Research in context
TB, death, tuberculosis
DRUG-SENSITIVE TUBERCULOSIS, EVENT, RECURRENCE, TUBERCULOSIS

We searched Medline and Embase in December, 2015, for papers published from Jan 1, 2000, to Dec 1, 2015, with no language restrictions, using the terms (“digital pill box*” OR “smart pill box*” OR “SMS” OR “text messag*”) AND “TB” OR “tuberculosis”. We found one systematic review assessing the effect of mobile phone text messaging on treatment adherence used as a proxy for treatment outcomes and development of drug resistance. Four studies (three observational cohort studies and one randomised trial) were included in the review, meta-analysis was not conducted, and the authors concluded that there were mixed findings for the effectiveness of text messaging to promote adherence to tuberculosis treatment. Our previous study in China, published in 2015, reported improved adherence to tuberculosis treatment in patients who received text messaging or smart pill box reminders compared with those who did not. The study was not powered to evaluate treatment outcomes. Since 2019, three studies have reported improved tuberculosis outcomes using digital treatment adherence technologies. A study in Kenya assessed weekly motivational messages, daily text message reminders, an unstructured supplementary service data platform for patients to confirm daily adherence followed by text message and calls from the research team for patients who had not confirmed adherence, and clinic notification of patients with no confirmation for more than 2 days. The intervention reduced the risk of poor treatment outcomes (on-treatment death, loss to follow-up, or treatment failure) by 68%, entirely through reducing loss to follow-up. A stepped-wedge trial in Uganda assessed a text-message-based intervention, where patients received daily text message dosing reminders and were asked to confirm a dose taken using a toll-free phone number. Adherence data were reviewed at clinics visits every 2 weeks or monthly and resulted in differentiated management. The authors showed improved successful treatment outcomes (defined as cured or completed treatment) with the intervention, although only among a per-protocol population (which included 97% of patients in the control phase and 52% in the intervention phase) who enrolled within the first 2 months of treatment. In Peru, a per-protocol analysis of an individually randomised trial showed higher treatment success (cured or completed treatment) among patients who had a real-time medication event reminder monitor versus those who received standard of care. A systematic review in 2022 reported variable effects of digital adherence technologies on tuberculosis treatment outcomes.
To our knowledge, this is the first trial to evaluate the effect of a digital adherence technology intervention (smart pill box reminder, monthly review of adherence data, and differentiated care for patients with adherence issues) on a composite outcome of death, loss to follow-up, treatment failure, or subsequent retreatment including culture-confirmed recurrence, among patients with drug-sensitive tuberculosis. We found that the intervention was not adequate to influence poor treatment outcomes, in particular loss to follow-up or tuberculosis recurrence. There was a failure to change patient management following identification of non-adherence at the monthly reviews. We did, however, show a reduction in treatment non-adherence in the intervention group compared with the standard of care group, similar to in our previous study, indicating that the smart pill box intervention improved treatment adherence.
There is no strong evidence that digital adherence technology interventions improve treatment outcomes, including incidence of tuberculosis recurrence, among patients with drug-sensitive tuberculosis. More frequent review of adherence data, with a streamlined approach for identifying patients with adherence issues and escalating supportive management of these patients, might be key to improving tuberculosis treatment outcomes.Digital adherence technologies, including SMS and electronic pill boxes, which support patients in their adherence to treatment, have the potential to enhance patient care through improving interactions between patients and health-care providers, and improving treatment adherence and outcomes.Three studies have shown improved tuberculosis treatment outcomes with digital adherence technologies. An individually randomised trial in Kenya showed a reduction in poor outcomes (on-treatment death, loss to follow-up, or treatment failure), mainly through reducing loss to follow-up, when using SMS reminders and an unstructured supplementary service data intervention.We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes.