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Abstract
Background Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO’s End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain.
Objective To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings.
Methods We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted.
Ethics and dissemination Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals.
PROSPERO registration number CRD42023443260.
- tuberculosis
- patients
- pulmonary disease
- community-based participatory research
- health economics
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and PROSPERO registration ensures methodological rigour and transparency.
Comprehensive search strategy across multiple databases enhances the likelihood of identifying relevant studies.
Subgroup analysis will provide valuable insights into specific factors affecting intervention outcomes.
Excluding studies with significant selection bias enhance internal validity but may limit the generalisability of findings to populations with different characteristics or contexts.
Introduction
Tuberculosis (TB) is a chronic communicable infection that continues to be a significant cause of morbidity and mortality globally. In 2022, an estimated 10.6 million individuals became sick with TB, and 1.3 million died from TB. Around 23% of TB cases in 2022 were in the WHO Africa region.1 Due to the public health burden, there have been global efforts to stop the impact of TB worldwide.
The WHO’s End TB Strategy and the adoption of UN Sustainable Development Goals at the World Health Assembly in May 2014 and September 2015, respectively, are crucial steps taken by the global community: by 2035, a 95% reduction in mortality and a 90% reduction in incidence, relative to the baseline in 2015. One essential component effort to achieve these goals is directly observing therapy (DOT). One of the primary challenges in managing TB is ensuring that patients follow through with the entire course of treatment.2 To address this challenge, the WHO recommends DOT for patients who fail to achieve a minimum 90% completion rate for their treatment, aiming to enhance adherence to the prescribed regimen.3
In many countries, the pathway to TB treatment is characterised by repeated visits to health institutions and healthcare providers. Even though public health service is commonly available and mostly free of charge for patients, some proportion of costs fall patients and families.4 Though international TB programmes often emphasise promoting access to effective TB care through health facility-based directly observed treatment (HF DOT), there is now an increased emphasis on access to effective TB care through community-based directly observed treatment (CB DOT).5 Health facility DOT imposes both direct and indirect costs on clients, thereby adding to the overall expense of treatment.6 Therefore, finding a new approach for the treatment of TB that maintains effectiveness and requires fewer demands on meagre health resources by alleviating pressure and reducing the cost of providing TB treatment becomes a priority. One preferable approach can be following CB DOT.7 However, it needs monitoring, some initial funding and a carefully planned TB control campaign. The effectiveness of the health system relies heavily on the degree of integration with the community it serves.8
The effects of CB DOT and HF DOT on the treatment of TB have been examined in several research studies. However, the findings of these studies are inconsistent.9 For instance, some research revealed that patients with TB treated by CB DOT had a higher treatment success rate than those treated under HF DOT,10 while other studies showed that there were insignificant variations between the two options.11 According to a randomised control experiment, CB DOT resulted in fewer treatment-related deaths than HF DOT,12 whereas another investigation revealed no difference in mortality rates between the two modalities of treatment.13 These contradictory findings may be due to differences in the study demographics, sample size and the type of CB DOT providers (family members, community health workers (CHWs) or community volunteers (CVs)), and they are likely to vary when these factors change. The cost-effectiveness of CB DOT versus HF DOT for treating TB in African settings has been examined in a few model-based economic studies.14–20 However, there is no systematic review and meta-analysis study that directly compares the effectiveness and cost-effectiveness of CB DOT versus HF DOT.
A systematic review and meta-analysis that compares the effectiveness and cost-effectiveness of CB DOT to HF DOT is recommended in light of the potential use of CB DOT as a method of TB care, particularly in areas with limited resources like Africa. The objectives of this study are to identify the relevant economic appraisal studies of HF DOT versus CB DOT, evaluate the quality of the included studies to support future cost-effectiveness studies in this area and summarise the effectiveness and cost-effectiveness of CB DOT, in terms of treatment success rate and the incremental cost-effectiveness ratio (ICER), compared with HF DOT for care of patient with TB in Africa.
