Dataset Information

Directly Observed Therapy to Measure Adherence to Tuberculosis Medication in Observational Research: Protocol for a Prospective Cohort Study.

ABSTRACT:

Background

A major challenge for prospective, clinical tuberculosis (TB) research is accurately defining a metric for measuring medication adherence.

Objective

We aimed to design a method to capture directly observed therapy (DOT) via mobile health carried out by community workers. The program was created specifically to measure TB medication adherence for a prospective TB cohort in Western Cape Province, South Africa.

Methods

Community workers collect daily adherence data on mobile smartphones. Participant-level adherence, program-level adherence, and program function are systematically monitored to assess DOT program implementation. A data dashboard allows for regular visualization of indicators. Numerous design elements aim to prevent or limit data falsification and ensure study data integrity.

Results

The cohort study is ongoing and data collection is in progress. Enrollment began on May 16, 2017, and as of January 12, 2021, a total of 236 participants were enrolled. Adherence data will be used to analyze the study's primary aims and to investigate adherence as a primary outcome.

Conclusions

The DOT program includes a mobile health application for data collection as well as a monitoring framework and dashboard. This approach has potential to be adapted for other settings to improve the capture of medication adherence in clinical TB research.

Trial registration

Clinicaltrials.gov NCT02840877; https://clinicaltrials.gov/ct2/show/NCT02840877.

SUBMITTER: Ragan EJ

PROVIDER: S-EPMC8277341 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended that countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness of the intervention from the patient and provider perspectives.MethodsThis is a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial. The study is designed to enroll 144 outpatients with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who are eligible to start the standard 6-month first-line anti-TB regimen. Participants in the intervention arm (n = 72) will receive 15 days of HRZE-isoniazid, rifampicin, pyrazinamide, and ethambutol-fixed-dose combination therapy in the evriMED500 medication event reminder monitor device for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits. Providers will handle participants in the control arm (n = 72) according to the standard in-person DOT. Both arms will be followed up throughout the 2-month intensive phase. The primary outcomes will be medication adherence and sputum conversion. Adherence to medication will be calculated as the proportion of patients who missed doses in the intervention (pill count) versus DOT (direct observation) arms, confirmed further by IsoScreen urine isoniazid test and a self-report of adherence on eight-item Morisky Medication Adherence Scale. Sputum conversion is defined as the proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase BACTEC MGIT TB liquid culture. Pre-post treatment MGIT drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion. Secondary outcomes will include other clinical outcomes (treatment not completed, death, or loss to follow-up), cost-effectiveness-individual and societal costs with quality-adjusted life years-and acceptability and usability of the intervention by patients and providers.DiscussionThis study will be the first in Ethiopia, and of the first three in sub-Saharan Africa, to determine whether electronic pillbox-enabled SAT improves adherence to TB medication and treatment outcomes, all without affecting the inherent dignity and economic wellbeing of patients with TB.Trial registrationClinicalTrials.gov, NCT04216420. Registered on 2 January 2020.

Project description: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.Trial registration: ClinicalTrials.gov NCT01960257.

Project description:BackgroundTuberculosis (TB) remains one of the most common infectious diseases worldwide. Although TB is curable provided the treatment commenced quickly, appropriately and uninterrupted throughout TB treatment duration. However, high default rate, treatment interruption and therapy non-adherence coupled with inadequate disease knowledge significantly contribute to poor TB treatment outcome, especially in developing countries. This study therefore assessed knowledge about TB and possible reasons for treatment non-adherence among drug-sensitive TB (DS-TB) patients, as well as evaluated treatment outcomes for the DS-TB managed within a 5-year period.MethodsA mixed-method design comprising a cross-sectional questionnaire-guided survey among 140-ambulatory DS-TB patients from January-March 2019, and a retrospective review of medical-records of DS-TB managed from 2013 to 2017 in two WHO-certified TB directly-observed-treatment centres. Data were summarized using descriptive statistics, while categorical variables were evaluated with Chi-square at p < 0.05.ResultsAmong the prospective DS-TB patients, males were 77(55.0%) and females were 63(45.0%). Most (63;45.0%) belonged to ages 18-34 years. A substantial proportion knew that TB is curable (137;97.9%) and transmittable (128;91.4%), while 107(46.1%) accurately cited coughing without covering the mouth as a principal mode of transmission. Only 10(4.0%) mentioned adherence to TB medications as a measure to prevent transmission. Inaccessibility to healthcare facility (33;55.0%) and pill-burden (10,16.7%) were topmost reasons for TB treatment non-adherence. Of the 2262-DS-TB patients whose treatment outcomes were evaluated, 1211(53.5%) were cured, 580(25.6%) had treatment completed, 240(10.6%) defaulted, 54(2.3%) failed treatment and 177(7.8%) died. Overall, the treatment success rate within the 5-year period ranged from 77.4 to 81.9%.ConclusionsKnowledge about TB among the prospective DS-TB patients is relatively high, especially with respect to modes of TB transmission and preventive measures, but a sizeable number lacks the understanding of ensuring optimal TB medication-adherence to prevent TB transmission. Inaccessibility to healthcare facility largely accounts for treatment non-adherence. Outcomes of treatment within the 5-year period show that nearly half were cured, while almost one-tenth died. Overall treatment success rate is about 12% below the WHO-defined target. There is generally a need for concerned stakeholders to step-up efforts in ensuring consistent TB enlightenment, while improving access to TB care is essential for better treatment outcome.

