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Abstract
Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.
- Pulmonary Rehabilitation
- Exercise
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Introduction
Pulmonary rehabilitation (PR) is an integrated component of the management of chronic obstructive pulmonary disease (COPD).1 However, there are well-recognised challenges with uptake and adherence.1 2 Consequently, there has been growing interest in novel PR models and, therefore, recent randomised clinical trials have compared home-based pulmonary telerehabilitation (PTR) to traditional PR.2 3 However, more recently, RCT studies have been challenged by the lower than anticipated benefits in the PR arms,3–6 making superiority, equivalence and non-inferiority analyses difficult to interpret. Moreover, it is known from large retrospective cohorts receiving state of the art PR that 40 to 50% of the participants do not achieve the minimal important changes (MIC) despite being adherent to the traditional PR programme.7
The purpose of this report was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups receiving home-based PTR or traditional hospital-based outpatient PR on walking capacity, respiratory symptoms, quality of life (QoL) and muscle strength, and secondary to explore possible interactions between PTR/PR groups and baseline variables. Participants were originally included in a previously published RCT study.4
Methods
In brief, data derived from 134 participants recruited to a randomised clinical multicenter trial comprising two parallel arms (allocated 1:1), comparing the effect of 10 weeks supervised PTR with 10 weeks traditional supervised hospital-based PR in patients eligible for outpatient hospital-based PR. Inclusion and exclusion criteria corresponded to the criteria for outpatient hospital-based routine PR in the Capital Region of Denmark, and pertained to adults with a verified diagnosis of COPD, FEV1 <50%, Medical Research Council Dyspnoea scale ≥2 and no participation in PR within 6 months. Details on study registration (NCT02667171), ethical approval (H-15019380), intervention content and components is published previously.4 All assessments and analyses were performed allocation blinded. Both PR and PTR were delivered according to the recently updated guidelines from the Danish Health Authorities.4 Maintenance exercising was encouraged but not provided in either group during the 52 weeks follow-up.
The minimal important change (MIC) for each outcome was decided prior to initiation of the RCT study and thus used for the responder analysis.4 The primary outcome measure was walking capacity (6MWD; MIC ≥26 m).8 Secondary outcome measures were respiratory symptoms (CAT; MIC ≥−3.0 points),9 10 hospital anxiety and depression scores (HADS A and D; MIC ≥−1.5 point),11 health-related quality of life (EQ-5D-VAS; MIC ≥8),12 and leg muscle endurance (30sec-STS; MIC ≥2.0 repetitions).13
Statistical analysis
Proportions of outcome responses with 95% Wilson score confidence intervals (CI)14 were estimated for both PR and PTR. OR with CI for outcomes comparing PTR to PR and interaction of PTR/PR with characteristic variables were estimated by logistic regression models. P-values for interaction were adjusted for multiple testing by Bonferroni correction within each outcome. Distribution and change in MIC responses sum, categorised as good (MIC≥3 outcomes), moderate (MIC on 1–2 outcomes) and non-response (MIC on 0 outcomes) is presented in a Sankey plot. All analysis was done using R 4.1.0 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Sixty-seven patients were randomised to each group (55% females, 75% former smokers, mean±SD age 68±9 years, FEV1 33.1±9.4% predicted, 6 min walking distance 331±99 metres, CAT 20±7 points, HADS-A 6.3±3.5 points, HADS-D 4.3±3.0 points, and EQ5D-VAS 52.7±19.2 points).4
There was no statistical difference in 6MWD MIC response between PTR and PR, 34% and 42% respectively (OR=0.72, CI=0.34 to 1.51, p=0.381) at 10 weeks follow-up or at 62 weeks follow-up, 28% and 26% respectively (OR=1.12, CI=0.40 to 3.14, p=0.834). For secondary outcomes only HADS-A score at 10 weeks showed a difference between PTR and PR (OR=2.2, CI=1.01 to 4.93, p=0.048) table 1). No significant interaction was found for any of the characteristic variables in PTR/PR grouping (all p≥0.104), although estimates also had wide CI (table 2).
Within and between group proportional responses to minimal important change
Interaction estimates for PTR/PR difference dependency of baseline variables
A total of 36 (36%) and 23 (23%) of participants achieved a good MIC response (MIC on≥3 outcomes from 6MWD, CAT, HADS-A, HADS-D, EQ-5D-VAS and 30sec-STS) at 10 and 62 weeks follow-up respectively. Seventeen (47%) of the 36 maintained a good MIC response from 10 to 62 weeks follow-up, with 24 (55%) maintaining a moderate response and 11 (58%) no response. Overall, 13 (13%) had an improvement and 34 (34%) a decline response category from 10 to 62 weeks follow-up. (figure 1 - Sankey diagram).