Methods
The systematic review and meta-analysis protocol will adhere to the Preferred Reporting Items for Systematic Review Protocols (PRISMA-P) guidelines to ensure transparency and clarity in the review process.21 This comprehensive reporting framework outlines the key components of the protocol, including the research questions, eligibility criteria, search strategy, data extraction methods and planned analyses. By following PRISMA-P (online supplemental file 1), we aim to enhance the rigour and reproducibility of our study methodology.
Supplemental material
Eligibility criteria
Study inclusion criteria
Inclusion criteria:
Population: individuals with all forms of TB (pulmonary, extrapulmonary, drug sensitive or drug resistant).
Intervention: CB DOT.
Comparator: HF DOT.
Both CB DOT and HF DOT must be administered for the same duration within a study, at least during the intensive phase of treatment.
Outcomes: treatment success rate, ICER.
Study design: full economic evaluation studies including cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis, whether model based or trial based.
Setting and country: African countries, encompassing all healthcare settings.
Exclusion criteria:
Studies lacking a full-text version in English.
Non-peer-reviewed materials such as letters to the editor, notes, comments, news items, doctoral theses, conference proceedings and meeting minutes.
Studies where CHWs, CVs or family members did not deliver CB DOT, at least during the intensive treatment phase.
Studies lacking HF DOT as a comparator group during the intensive treatment phase.
Studies where direct comparison between CB DOT and HF DOT is not feasible due to unreported outcomes or non-comparability of intervention and control groups.
Studies demonstrating significant selection bias in the allocation of CB DOT or HF DOT, including instances where allocation is influenced by patient compliance issues, geographical disparities or socioeconomic factors.
Partial economic evaluation studies or non-economic evaluation studies.
Information sources and search strategy
Our literature search will include PubMed, Embase, Web of Science, Scopus and the Cochrane Library. We will use a combination of keywords and Medical Subject Headings including terms such as economic evaluation, cost, cost-effectiveness, community health services, community health nursing, community-based care, home care services, directly observed therapy, DOT, tuberculosis, TB and Africa. These terms will be used both individually and in various combinations (table 1 and online supplemental file 2).
Supplemental material
Search strategy for PubMed
In addition to database searches, we will conduct grey literature searches using Google’s Advanced Search feature. To ensure comprehensiveness, we will also review the reference lists of included studies and identify relevant articles.
Our search will cover articles published up to 30 March 2024, with no restrictions on publication dates. We aim to complete our research by 30 June 2024.
Study selection
On retrieval, all studies obtained from various databases will be imported into EndNote V.20, where duplicates will be identified and removed. Subsequently, three authors (TB, DG, and GA) will autonomously assess the titles and abstracts of all retrieved studies to determine eligibility. Following this initial screening, the same authors will independently retrieve the full texts of potentially eligible studies. Any discrepancies in eligibility assessment will be resolved through discussion with the remaining authors (FG and ATK) until a consensus is reached.
A PRISMA flow chart, illustrating the selection process, is provided in figure 1.
Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols flow chart.
Data extraction and management
To extract study characteristics and findings comprehensively, we will create an Excel data extraction template. Two reviewers (TB and GA) will undertake the data extraction process, while the remaining reviewers (DG, FG and ATK) will validate the extracted data. In case of discrepancies, consensus will be achieved through discussion.
A custom-designed data extraction table will serve as our tool, ensuring consistency and accuracy in data extraction. The extracted information from each study will include details such as author name, publication year, country of study, sample size, demographic profile of participants (including age, gender, etc), HIV coinfection status, type of TB, community providers involved, study perspective, type of economic evaluation performed, currency and base year, modelling methodology, time horizon, discount rates, costing methodology, cost components included, type of sensitivity analysis conducted, population characteristics, details of the intervention (CB DOT), comparators (HF DOT), treatment success rate and ICER.
