An Evaluation of Traditional Directly Observed Therapy (DOT) and Electronic DOT for TB Treatment

Tuberculosis (TB) is among the most common infectious diseases and cause of death worldwide. The bacteria that causes TB, Mycobacterium tuberculosis (Mtb), is spread when a person with TB disease of the lungs or throat coughs, speaks, or sings. These bacteria can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB bacteria can become infected.

The World Health Organization (WHO) estimates that 9.6 million became ill with TB in 2014. Among this group, approximately 480,000 persons became ill with multidrug-resistant TB (MDR TB), which is TB caused by bacteria that are resistant to at least isoniazid and rifampin, the two most potent TB drugs used to treat persons with TB disease. Extensively drug resistant (XDR) strains of TB were reported by 105 countries in 2015. As such, the National Strategy for Combatting Antibiotic Resistant Bacteria (CARB) has designated Mtb a SERIOUS threat level pathogen.

Completion of treatment by persons with TB disease represents the optimal path to the prevention of morbidity and mortality, cure of the patient, interruption of transmission, and prevention of acquired drug resistance. The single best intervention in this regard has proven to be directly observed therapy (DOT).

DOT provides frequent interactions between the patient and the patient's healthcare team. This enables better monitoring and efficient response to medication side effects. This is especially important as medication side effects are among the top reasons patients are lost to follow-up during treatment therapy.

Experience in the U.S. in the 1990s demonstrated the efficacy of this intervention in the prevention and control of drug-resistant tuberculosis.Studies in the past 15 years in international settings have challenged the utility of DOT, but have been criticized for imperfect to poor design or implementation.

DOT entails a trained "observer" acceptable to both the patient and the health system being present to monitor treatment adherence as patients swallow anti-TB drugs. In the United States, DOT remains a cornerstone of TB control. While DOT represents the treatment standard, the implementation of DOT has been modified by some programs in an effort to reduce costs and conserve program resources. In the U.S., efforts recently have sought to utilize advances in communication technology to facilitate the implementation of DOT.

This study will evaluate traditional approaches to DOT compared to DOT by electronic methods. The study will be based within, and primarily conducted by the New York City Department of Health and Mental Hygiene (NYC DOHMH), Bureau of Tuberculosis Control (BTBC) clinics. This will enable the study to be to be conducted in a programmatic setting and reflect "real-life" situations.

Hypothesis: Directly observed therapy (DOT) that employs electronic communication methods (eDOT) is a non-inferior approach to monitor treatment adherence, compared to traditional forms of DOT, in which a trained person is in the physical presence of patients as anti-TB drugs are ingested (ipDOT).

Design: This will be a U.S.-based, 1 site (with 4 clinic settings), randomized, cross-over, 2-arm, non-inferiority trial with randomization to either traditional in-person DOT (ipDOT) or electronic DOT (eDOT)*, at the time outpatient treatment begins within participating health department clinics.

*Secondary analyses will evaluate DOT conducted in "real time" or "live" (eDOT-live) compared to DOT that uses a recorded video (eDOT-recorded).

Population:Patients newly diagnosed with drug-sensitive or non-rifamycin resistant TB.

Site: Four clinics of the New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control.

Study Duration: Duration per participant is approximately 6 months.

Description of Intervention: After providing written informed consent, participants will be randomly assigned to one of the following DOT study group assignments: (1) traditional in-person DOT (ipDOT) or (2) electronic DOT (eDOT).

Note: Patients and their providers will discuss and choose the type of eDOT they will use. The two options are: (2a) eDOT conducted "live" in which TB program staff interact with patients in real-time via a computer or phone application as they ingest their medication (eDOT-live), and (2b) eDOT in which patients record themselves ingesting their TB medication using "time-stamped, recorded" videos for TB program staff to review within 1 business day (24 hours), and verify that patients ingested their medication doses as scheduled (eDOT-recorded).

Following 20 observable medication doses under an initial DOT study group assignment participants will be assigned (crossed-over) to the opposite DOT method to collect data on another 20 observable medication doses. Specifically, participants who initially received ipDOT will switch to eDOT. Participants initially assigned to eDOT will switch to ipDOT.

At the conclusion of this Cross-Over Period with 40 observable medication doses, participants will continue treatment using their preferred DOT method.