Conceived and designed the experiments: WK PK YT VC SW. Performed the experiments: WK PK YT JY SN WM. Analyzed the data: WK PK. Contributed reagents/materials/analysis tools: WK PK YT. Wrote the paper: WK.
The authors have declared that no competing interests exist.
Health utilities of tuberculosis (TB) patients may be diminished by side effects from medication, prolonged treatment duration, physical effects of the disease itself, and social stigma attached to the disease.
We collected health utility data from Thai patients who were on TB treatment or had been successfully treated for TB for the purpose of economic modeling. Structured questionnaire and EuroQol (EQ-5D) and EuroQol visual analog scale (EQ-VAS) instruments were used as data collection tools. We compared utility of patients with two co-morbidities calculated using multiplicative model (UCAL) with the direct measures and fitted Tobit regression models to examine factors predictive of health utility and to assess difference in health utilities of patients in various medical conditions.
Of 222 patients analyzed, 138 (62%) were male; median age at enrollment was 40 years (interquartile range [IQR], 35–47). Median monthly household income was 6,000 Baht (187 US$; IQR, 4,000–15,000 Baht [125–469 US$]). Concordance correlation coefficient between utilities measured using EQ-5D and EQ-VAS (UEQ-5D and UVAS, respectively) was 0.6. UCAL for HIV-infected TB patients was statistically different from the measured UEQ-5D (p-value<0.01) and UVAS (p-value<0.01). In tobit regression analysis, factors independently predictive of UEQ-5D included age and monthly household income. Patients aged ≥40 years old rated UEQ-5D significantly lower than younger persons. Higher UEQ-5D was significantly associated with higher monthly household income in a dose response fashion. The median UEQ-5D was highest among patients who had been successfully treated for TB and lowest among multi-drug resistant TB (MDR-TB) patients who were on treatment.
UCAL of patients with two co-morbidities overestimated the measured utilities, warranting further research of how best to estimate utilities of patients with such conditions. TB and MDR-TB treatments impacted on patients' self perceived health status. This effect diminished after successful treatment.
Tuberculosis (TB) is a severe, often chronic, lung disease causing nearly nine million illnesses and more than one million deaths each year.
Health systems in Thailand are increasingly cost effective. In an effort to respond better to patients' needs, healthcare providers are integrating services.
Our systematic review showed that data on formal assessment of HRQL in TB patients are rather sparse, particularly in the Thai setting. To date, there were only two studies conducted in Thai populations.
The main purpose of this study was to collect health utility data, using EuroQol 5D (EQ-5D) and EuroQol visual analogue scale (EQ-VAS) instruments from Thai TB patients and those cured or having completed treatment. The data were collected for use in our economic evaluation analysis of screening and diagnostic algorithms for pulmonary TB among HIV-infected patients in Thailand (to be published). In this study, we explored how socio-demographic characteristics and co-morbidity such as HIV infection affect TB patients' health utility and whether health utilities of patients with different medical conditions were different. Further, we examined concordance of health utilities measured using the two instruments. Lastly, we examined how health utility of patients with two morbidities calculated using multiplicative approach (UCAL) differed from the measured utilities.
This study was approved by ethical review committees of Chiang Rai Regional Hospital and Bamrasnaradura Infectious Diseases Institute. Involvement of Centers for Disease Control and Prevention (CDC) investigators in this study was determined not to meet the definition of engagement in human subjects research per U.S. human subjects research regulations and additional review by the CDC institutional review board was not required. All participants had provided written informed consent.
From August to October 2009, we conducted a cross-sectional survey and recruited consecutive patients from respective clinics at Chiang Rai Regional Hospital and Bamrasnaradura Infectious Diseases Institute. These two hospitals were part of our multi-site population-based TB surveillance conducted in six provinces in Thailand and were chosen because they serve a high number of TB, HIV-infected TB, and HIV patients.
At enrollment, trained study nurses administered: 1) structured questionnaire to collect socio-demographic characteristic data, 2) EQ-5D, and 3) EQ-VAS instruments (with permission to use from the developer [the EuroQol Group]) to collect patients' HRQL data. The two instruments are recommended by the Thai Health Technology Assessment Guidelines to be used to value health utility for economic purposes.
