Directly Observed Therapy to Measure Adherence to Tuberculosis Medication in Observational Research: Protocol for a Prospective Cohort Study.
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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:BACKGROUND:To 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. METHODS:This 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. DISCUSSION:This 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 REGISTRATION:ClinicalTrials.gov, NCT04216420. Registered on 2 January 2020.
| S-EPMC7201596 | biostudies-literature
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.
| S-EPMC6777756 | biostudies-literature
Project description:Purpose of reviewTraditional methods to assess antiretroviral adherence, such as self-report, pill counts, and pharmacy refill data, may be inaccurate in determining actual pill-taking to both antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP). HIV viral loads serve as surrogates of adherence on ART, but loss of virologic control may occur well after decreases in adherence and viral loads are not relevant to PrEP.Recent findingsPharmacologic measures of adherence, electronic adherence monitors, and ingestible electronic pills all serve as more objective metrics of adherence, surpassing self-report in predicting outcomes. Pharmacologic metrics can identify either recent adherence or cumulative adherence. Recent dosing measures include antiretroviral levels in plasma or urine, as well as emtricitabine-triphosphate in dried blood spots (DBS) for those on tenofovir-emtricitabine-based therapy. A urine tenofovir test has recently been developed into a point-of-care test for bedside adherence monitoring. Cumulative adherence metrics assess adherence over weeks to months and include measurement of tenofovir-diphosphate in peripheral blood mononuclear cells or DBS, as well as ART levels in hair. Electronic adherence monitors and ingestible electronic pills can track pill bottle openings or medication ingestion, respectively. New and objective approaches in adherence monitoring can be used to detect nonadherence prior to loss of prevention efficacy or virologic control with PrEP or ART, respectively.
| S-EPMC7363551 | biostudies-literature
Project description:Introduction:Nonadherence to treatment remains an obstacle to tuberculosis (TB) control worldwide. The aim of this study was to evaluate the feasibility of using video directly observed therapy (VDOT) for supporting TB treatment adherence in Uganda. Methods:From May to December 2018, we conducted a pilot cohort study at a TB clinic in Kampala City. We enrolled patients aged 18-65?years with ?3?months remaining of their TB treatment. Participants were trained to use a smartphone app to record videos of medication intake and submit them to a secured system. Trained health workers logged into the system to watch the submitted videos. The primary outcome was adherence measured as the fraction of expected doses observed (FEDO). In a secondary analysis, we examined differences in FEDO by sex, age, phone ownership, duration of follow-up, reasons for missed videos and patients' satisfaction at study exit. Results:Of 52 patients enrolled, 50 were analysed. 28 (56%) were male, the mean age was 31?years (range 19-50?years) and 35 (70%) owned smartphones. Of the 5150 videos expected, 4231 (82.2%) were received. The median FEDO was 85% (interquartile range 66%-94%) and this significantly differed by follow-up duration. Phone malfunction, uncharged battery and VDOT app malfunctions were the commonest reasons for missed videos. 92% of patients reported being very satisfied with using VDOT. Conclusion:VDOT was feasible and acceptable for monitoring and supporting TB treatment. It resulted in high levels of adherence, suggesting that digital technology holds promise in improving patient monitoring in Uganda.
| S-EPMC7132038 | biostudies-literature
Project description:ObjectiveMedication non-adherence is a widespread problem and has been known to be associated with worse health outcomes and increased healthcare costs. Although many measures of adherence have been developed, their usage is not consistent across studies. Furthermore, statistical methods for analyzing adherence measures have not been rigorously evaluated.MethodsUsing Proportion of Days Covered (PDC), a commonly used adherence measure, we examine the variability inherent to study inclusion criteria and several variations of the PDC calculation method using a motivating data example. We illustrated via sensitivity analyses the potential for flawed inference when modeling PDC as an outcome measure. We also performed simulation studies to investigate the statistical properties of three statistical models: logistic regression, negative binomial, and ordinal logistic regression models.ResultsOur sensitivity analysis showed that parameter estimates can vary greatly depending on the rules for determining the study end date in calculating PDC, or the minimum number of fills in defining the cohort. In simulation studies, logistic regression had lower power than ordinal logistic and negative binomial regression models. Naivete to treatment was an important predictor of adherence and omitting it from statistical models can lead to inflated type I errors.ConclusionsWe discourage dichotomizing adherence data as it results in low power. The negative binomial model offers advantages in modeling adherence data, as it avoids the problematic use of a ratio in regression models. The ordinal logistic regression is robust to distributional assumptions with greater power, but naivete to treatment should be adjusted to reserve type I error rate. We also provide a recommendation for defining the observation window in calculating PDC.
| S-EPMC7886011 | biostudies-literature
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.