Outcomes
Data extracted from the included studies will undergo analysis focusing on both the CB DOT and HF DOT interventions. In cases where studies involve patients undergoing various forms of DOT supervision, such as DOT provided by private physicians or Self-Administered Therapy, only data pertaining to patients receiving CB DOT or HF DOT will be considered for inclusion in our analysis.
The primary outcome of our analysis will focus on the proportion of patients successfully treated, known as the treatment success rate, while the secondary outcome will be the ICER.
The treatment success rate will be calculated as the percentage or proportion of patients with TB who achieve successful treatment, derived from the number of successfully treated patients divided by the total number of patients.
Regarding ICER, it will be determined using the formula: (Costs of intervention – Costs of comparator)/(Effectiveness of intervention – Effectiveness of comparator). Here, the intervention refers to ‘CB DOT’ and the comparator to ‘HF DOT’. The cost component will be the average cost per successfully treated patient, while effectiveness will be measured by the treatment success rate.
To ensure comparability of costs across studies, all costs will be converted to 2024 US dollars using the Consumer Price Index and Foreign Exchange Rates from the Federal Reserve Bank. For studies that do not specify the year of cost inputs, we will assume that costs are current as of the year preceding publication.
The ICER reflects the additional cost incurred for each additional unit of effectiveness gained, such as each additional patient successfully treated. Meta-analyses will be conducted only for the primary outcome, which is the treatment success rate.
Assessment of study quality and risk of bias
To evaluate the quality of the included studies, we will employ the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist,22 which is designed to assess methodological rigour and the handling of potential biases in study design, conduct and analysis. This checklist comprises 28 items organised into 7 sections: title, abstract, introduction, methods, results, discussion and other relevant information, as detailed in CHEERS checklist (online supplemental file 3).
Supplemental material
Two authors (TB and GA) will independently assess each article’s quality using the CHEERS checklist. In instances of disagreement, consensus will be reached through discussion and consultation with other team members (DG, FG and ATK).
Each item on the CHEERS checklist will be scored as follows: 1 for fully reported, 0.5 for partially reported and 0 for items not reported or not applicable. This scoring system will enable us to calculate a reporting score for each study, with a maximum possible score of 28.22 Based on quantitative CHEERS ratings, studies will be categorised into three groups: ‘high quality’ for scores over 75%, ‘moderate quality’ for scores between 50% and 75% and ‘low quality’ for scores below 50%.
For randomised controlled trials, the risk of bias will be assessed following the Cochrane Collaboration’s guidelines. Similarly, applicable parts of these guidelines will be used to evaluate the risk of bias in non-randomised studies.23
Synthesis and data analysis
The meta-analysis will specifically target studies that report treatment success rates, either in percentage or proportion form, or total patients treated successfully, for both the intervention (CB DOT) and comparator (HF DOT) groups. The primary outcome, the treatment success rate, will be analysed by computing ORs along with their respective 95% CIs for each study. To pool the data, we will employ meta-analysis using the Mantel-Haenszel method with a random-effect model,24 which is well-suited for proportions, and allows to effectively pool the ORs. Heterogeneity among studies will be assessed using the I2 statistic, with thresholds set at 25% for low and 75% for high heterogeneity.25 Subgroup analyses will explore the influence of various factors such as the category of community providers involved and clinical characteristics like HIV coinfection status on the outcomes of CB DOT compared with HF DOT.
After subgroup analysis, if heterogeneity is acceptable, we will proceed with meta-analysis. Otherwise, a narrative description of findings will be provided. Sensitivity analysis will examine the robustness of pooled data, considering factors such as the risk of bias and inclusion of biased studies.
For the secondary outcome, ICER, we will conduct a narrative synthesis or systematic review of studies reporting cost-effectiveness data comparing CB DOT and HF DOT. The quality and reliability of cost-effectiveness estimates will be assessed, considering study design, perspective, time horizon, discount rate and currency adjustment. Sensitivity analyses will explore the impact of uncertainty in cost and effectiveness estimates on the ICER.
