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Abstract
Objectives To determine patients’ acceptability, satisfaction and adherence to shorter all-oral multidrug-resistant tuberculosis (MDR-TB) regimen in Tanzania.
Design A two-phase cross-sectional study with data collected within 6 months of Removed Injectable modified Short-course regimens for EXpert MDR-TB (RISE) study implementation and the second phase within 15 months of implementation using the same reference populations.
Settings 18 health facilities across eight regions of Tanzania.
Participants Rifampicin-resistant TB/MDR-TB patients enrolled in the RISE study.
Outcome measures We assessed patients’ acceptability, adherence and satisfaction with the regimen using an interval scale structured questionnaire.
Results The majority of the patients found the shorter oral MDR-TB treatment acceptable, adhered to it well and were generally satisfied. The median score (IQR) for acceptability was 1.7 (1.03–2.00) but it ranged between 1.3 (1.3–2) and 1.7 (1–1.79) for the first and second phases, respectively. Regarding adherence, the median score (IQR) stood at 4 (3.67–4.67) with scores significantly higher in the second phase at 4.33 (4.00–5.007) compared with the first at 4.67 (4.00–5.0), p value=0.01. The overall satisfaction was high at 1.5 (1.33−1.78) but it ranged between 1.22 (1.00–1.78) and 1.42 (1.11–1.78) for the first and second phases, respectively. Worrying about side effects was statistically associated with adherence (p value<0.05). No statistically significant associations were found for acceptability and satisfaction.
Conclusion Generally, the modified shorter oral MDR-TB regimen was accepted, and patients reported good adherence and were satisfied. More engagement with patients could provide more insights into factors that can maximise acceptability, adherence and satisfaction with the regimen.
- Tuberculosis
- Medication Adherence
- Patient Satisfaction
Data availability statement
Data are available upon reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This study collected data in two waves, thus capturing the dynamics of change between the initial situation (start of the study) and subsequent outcomes in relation to acceptability, adherence and satisfaction with the regimen.
The use of the cross-sectional study design limits the causal links between the variables.
Although the data were collected across the country, the variation of sample sizes in the two waves in relation to the total population (enrolled patients in the Removed Injectable modified Short-course regimens for EXpert MDR-TB study) may limit the generalisability of the findings beyond Tanzania.
The fact that the collected information in this study relied on patients’ self-reports may be prone to response bias, as participants may under-report or over-report their practices.
Introduction
Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to rifampicin (RIF) and isoniazid, continues to be a public health problem.1 2 In 2020, 132 222 people were diagnosed to have RIF-resistant TB (RR-TB)/MDR-TB globally.3 In Tanzania, approximately 1900 cases were estimated to have RR/MDR-TB in the year 2018, of which only 449 cases were notified.4 RR/MDR-TB treatment is complicated and longer, with treatment duration and type being dynamic, and therefore it has been associated with many drug adverse events and implementation challenges, hence poor treatment outcomes.5 6 In the year 2020, WHO recommended the use of a shorter all-oral bedaquiline-containing regimen of 9–12 months duration in eligible patients with confirmed MDR/RR-TB, who have not been exposed to treatment with second-line TB medicines used in this regimen for more than 1 month and in whom resistance to fluoroquinolones has been excluded.2
Tanzania uses an 18–20 months oral regimen as a standard of care since November 2019;4 however, the country has started using a shorter all-oral bedaquiline-containing regimen of 9–11 months duration under a programme research setting since June 2020.7
Acceptability is a key consideration in designing, evaluating and implementing healthcare interventions. Acceptability and satisfaction with a new intervention have been shown to have an influence on a patient’s adherence and also clinical outcomes.8–11 They have also been shown to influence the total conduct and overall effectiveness of the intervention.12 Successful implementation of any new intervention has been shown to be dependent on the acceptability and satisfaction of the intervention to both intervention deliverers (eg, patients, researchers or healthcare professionals) and recipients (eg, patients or healthcare professionals), and therefore, they have been said to be a necessary but not a sufficient condition for the effectiveness of an intervention.12
Multiple studies have identified several factors that contribute to the acceptability of a health intervention.12–14 For an intervention to be acceptable, it should be effective, minimally restrictive, minimally intrusive and convenient.15 Other factors like the treatment’s formulation, lesser side effects and the process used to deliver the treatment have also been reported to affect the acceptability of any new intervention.16 Personal factors like sociodemographic characteristics of the individuals and the severity of the health problem being addressed have also been reported to influence one’s acceptability.15
As part of a broader study that aimed to unpack the implementation of the ‘Removed Injectable modified Short-course regimens for EXpert MDR-TB’ (RISE) in Tanzania,17 this paper specifically reports the quantitative part of the study that focused on patients’ acceptability, satisfaction and adherence to the shorter all-oral MDR-regimen in Tanzania.
