Introduction
The global individual and economic burden of cardiovascular disease demands continual innovation of prevention and treatment strategies for effective patient management [
1,
2]. Competition between interventions is accentuated by increasing financial constraints on healthcare resources [
2]. Economic evaluations provide a useful comparative approach for effective and efficient policy and decision-making considering both costs and consequences on patient outcomes [
3,
4].
Cardiac rehabilitation (CR) programs are a standard part of cardiac patient care [
5]. Exercise is recognised as a core component of CR and is provided alone, or within a multidisciplinary program combining risk factor management, behaviour modification and psychosocial support [
6,
7].
For cardiac patients, the cost-effectiveness of CR compared to standard care has been estimated to cost between USD$2000–$28,000 per life-year gained or leading to increased health-related quality of life (HRQL) at a cost of USD$700–$16,000 per quality-adjusted life-year (QALY) gained [
3].
With new CR service-delivery models emerging and healthcare resources becoming more limited, it is timely to reassess the cost-effectiveness of CR-services. Also with the recent development of updated standards for economic evaluations of healthcare interventions, it is necessary to bring the findings of previous reviews [
3,
5] into context with these guidelines as to provide a platform for future studies looking at the cost-effectiveness of CR services to build upon. With that in mind, this systematic review aims to understand how economic evaluations of exercise-based CR are conducted with the following objectives: (i) to review the characteristics of published economic evaluations of exercise-based CR with exercise as the primary outcome of interest; (ii) to evaluate the methodological quality of these CR economic evaluations using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [
8] and (iii) to make recommendations for future economic evaluations of CR services. This descriptive study will inform the quality of future research addressing the cost-effectiveness of exercise rehabilitation interventions.
Discussion
This review assessed how economic evaluations of exercise-based CR programs are conducted and evaluated their methodological quality against the recently published CHEERS guidelines for healthcare interventions [
8]. Exercise was the primary outcome of interest in this review as it has proven health benefits [
25] and is a principal component of CR services; other aspects of CR including psychological or educational interventions were not evaluated.
An extensive literature search identified 15 economic evaluations of exercise-based CR services. In consensus with previous reviews we identified wide variability amongst CR programs and service delivery [
3,
5]. In this review, such variability was particularly evident in study perspective, time horizon, setting, comparators, included costs, and in exercise dose (FITT) between interventions. We critically appraised included evaluations against recently expanded and updated economic guidance, finding that none fully met the reporting criteria; while included studies predated development of this guidance, future studies may wish to adhere to these up-to-date standards [
8].
As most evaluations (10) were RCTs, their meticulous patient selection process will question the wider generalisability of their findings. Comparatively other study types report higher proportions of males (60–89%) and greater CR uptake (64–72%). [
25]. Patients in these RCTs were also younger than the average age distribution for CR participants (67 for men and 70 for women) [
25]. The use of short time horizons (6–24 months) also seems incompatible with a chronic condition. Given the likelihood that patients registering with a controlled trial may be more inclined to adhere to exercise requirements, these elements suggest economic evaluations of exercise-based CR programs using RCT’s risk providing non-generalizable results.
Compared to RCT’s reporting non-conclusive or weak results, evaluations utilising studies with longer time horizons (3.5 – 5 years) suggest a long-term exercise-based CR program results in lower costs [
13,
14], reduced hospitalisations [
13,
14], and longer cumulative lifetime [
21]. Longer follow-up times may allow for more benefits of the intervention to be accrued and suggest that interventions should be carried out with a long-expanding time horizon.
Despite a reported 60–70% of cardiac patients accessing CR services having comorbidities, these patients were largely absent from included studies. This has been recognised and it is estimated that 48% are deemed inappropriate for rehabilitation by their referrer [
25]. In this review most studies failed to report co-morbidities or simply excluded such patients [
11,
12]. The likely presence of comorbidities in the population, particularly in older individuals, questions generalisability of findings, and reflects a missed opportunity for their management.
This review identified extensive heterogeneity between studies in exercise dose (FITT) [
25]. Session frequency ranged from once to four times weekly, exercise intensity was patient dependent or categorised in broad groups (low, moderate or high intensity), and exercise type often involved combinations of aerobic activity (e.g. walking, running, cycling, rowing, arm cranking, dumbbell or weight training). This reflects a lack of knowledge and absence of guidance on the most effective CR exercise program. Standardising CR would allow more accurate economic assessments, although risk eliminating the potential for more cost-effective results to be obtained from patient-dependent CR exercise regimes [
18]. Alternatively, harmonising physical exercise dose into a common standard unit, such as the metabolic equivalent of tasks (METs), would allow for an effective comparison of the very diverse interventions found in the literature [
26,
27].
