Directly Observed Therapy (DOT) is universally recommended to ensure Mycobacterium Tuberculosis Complex (TB) treatment adherence. DOT is resource intensive, intrusive and expensive, limiting implementation in high burden areas. Mobile technologies to confirm medication adherence have emerged recently. However, technology validation and comparison to the existing DOT Gold Standard is lacking. FDA approved Wirelessly Observed Therapy (WOT) is the first digital technology to detect medication ingestion and provide a stand-alone system to track TB medication adherence. WOT consists of an edible ingestion sensor (IS), external wearable patch and paired mobile device, it time-and-date stamps ingestions; recordings are uploaded to a secure Internet server, for remote viewing. We have previously ‘digitized’ fixed-dose Isoniazid/Rifampin (IS-INH/RIF) by co-encapsulation with IS (see doi:10.1002/cpt.760) and have validated WOT ingestion detection accuracy using IS-INH/RIF as 98.4% (CI 97.5-99%). We now report findings from a randomized controlled trial performed in highly funded US DOT programs comparing the proficiency of WOT and DOT to confirm TB medication adherence.
Sixty-one subjects with active MTB in the continuation phase of treatment were randomized 2:1 to receive WOT using IS-INH/RIF or standard of care DOT (5 days per week). In the WOT arm, if ingestions were not remotely confirmed, the subject was contacted within 24-48 hrs. The number of doses taken confirmed by DOT versus WOT were collected, length of observation varied according to treatment prescribed. The percentage of prescribed doses that were confirmed by DOT or WOT was calculated separately for each arm, using 7 and 5 days a week comparisons. Wilcoxon rank sum test was used to compare arms.
The subjects’ demographics were: mean age 41.9 years, 54% male, 77% reported income < $2000/month, 61% GED or less education. Duration of observation in days was Mean (SD) 97.1 (44.8), DOT 95 (30.1), WOT 98.1 (50.8). Table 1 shows the percentage of confirmed/prescribed doses for DOT and WOT analyzed at the group and individual subject level. WOT associated adverse events were skin rash and pruritus (10%).
WOT remotely confirmed a significantly greater percentage of prescribed doses than DOT over both 7 and 5 day analysis periods within highly funded US TB DOT programs. WOT is highly accurate and was a superior alternative to DOT for confirming adherence to TB medication in the continuation phase of treatment.