Methods
Study design
This study employed a two-phase cross-sectional study design to evaluate patients’ acceptability, satisfaction and adherence to shorter all-oral MDR regimen. The data for the study were collected in two phases. The first phase of data collection was done within 6 months (December 2020) of enrolment of patients in the RISE study, and the second phase of data collection was done within 15 months of enrolment (September 2021), using the same reference populations. The authors follow the Strengthening the Reporting of Observational Studies in Epidemiology checklist (online supplemental file 1) for reporting the study.
Supplemental material
Evaluated study
The evaluated implementation was the shorter modified oral MDR-TB regimen under the RISE study. The RISE study is a pragmatic open-label prospective cohort study with a continuous enrolment of eligible patients measuring uptake (enrolment), 6-month conversion, severe adverse events, treatment results at 9 months (primary endpoint) and relapse and death during a follow-up period of 12 months (secondary endpoint). The RISE trial uses a combination of six medications, namely, bedaquiline, levofloxacin, linezolid/delamanid, pyrazinamide, clofazimine and cycloserine during the intensive phase of treatment for 6 months and a combination of four drugs, namely, levofloxacin, pyrazinamide, clofazimine and cycloserine during the continuation phase of treatment for 3–5 months. The number of tablets taken within the RISE operational trial ranges from 12 to 16 for those with minimal to maximal ranges of body weight.
Study population
The study population was RR/MDR patients enrolled in the RISE study who provided written consent for participation in this study.
Sampling and sample size
For this quantitative survey, the selection of study sites and subjects was based on the enrolment status for the RISE study. During the first phase of data collection, all sites that had at least one subject enrolled in the RISE study were included. All RR/MDR patients who were enrolled in the study and agreed to participate in this study were included in this implementation study. A total of 47 patients from 12 sites, of which 8 are in Dar-es-Salaam, 1 in Dodoma, 1 in Kilimanjaro, 1 in Mtwara and 1 in Ifakara-Morogoro, agreed to participate and therefore were included in this study. During the second phase of data collection, a total of 77 patients from 15 sites, of which 3 sites were added to the sites that were included during the phase I period of data collection. The added sites were in Mbeya City, Arusha City and Lindi.
Data collection tools
To quantitatively assess patients’ acceptability and satisfaction, a structured questionnaire was used to collect information from patients. An exit interview was administered to consecutive patients exiting the health facility after receiving shorter regimen services. The questionnaire measured experiences of the encounters related to shorter regimen processes and procedures. The questionnaire covered aspects such as sociodemographic characteristics (age, gender, marital status and occupation, when starting the regimen), acceptability of shorter regimen, adherence to shorter regimen and clinic visits, satisfaction with the regimen and moderating factors. The questionnaire was composed of multiple questions, yes/no and Likert scale questions. The Likert scale questions had scores of 1–5, of which 1 was scored for strongly agree and 5 was scored for strongly disagree.17
For data collection tools development, we relied on the theoretical framework of acceptability12 and the framework put forward by Wierenga et al to guide the conduct of the process evaluation.18
Measurement of variables
Independent variables
The independent variables in this study were sociodemographic variables, health status and level of the facility. The sociodemographic variables considered in this study include: age, sex, education level, marital status and occupation. Age was measured in years as a continuous variable and was categorised when deemed important, whereas sex was classified as male or female. The marital status of the respondents was categorised as married, single, divorced or widowed. We categorised the education level as no formal education, primary level and secondary level and above. The occupation of respondents was categorised as self-employed, employed, dependent and others. The health status of the respondents was classified as poor, fair and good. The level of health facility was categorised into hospital and health centre.