Project description:BackgroundThe health care system in Thailand has struggled to cope with the COVID-19 pandemic, resulting in decreased administration of community-based directly observed therapy (DOT) for tuberculosis (TB). As an alternative to failed DOT, video-observed therapy (VOT) or the Thai asynchronous VOT system, "TH VOT," was devised. We developed a protocol for a study to test the superiority of VOT over DOT in ensuring treatment compliance.ObjectiveWe aim to compare the mean cumulative compliance days of TB patients and their observers under the VOT program with that of individuals under the DOT program during the intensive phase of TB treatment.MethodsA cluster randomized controlled trial of pulmonary TB patients and their observers will be conducted over a 2-month period. This study will be conducted in the Hat Yai and Meuang Songkhla districts of Songkhla Province, Southern Thailand. A total of 38 observers working at 38 primary care units (PCUs) will be randomized equally into VOT and DOT groups. The TH VOT system will be implemented in 19 PCUs in the VOT group while the other 19 PCUs will continue with the traditional DOT program. Approximately 1-5 TB patients will be under observation, depending on the PCU jurisdiction in which the patients reside. The inclusion criteria for TB patients will be as follows: patients diagnosed with newly active pulmonary TB with a positive acid-fast bacilli sputum smear, aged >18 years, own a smartphone, and are able to use the LINE (Line Corporation) app. The exclusion criteria will be patients with a condition that requires the intervention of a specialist, rifampicin resistance according to a cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF), unable to continue the treatment, and/or alcohol dependence. After the 2-month observation period, all sessions and follow-up clinical outcomes recorded will be retrieved. An intention-to-treat analysis will be performed to assess the compliance of both patients undergoing drug administration and their observers.ResultsThe Human Research Ethics Committee, Faculty of Medicine, Prince of Songkla University approved the trial on February 19, 2021 (approval number 64-03618-9). The trial was funded in May 2021. The recruitment period will be from January 2022 to July 2022. The observation is scheduled to end by September 2022.ConclusionsIf the VOT shows superiority in observational compliance among patients and observers, the existing DOT policy will be replaced with VOT.Trial registrationThai Clinical Trials Registry TCTR20210624002; https://www.thaiclinicaltrials.org/show/TCTR20210624002.International registered report identifier (irrid)DERR1-10.2196/38796.

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Project description:BackgroundMedication adherence plays a critical role in controlling the evolution of chronic disease, as low medication adherence may lead to worse health outcomes, higher mortality, and morbidity. Assessment of their patients' medication adherence by clinicians is essential for avoiding inappropriate therapeutic intensification, associated health care expenditures, and the inappropriate inclusion of patients in time- and resource-consuming educational interventions. In both research and clinical practices the most extensively used measures of medication adherence are patient-reported outcome measures (PROMs), because of their ability to capture subjective dimensions of nonadherence. Machine learning (ML), a subfield of artificial intelligence, uses computer algorithms that automatically improve through experience. In this context, ML tools could efficiently model the complexity of and interactions between multiple patient behaviors that lead to medication adherence.ObjectiveThis study aimed to create and validate a PROM on medication adherence interpreted using an ML approach.MethodsThis cross-sectional, single-center, observational study was carried out a French teaching hospital between 2021 and 2022. Eligible patients must have had at least 1 long-term treatment, medication adherence evaluation other than a questionnaire, the ability to read or understand French, an age older than 18 years, and provided their nonopposition. Included adults responded to an initial version of the PROM composed of 11 items, each item being presented using a 4-point Likert scale. The initial set of items was obtained using a Delphi consensus process. Patients were classified as poorly, moderately, or highly adherent based on the results of a medication adherence assessment standard used in the daily practice of each outpatient unit. An ML-derived decision tree was built by combining the medication adherence status and PROM responses. Sensitivity, specificity, positive and negative predictive values (NPVs), and global accuracy of the final 5-item PROM were evaluated.ResultsWe created an initial 11-item PROM with a 4-point Likert scale using the Delphi process. After item reduction, a decision tree derived from 218 patients including data obtained from the final 5-item PROM allowed patient classification into poorly, moderately, or highly adherent based on item responses. The psychometric properties were 78% (95% CI 40%-96%) sensitivity, 71% (95% CI 53%-85%) specificity, 41% (95% CI 19%-67%) positive predictive values, 93% (95% CI 74%-99%) NPV, and 70% (95% CI 55%-83%) accuracy.ConclusionsWe developed a medication adherence tool based on ML with an excellent NPV. This could allow prioritization processes to avoid referring highly adherent patients to time- and resource-consuming interventions. The decision tree can be easily implemented in computerized prescriber order-entry systems and digital tools in smartphones. External validation of this tool in a study including a larger number of patients with diseases associated with low medication adherence is required to confirm its use in analyzing and assessing the complexity of medication adherence.