This is a cohort study using quantitative data collection methodologies to evaluate the acceptability of the EMM among health care workers and patients. A self-administered questionnaire was used to assess health care workers’ acceptance of the device in relation to its operation, usefulness, and effect on their workload. Acceptability among patients was assessed based on the proportion of eligible patients who chose to use EMM and the factors associated with this choice, as well as the proportion who switched to DOT and the associated factors.
Zhenjiang City in Jiangsu Province was purposively selected for the study. The city has well-established TB control and prevention services, with sufficient human resource capacity. In addition, in the 3 years prior to the study, approximately 1200 active pulmonary TB cases were detected annually and notified in the TB information management system (TBIMS), allowing the study to be implemented quickly to provide results prior to scale-up. Zhenjiang is located in eastern China, has four designated TB hospitals, and has a total population of about 3 million .
Each active TB case was tested using Cepheid’s GeneXpert® system to identify drug resistance, and all the patients were treated with standard short-course chemotherapy for 6 to 8 months according to China’s national TB control program guidelines, using once-daily fixed-dose combination (FDC) tablets produced by a single manufacturer.
All the health care workers (four physicians and five nurses) from designated hospitals who were responsible for EMM use were surveyed through the use of self-administered questionnaires. Respondents sent the questionnaires anonymously to a designated email address, and the research group promised to not give the results to their direct superiors. In addition, the research group looked for differences in the total number of patient visits by community physicians depending on whether patients were using DOT or the EMM.
Patient enrollment and withdrawal
Study participants who met the following criteria were enrolled in the study: active pulmonary TB patient notified between October 1, 2017, and January 31, 2018; receiving daily outpatient treatment; and having no communication impairment (mental, visual, auditory, or speech). The study excluded rifampicin-resistant patients and patients not being treated locally.
All eligible patients were advised to use the EMM by physicians at the designated TB hospitals but verbal consent was required. If patients consent to use EMM, they were required to sign a consent form later by the community physicians at the first home visit. If patients refused to use the EMM, the physicians would record the reasons. If patients stopped using the EMM midway through the study, the physicians would also record the reasons.
The EMM was designed to monitor treatment adherence throughout a one-month FDC regimen. The device components include a plastic box and an electronic module. The electronic module can be reused for at least three patient cycles (each patient being treated for up to 6 or 8 months), and use by each patient costs approximately US$5.
Nurses programmed the study devices to provide a medication reminder at the same time each day for each TB patient, at a time selected by the patient. The EMM recorded each time the patient opened the device, indicating the patient had taken his or her medication, and clinicians accessed the data from the EMM management system while the device was connected to a computer. TB patients were required to visit a designated hospital monthly for follow-up examination, review of their EMM data and treatment adherence by a physician, and collection of the next month’s anti-TB drugs. Based on the previous month’s medication adherence data, if < 20% doses were missed, the patient was counselled. If 20 to 49% of doses were missed, the frequency of home visits by village doctors was increased (once every 7 days for the rest of the treatment). And if 20 to 49% of doses were missed twice, or ≥ 50% of doses were missed once, then the patient was transitioned to DOT for the remainder of treatment .
Community physicians were required to visit patients enrolled in the EMM study once every 10 days during the intensive phase (the first 2 months of treatment) and once a month in the continuation phase to check on their health status and monitor EMM usage. A reading on a small LED screen in the EMM displayed the regularity with which the patient took his or her doses. In addition, the EMM data were regularly uploaded to the online EMM information management system (EMMIMS) by county-designated hospital staff so health care workers at all levels could query the medication adherence of TB patients within their jurisdiction.
Data management and analysis
Case data were collected from all TB patients notified in the electronic TBIMS from October 1, 2017, to January 31, 2018. Data were collected on variables such as TBIMS code for basic management unit (BMU) (the hospitals which are established at the county level in China, in contrast to TB management units, which are established at the provincial, prefecture and county levels), registration number, sex, age, occupation, migrant status, treatment type (new or retreated), bacteriological results (bacteriologically confirmed or clinically diagnosed), and the treatment initiation date. Patients’ TBIMS data were matched to the EMMIMS, where uploaded case data were also collected from October 1, 2017, to January 31, 2018, including variables such as TBIMS code for BMU, registration number, sex, age, date of EMM initiation, date of EMM completion, missed doses, and days the patient should have taken medication. The two systems could be matched by the TBIMS code for BMU and registration number. Other variables, including reasons for declining or discontinuing use of the EMM, were collected from medical records by the research team.
A database was constructed and cleaned with Microsoft Excel, and analysis was conducted using SPSS version 19. The proportions of patients who were eligible for EMM use, who used the EMM, and who stopped using the EMM midway through the study were calculated. And among patients who used the EMM and who completed treatment, the average percentage of doses taken was calculated. Unadjusted and adjusted odds ratios (0.95 CI) were calculated using log binomial regression to summarize (infer) factors associated with a patient’s refusal to use the EMM at enrollment. Unadjusted and adjusted odds ratio (0.95 CI) were also calculated using log binomial regression to summarize (infer) factors associated with patients who were switched to DOT due to poor adherence. Age, sex, occupation, migrant status, treatment category, and diagnosis classification were considered in the model regardless of the unadjusted p value.
The workload of community physicians was evaluated by assessing the number of patient visits. In the DOT management program, the community physicians are required to visit a new TB patient 180 times (daily visits for 6 months) and a retreated TB patient 240 times (daily visits for 8 months). However, under the EMM management program, the physician visits are reduced to 10 visits for a new TB patient and 12 visits for a retreated TB patient (once every 10 days during the intensive phase followed by once per month in the continuation phase). If a patient is switched to the DOT program, the physician’s visits must revert back to the daily visits upon ceasing use of the EMM.
All the physicians and nurses received a detailed implementation standard operating procedure and were trained by the research team. Onsite technical support was conducted quarterly, and questions were addressed through social media networking platforms (WeChat) within 24 h.