Dependent variables
The dependent variables for this study were: (1) acceptability, (2) adherence and (3) satisfaction with the regimen. They were measured using multiple questions consisting of yes/no and Likert scale questions with scores ranging from 1 to 5 (from strongly agree to strongly disagree).
Acceptability
Acceptability was assessed by checking whether the study participants were informed that the regimen they were using was still under operational trial and that there were other treatment options. Additionally, it was assessed by checking whether participants provided informed consent before treatment started, if they were informed of possible side effects of the study regimen and whether they would recommend the trial regimen to other MDR-TB patients.
Adherence
Adherence was defined as the self-reported extent to which patients take medications as prescribed by their healthcare providers.19 20 It was assessed to check whether patients could stop using MDR-TB medication when symptoms resolved and whether they were taking medications as directed by physicians.
Satisfaction
Satisfaction was assessed by checking satisfaction on physician consultation, physician response to adverse events, pharmacist/nursing advice about drug adherence, pharmacist/nursing advice about possible drug side effects, route of drug administration, symptom resolutions, drug prescription frequency period, treatment period and overall health improvement.
Median scores were calculated for each variable, whereby a median score of 1 indicated strong agreement and that of 5 indicated strong disagreement.
Statistical analyses
Data were entered into an open clinical database. Data management and analysis were conducted using STATA software V.15.0. Descriptive statistics were computed to explain variable distributions. Responses to binary acceptability, satisfaction and adherence scales were compared across phases to ascertain whether there was a statistically significant difference in response over time using Pearson’s χ2 test or Fisher’s exact test where applicable. Specifically, items were measured on a five-point Likert scale, ranging from ‘strongly agree’ to ‘strongly disagree’. Positive Likert scale responses (responses of either ‘agree’ or ‘strongly agree’) were coded as 1, while negative responses (‘neutral’, ‘disagree’ or ‘strongly disagree’) were coded as 0. Dichotomous responses of ‘yes’ or ‘no’ were coded as 1 or 0, respectively. Proportions were calculated to give the overall acceptability, satisfaction and adherence score as a percentage for each sample. The median values for each item were calculated, and the Wilcoxon rank sum test was conducted to explore the difference between phases. To assess the internal consistency of the scale, Cronbach’s alpha analysis was used. The results demonstrated good internal validity, with Cronbach’s alpha values of 0.80 for acceptability and 0.84 for satisfaction, respectively. This indicates that the items within each subscale measure a consistent underlying construct, and all items were deemed relevant and retained in the final scale. The significance of the test was assessed by examining the p value. A p value <0.05 was considered statistically significant.
Patient and public involvement
This study was conducted within the RISE study. Patients provided their views regarding the implementation processes of the RISE study. However, patients and the public were not directly involved in the design, conduct and dissemination plan of the study.
Results
Characteristics of study participants
A total of 47 RR/MDR patients were interviewed, who were all on shorter RR/MDR-TB regimens from 12 health facilities located in different cities in Tanzania, namely, Dar-es-salaam, Dodoma, Ifakara, Kilimanjaro and Mtwara during the first phase of data collection. The median age was 39.5 years (29–49 years), 68% were males, a majority reported to have a good health status of 66% and the median duration in treatment in weeks was 14 (8–17).
During the second phase of data collection, a total of 77 RR/MDR patients were from 15 health facilities located in Dar-es-Salaam, Dodoma, Ifakara, Kilimanjaro, Mtwara, Lindi and Mbeya. The median age was 43 years (33–51 years), 74% were males, a majority reported to have a good health status of 62.3% and the median duration of treatment in weeks was 13 (5–21). Table 1 provides details on the characteristics of the participants in both phases. There were no statistical differences between the two groups.