The analysis was divided into four parts. First, we described socio-demographic and health characteristics. Second, we calculated EQ-5D utility value (UEQ-5D) by assuming that health utilities were additive and that the health utility of a person declined when his/her health deteriorated.
Third, we fitted tobit regression models to examine associations between socio-demographic characteristics and UEQ-5D and UVAS. We assessed whether there was any difference in health utility scores of patients in different medical conditions. Tobit regression models are designed to estimate linear relationships between variables when there is upper- or lower-censoring in the dependent variable.
During the enrollment period, 223 patients with TB and/or HIV were enrolled in the study. Of these, 222 were analyzed. We excluded MDRTX/HIV from the analysis because there was only one patient in this group. The analytic dataset included 32 TBTX, 11 MDRTX, 32 anyTBC, 49 anyHIV, 49 TBTX/HIV, and 49 anyTBC/HIV. Of the 222 patients, 138 (62%) were male, 128 (58%) were married/cohabitating, and 172 (77%) finished either primary or high school.
All (n = 222) | TBTX (n = 32) | MDRTX (n = 11) | anyTBC (n = 32) | anyHIV (n = 49) | TBTX/HIV (n = 49) | anyTBC/HIV (n = 49) | |
|
|
|
|
|
|
|
|
Mobility | |||||||
No problem | 172 (77) | 21 (66) | 5 (45) | 28 (88) | 41 (84) | 32 (65) | 45 (92) |
Moderate problem | 50 (23) | 11 (34) | 6 (55) | 4 (12) | 8 (16) | 17 (35) | 4 (8) |
Severe problem | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Self care | |||||||
No problem | 210 (95) | 26 (81) | 9 (82) | 32 (100) | 48 (98) | 47 (96) | 48 (98) |
Moderate problem | 12 (5) | 6 (19) | 2 (18) | 0 (0) | 1 (2) | 2 (4) | 1 (2) |
Severe problem | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Usual activities | |||||||
No problem | 161 (73) | 22 (69) | 3 (27) | 29 (91) | 40 (82) | 26 (53) | 41 (84) |
Moderate problem | 57 (26) | 9 (28) | 6 (55) | 3 (9) | 9 (18) | 22 (45) | 8 (16) |
Severe problem | 4 (1.8) | 1 (3) | 2 (18) | 0 (0) | 0 (0) | 1 (2) | 0 (0) |
Pain/discomfort | |||||||
No problem | 95 (43) | 10 (31) | 0 (0) | 18 (56) | 23 (47) | 12 (24) | 32 (65) |
Moderate problem | 122 (55) | 21 (66) | 9 (82) | 14 (44) | 25 (51) | 36 (73) | 17 (35) |
Severe problem | 5 (2) | 1 (3) | 2 (18) | 0 (0) | 1 (2) | 1 (2) | 0 (0) |
Anxiety/depression | |||||||
No problem | 125 (56) | 15 (47) | 3 (27) | 25 (78) | 27 (55) | 23 (47) | 32 (65) |
Moderate problem | 93 (42) | 17 (53) | 7 (64) | 7 (22) | 20 (41) | 26 (53) | 16 (33) |
Severe problem | 4 (2) | 0 (0) | 1 (9) | 0 (0) | 2 (4) | 0 (0) | 1 (2) |
TBTX, TB patients receiving TB treatment; MDRTX, MDR-TB patients receiving MDR-TB treatment; anyTBC, patients who had been successfully treated for TB or MDR-TB for ≥6 months; anyHIV, HIV-infected patients at any stage; TBTX/HIV, HIV-infected TB patients receiving TB treatment; anyTBC/HIV, HIV-infected patients who had been successfully treated for TB or MDR-TB for ≥6 months.
UEQ-5D of the 222 patients ranged from −0.02 to 1.0 (median, 0.7; IQR, 0.6–1.0). One of eight MDRTX (9%) perceived his overall health was worse than death (UEQ-5D, −0.02). This patient was diagnosed with and had been taking medication for MDR-TB for 26 months. By contrast, 7 TBTX (22%), 16 anyTBC (50%), 17 anyHIV (35%), 6 TBTX/HIV (12%), and 27 anyTBC/HIV (55%) perceived they were in full health (UEQ-5D, 1.0).
