Methods
HRQoL Instruments
The Duke Health Profile (DHP) is a generic health-related quality of life (HRQoL)
instrument. It is a brief self-report instrument with good acceptability [198,214]. The DHP has 17 questions that form 10 domains. Six of the 10 domains refer to health function (higher scores indicate better health status): physical health (5 items), mental health (5 items), social health (5 items), general health (combining the 15 items used for the physical, mental and social health dimensions to indicate overall well-being), perceived health (single item) and self-esteem (5 of the items used for the mental and social health domains). The remaining four domains refer to health dysfunction (higher scores indicate poorer health status): anxiety (6 of the items used for general health), depression (5 of the items used for physical and mental health), pain (single item used for physical health) and disability (single item). Each question has 3 possible responses scored as 0, 1 or 2. Responses to the constituent items in each domain are added and the mean of the raw scores is normalized to lie on scale of 0 to 100. In reporting the results of this study, the scores for anxiety, depression, pain and disability were subtracted from 100 so the scale ranged from 0 (poorest health) to 100 (best possible health) for each of the 10 dimensions. Prior to use, the DHP was translated and back-translated. This version has previously been validated among healthy adolescents in Viet Nam [212].
The EQ-5D instrument is a standardized measure of health status developed by the EuroQoL Group in order to provide a simple, generic measure of health for clinical and economic appraisal [220-222]. Applicable to a wide range of health conditions and treatments, it
provides a simple descriptive profile and a single index value for health status. The version of the EQ-5D used in this study was the EQ-5D-3L. It contains the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). The descriptive system comprises 5
components: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each component has 3 response levels: no problems (0), some problems (1), and inability or extreme problems (2). The respondent is asked to indicate his/her health state by marking the box against the most appropriate statement in respect of each of the 5 components. The EQ VAS requires a respondent to record their self-rated health on a visual analogue scale with the endpoints labelled as “Best imaginable health state” and “Worst imaginable health state”. Statistical Analysis
The ten dimensions of the DHP were coded and calculated according to the manual [214]. To calculate an EQ-5D utility score, the components were weighted and summed using weights for the South Korean general population [296] in the absence of a value set specific for the population of Viet Nam.
Inter-method comparisons were undertaken to assess convergent validity by calculating rank correlations between the DHP dimension scores and EQ-5D component scores, overall score or EQ-VAS scores. Patterns of departure between the scores from each instrument were assessed by visual inspection of Bland Altman plots. For this purpose, the score from each
153 instrument was standardized by subtracting the mean of its scores from the instrument and dividing by the standard deviation of all scores from that instrument. Linear regression methods were used to investigate whether the differences between standardized scores varied systematically with study factors such as sex, age and severity of stroke severity of disability at admission, severity of disability at 3 month follow up and type of stroke.
Results
Characteristics of the total cohort
Characteristics of the 108 participants (66 participants from the cohort study) in the validation study are summarized in Table 6.1. The remaining 315 subjects, in the cohort of 381,
included 54.9% (173/315) males and with mean age at time of diagnosis of 58.3 (SD 12.8) years for males and 64.7 (SD 14.4) years for females. Ischemic stroke accounted for 76.5% (241/315) of their diagnoses, 41.5% (127/306) had severe impairment at admission, 73.2% (229/315) had severe disability at admission and 43.2% (134/313) had severe disability at three months. In these key respects, the participants in the validation study and non-
participants were generally alike. Characteristics of 94 caregivers are summarized in Table A6.1.
Table A6.1: Characteristics of caregivers who participated in the study.
Characteristics % (n/N)
Age: Mean(SD) 48.3 (12.1)
Female sex 77.0% (67/87)
Relationship with patients
Spouse 41.8% (38/91)
Children 41.8% (38/91)
Siblings 6.6% (6/91)
Parents 2.2% (2/91)
Others 7.6% (7/91)
Assessment of HRQOL made with EQ-5D
The assessments of HRQoL made with EQ-5D are also shown in Table A6.2. The overall scores were slightly greater (indicating better HRQoL) for males than for females, and decreased with age (r = –0.33), severity of disability at admission (r = –0.45), severity of impairment at admission (r = –0.45) and severity of disability at three months (r = –0.83). Contrary to the results for DHP, they were slightly greater for patients with ICH than for patients with IS. The scores on individual components mirrored the associations with the overall score. With higher scores reflecting poorer HRQoL, the component scores were slightly greater for females but none of the differences by sex reached statistical significance. Consistent with those for EQ-5D, the EQ-5D visual analogue scale (EQ-VAS) scores were slightly greater (indicating better health) for patients with ICH than for patients with IS (p = 0.72). The VAS scores were greater on average (p = 0.40) for men [65.7 (SD 17.9)] than for women [62.3 (SD 23.7)], and decreased with age (r = –0.06), and with severity of impairment at admission (r = –0.19), severity of disability at admission (r = –0.18) and at three months (r = –0.49).
