Measuring Tuberculosis Medication Adherence: A Comparison of Multiple Approaches in Relation to Urine Isoniazid Metabolite Testing Within a Cohort Study in India

Abstract

Background. Nonadherence to tuberculosis medications is associated with poor outcomes. However, measuring adherence in practice is challenging. In this study, we evaluated the accuracy of multiple tuberculosis adherence measures. Methods. We enrolled adult Indians with drug-susceptible tuberculosis who were monitored using 99DOTS, a cellphone-based technology. During an unannounced home visit with each participant, we assessed adherence using a pill estimate, 4-day dose recall, a last missed dose question, and urine isoniazid metabolite testing. We estimated the area under the receiver operating characteristic curve (AUC) for each alternate measure in comparison to urine testing. 99DOTS data were analyzed using patient-reported doses alone and patient- and provider-reported doses, the latter reflecting how 99DOTS is implemented in practice. We assessed each measure's operating characteristics, with particular interest in specificity-that is, the percentage of participants detected as being nonadherent by each alternate measure, among those who were nonadherent by urine testing. Results. Compared with urine testing, alternate measures had the following characteristics: 99DOTS patient-reported doses alone (area under the curve [AUC], 0.65; specificity, 70%; 95% CI, 58%-81%), 99DOTS patient- and provider-reported doses (AUC, 0.61; specificity, 33%; 95% CI, 22%-45%), pill estimate (AUC, 0.55; specificity, 21%; 95% CI, 12%-32%), 4-day recall (AUC, 0.60; specificity, 23%; 95% CI, 14%-34%), and last missed dose question (AUC, 0.65; specificity, 52%; 95% CI, 40%-63%). Conclusions. Alternate measures missed detecting at least 30% of people who were nonadherent by urine testing. The last missed dose question performed similarly to 99DOTS using patient-reported doses alone. Tuberculosis programs should evaluate the feasibility of integrating more accurate, objective measures, such as urine testing, into routine care.