Social demographic characteristics of study participants during the first phase and second phase of data collection
Acceptability, adherence and satisfaction on shorter RR/MDR-TB regimen
Acceptability
Generally, 58% of interviewed patients accepted the shorter-oral RR/MDR-TB regimen (median scores of 1.2 and 1.30 for phase I and phase II, respectively). The majority reported that they were informed that the regimen they are using is still under operational research trial (median score of 1 for both study phases) and there are other treatment options for MDR-TB apart from this regimen (median scores of 2 and 1). In addition, the majority reported that they voluntarily agreed to use this regimen after consenting (median scores of 2 and 1) and would recommend this regimen to other MDR patients in Tanzania (median score of 1 for both study phases). Details for median scores on acceptability are given in table 2.
Median scores for acceptability items, satisfaction items and adherence items on the shorter duration injectable-free multidrug-resistant tuberculosis regimen during the first phase of data collection (N1=47) and second phase of data collection (N2=77)
Overall, Fisher’s exact test on different factors to check their association with acceptability showed no statistical significance between these factors and acceptability.
Furthermore, for the first phase of data collection, high numbers of tablets (p value =0.02) and spending more than 2 hours to reach the TB clinic so as to get MDR-TB services (p value =0.01) were found to be statistically and significantly associated with acceptability (online supplemental file 2).
Supplemental material
During the second phase of data collection, getting transport support (p value =0.04) was found to be statistically and significantly associated with acceptability. See table 3 for further details.
Fisher’s exact test for the influencing acceptability, satisfaction and adherence of the shorter duration multidrug-resistant tuberculosis regimen, N (%)
Adherence
The overall reported adherence was satisfactory. All interviewed patients denied any history of taking medications against healthcare professionals’ directions (5 (5.00–5.00)) during the second phase of data collection. Some patients reported being worried about drug side effects both during the first and second phases of data collection. Being worried about drug side effects (p value=0.02) was found to be statistically associated with adherence (online supplemental file 2).
Satisfaction
The majority of participants were satisfied with the regimen, with higher satisfaction scores observed during the second phase of data collection (1.22 (1.00–1.78) and 1.50 (1.00–1.78) for phase I and phase II, respectively) (see table 2).
During the first phase of data collection, the majority of the patients reported more satisfaction on the route of drug administration (1 (1.00–2.00)) while least satisfaction was reported on treatment duration (2 (1.00–2.00)). During the second phase, more satisfaction was reported on pharmacist/nursing advice about drug adherence (1 (1.00–2.00)) while least satisfaction was reported on symptom resolutions (11 (1.00–2.00)). No factor was found to be statistically associated with satisfaction (see online supplemental file 2 and table 3).
Discussion
To the best of our knowledge, this is the first study to assess patient’s acceptability, satisfaction and adherence to shorter oral RR/MDR regimens in Tanzania. The majority of the interviewed patients in our study accepted they were satisfied and had reported good adherence to the shorter MDR-TB regimen. The observed difference between acceptability, satisfaction and adherence scores between the two phases of data collection may be due to the implementation improvement of the RISE operational study, as more improved scores were observed during the second phase of data collection.
In this study, the analysis did not reveal any statistically significant relationship between the number of pills and medication adherence or patient acceptability. The RISE operational trial regimen comprised 12–16 tablets daily dosage for those with minimal to maximal ranges of body weight. Although this number of tablets is considered to be high, this factor was not found to be statistically associated with adherence or acceptability. The findings are not different from other studies that reported the association of the number of pills and adherence.13 21–23 These findings were similar to what was observed in drug-sensitive patients, where Bea et al reported no association between adherence and concomitant medication use.24
In this study, it was found that being worried about side effects was statistically associated with adherence. This finding is similar to what has been reported by multiple studies on TB concerning the influence of side effects on adherence among both drug-sensitive and drug-resistant patients.9 25–27 The observed findings therefore continue to build evidence on what is already known about the role of side effects on adherence among TB patients.
