A mixed methods study (sequential explanatory design) with quantitative-retrospective cohort study through record review and patient interviews and qualitative-descriptive design was used. The qualitative findings were used to supplement the quantitative data.
The study was conducted in Ahmedabad district of Gujarat state, India. There are 34 DR district tuberculosis centers (DTC) in the state which have notified 2266 DR-TB cases in the year 2018 (16). Treatment success rate for patients with DR-TB was reported to be 43% and loss to follow up was 15% in the year 2017. The Ahmedabad district (including Ahmedabad municipal area and rural area) has a population of 7,045,314 including 5,633,927 population of Ahmedabad city, which makes it the most populous city in Gujarat and the fifth most populous in India (16,17).
Ahmedabad DR-TB center: The DR-TB Centre in Ahmedabad is situated in State TB demonstration and training centre (STDC), Civil Hospital campus, Ahmedabad. The state nodal DR-TC and Intermediate state reference laboratory is also situated within the campus. It has facility for solid culture and drug susceptibility testing (DST), liquid culture and DST and Line probe Assay (LPA) and Cartridge Based Nucleic Acid Amplification Test (CBNAAT). Patients diagnosed with DR-TB are put on conventional treatment regimen, Universal drug sensitivity guided treatment regimen and Bedaquiline containing treatment regimen. There is a TB and Chest ward which is attached with the centre with advanced treatment facilities (16).
DR TB Centre attached to tertiary care hospital in Central Gujarat.
For quantitative study, all patients initiated on DR-TB treatment between 1st July to 30th September 2018 and having completed the first three months of treatment under the Revised National Tuberculosis Control Program (RNTCP) at the DR-TB Center, Ahmedabad, Gujarat were included in the study. Interviews were conducted in the fourth month of their treatment. Those patients who were ‘loss to follow up’ were also included irrespective of ‘treatment taken’ duration. Those patients a) who did not consent for the interviews; b) transferred out to other district DR-TB center and c) on Bedaquiline regimen were excluded.
For the qualitative component, in-depth interview (IDI) was conducted among conveniently selected patients and DOTS providers. Key-informant interview (KII) was conducted among medical officers, DR-TB supervisor and district programme managers.
Data collection and analysis
A list of patients with DR-TB, who were diagnosed and/or initiated on treatment during 1stJuly 2018 to 30th September 2018 were obtained from DR-TB center. Further, relevant information like name, address, and contact number, date of initiation of treatment, drug resistance status, name of designated DOTS provider and Senior TB supervisor and data on AEs were abstracted from treatment cards. The patients were telephonically interviewed once at end of third month of treatment initiation for AEs experienced by them month wise in the last three months using a semi-structured questionnaire. The details collected during the interview were noted down using electronic data collection tool (KoBo Collect v1.14) (19).If any AE was experienced by them in past three months, details like the month of AE occurrence, classification of system involved (including the symptoms) as per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-ICH classification (20) with expert recommendation which has been used in various studies (5,21); and whether treatment was sought for the reported AE were noted. Socio-demographic characteristics like age, gender, residence (urban/rural), occupation, education and clinical characteristics like co-morbidities (HIV, Diabetes mellitus and other chronic conditions) and addiction (tobacco and alcohol), previous TB history were collected. The information related to healthcare provider from whom patient is taking daily injections (Auxiliary nurse midwife/qualified Private practitioner / unqualified private practitioner/ primary health centre-medical officer/other) was also obtained.
The data extracted through record review were entered in the excel. The data collected through the electronic data capture tool was downloaded, merged with extracted data in excel and exported to EpiData version 220.127.116.11 for analysis (EpiData Association, Odense, Denmark). Incidence of AEs has been reported as 100 person days month wise and for total duration of three months of initial treatment. Number and proportion were calculated for gender, occupation, residence, per capita income, characteristics of the patients like HIV status, DM status, addiction (tobacco, alcohol), past history of TB, patients with DR-TB on treatment experienced AE, pattern of AEs, AEs reported and its pattern, type of healthcare facility and healthcare providers contacted for management of AEs. Age was reported in mean (Standard deviation). A p-value of 0.05 was considered statistically significant. The findings have been reported using strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines (22).
For qualitative data
The principal investigator, trained and experienced in qualitative research methods conducted IDIs among patients after consent during their quantitative interview, using an interview guide. The interview explored the views and experiences of the patients related to DR-TB treatment and AEs. Similarly, this also explored their treatment seeking behavior and “emic” view (patient perspective) on facilitators and barriers of seeking medical assistance from healthcare providers. IDIs and KII were also conducted among purposively selected health care providers using interview guide in local language and each interview lasted for nearly 15-20 minutes. Verbatim notes were taken during the interview. Transcripts were made on the same day of the IDI based on the verbatim notes by co-field investigator. The transcripts obtained were compiled and the PI read the transcripts to become familiar with the data. Manual descriptive content analysis was used to analyze the transcripts. It was reviewed by a second investigator (KS) to reduce bias and interpretive credibility. The decision on coding rules and theme generation were done by using standard procedures and in consensus (23). Any difference between the two were resolved by discussion. The findings have been reported by using ‘Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (24).
Ethical Issues: Ethical approval was obtained from the Institutional Ethics Committee of the B. J. Medical College, Ahmedabad, India, and the Ethics Advisory Group of the International Union against Tuberculosis and Lung Disease, Paris, France. A verbal informed consent was obtained from the patients and the stakeholders for interviews and confidentiality has been maintained.