COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD

Discussion

A novel multicomponent home-based COPD disease management intervention across four European countries did not achieve a statistically significant difference in the predefined primary outcome, although patients in the DM group had 23% fewer all-cause hospitalisation days than patients in the UM group. Acute care hospitalisation days in the PP population, BODE index scores at 12 months, and the overall mortality rate, were all statistically significantly lower in the DM group than in the UM group. However, as these were supportive or secondary outcomes intended to support the interpretation of the primary outcome, and mortality was a safety outcome, these results should be considered with caution.

To date, the results of COPD self-management interventions in clinical trials have been inconsistent [26], which has created ambiguity regarding self-management interventions and has discouraged their implementation in clinical practice. Recently, a group of experts reached a consensus regarding a conceptual definition of COPD self-management: “A COPD self-management intervention is structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their health behaviour(s) and develop skills to better manage their disease” [19]. In retrospect, COMET nevertheless applied many of these concepts and included quality control to optimise delivery of the self-management component. Two-thirds to 90% of the DM group patients received at least 80% of the planned number of coaching sessions, or were 80% compliant with the weekly phone calls to transmit health status, and most acquired disease management skills. Training and education of COPD patients is necessary but insufficient, and behaviour must be modified successfully to realise tangible benefits [22, 26].

Although there appeared to be a study-group effect in many supportive hospitalisation outcomes, a number of factors likely contributed to the lack of statistical significance. Approximately one-half of the patients had no hospitalisations and less than half of the hospitalisation days were due to COPD exacerbation, both of which were unexpected given the high COPD severity and the high proportion of patients on LTOT and/or HMV. Hospitalisations due to COPD exacerbations were slightly higher in the DM group, which could be explained by the slightly, but not significantly, higher mean number of severe exacerbations in the DM group. Statistical power was based on a difference of 10 unplanned hospitalisation days between groups with a standard deviation of 25 days; however, the actual difference was only 5.2 days, with standard deviations >35 days. This was probably because hospitalisation rates and hospitalisation days differed widely across the four countries owing to country-specific differences in patient baseline characteristics, hospitalisation practices, admission criteria, resource and bed availability, and healthcare reimbursement programmes. For example, the countries differ substantially in hospital bed availability, which is lowest in Spain (297 beds/100 000 inhabitants) and highest in Germany (823 beds/100 000 inhabitants) [27]. This also correlated roughly with hospitalisation days per year (supplementary table E1). It is also possible that we overestimated the hospitalisation risk of this patient population and that a statistically significant difference between groups could have been realised had we enrolled patients with a higher risk of hospitalisation, owing either to comorbidities or to greater COPD severity. Nevertheless, as a consequence of this unforeseen low hospitalisation rate, COMET was statistically underpowered to detect a significant difference in unplanned hospitalisation days, and a larger sample size would have been necessary to compensate for such variability across countries. These factors should be carefully considered in designing future studies of COPD interventions.

The 12-month mortality rate was significantly and markedly lower in the DM group (1.9%) than in the UM group (14.2%), the latter of which is consistent with, or lower than, the 12-month mortality rates of 12.5% [28], 16.8% [29], 21% [30] and >23% [31] that have been reported previously for COPD patients following a hospitalisation for an acute exacerbation of COPD. That mortality was lower than expected in the DM group, rather than excessively high in the UM group, suggests that the disease management intervention reduced mortality. This may be because most of the deaths (56%) in the UM control arm were due to COPD exacerbations. It is possible that the disease management intervention reduced mortality by successfully optimising the self-management of exacerbations, leading to early and prompt treatment, which could have prevented additional complications, including death. The home monitoring aspect of the intervention may have also contributed to the success of the intervention by providing a means of rapidly communicating symptoms and disease severity variables to case managers, which may have shortened the time from the beginning of an exacerbation to the institution of appropriate therapy.

Mortality was carefully monitored as a safety outcome in COMET because the disease management intervention was implemented in patients with severe COPD, many of whom had multiple comorbidities and were at high risk of death. Indeed, a prior study by Fan et al. [15] was stopped owing to excess mortality in the self-management group. The COMET disease management intervention was substantively different than that used by Fan et al. [15]. COMET focused on: close patient–physician communication; prompt recognition of exacerbations by regular transmission of symptoms through an e-health system; thorough training and monitoring of case managers, who were followed for quality improvement for the duration of the study; and physicians who maintained responsibility for all medication decisions [21]. By contrast, and as a consequence of the study being conducted at US Veterans Administration hospitals, where healthcare resources may be limited, patients in the Fan et al. [15] study were responsible for much of their own care decisions. Although patients were instructed to call in if they needed to start medications for exacerbations, calls were made by only 4.5%. Furthermore, assessment of exacerbation was done by professionals who may not be experienced in managing this type of patient.

All study deaths in COMET were closely reviewed by the sponsor and the EVC. Although such a large apparent difference in mortality between study groups could have warranted interruption of the study, such a large final reduction in mortality was not expected in COMET, especially since the mortality rate in the usual management arm was not excessive. Additionally, many of the patients who died did so near the end of their first year of follow-up, when most patients had nearly completed the study. Patients who died tended to have a high BODE index and to record high numbers of hospitalisation days during the study, both of which are recognised predictors of mortality in COPD patients [32–34].

The strengths of this study included the use and adaptation of a self-management programme previously demonstrated to be clinically beneficial rather than a new programme. The COMET disease management programme may thus provide a basis for future self-management interventions or for designing studies to evaluate such interventions. Particular attention was given to patient coaching by healthcare professionals (case managers) aimed at optimising self-management through a 4-day training that included a specific focus on motivational communication, continuous access to programme resources (programme objectives, interventions, suggested questions, expected results), and feedback achieved through monthly telephone contacts with a pneumologist from the coordinating study centre in each country. Novel aspects of the disease management intervention included an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Another strength was the international design of COMET, which was the first study to specifically address a disease management intervention for severe COPD, delivered by centrally trained and supported case managers, across four countries with different medical practices and healthcare systems. Lastly, although the trial was open-designed, hospitalisations were rigorously and blindly reviewed by the EVC and followed-up with additional enquiries if necessary, ensuring the reliability of the outcomes.

The study has some limitations. The inclusion of days spent in acute care wards, as well as subsequent stays in nursing facilities in the primary outcome, may have been suboptimal. Stays in nursing facilities are sometimes extended beyond a clear medical need for hospitalisation, which might have influenced the results. However, the EVC reviewed all stays longer than 30 days and these were removed from the EVC analysis, if warranted. Additionally, the two groups contained similar numbers of patients with very long stays (figure 3). Acute care hospitalisations alone might be considered more appropriate and less subjective, better reflecting immediate patient needs than resource availability or local reimbursement practices. Indeed, acute care hospitalisations appeared to be a more sensitive indicator of hospitalisation needs in COMET, but as the study was not specifically designed to measure this outcome as the primary end-point, these results have limited value. Despite case managers receiving formal training prior to study initiation and being supported throughout the study as part of the quality assurance, there was no quantifiable measure to confirm the quality of intervention delivery. However, the quality assurance used in the study was considered realistic and practical for a real-life disease management programme. Despite the use of three stratification factors to promote the allocation of balanced study groups, differences among countries in baseline characteristics and hospitalisation days were not avoided. These factors, coupled with the site- and country-specific differences in routine care, may have reduced the likelihood of detecting significant differences in many study outcomes. The open design of the study, though necessary owing to the extensive differences between the two disease management programmes, may have led to some bias because doctors could have had a tendency to discharge patients in the disease management arm earlier than those in the usual management arm.

In conclusion, although unplanned annual hospitalisation days tended to be lower in the DM group than in the UM group, the reduction in hospitalisation was statistically significant only for acute care hospitalisation days in patients who received at least 25% of their planned coaching sessions. One apparent benefit of the disease management intervention was a marked and statistically significant reduction in mortality in which most deaths in the usual management control group resulted from acute exacerbations. The disease management programme may have promoted earlier appropriate treatment for exacerbations, which could have prevented some fatal complications. However, this result should be considered informational because mortality was a safety outcome rather than a primary outcome. Forthcoming medical-economic analyses may also reveal the cost-effectiveness and cost–utility benefits of the disease management intervention. This international study supports the feasibility of a multicomponent home-based disease management intervention in severe COPD patients (many being on LTOT), and demonstrated that most patients adhered to the intervention. However, patient needs and self-management skills at programme entry could be more carefully assessed and followed over time for subsequent programme tailoring. Some very severe patients presenting with severe comorbidities should be clearly identified as they may not be able to fully implement the programme and thus benefit from it. Lastly, the characteristics of the healthcare systems and healthcare coordination need to be carefully considered in studies of multicomponent disease management interventions.