Tuberculosis (TB) is a severe, often chronic, lung disease causing nearly nine million illnesses and more than one million deaths each year. [1] With appropriate treatment, approximately 90% of patients with active TB disease can be cured, even in patients with HIV infection. [2], [3] Despite the discovery of the first TB drug over 50 years ago, current treatment regimens for susceptible TB still require the use of a combination of potentially toxic antibiotics for a minimum of six months to ensure eradication. [4], [5] For multi-drug resistant TB (MDR-TB), available regimens are less potent (but more noxious), requiring longer treatment durations. [6], [7], [8] As such, patients' health-related quality of life (HRQL), i.e., valued aspects of life, may be diminished by side effects from medication, prolonged treatment duration, and in some cultures, social stigma attached to the disease. [9], [10], [11] TB disease itself may also have a negative impact on TB patients' self perceived health status. [12], [13]

Health systems in Thailand are increasingly cost effective. In an effort to respond better to patients' needs, healthcare providers are integrating services. [14], [15], [16] Economic and decision analyses are frequently conducted to inform resource allocation decisions. HRQL data are widely recognized as an important input in such exercises, particularly for chronic diseases. [17] HRQL can be derived using generic and specific instruments. [9] Generic instruments collect descriptive data and generate health utilities: preference-based, numeric representations of overall health that are the most commonly used measures for evaluating HRQL in economic analyses. [18] While health utilities, as input in cost-utility analyses, allow comparison between populations and across diseases, settings, and countries, information generated from specific instruments focus on problems associated with single disease states, patient groups, or areas of function and do not allow broad comparison. [9], [18], [19]

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. [20], [21] The first study administered a generic instrument (Medical Outcomes Study 36-Item Short-From Health Survey) to measure HRQL among 84 pulmonary TB patients in Yunnan province of China and Southern Thailand. [20] Findings of this study, however, were published in Chinese, compromising dissemination of the results to non-Chinese speaking researchers. In 2008, Kittikraisak et al. conducted a prospective observational study to evaluate the impact of TB and HIV treatment on HRQL among 849 TB patients in Thailand. This study, however, focused on the patients who were HIV-infected and used a study specific questionnaire to collect HRQL data. [21] The investigators found impairment in physical and mental health when Thai HIV-infected patients studied were first diagnosed with TB. Additionally, completing TB treatment relieved some physical symptoms, but had little impact on mental health. Data, however, cannot be used for economic modeling purposes because neither generic nor specific instruments were employed to collect data. With increasing interest in identifying cost-effective interventions that are responsive to patients' needs, HRQL data collected using standardized instruments are urgently needed.

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 (U_CAL) differed from the measured utilities.

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 U_EQ-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. [34], [35] Both instruments could identify differences in health utilities among patients with different medical conditions. In this study, more than half were elderly or adults with co-morbidity who had finished basic schooling. All successfully completed the study task using the EQ-5D and EQ-VAS. We believe that this would not be possible with the original English language self-administered instruments. It should be noted that assistance from study personnel was only to read questions on instruments to participants who had difficulty reading. Color-coded supplemental tool was used to help participants who had trouble remembering answer choices. Further, a study by Puhan et al has documented that administration formats do not have a meaningful effect on repeated measurements of patient-reported HRQL outcomes. [36] While our study was conducted among a sample of TB patients, the socio-demographic and health characteristics of our population were similar to those of the population-based TB surveillance network in Thailand. This suggests our findings may be generalisable to the wider Thai TB population. [22], [37]

Consistent with previously studies, higher HRQL, the U_EQ-5D in our study, was correlated with younger age and higher household income, likely because of better prognosis. [12], [38], [39], [40] Yet, we did not find significant associations between sex, education, health insurance coverage, and HRQL as found in other studies or any predictor for U_VAS. [39], [41] This may be due to different characteristics of the populations studied. Our population was out-patients receiving services at hospitals and more than 90% were covered by health insurance. In contrast, those in Duyan's study were hospitalized TB patients with low levels of education and no social insurance coverage. [39] Additionally, those in both Duyan's and Nyamathi's studies reported insufficient housing conditions. [39], [41]

The U_EQ-5D and U_VAS obtained from this study were in line with other studies which suggested that impaired health utility occurred during TB and MDR-TB treatments. [21], [38], [42] Nearly half of our TB patients were still in the intensive phase of TB treatment, making them more prone to disutility. Moreover, 63% of MDR-TB had been on treatment for more than six months with one patient being on treatment for more than two years. This finding together with those from our previous study suggests that provision of a more holistic approach to medical care not limited only to HIV and TB treatment may be beneficial to the patients. [21] Interventions focusing on symptom management and coordination of care may help relieve symptoms and improve patients' ability to tolerate medical treatment as well as help them gain the strength to carry on with daily life. In this study, we also found that improved health utility after TB treatment was more pronounced in HIV-infected patients than those uninfected in nearly all domains. This is likely due to relief of some TB symptoms and adverse events from HIV and TB drug interactions. [21], [43] Our study did not measure markers of disease progression (e.g., CD4+ T-lymphocyte) among those HIV-infected. Nonetheless, studies have reported that HIV-infected patients with or without AIDS appeared to have similar levels of HRQL in the era of highly active ART. This could likely be explained by the effectiveness of medication in reversing the progression of disease in individuals with AIDS and accommodation to the stress of living with the disease. [44], [45] In fact, over 80% of HIV-infected patients in our study were receiving ART and were among those whose U_EQ-5D were highest. This finding implies that ART delivery in the public sector of Thai healthcare system may have an impact not only on patients' survival as has been found in other studies, but also HRQL and ability to function in society. [46], [47], [48]

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 MDR_TX/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 MDR_TX/HIV is more prevalent. Further, the required sample size for MDR_TX 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. [49] We were unable to investigate if this difference existed in our study. Fourth, screening for active TB among our HIV-infected patients may not have been optimal. It is possible that some patients may have had undiagnosed TB, resulting in misclassification. However, patients in our study were routinely asked if they had coughed along with other symptoms. This information was passed to attending physicians. Therefore, we believe that number of undiagnosed TB should be small. Lastly, as for other HRQL instruments, the EQ-5D and EQ-VAS reflect patients' opinions. Different individuals assign different values to the same health state, and consequently vary in their preferences. Further, as pointed out by Aghakhani et al, the overall responses to the EQ-5D instrument (which has three possible answers) may be forced to the mid-range category because few patients endorse the ‘severe’ value and some limitation is often present. This possibly results in diverting responses away from the ‘no limitation’ option. [50] The EQ-5D has been critiqued as less sensitive than disease-specific measurements resulting in possible overestimation of patients' HRQL. Nonetheless, because one of the study goals was to identify utility values that could be used for economic modelling in the future, the ability to compare across diseases outweighed the sensitivity concerns.

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.