Electronic Monitoring of Treatment Adherence and Validation of Alternative Adherence Measures in Tuberculosis Patients: A Pilot study/Suivi Electronique De L'adhesion Au Traitement et Validation De Mesures D'adhesion Alternatives Des Patients Tuberculeux: Une Etude pilote/Control Electronico del Cumplimiento Terapeutico De Pacientes Con Tuberculosis Y Validacion De Medidas Alternativas De Cumplimiento: Estudio Piloto

Introduction Non-adherence to treatment for tuberculosis is a major barrier to global tuberculosis control. To ensure adherence to treatment by tuberculosis patients, the direct observation of treatment by a trained supervisor is recommended. (1) Initially, such directly observed treatment (DOT) was provided in health-care facilities only, but because of workload demands, several countries have started to involve community members in the provision of DOT. (2) Studies have shown that community-based DOT is a cost-effective strategy that yields treatment outcomes similar to those obtained with facility-based DOT. (3-6) However, community-based DOT has been criticized for being beyond the control of health-care providers and hence conducive to self-administered (unsupervised) treatment and non-adherence. (6,7) The actual degree of adherence by patients on community-based DOT has not yet been assessed. Measuring adherence is difficult because most available direct and indirect measures have limitations. Direct adherence measures, such as tests to measure drug levels in plasma or urine, cover brief medication intake periods only. Indirect measures, such as pill counts and self-report questionnaires, cover longer periods but assume rather than prove the patient's actual medication intake. (8) A sophisticated indirect adherence measure is the Medication Event Monitoring System (MEMS). MEMS medication bottles contain a microelectronic chip that registers the date and time of every bottle opening. Assuming that bottle openings represent medication intake, MEMS provides a detailed profile of the patient's adherence behaviour. MEMS is currently regarded as the gold standard to measure adherence, (8) It has been used as such in a wide range of studies on adherence to antihypertensive and lipid-lowering therapy, (9,10) therapy for neurologic and psychiatric disorders, (11,12) post-transplantation immunosuppressive therapy (13,14) and antiretroviral therapy. (15-17) Few studies report on the use of MEMS to monitor adherence to tuberculosis treatment. (18-21) Because of the high cost involved, MEMS is not feasible for use in routine practice in most settings with a high tuberculosis burden but could be used as a reference standard to validate simple and affordable measures that can be used in patients on community-based DOT. (8,21) In this pilot study, we used MEMS to: (i) describe adherence rates among Tanzanian tuberculosis patients on community-based DOT and (ii) determine the validity of several direct and indirect adherence measures of potential use in resource-limited settings. Methods Study setting The study was conducted in the Kilimanjaro region of the United Republic of Tanzania, where the annual tuberculosis case notification rate is 178 per 100 000 population. (6) The national tuberculosis programme empowers patients to choose between community- and facility-based DOT. Most patients opt for community-based DOT and those on facility-based DOT are mostly inpatients. (6) Patients on community-based DOT have to select a treatment supporter from their community (usually a relative or spouse) who is instructed on how to provide daily DOT at home. Patients on community-based DOT are supposed to collect their medication once a week in the first two months of treatment and once every two weeks in the remaining four months. They should return medication blisters for pill counts and their clinic attendance is registered. (22) Study design and procedures This was a longitudinal pilot study in which treatment adherence among 50 patients on community-based DOT was monitored by MEMS throughout treatment. MEMS was used as a gold standard to validate several other adherence measures (single and in combinations) in this patient group. The adherence measures were selected for their applicability in the Tanzanian setting and included an isoniazid (INH) urine test, a urine colour test for rifampicin, the Brief Medication Questionnaire (BMQ), the Morisky scale, an adapted version of the AIDS Clinical Trials Group (ACTG) adherence questionnaire, pill counts and clinic attendance for medication refills. …