Furthermore, our study did not find any association between spending more than 2 hours travelling to the TB clinic to access MDR-TB services and acceptability. This may be explained by the fact that the majority (over 50%) of the facilities included in the study were located in Dar-es-Salaam, Tanzania’s largest city with a well-developed infrastructure, making it easier for patients to reach MDR-TB clinics. Although this factor was not statistically linked to adherence in this study, other research has identified inaccessibility due to geographic location as a significant barrier to treatment adherence and retention in TB care.11 21 24 26 28–30 Even though this study did not show a significant association between long travel times and adherence, the authors still recommend making MDR-TB services easily accessible to all patients, as this would improve treatment and management, leading to better adherence and outcomes.
The finding that patients in this study were satisfied with the route of administration is consistent with existing evidence that reports that patients would often prefer oral regimens when compared with injectables.31 This finding also extends the evidence that injectable-free regimens, either shorter or longer, implemented under programme conditions are associated with better quality of life for patients and treatment outcomes.32 33
In this study, patients were more satisfied with counselling on drug adherence that was offered by healthcare workers. This finding is consistent with previous studies that underscore the importance of psychosocial counselling on drug adherence, patient retention in care and improvement in quality of life.34 35
Strengths and limitations
Strengths
This is the first study to assess acceptability, satisfaction and adherence to the modified shorter MDR regimen in pragmatic settings in Tanzania. The findings from this study are set to inform the National Tuberculosis and Leprosy Programme on different factors that have been found to influence acceptability, adherence and satisfaction of the modified shorter MDR regimen to improve MDR services in the country.
Limitations
This study had some limitations that need to be acknowledged. The study had a minimal sample size of 47 patients during the first phase of data collection and 77 during the second phase of data collection, therefore, the obtained results may not be representative of the total population. A total of 222 patients were enrolled in the RISE operational trial and were on the shorter-oral RR/MDR regimen, therefore, only one-third of the total subjects who were on the shorter-oral RR/MDR regimen were included in this implementation study. Several reasons may have led to this; however, the strongest reason for this is the late start of the RISE operational study due to COVID-19 interruption and slow recruitment within the RISE operational study. Furthermore, adherence results that are reported in this study are based on the reported responses from the patients. This may have overestimated the reported results, with about 100% of patients reporting that they were using medication as they were directed by the healthcare workers. The authors recommend the use of other modalities of assessing adherence, for example pill count and other tests, while doing adherence assessment on further studies for true estimation of adherence.
Conclusion
Generally, the shorter all-oral modified regimen was accepted by MDR patients in Tanzania. Multiple factors, including getting transport support, the number of tablets and being worried about side effects were found to affect acceptability and adherence. It is therefore more important to evaluate these factors and have a good mechanism on how to deal with them so that the intervention can be delivered as planned and have the intended effectiveness.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
This process evaluation study was conducted in the framework of the RISE project which was granted with the ethical approvals from the National Institute of Medical research (NIMR) in November 2019 (Ref. NIMR/HQ/R.8a/Vol.IX/3269) and from the Mbeya Medical Research and Ethics Review Committee (MMREC) in October 2019 (Ref. SZEC-2439/R.A/V.I/38). Written informed consent was sought from all study participants prior to their participation in this study.
Footnotes
NEN and AK are joint senior authors.
Contributors JL designed the study, participated in data acquisition and drafted the manuscript. AK, HM and NEN conceived the idea, designed of the study and also drafted the manuscript. ZM and WO performed statistical analysis with input from JL, HM, SGM, EM, IL, RK, NEN and AK. DP, AM, CG and PJS participated in data acquisition. All authors read and approved the final version. In this study, AK acted as a guarantor.
Funding This project was funded by the Global Fund (GF). The funder did not play any role in the conduct of this study other than ensuring the correct utilisation of the funds.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.