RESULTS (1) 50 patients were enrolled: 62% male, mean age 42 yrs, 76% completed primary education only, 4% HIV-positive; 27% of HIV-positives on antiretroviral.

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RESULTS (1) 50 patients were enrolled: 62% male, mean age 42 yrs, 76% completed primary education only, 4% HIV-positive; 27% of HIV-positives on antiretroviral treatment 7/50 patients had no formal treatment supporter despite being on community-based DOT 37 completed TB treatment, 6 died, 3 defaulted and 4 dropped out of the study MEMS adherence rates: In all patients, mean MEMS adherence was 96.3%, SD 7.7% Among all patients, 70% were <100% adherent, 21% were < 95% adherent and 2% were <80% No difference in MEMS adherence was found between those with and without a treatment supporter (p=0.79, independent -samples T-test) ELECTRONIC MONITORING TO ASSESS ADHERENCE AND VALIDATE ALTERNATIVE ADHERENCE MEASURES IN TUBERCULOSIS PATIENTS ON COMMUNITY-BASED DIRECTLY OBSERVED TREATMENT Jossy van den Boogaard 1,2, Ramsey Lyimo 2, Martin Boeree 1, Gibson Kibiki 2, Rob Aarnoutse 1 1 Radboud University Nijmegen Medical Centre, The Netherlands; 2 Kilimanjaro Christian Medical Centre, Tanzania ABSTRACT Problem statement: Community-based Directly Observed Treatment (DOT) can be an effective strategy to improve adherence to tuberculosis (TB) treatment in settings where facility-based DOT is causing overburdened healthcare facilities. However, the strategy may lead to irregular drug intake in practice. This is difficult to prove in the absence of a simple and valid adherence measure. Objectives: We assessed adherence rates of TB patients on community-based DOT by using the Medication Event Monitoring System (MEMS bottles), and we used MEMS as a reference standard to determine the validity of alternative adherence measures. Design and setting: This was a longitudinal study among outpatients attending four public TB clinics in Tanzania’s Kilimanjaro Region. The Tanzanian TB programme allows patients to choose between facility- and community-based DOT. Patients on community-based DOT have to select a treatment supporter (usually a relative or spouse) who should provide DOT in the home setting. Study population: Adult TB patients who presented with newly diagnosed TB between February and May 2010 and who had chosen for community-based DOT were eligible to participate. Fifty patients were enrolled; 37 completed treatment, six died, three defaulted and four dropped out. Outcome measures: MEMS data was used to calculate adherence rates by dividing the number of days on which at least one bottle opening was registered by the total number of monitored days, multiplied by 100%. Adherence rate cut-off values of 100% and 95% were used to differentiate between adherence and non-adherence, and to determine the validity and accuracy of the test measures. The test measures included a urine test for isoniazid, urine colour test for rifampicin, Morisky scale, Brief Medication Questionnaire (BMQ), adapted version of the AIDS Clinical Trials Group (ACTG) adherence questionnaire, pill counts and clinic attendance for medication refills. Results: Adherence rates ranged from 50.0 to 100% (median 98.4%) in all patients, and from 89.3 to 100% (median 98.4%) in the patients who completed treatment. In the latter group, 70% of patients were less than 100% adherent and 19% less than 95%. The ACTG questionnaire and urine colour test had the highest sensitivity (70-100%) but lowest specificity (20-37%) for detecting non-adherence, and the Morisky scale and clinic attendance the highest specificity (80-100%) but lowest sensitivity (14-35%). The sensitivity of the routinely used combination of pill counts and clinic attendance improved when the ACTG questionnaire was added. Conclusions: The high adherence rates suggest that the Tanzanian model of community-based DOT can be an effective strategy to prevent non- adherence. Studies in patient populations with a wider range of adherence rates are needed to confirm the validity of (combinations of) adherence measures that are feasible for use in resource-limited settings. Funding: This study was financially supported by KNCV Tuberculosis Foundation (the Netherlands). RESULTS (3) Table 1. Sensitivity, specificity and accuracy of adherence measures to differentiate between adherent (= at least 95% adherent according to MEMS) and non-adherent patients RESULTS (4) The combination of pill counts and refill visits that is used