Our study results provide evidence to support the validity of two recently developed generic measures of HRQL, EQ-5D-5L and PROMIS-43, in COPD. The convergent construct validity of the two measures was supported by the moderate to strong correlations between related domains, and between the domain and summary scores of the generic measures and the dyspnea measures. EQ-5D-5L index, EQ-VAS, and two domains of PROMIS (physical function and social roles) had higher RE ratios among the HRQL measures, suggesting that these scores provide greater statistical power (discriminative ability) to capture differences in HRQL in relation to disease severity as measured by lung function.
Level of dyspnea is a strong predictor for health status [31–33]. Both EQ-5D and PROMIS had moderate associations with at least one measure of dyspnea, with the correlations varying across the PROMIS-43 subscales. Our results concur with previous reports that spirometric parameters (% of predicted FEV1), unlike severity of breathlessness, does not correlate well with HRQL [31, 32, 34, 35]. While lung function test with spirometry serves as an important clinical tool to measure the degree of airflow limitation, a number of studies have demonstrated that it provides an incomplete assessment of health burden to the patient, which can include physical and psychosocial functioning. This discernment coincides with the new COPD assessment tool recently proposed by the GOLD, which recommends evaluation of COPD based on not only lung function, but also the assessment of symptoms and exacerbation risk . This also reinforces the importance of evaluating patient-reported outcomes along with clinical measures (e.g., lung function test) when gauging the effect of health interventions.
COPD severity has been shown to influence the degree of physical disability, impairing the ability to perform activities of daily living, and contributing to poor HRQL . Patients with COPD had relatively worse self-rated HRQL in multiple PROMIS domains as compared with individuals without COPD or any condition . The negative impact of COPD is more pronounced on the physical aspect of health than on the mental component . Consistent with the study by Gonzalez-Moro and colleagues , our findings suggest that, in general, physical functioning tends to be affected in all grades of COPD patients while mental health is impaired only in patients at more severe stages. The mean scores of PROMIS domains indicated that physical function, among all the domains measured in the PROMIS, was the aspect of health status most affected by COPD; physical function was considerably impaired even in patients with mild COPD, as the mean domain score of PROMIS physical function in patients with GOLD grade 1 was less than 50 (the mean score of the general population). The mean domain scores of PROMIS anxiety and depression were higher than 50 only in patients with very severe COPD (i.e. GOLD 4).
Evidence on the properties of the EQ-5D-5L is only beginning to emerge. The first paper was a multi-country study by Janssen et al. in 2012 that compared the measurement properties of the 5-level and 3-level EQ-5D, including 342 patients with respiratory disease (COPD or asthma) as one of the eight patient groups with chronic conditions . The 5-level EQ-5D descriptive system (EQ-5D-5L) reduced ceiling effects of the 3-level EQ-5D (EQ-5D-3L) and improved the discriminatory power and convergent validity. In our study, broad use of 4 of the 5 Levels of the EQ-5D-5L suggests that it could provide higher discriminative power than the standard EQ-5D-3L in COPD, although the most severe category appears to be rarely utilized. A previous study showed that EQ-5D-3L index score (both UK and US) failed to differ across COPD severity stages . The mean EQ-5D-5L index score significantly decreases as COPD severity deteriorates, particularly in the advanced stages of disease (Table 3), which may suggest better discriminatory power of EQ-5D-5L than EQ-5D-3L to distinguish COPD patients of different severity. Similar to studies of the EQ-5D-3L in COPD, self-care is the dimension least affected by COPD [39, 40]. In accordance with a study by Punekar et al. , about 80% of COPD patients reported no problems in self-care. As the severity of COPD increased, COPD patients reported more problems with mobility, self-care, and usual activities. However, pain/discomfort and anxiety/depression tended not to differ by disease severity using the EQ-5D-5L or the PROMIS. Our study also suggested that EQ-5D-5L index scores were less able to discriminate among patients with milder disease, i.e. GOLD grades 1 and 2. This is consistent with a previous study by Antonelli-Incalzi et al. who observed that health status dramatically declined when predicted FEV1 was 49% or less (upper limit of GOLD grade 3) . Alternatively, the lack of discrimination between grade 1 and 2 may also suggest that the EQ-5D-5L descriptive system does not entirely address some of the limitations of the three-level EQ-5D , assuming there is a meaningful difference in self-reported health based on GOLD grades 1 and 2. Unlike the EQ-5D index score which is derived based on the five dimensions using population preference weights, the EQ-VAS provides a direct rating of health from the patient’s point of view. Consistent with previous reports , EQ-VAS had a more monotonic relationship with disease severity and better ability to discriminate according to disease severity compared to EQ-5D index.
Among the PROMIS subscales, physical functioning was most strongly associated with disease grades and measures of breathing difficulty and functioning. Only physical function (P-PF), depression (P-D), fatigue (P-F), and social roles (P-SR) varied significantly across COPD grades and the magnitude of differences in the PROMIS scores of depression and fatigue across different GOLD grades were smaller than half of their SD, a commonly used cutoff for interpreting important differences in HRQL scores . Anxiety, sleep, and pain domains of PROMIS, although moderately related to other HRQL measurements and dyspnea scores (mainly FACIT-Dyspnea), did not vary by COPD GOLD grade. The lack of correlation between pain, anxiety, and sleep disturbance and the degree of COPD severity does not preclude the importance of these HRQL parameters in COPD patients. In fact, it has been reported that 35%, 37% and 51% of advanced COPD patients suffer from sleep disturbance, pain and anxiety, respectively, arguably among the most prevalent symptoms associated with advanced COPD . Despite the inability of these domains to discriminate patients with different level of airflow limitation, the domains present convergent validity and it suggests that they may capture patient-reported outcomes other than those associated with spirometry. In addition, the observation that the parameters of physical or physiological measures (dyspnea scores; mobility, self-care and usual activities in EQ-5D-5L; physical function in PROMIS) deteriorate more with the increase in COPD severity, as compared to psychosocial measures (anxiety/depression in EQ-5D-5L; anxiety, depression and social roles in PROMIS), suggests the possibility of adapation and coping mechanisms developed in COPD patients as the disease severity progresses, which is often observed with chronic illnesses and disabling conditions .
EQ-5D and PROMIS, both generic measures of HRQL, are distinctive in several ways. While EQ-5D index and VAS scores both provide summary scores for evaluating general health status as a whole, PROMIS describes different aspect of health status individually using domain scores. The domains of anxiety, depression, and pain are apparently covered by both of the measures, but it is arguable if fatigue (PROMIS) overlaps with pain/discomfort (EQ-5D), as well as the extent of overlap between physical functioning, fatigue, sleep disturbance, or social roles (PROMIS) and mobility, self-care, or usual activities (EQ-5D). EQ-5D index-based scores are generated from societal preferences for health that can be applied to economic evaluations. Although PROMIS-43 does not include global items and was not designed as a preference-based measure as EQ-5D, at least one scoring function is available to convert PROMIS selected domain scores into a single index value by mapping onto the EQ-5D . Comparing to PROMIS, EQ-5D is presumably briefer to administer as it contains 6 items (including VAS) rather than 43, but the PROMIS-43 contains more items in each domain, thereby providing the potential of a higher level of precision and sensitity than EQ-5D. Alternatively, even briefer short-form versions of the PROMIS are available.
This study has several limitations. Since patients did not complete EQ-5D-3L, we could not directly determine whether the EQ-5D-5L improves upon the properties of the EQ-5D-3L in COPD. In addition, longitudinal data are needed to examine and compare the responsiveness of the measures to detect meaningful change following interventions. Lastly, in our study, patients with more severe COPD (GOLD 3 and 4) were younger than those with milder disease, which was contrary to our expectation but may be due to the eligibility of study participation or possibly a survivor effect. The representativeness of patients included in this analysis could also be restricted by the relatively low response rate (36%) for participating in the in-person evaluations. Age is a known factor that could confound the association between HRQL and disease severity . In order to rule out the confounding effect, we also conducted an analysis of covariance (ANCOVA) to control for age when comparing the responses in EQ-5D, PROMIS domain scores, dyspnea measures, and 6MWD among patients with different GOLD grades (data not shown). Similar results (F-statistic and significance level) were found as in Table 3 after controlling for age effect, except that the discriminative ability of 6MWD and PROMIS sleep disturbance (P-SD) to distinguish COPD patients of different severity was improved.