem 10? * "We used a computer generated two-block randomization procedure, stratifying for healthcare centre. Allocation order was determined by the order in which eligible patients responded to our invitation to participate (kept by the research assistant). Participants were assigned to one of the groups after signing informed consent, during the group meeting by the researcher (LB). " 11a-i) Specify who was blinded, and who wasn't Does your paper address subitem 11a-i? * "Due to the type of intervention, patients and healthcare professionals could not be blinded for group assignment. Also, the research team could not be blinded, since it was responsible for the personalisation and technical support of the mHealth tool. The study statistician (RA), who was responsible for analysing the data, was blinded for study assignment of the participants until the analyses had been finished." 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item) Does your paper address CONSORT subitem 12b? * "Negative binomial regression analyses, controlling for follow-up time per participant, age and gender, were used to analyse our primary outcome, i.e. the number of exacerbation-free weeks, as well as the number of unscheduled healthcare contacts, self-reported exacerbations, exacerbations treated with antibiotics and/or prednisolone, and exacerbation-related hospital admissions. To test the effect of the mHealth tool on the rate of symptom-based exacerbations and self-management behaviour, we extracted exacerbation episodes from the TEXAS database. Each new episode was preceded by at least two exacerbation-free weeks or two weeks with missing data. [22] To assess patient delay in taking action when an exacerbation was imminent, the numbers of days were calculated between the date of exacerbation onset and the following actions: a) the first date of contact with a healthcare professional, b) starting date of course of prednisolone and/or antibiotics, or c) date of increase of bronchodilators. We categorised these variables into two groups: <3 days (according to instructions), and ≥3 days. Separate multilevel logistic regression analyses were performed, taking into account the clustering effect of exacerbations within patients, and controlling for age and gender, to examine a) whether the mHealth tool led to higher percentages of self-management actions in case of an exacerbation compared to the paper action plan, and b) whether these actions were more often taken timely by patients in the intervention group compared to the control group. 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting Does your paper address subitem 21-ii? "Additionally, we chose to provide our control group with a paper action plan, according to the recommendations in the current national COPD guideline. [19] However, many general practitioners and chest physicians in the Netherlands have not (yet) integrated the use of paper action plans in their daily practice. Our choice might have upgraded self-management knowledge and skills of all participants, which may have reduced the room for improvement by mHealth and may have diluted potential differences in our outcomes, compared to a situation with 'real' (partially insufficient) usual care. " Does your paper address CONSORT subitem 23? * This study has been registered at Clinicaltrials.gov (Identifier: NCT02553096) Does your paper address CONSORT subitem 24? * trial protocol can be checked at Clinicaltrials.gov Does your paper address CONSORT subitem 25? * not relevant STOP -Save this form as PDF before you click submit To generate a record that you filled in this form, we recommend to generate a PDF of this page (on a Mac, simply select "print" and then select "print as PDF") before you submit it.
When you submit your (revised) paper to JMIR, please upload the PDF as supplementary file.
Don't worry if some text in the textboxes is cut off, as we still have the complete information in our database. Thank you! Final step: Click submit ! Click submit so we have your answers in our database! Would you like to become involved in the CONSORT EHEALTH group?
Any other comments or questions on CONSORT EHEALTH VERZENDEN