| S-EPMC8028094 | biostudies-literature
Project description:Tuberculosis is a major public health concern resulting in high rates of morbidity and mortality worldwide, particularly in low- and middle-income countries. Tuberculosis requires a long and intensive course of treatment. Thus, various approaches, including patient empowerment, education and counselling sessions, and involvement of family members and community workers, have been suggested for improving treatment adherence and outcome. The current randomized controlled trial aims to evaluate the effectiveness over usual care of an innovative multicomponent people-centered tuberculosis-care strategy in Armenia.Innovative Approach to Tuberculosis care in Armenia is an open-label, stratified cluster randomized controlled trial with two parallel arms. Tuberculosis outpatient centers are the clusters assigned to intervention and control arms. Drug-sensitive tuberculosis patients in the continuation phase of treatment in the intervention arm and their family members participate in a short educational and counselling session to raise their knowledge, decrease tuberculosis-related stigma, and enhance treatment adherence. Patients receive the required medications for one week during the weekly visits to the tuberculosis outpatient centers. Additionally, patients receive daily Short Message Service (SMS) reminders to take their medications and daily phone calls to assure adherence and monitoring of treatment potential side effects. Control-arm patients follow the World Health Organization--recommended directly observed treatment strategy, including daily visits to tuberculosis outpatient centers for drug-intake. The primary outcome is physician-reported treatment outcome. Patients' knowledge, depression, quality of life, within-family tuberculosis-related stigma, family social support, and self-reported adherence to tuberculosis treatment are secondary outcomes.Improved adherence and tuberculosis treatment outcomes can strengthen tuberculosis control and thereby forestall tuberculosis and multidrug resistant tuberculosis epidemics. Positive findings on effectiveness of this innovative tuberculosis treatment people-centered approach will support its adoption in countries with similar healthcare and economic profiles.ClinicalTrials.gov registration number: NCT02082340. Date of registration: 4 March 2014.
| S-EPMC4479352 | biostudies-literature
Project description:IntroductionHealth-related quality of life (HRQOL) has become an important measure to identify and shape effective and patient-relevant healthcare interventions innovations through outcomes. Adherence to tuberculosis (TB) treatment is a public health concern. The main objective of this research is to develop a study design for evaluation of HRQOL and its association with medication adherence in TB in South Africa.MethodologyA conceptual framework for HRQOL in TB has been developed to identify Patient-Reported Outcomes and Quality of Life Database (PROQOLID), (n.d.) measures for HRQOL and adherence and to generate an endpoint model. Two generic (SF-12 and EQ-5D-5L), one disease-specific (St. George's Respiratory Questionnaire) and one condition-specific (Hospital Anxiety and Depression Scale) measure for HRQOL and Morisky Medication Adherence Scale for adherence assessment were identified. All measures are applied in a longitudinal multi-center study at five data collection time points during standard TB treatment. Statistical analysis includes multivariable analysis. Change over time in the physical component score of SF-12 is defined as primary endpoint. Sample size estimation based thereupon has led to a recruitment target of 96 patients. This study is on-going.DiscussionThis is the first longitudinal study in South Africa which evaluates HRQOL and its association with medication adherence in TB in a comprehensive manner. Results will help to improve current treatment programs and medication adherence and will support the identification of sustainable health innovations in TB, determining the value of new products, and supporting decision making with regard to health policy and pricing.
| S-EPMC4886690 | biostudies-literature
Project description:IntroductionIn heart transplant recipients (HTRs), non-adherence (NA) to immunosuppressive (IS) medication and to recommended lifestyle behaviours are a common phenomenon and associated with higher risk of allograft rejection, organ loss and mortality. Risk factors for NA are highly diverse and still insufficiently researched. Precise measures of NA and an accurate understanding of its aetiology are of undisputable importance to detect patients at risk and intervene accordingly. The aim of this study is to assess the accuracy and concordance of different measures for NA as well as to determine potential risk factors.Methods and analysisThis is a single-centre prospective observational trial. HTRs who are at least aged 18 are no less than 6 months post-transplant and receive tacrolimus (Prograf or Advagraf), cyclosporine (Sandimmun) or everolimus (Certican) as their prescribed IS medication are eligible for participation. We only include patients during the phase of medication implementation. At study enrolment, we assess depression, health-related quality of life, self-efficacy, social support, attachment, experiences and attitudes towards IS medication, emotional responses after transplantation, satisfaction with information about IS medication and perceptions and beliefs about medications. We further ask patients to rate their lifestyle behaviours concerning alcohol, smoking, diet, physical activity, sun protection and appointment keeping via questionnaires. Three different measurement methods for NA are applied at T0: self-reports, physician's estimates and IS trough levels. NA is monitored prospectively using an electronic multicompartment pillbox (MEMS, VAICA) over a 3-month period. Meanwhile, participants receive phone calls every second week to obtain additional self-reports, resulting in a total of seven measurement points.Ethics and disseminationThe study was approved by the Clinical Ethics Committee of the University Hospital Erlangen (Friedrich-Alexander-University, Erlangen-Nürnberg). Written informed consent is attained from all participants. The results of this study will be published in peer-reviewed journals and presented at conferences.Trial registration numberDRKS00020496.
| S-EPMC7542932 | biostudies-literature
Project description:BackgroundMedication adherence is important in managing the progression of chronic diseases. A promising approach to reduce cognitive burden when measuring medication adherence lies in the use of computer-adaptive tests (CATs) or in the development of shorter patient-reported outcome measures (PROMs). However, the lack of an item bank currently hampers this progress.ObjectiveWe aim to develop an item bank to measure general medication adherence.MethodsUsing the preferred reporting items for systematic review and meta-analysis (PRISMA), articles published before October 2019 were retrieved from PubMed, Embase, CINAHL, the Cochrane Library, and Web of Science. Items from existing PROMs were classified and selected ("binned" and "winnowed") according to standards published by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cooperative Group.ResultsA total of 126 unique PROMs were identified from 213 studies in 48 countries. Items from the literature review (47 PROMs with 579 items for which permission has been obtained) underwent binning and winnowing. This resulted in 421 candidate items (77 extent of adherence and 344 reasons for adherence).ConclusionsWe developed an item bank for measuring general medication adherence using items from validated PROMs. This will allow researchers to create new PROMs from selected items and provide the foundation to develop CATs.
| S-EPMC7582150 | biostudies-literature