Ingestible sensor could revolutionise TB treatment

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An ingestible sensor that enables health workers to check that patients have taken their medication could revolutionise tuberculosis treatment, particularly in developing countries, The Daily Telegraph reports researchers believe.

New ways to ensure TB patients comply with their treatment are desperately needed. The report says patients with the most straightforward form of the deadly infectious disease have to take a cocktail of drugs over a six-month period – and if they fail to stick to the regime, they risk the disease returning in a drug-resistant form.

In the study, patients in California were given a standard TB drug alongside an “edible” sensor, coated with minerals. When ingested, the sensor communicates with a patch attached to the patient’s torso that in turn sends a message to a mobile phone. The data is then automatically uploaded to a secure, centralised computer for a health worker to check.

To avoid high treatment drop-out rates it is recommended that patients take their medication under the supervision of a health worker in a procedure called directly observed therapy (DOT). But, the report says, this is time consuming – requiring a health worker to visit the patient at work or home or vice versa – as well as costly and inconvenient.

But this new “wireless observed therapy” (WOT) avoids the need for daily visits and enables the patient to take the drugs in private and at a time that suits them.

Some 77 patients, who were no longer infectious but still needed to finish their course of treatment, took part in the study, carried out by researchers at the University of California – San Diego (UCSD).

The study showed that WOT had a 99.3% accuracy rate in recording adherence to treatment and all those patients on the wireless therapy wanted to continue with it after the trial had ended. All finished treatment and were cured of TB.

Sara Browne, lead author of the study and associate professor of infectious diseases at the UCSD, said the ingestible sensor gave patients more autonomy. “The system allows patients to determine how they want to take their pills with minimum interference. It preserves the highest standards of privacy but it also enables the health system to focus on people who need the most support,” she said.

According to the report, the researchers believe that WOT has great potential in Africa, where mobile technology is rapidly spreading. The Californian patients were given smartphones but Browne said that the technology would also work with more straightforward devices.

Abstract
Background: Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment.

Methods and findings: We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2–3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18–80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [−1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course.
Conclusions: In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs.

Authors
Sara H Browne, Anya Umlauf, Amanda J Tucker, Julie Low, Kathleen Moser, Jonathan Gonzalez Garcia, Charles A Peloquin, Terrence Blaschke, Florin Vaida, Constance A Benson

The Daily Telegraph report PLOS Medicine abstract

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