154 Table A6.2:EQ-5D domains, utility score and visual analogue scale (VAS).
Male (N=55) Female (N=53) % (n/N) % (n/N) Mobility No problem 45.5 (25/55) 34.0 (18/53) Some problem 41.8 (23/55) 56.6 (30/53) Extreme problem 12.7 (7/55) 9.4 (5/53) Self-care No problem 61.8 (34/55) 54.7 (29/53) Some problem 9.1 (5/55) 22.6 (12/53) Extreme problem 29.1 (16/55) 22.6 (12/53) Usual activity No problem 46.3 (25/54) 41.5 (22/53) Some problem 25.9 (14/54) 26.4 (14/53) Extreme problem 27.8 (15/54) 32.1 (17/53) Pain/Discomfort No problem 47.3 (26/55) 43.4 (23/53) Some problem 50.9 (28/55) 49.1 (26/53) Extreme problem 1.8 (1/55) 7.6 (4/53) Anxiety/Depression No problem 56.4 (31/55) 54.7 (29/53) Some problem 40.0 (22/55) 37.7 (20/53) Extreme problem 3.6 (2/55) 7.6 (4/53)
Utility score: Mean (SD*) 0.68 (0.30) 0.67 (0.30)
VAS: Mean (SD*) 65.7 (17.9) 62.3 (23.7
* Standard Deviation
Test and retest reliability of EQ-5D
Additional findings of rank correlation of patient-proxy difference on assessments of DHP dimensions with study factors were shown in Table A6.3, Table A6.4 and Table A6.5 contains the results for the components of the EQ-5D, its overall score, and the EQ-VAS. Consistent with the re-test measurements made using the DHP, the assessments of HRQoL using the EQ-5D were generally higher on the second occasion. For the EQ-5D utility score, the mean difference of 0.01 (SD 0.04) was significantly greater than zero (p = 0.02). The component score with the greatest mean difference was anxiety/depression (p = 0.11). After weighting, however, the greatest contributor to the mean difference in EQ-5D overall scores was usual activities (p = 0.18), ahead of anxiety/depression (p = 0.36). The change in usual activities occurred because six (an unusually large number) of the most severely-affected patients reassessed their capacity to perform usual activities from 3 (“I am unable to perform my usual activities”) to 2 (“I have some problems with performing my usual activities”) on the
second occasion. On each of the component items, and in respect of the overall score (p = 0.17) for which the mean differences were 0.16 (SD 0.50) for men and 0.04 (SD 0.03) for women, the disagreements were principally due to men upgrading their assessment of HRQoL on the second occasion.
155 Table A6.3: Rank correlation of patient-proxy difference on assessments of DHP dimensions with study factors.
The DHP dimensions
PH MH SH Per SE Anx Dep AD Pain Dis GH
Patient characteristics
Age 0.17 0.03 0.17 0.15 0.25 0.03 0.11 0.13 -0.02 -0.15 0.22
Female sex 0.15 -0.04 -0.08 -0.03 0.02 0.10 0.06 -0.12 -0.12 0.00 0.07
Severe stroke at admission -0.11 0.00 -0.03 -0.03 -0.03 -0.16 -0.10 -0.14 -0.19 -0.12 -0.13 Severe disability at admission -0.13 -0.13 -0.03 0.15 -0.02 -0.15 -0.23 -0.18 -0.15 -0.15 -0.13 Severe disability at three months -0.03 -0.14 0.13 0.20 0.02 -0.09 -0.18 -0.16 -0.17 -0.08 -0.05 Proxy characteristics
Age 0.15 -0.03 0.05 -0.05 -0.02 -0.02 0.03 -0.04 0.06 -0.04 0.05
Female sex 0.01 -0.01 0.01 0.06 -0.19 -0.11 -0.16 -0.20 -0.03 0.09 -0.13
PH: physical health, MH: mental health, SH: social health, Per: perceived health, SE: self-esteem, Anx: anxiety, Dep: depression, AD: anxiety-depression, Dis: disability, GH: general health.
156 Table A6.4: Test and retest reliability of measurements of HRQoL made one week apart of patient responses to the EQ-5D.
Test Re-test Difference
Mean SD Mean SD Mean SD ICC* SEM† MDD‡
Morbidity 0.094 (0.123) 0.092 (0.129) -0.001 (0.052) 0.915 0.037 0.102
Self-care 0.043 (0.058) 0.041 (0.056) -0.001 (0.024) 0.909 0.017 0.048
Usual activity 0.076 (0.089) 0.068 (0.084) -0.007 (0.052) 0.818 0.037 0.103
Pain/Discomfort 0.025 (0.033) 0.025 (0.033) 0 (0.023) 0.777 0.017 0.046
Anxiety/Depression 0.026 (0.038) 0.027 (0.037) 0.004 (0.042) 0.433 0.030 0.083
EQ-5D overall score 0.676 (0.299) 0.686 (0.304) 0.010 (0.04) 0.989 0.031 0.084
VAS 64.1 20.9 64.7 (18.4) 1.00 (18.8) 0.545 13.20 30.80
* ICC= Intra-class Correlation Coefficient, † SEM= Standard Error of Measurement, ‡ MDD= Minimal Detectable Difference
157 Table A6.5: Percent agreement and weighted Kappa for test-retest measurements
made one week apart of patient responses to the EQ-5D.