We will use GRADE profiler software to assess the quality of evidence per outcome and generate a summary of findings table and evidence profile. Meta-analysis will be conducted using STATA software V.17, with statistical significance set at p<0.05.
Addressing missing data
In instances where individual participant data are not readily accessible, we will thoroughly review the original sources and published study reports. Additionally, we will reach out to the authors for clarification and to request the necessary data.
Reporting bias
We will evaluate any possible publication bias by using funnel plots if 10 or more studies are included in this study.26
Patient and public involvement
Patients and public will not be involved in this systematic review and meta-analysis. However, once our findings are disseminated, it will be shared through social networks.
Ethics and dissemination
As this study will only include publicly available previously published articles, ethical approval is not a requisite for its implementation. Our plan involves sharing our findings through presentations at both international and national conferences, alongside publication in open-access, peer-reviewed journals.
Amendments
The protocol for this study will be amended as necessary.
Discussion
The systematic review and meta-analysis proposed in this protocol aim to build on existing literature by providing a comprehensive comparison of CB DOT and HF DOT for TB care in African settings. Comparisons to existing studies reveal both consistencies and discrepancies in findings, underscoring the need for a robust synthesis of evidence.
In terms of effectiveness, previous research has reported mixed results regarding the superiority of CB DOT over HF DOT.9 Some studies have suggested that CB DOT leads to higher treatment success rates among patients with TB, revealing improved adherence and support systems within communities.10 However, other investigations have found no significant differences between the two modalities,11 showing the complexity of TB treatment outcomes and the influence of various contextual factors. Similarly, economic evaluations in the literature have shown varying cost-effectiveness outcomes between CB DOT and HF DOT.27 These discrepancies may stem from differences in study methodologies, healthcare settings and healthcare delivery systems across different contexts.
Despite these inconsistencies, there is a consensus among existing studies regarding the potential benefits of community involvement in TB care. Community-based interventions, such as CB DOT, have been recognised for their ability to improve treatment adherence, reduce transmission rates and alleviate the socioeconomic burden of TB.28 These findings align with the broader literature emphasising the importance of community engagement in public health initiatives, particularly in resource-constrained settings.
The findings of this systematic review and meta-analysis will contribute to the understanding of the optimal delivery method for TB treatment in resource-limited settings, particularly in Africa, where TB remains a significant public health concern.1 The synthesis of available evidence will provide valuable insights into the comparative effectiveness of CB DOT and HF DOT, providing insight on their respective impacts on treatment success rates and ICER. The review will not only focus on treatment outcomes but also on economic evaluations, which are essential for informing healthcare policy and resource allocation decisions. By evaluating the cost-effectiveness of CB DOT versus HF DOT, we aim to provide policy-makers and healthcare practitioners with evidence to guide the selection and implementation of TB care strategies that offer the best value for money, considering the limited resources available in many African countries.
The results of this study will have several implications for TB control programmes and health systems in Africa. First, if CB DOT is found to be more effective and cost-effective compared with HF DOT, it may warrant greater investment and integration into existing healthcare delivery systems. Community-based approaches have the potential to reduce the burden on health facilities, improve patient adherence to treatment and ultimately contribute to better TB outcomes.28
However, it is essential to acknowledge the limitations of this study. The study’s focus on African countries may limit the generalisability of findings to other regions, reducing the global applicability of the results. Moreover, limitations such as selection bias, incomplete reporting and methodological flaws may influence the validity of the results.
Supplemental material
Ethics statements
Patient consent for publication
Acknowledgments
We express our gratitude to the Pharmacy department at Woldia University for arranging the office and providing free internet access.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors TB initially conceived the study. TB, DG and GA performed the preliminary search. TB, FG and DG developed the study criteria, wrote the protocol and drafting of the manuscript which has been consecutively discussed with GA and ATK. The manuscript was read and approved by all authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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.