Data are numbers and percentages of participant with good- (reaching MIC on ≥3 outcomes) moderate- (reaching MIC on 1–2 outcomes) and none-response (reaching MIC on 0 outcomes) at 10 weeks from baseline, 62 weeks from baseline and response changes.
Discussion
Only HADS-A response at 10 weeks follow-up showed significant difference. With large uncertainties for OR (wide CI) for all responses. Thus, any clinically relevant differences between treatments could not be shown. Dependency between the PTR and PR differences and baseline characteristics could not be shown, however again with large uncertainty for estimates. The majority of the participants exceeded the MIC on one or more outcomes, both short- and long-term.
While the difficulty to achieve group-level MIC in contemporaneous rigorously conducted RCT3–6 has raised concern of patients being insufficiently exercised, it is important to highlight that lack of sufficient group average effect from PR programmes are not uncommon in RCT studies. In the 2015 hallmark Cochrane review by McCarthy et al it is evident that 1 in 3 RCT studies do not reach the MIC when compared with usual care (no rehabilitation) on respectively maximal exercise capacity, 6MWD, Chronic Respiratory Questionnaire (CRQ) and St George’s Respiratory Questionnaire (SGRQ).15 Unfortunately nor the proportional number of responders or the numbers needed to treat (rehabilitate) were reported in the included RCT studies.15 Analogously, a Cochrane review published in 2019, comparing long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler vs placebo, concluded that fixed combination inhaler would result in only 138 more people per 1000 with COPD reaching a MIC in SGRQ compared with placebo.16 Additionally, 4 in seven included RCT studies failed to exceed the group average MIC on SGRQ compared with placebo.16 Unblinded, prospective and retrospective test-retest studies appear to provide somewhat larger proportional responses with 40–60% of patients reaching the MIC.7 17 Yet, the proportional responses are similarly very heterogenous depending on the specific outcome and also include methodological high risk of bias.7 17
We performed exploratory analysis of possible interactions between PTR/PR groups and baseline variables with the intention to highlight any interaction that might indicate an effect. However, our exploratory analysis did not reveal any interactions of the baseline characteristics within PTR/PR grouping. It remains unclear what drives non-response, single outcome response and multiple outcome responses among participants. Current evidence suggests that patients with COPD are highly unlikely to respond similarly and sufficiently to an intervention and to one restricted primary outcome in an RCT design.7 15 16 While choosing the one mandatory methodologically outcome as key performance indicator in RCT studies (eg, exercise performance or health status) we risk ignoring the clinical complexity of rehabilitating and treating patients with COPD with various traits and responses. Thus, further research in the context of composite outcomes is needed.
A limiting factor in this report is the uncertainty of the estimates, which is a result of number of observations and skewed distribution of some variables, such as oxygen use at 62 weeks follow-up. Additionally, we used prefixed upper-limit MIC for some patient reported outcomes. Thus, the numbers of responders may be underestimated or considered as a lower-limit in number of responders.
In conclusion, differences in 6MWD responses between PTR and PR could not be shown. A small difference was found for HADS-A at 10 weeks follow-up in favour of PTR. However, given the uncertainty in the result a large sample size would be needed to elucidate the specific proportions and possible differences between PTR and PR.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Ethics committee of the capital region of Denmark (h-15019380) and the Danish Data Protection agency (jr. no.: 2012–58–0004) Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We thank the patients for participating in our study. We also thank the departments of respiratory medicine and departments of physiotherapy and occupational therapy for their commitment and for providing the necessary resources for this multicenter project to be completed.
References
Footnotes
Twitter @HansenH03
Contributors Concept and Design of study: HH, NSG, CSU; Acquisition of Data: HH, AT, TK; Analysis of Data: HH, AT, TK; Drafting of Manuscript: HH; Revision of manuscript critically for important intellectual content: all authors; approval of final manuscript: all authors.
Funding AT, TK, CSU and NSG have no competing interests to report in relation to the presented work. HH received personal grants from the Danish Lung Foundation (charitable funding nr.: na), Telemedical Center, Regional Capital Copenhagen (governmental funding nr.: na), TrygFonden Foundation (charitable funding nr.: 111704) during the conduct of this study. The grants covered expenses conducting the trial, salary and university fee for the PhD study.
Competing interests AT, TK, CSU and NSG have no competing interests to report in relation to the presented work. HH received personal grants from the Danish Lung Foundation (charitable funding), Telemedical Center, Regional Capital Copenhagen (governmental funding), TrygFonden Foundation (charitable funding) during the conduct of this study. The grants covered expenses conducting the trial, salary and university fee for the PhD study.
Provenance and peer review Not commissioned; externally peer reviewed.