EQ-5D components Percent agreement Weighted Kappa
Morbidity 96.3% 0.86
Self-esteem 94.1% 0.86
Usual activity 91.6% 0.80
Pain/discomfort 93.8% 0.65
Anxiety/Depression 87.3% 0.40
The test-retest differences were not influenced strongly by age (r = 0.03), type of stroke (r = 0.20), severity of impairment (r = 0.06), or severity of disability at admission (r = 0.11) and at three months (r = -0.04). Inspection of Bland-Altman plots of difference against average did not reveal systematic patterns in the differences or greater than expected numbers of outlying values. The greatest number of differences (n=35) occurred on re-measurement of anxiety. The intra-class correlation coefficients (ICC) ranged from 0.41 for anxiety to 0.89 for self- care. It was 0.99 for the overall score, in which the component scores are weighted and the penalty for the overwhelmingly most frequent change (moving from 1 = least severely affected to 2 = moderately affected, or conversely) is minor.
Consistent with the measurements made by the DHP and EQ-5D, the EQ-VAS scores on the EQ-5D instrument were generally greater on re-test but the mean difference was small (p = 0.58). The mean differences were almost identical for males (1.02 [SD 16.6]) and females (1.00 [SD 20.8]) and, whilst not influenced strongly by the following factors, decreased with age (r = –0.08), severity of impairment at admission (r= –0.12), severity of disability at admission (r = –0.08) and at three months (r = –0.02). Inspection of Bland-Altman plots of difference against average did not reveal systematic patterns in the differences or greater than expected numbers of outlying values. Reflecting the greater contribution of within-person differences, the ICC was moderate (0.56).
Patient-proxy reliability of EQ-5D
Also shown in Table A6.6 and Table A6.7 are the mean proxy-patient differences for components of the EQ-5D and its overall score, and for the EQ-VAS. The assessments of morbidity (p = 0.16), usual activity (p = 0.06) and pain (p = 0.37) using the EQ-5D were greater on proxy assessment. For all components of EQ-5D, the proxy-patient differences were more extreme when the proxy was a male than when the proxy was a female but these differences were not statistically significant. The proxy-patient differences in self-care (p = 0.01), usual activity (p = 0.01) and EQ-5D overall score (p = 0.01) were associated with age of the patient. For most EQ-5D components, the proxy-patient differences were greater for patients with ischemic stroke and for patients with severe impairment or disability at admission or severe disability after three months.
158 Table A6.6: Patient-proxy reliability of measurements of HRQoL using the EQ-5D.
Test Re-test Difference
Mean SD Mean SD Mean SD ICC* SEM† MDD‡
Morbidity 0.100 (0.130) 0.094 (0.132) -0.006 (0.068) 0.845 0.049 0.134
Self-care 0.459 (0.596) 0.047 (0.059) 0.014 (0.031) 0.854 0.022 0.060
Usual activity 0.084 (0.091) 0.074 (0.088) -0.089 (0.046) 0.855 0.033 0.091
Pain/Discomfort 0.027 (0.035) 0.026 (0.037) -0.001 (0.034) 0.513 0.024 0.067
Anxiety/Depression 0.026 (0.038) 0.029 (0.047) 0.003 (0.039) 0.571 0.027 0.076
EQ-5D overall score 0.66 (0.31) 0.67 (0.32) 0.01 (0.16) 0.858 0.113 0.160
VAS 63.0 (20.5) 62.7 (18.8) -1.40 (18.8) 0.539 13.25 36.74
* ICC= Intra-class Correlation Coefficient, † SEM= Standard Error of Measurement, ‡ MDD= Minimal Detectable Difference
159 Table A6.7: Percent agreement and weighted Kappa for measurements of patient
responses and proxy responses to the EQ-5D.
EQ-5D components Percent agreement Weighted Kappa
Morbidity 95.4% 0.84
Self-esteem 93.3% 0.85
Usual activity 93.0% 0.84
Pain/discomfort 91.0% 0.56
Anxiety/Depression 88.6% 0.51
The proxy-patient differences on EQ-5D were relatively smaller than those on the DHP, and without a consistent pattern but with proxies providing slightly lower HRQoL assessments overall and on the EQ-VAS. The stratified results indicate that, other than by the EQ-VAS, male proxies tend to over-estimate HRQoL relative to patients and/or relative to female proxies (data not shown), and that female proxies tend to underestimate HRQoL relative to patients and/or relative to male proxies (data not shown). The ICC for proxy-patient variation in overall EQ-5D was lower, and the ICC for the anxiety component was higher, but
160