Generic quality-of-life measures (i.e. QALY) allow a common measure across health conditions to facilitate healthcare resource allocation, but their broad scope fails to capture other health-related benefits outside the dimensions of the questionnaire (mobility, self-care, usual activities, pain/discomfort and anxiety/depression in the EQ-5D). The difficulty associated with measuring exercise is a challenge for such interventions and its effects has been captured elsewhere [
28]. Exercise is known to have far-reaching benefits proven effective at reducing the disease burden of diabetes, osteoarthritis and cancer [
25], however generic HRQL instruments (e.g. EQ-5D and the SF-36) are likely to be insensitive to detecting change brought about by exercise-based CR [
25]. Using more specific outcome measures, such as the change in physical activity level or evaluating the psychology of exercise behaviour (e.g. BREQ questionnaire), will provide a more complete picture of the benefits produced by the interventions and avoid producing inaccurate and misleading cost-effectiveness results. Given many studies found non-significant differences in costs between interventions, differences in health outcomes have the capacity to be the main drivers of cost-effectiveness. Appropriate criteria to detect and measure health impact according to the specific study design must be applied. [
29‐
31].
All studies incorporated direct CR medical costs into their evaluations, but lacked consistency in the types of costs included and would likely result in two evaluations of the same clinical study reporting different cost-effectiveness results. Use of standardised cost categories consistent with the study aims, perspective and nature of exercise is recommended. For exercise-based CR, the cost-savings attributable to reduced cardiovascular events and potential reduction of general healthcare resource use should be reported. Given that several studies found a non-significant difference in health outcomes between interventions, costs are a potential driving force behind cost-effectiveness.
Few studies reported statistically significant evidence in both costs and effects for CR (Table
2). These were predominantly cost-benefit analyses comparing exercise-based CR to no exercise or where the use of exercise was unclear [
21]. Consequently, exercise-based CR was considered cost-saving compared to CR without exercise, and an effective secondary prevention strategy in reducing subsequent cardiac events and re-admissions, and increased survival [
21]. Comparatively, other studies did not find significant evidence identifying any interventions as conclusively cost-effective, and this is likely due to inappropriate use of time horizons, perspective, choice of health outcomes, or cost categories.
Nevertheless, cost-effectiveness results can accurately be non-conclusive. Only two evaluations performed subgroup analysis, finding that interventions were more cost-effective depending on gender and risk of disease progression [
2]. Given expected differences in cost and health effects for patients of different gender, ages, disease severity, and comorbidities, subgroup analysis is recommended to explore heterogeneity of results between relevant patient groups.
When analysing cost-effectiveness estimates for CR evaluations, it is key to consider input uncertainty on results, and observe whether statistical significance or minimally important differences are achieved. Presenting only deterministic results can be misleading and may show the intervention to be highly cost-effective, yet closer scrutiny of the confidence intervals in some cases reveals very limited certainty around the result [
4]. Findings should therefore be reported showing deterministic results of the base case as well as subgroup analyses and measures of uncertainty such as confidence intervals and/or (probabilistic) sensitivity analyses. These will provide a fair representation of findings, statistical significance, achievement of MID, and the potential effect of unknowns on the decision to be made.
These findings provide the basis for the following recommendations for future economic evaluations of CR programs:
(1)
Include comorbid patients.
(2)
Use of longer time-horizons (ideally lifetime) to capture the long-term health and cost-related outcomes of exercise-based CR for chronic cardiovascular-related conditions.
(3)
Develop an effective standardised exercise-based CR program to enhance comparability of health outcomes between studies.
(4)
Develop standardised cost categories consistent with the study perspective to enhance comparability of economic findings between studies, potentially including relevant non-health care costs such as productivity loss.
(5)
Adhere to up-to-date standards for economic evaluations of healthcare interventions.
(6)
Use subgroup analysis to capture the effects of exercise-based CR on different patient groups.
(7)
Use standardised reporting guidelines (e.g. CHEERS) to enhance study comparability.
(8)
Report confidence intervals, outcome measures and MIDs to enhance the quality of methodological reporting.
Crucially, following the above recommendations will allow carers and providers to make better-informed choices about the CR programs most suitable for their specific patient groups or setting, as the particulars of each will bring specific value weights to the various elements of the costs and outcomes associated to specific modalities of CR programs.
Limitations of this review include incomplete retrieval of all economic evaluations of exercise-based CR-services, which may have arisen from the exclusion of some electronic or grey literature sources. As most economic evaluations are published or cited in economic and scientific journals, it is likely these effects will be minimal following an extensive literature search of several online databases.