Patients | TB treatment | % receiving anti-retroviral therapy | N | Health utility by instrument | |||
Median EQ-5D (IQR) | SD | Median EQ-VAS (IQR) | SD | ||||
TB | On TB treatment | Not applicable | 32 | 0.69 (0.57–0.77) | 0.22 | 0.80 (0.70–0.90) | 0.15 |
MDR-TB | On MDR-TB treatment | Not applicable | 11 | 0.51 (0.39–0.73) | 0.21 | 0.60 (0.40–0.80) | 0.25 |
TB or MDR-TB | Cured or completed treatment | Not applicable | 32 | 0.88 (0.67–1.00) | 0.17 | 0.85 (0.80–1.00) | 0.15 |
HIV | Not applicable | 94% | 49 | 0.73 (0.63–1.00) | 0.19 | 0.80 (0.70–0.90) | 0.15 |
TB with HIV | On TB treatment | 55% | 49 | 0.67 (0.57–0.73) | 0.16 | 0.70 (0.60–0.80) | 0.16 |
TB or MDR-TB with HIV | Cured or completed treatment | 100% | 49 | 1.00 (0.69–1.00) | 0.18 | 0.80 (0.70–0.90) | 0.14 |
222 | 0.73 (0.62–1.00) | 0.21 | 0.80 (0.70–0.90) | 0.17 |
TB, tuberculosis; MDR-TB, multi-drug resistant tuberculosis; EQ-5D, EuroQol 5D instrument; EQ-VAS, EuroQol visual analogue scale instrument; IQR, interquartile range; SD, standard deviation.
The UVAS ranged from 0.0 to 1.0 (median, 0.8; IQR, 0.7–0.9).
Concordance correlation coefficient between UEQ-5D and UVAS was 0.6 (95% confidence interval [CI], 0.5–0.7). Twenty-two patients (10%) rated equivalent health utilities on the two instruments. Eighty-six patients (39%) rated UEQ-5D higher than UVAS; 114 patients (51%) rated UEQ-5D lower than UVAS. Bland-Altman plot in
In tobit regression analysis, factors independently predictive of UEQ-5D included age and monthly household income.
Estimates | 95% confidence interval | p-value | ||
Lower | Upper | |||
Patient group | ||||
TBTX | −0.24 | −0.37 | −0.10 | <0.01 |
MDRTX | −0.41 | −0.58 | −0.24 | <0.01 |
anyTBC | ref | ref | ref | |
anyHIV | −0.13 | −0.26 | 0.01 | 0.04 |
TBTX/HIV | −0.27 | −0.39 | −0.15 | <0.01 |
anyTBC/HIV | −0.01 | −0.14 | 0.13 | 0.93 |
Age group (years) | ||||
<40 | ref | ref | ref | |
≥40 | −0.08 | −0.15 | −0.003 | 0.04 |
Monthly household income (Thai Baht) |
||||
<5,000 | ref | ref | ref | |
5,000–9,999 | 0.09 | 0.004 | 0.17 | 0.04 |
10,000–19,999 | 0.13 | 0.03 | 0.23 | 0.01 |
≥20,000 | 0.17 | 0.06 | 0.28 | <0.01 |
TB, tuberculosis; MDR-TB, multi-drug resistant tuberculosis; TBTX, TB patients receiving TB treatment; MDRTX, MDR-TB patients receiving MDR-TB treatment; anyTBC, patients who had been successfully treated for TB or MDR-TB for ≥6 months; anyHIV, HIV-infected patients at any stage; TBTX/HIV, HIV-infected TB patients receiving TB treatment; anyTBC/HIV, HIV-infected patients who had been successfully treated for TB or MDR-TB for ≥6 months; ref, referent group.
*32 Thai Baht = 1 US$.
We found that UEQ-5D were highest in anyTBC, followed by anyTBC/HIV, anyHIV, TBTX, TBTX/HIV, and MDRTX, adjusting for age and monthly household income. With Bonferroni's adjustment, patients could be divided, according to the fitted utilities, into three non-mutually exclusive groups: 1) anyTBC, anyTBC/HIV, anyHIV; 2) anyHIV, TBTX, TBTX/HIV; and 3) TBTX, TBTX/HIV, MDRTX.