in routine practice had moderate sensitivity and specificity Sensitivity of routine combination improved when an adherence questionnaire was added Adherence questionnaires have the additional advantage that they provide information about perceived facilitators of and barriers to adherence STUDY LIMITATIONS Adherence rates in this study could have been biased due to study participation. However, other studies suggest that the ‘interventional effect’ by MEMS ceases when used for months. The small sample size does not allow for firm conclusions with regard to the effectiveness of community- based DOT Due to the generally high adherence rates found in this study, only adherence rate cut-off values of 95% and 100% could be applied CONCLUSIONS This is the first study in which MEMS was used to assess adherence in community-based DOT during the full 6-months TB treatment High adherence rates were observed in a Tanzanian population, not confirming the concern that patients on community-based DOT are prone to non-adherence. However, community-based DOT was turned into self-administered treatment by some patients Supplementing pill counts and clinic attendance with a third measure such as the ACTG questionnaire, helps to identify potentially non-adherent patients who could benefit from tailored adherence-promoting interventions RESEARCH AND POLICY IMPLICATIONS Community-based DOT seems to be an effective alternative in settings where facility-based DOT is causing overburdened healthcare facilities Additional research in larger patient populations is needed to confirm this finding The combination of pill counts, clinic attendance and an adherence questionnaire can be a useful tool to monitor adherence of patients on community-based DOT Additional research is needed to confirm the sensitivity and specificity of this and other combinations of adherence measures that are feasible to use in resource limited settings BACKGROUND Active TB is the second leading cause of death from infectious diseases worldwide, causing 1.6 million deaths every year Non-adherence to TB treatment is a major barrier to global TB control WHO’s solution of Directly Observed Treatment (facility-based DOT) is causing overburdened healthcare facilities worldwide Involvement of community members in the provision of DOT is an alternative, but adherence under community-based DOT is unknown and this strategy may need monitoring by adherence measures Medication Event Monitoring System (MEMS) bottles can be used to validate other simple and affordable adherence measures METHODS (2) MEMS adherence rate cut-off values of 100% and 95% were used to differentiate between adherence and non-adherence and to calculate sensitivity, specificity and accuracy of the test measures OBJECTIVES To assess adherence rates of TB patients on community-based DOT by direct and indirect adherence measures To determine the validity of other locally feasible adherence measures with MEMS as the reference standard METHODS (1) Longitudinal study among 50 adult TB outpatients on community- based DOT in Tanzania’s Kilimanjaro Region Adherence to once-daily TB drugs was assessed throughout 6 months TB treatment Patients filled a questionnaire about MEMS use at completion of treatment. Pocket dosing (taking out medication for later use) as identified by this questionnaire was excluded from analysis RESULTS (2) Figure 1. Non-adherence to TB treatment of patients who completed treatment (n=37), assessed by the different test measures MeasureWhen applied Indirect MEMSContinuously Drug refill visitsEvery week in first 2 months; Every 2 weeks in last 4 months Pill countsEvery week / every two weeks Morisky scaleWeek 4, Brief Medication Questionnaire (BMQ)Week 4, 8, 12 Adapted AIDS Clinical Trials Group (ACTG) questionnaireWeek 16 Direct Urine colour test for rifampicinWeek 4, 8, 12, 16 Urine test for isoniazidWeek 4, 8, 12, 16 SensitivitySpecificityAccuracy Drug refill visits Pill counts Morisky scale BMQ ACTG questionnaire Urine colour test INH urine test Refill visits + pill count Refill visits + pill count + ACTG Refill visits + pill count + urine colour test Refill visits + pill count + BMQ Refill visits + pill count + INH urine test Refill visits + pill count + Morisky scale This study was financially supported by the ‘Netherlands-African partnership for capacity development and clinical interventions against poverty-related diseases’ (NACCAP/EDCTP) and by the KNCV Tuberculosis Foundation, The Netherlands