The median health utility of 49 TBTX/HIV was relatively high (0.7 for both UEQ-5D and UVAS). UCAL for patients with TB and HIV co-infection (0.8) was statistically different from the measured UEQ-5D (p<0.01), and UVAS (p<0.01). Of the 49 TBTX/HIV, 43 (88%) rated UEQ-5D lower than UCAL. Six (12%) rated UEQ-5D higher than UCAL. None of TBTX/HIV rated UEQ-5D equal to UCAL. Likewise, 31 patients (63%) rated UVAS lower than UCAL. Nine (18%) rated UVAS higher than UCAL. Nine patients (18%) rated UVAS equal to UCAL.
In this study, we found that the Thai language EQ-5D and EQ-VAS instruments could be used for measuring and evaluating health utility in a selected group of TB and HIV patients. Further, patients' age and monthly household income were found to be determinants of UEQ-5D. TB and MDR-TB treatment may impact health utilities of patients receiving such treatment. This effect diminished after successful treatment of the disease. Health utilities of patients with HIV and TB calculated using multiplicative model for two co-morbidities overestimated the directly measured utilities.
To our knowledge, this is the first study that elicited health utility in HIV-infected TB patients and compared health utilities between HIV-infected and HIV-uninfected TB patients. Our study is also the first study demonstrating feasibility of the Thai language EQ-5D and EQ-VAS instruments in measuring health utility in a Thai TB population regardless of HIV-infection. The English versions of the instruments were recommended for use in all groups of patients and the Thai versions have recently been ratified by the EuroQol Group's Translation Committee.
Consistent with previously studies, higher HRQL, the UEQ-5D in our study, was correlated with younger age and higher household income, likely because of better prognosis.
The UEQ-5D and UVAS obtained from this study were in line with other studies which suggested that impaired health utility occurred during TB and MDR-TB treatments.
It is noteworthy that health utilities of persons with two co-morbidities calculated using multiplicative model were overestimated compared to those measured directly using EQ-5D and EQ-VAS. Because co-morbidities are common, this finding warrants further research of how best to estimate utilities of patients with such conditions.
There are a number of limitations in our study. First, enrollment of patients was not done in a random or systematic manner due to operational constraints. As mentioned, socio-demographic and health characteristics of our patients were similar to those in a multi-site population-based TB surveillance system, suggesting interviewed patients may be broadly representative. Second, there was only one MDRTX/HIV enrolled in our study; this patient was subsequently excluded from the analysis because of small sample size. This implies the rarity of this sub-population in Thailand. HRQL in this particular group remains an open question that needs to be addressed by future research in settings where MDRTX/HIV is more prevalent. Further, the required sample size for MDRTX was not met, prompting caution when interpreting data of this particular group of patients. Third, we did not further stratify patients based on sputum smear microscopy results because of the restriction to enrol only patients who had received TB treatment for ≥2 weeks. Some of these patients were expected to have a conversion by the interview time. In India, Dhingra and Rajpal have documented difference in HRQL between smear positive and negative TB patients using a TB-specific instrument.
In resource-limited settings, economic analysis is increasingly carried out to inform practice guidelines, funding decisions, and research initiatives. Utility data collected from our study may be incorporated into cost-effectiveness and cost-utility analyses. These in turn allow TB control strategies to be compared more directly with other public health interventions, with respect to both costs and consequences and whether the interventions are of benefit in relation to HRQL. Our findings also suggest that the EQ-5D and EQ-VAS have discriminative power and are responsive to clinically important changes related to TB treatment.
(DOCX)
We are greatly indebted to all participants in our study. We thank the staff from TB Program of the Thailand Ministry of Public Health - U.S. Centers for Disease Control and Prevention, and staff of the Health Intervention and Technology Assessment Program, Chiang Rai Regional Hospital, and Bamrasnaradura Infectious Diseases Institute for their administrative support.
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of U.S. Centers for Disease Control and Prevention.