IOSR Journal of Nursing and Health Science (IOSR-JNHS)

e-ISSN: 2320–1959.p- ISSN: 2320–1940 Volume 11, Issue 1 Ser. I (Jan. – Feb. 2022), PP e12-e17

ADHERENCE INTERVENTIONS AND OUTCOMES OF TUBERCULOSIS TREATMENT IN LOW- AND MIDDLE-

INCOME COUNTRIES (LMIC): A SYSTEMATIC REVIEW PROTOCOL

BADEMOSI ADETOMI1, OSARO BENJAMIN1, OPARA CHIDINMA JUDITH 2

1
Department of Community Medicine, College of Medical sciences, Rivers State University Rivers state, Nigeria
2
Department of community medicine, PAMO university of medical sciences, Port Harcourt, Rivers state, Nigeria

ABSTRACT

Incomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued
transmission in the community, as well as treatment failure, relapse, and development or amplification of drug
resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly
observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes. However,
treatment outcomes for tuberculosis has been less than ideal in many high-burden countries especial countries with
low socio-economic index. A systematic analysis of the adherence interventions and outcomes of tuberculosis
treatment with be carried out using the referred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) protocols. The methodological quality of the RCTs will be assessed using the Jadad Scale. Where sufficient
data are available, A meta-analysis will be conducted to confirm the relationship between treatment adherence and
treatment outcomes. This systematic review will provide evidence in support or against the hypothesis that treatment
adherence leads to better treatment outcomes in tuberculosis. This conclusion will stem from the reported outcomes
of TB treatment among persons undergoing TB treatment in Low and middle-income countries.

Keywords: tuberculosis, treatment, adherence, outcomes LMIC,

1. INTRODUCTION

Treatment adherence is challenging, given the complexity, modest tolerability, and long duration of treatment
regimens currently available for both drug-susceptible and -resistant tuberculosis (TB). In turn, low adherence
increases the risk of poor outcomes, including treatment failure, relapse, and development or amplification of drug
resistance(1,2). Public health programs have used a variety of strategies to improve adherence at the health system
level via financial incentives or enablers to offset the cost of accessing treatment, improving coordination and logistics
around TB treatment delivery, and training healthcare providers. Other strategies tackle barriers to completing TB
treatment by addressing knowledge gaps, attitudes, and behaviors surrounding adherence to TB treatment(3–5). One
of the most commonly used adherence interventions is directly observed therapy (DOT), in which a health worker,
family member, or community member observes the patient taking TB medications(6). In recent years, video-observed
therapy (VOT) has gained attention as an alternative way of delivering DOT(7,8). Other interventions aimed at
supporting adherence through DOT include incentives, which are material or financial rewards provided to those
adhering to treatment(9), and enablers, which are interventions that allow patients to overcome economic constraints
associated with DOT, such as absence from work or the direct and indirect patient costs of accessing TB treatment.
Other interventions focus on providing education on TB, its treatment, and prevention to help patients make informed

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IOSR Journal of Nursing and Health Science (IOSR-JNHS)
e-ISSN: 2320–1959.p- ISSN: 2320–1940 Volume 11, Issue 1 Ser. I (Jan. – Feb. 2022), PP e12-e17

decisions and the healthcare team to deliver patient-centered care(10–12). Reminder systems and patient tracers are
targeted at assisting patients to keep appointments and to act when patients miss appointments(13,14). These
interventions include reminder letters, phone calls, home visits, and, more recently, short message service (SMS)
technology as well as electronic pillboxes. Psychological interventions aim to support via psychological or emotional
counseling or a social network of peers undergoing TB treatment as a means of improving adherence to TB treatment
(15,16). Given the significant losses patients and the health system incur as a result of poor TB treatment outcomes,
identifying those interventions that are most likely to improve adherence and outcomes, especially in resource-limited
settings, is crucial. The first pillar of the End TB Strategy of the World Health Organization (WHO)—Integrated,
Patient-Centered Care and Prevention—calls for “treatment of all people with tuberculosis including drug-resistant
tuberculosis; and patient support” (7,17). In 2015, WHO commissioned a series of systematic reviews and meta-
analyses ahead of a Guideline Development Group meeting tasked with the revision of its TB treatment guidelines in
accordance. However, there have been reports of less than ideal treatment outcomes and treatment failures in many
high-tb burden countries especially in Low- and Middle-income countries.

Research Question

What is the effect adherence interventions on the outcome of tuberculosis treatment?

2. METHODS

Search strategy
The search strategy will be performed using resources that enhance methodological transparency and improve the
reproducibility of the results and evidence synthesis. In this sense, the search strategy will be elaborated and
implemented before study selection, according to the PRISMA-P checklist as guidance.(18) Additionally, using the
Population, Intervention, Comparison, Outcome and Study design (PICOS) strategy.(18) The guiding question of this
review to ensure the systematic search of available literature will be: ‘Has the intermittent preventive treatment for
malaria reduced the prevalence of malaria in pregnancy?’ Studies will be retrieved using eight databases: MEDLINE
(via PubMed), Web of Science, Cochrane Library, Science Direct, PsycINFO, CINAHL, LILACS and SciELO. will
be performed. There will be no restriction regarding the language to avoid the reduce the yield of appropriate articles
and also generalizability. In addition, the reference section in the studies returned by the above search was scrutinized
for additional relevant articles. Initially, the existence of controlled descriptors (such as MeSH terms, CINAHL
headings, PsycINFO thesaurus and DeCS-Health Science Descriptors) and their synonyms (key words) will be
verified in each database. The search terms will be combined using the Boolean operators ‘AND’ and ‘OR’.
Subsequently, a search strategy combining MeSH terms and free-text words will be used. In order to locate the quasi-
experimental studies. In order to locate the clinical trials and experimental studies, a filter after the PICOS search
strategy will be added to include the following terms: AND (randomized controlled trial OR randomized controlled
trials as topic OR controlled clinical trial OR clinical trial OR nonrandomized controlled trials).

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IOSR Journal of Nursing and Health Science (IOSR-JNHS)
e-ISSN: 2320–1959.p- ISSN: 2320–1940 Volume 11, Issue 1 Ser. I (Jan. – Feb. 2022), PP e12-e17

Study selection criteria

A summary of the participants, interventions, comparators, and outcomes considered, as well as the type of studies
included according to PICOS strategy, is provided in Table 1.

Table 2 Inclusion criteria for study selection

Item Inclusion Criteria

Population • Patients on treatment for drug-sensitive TB

• Patients on MDR-TB treatment
• Children (≤14 years) and adult TB patients
infected with HIV and not infected with HIV
Intervention Any intervention to promote treatment adherence
· Supervising treatment (DOT, VOT)
· Measures to improve treatment adherence (e.g.,
medication monitors and/or SMS or phone call
reminders)
· Social support (educational, psychological, material)
· Combinations of the above interventions
Comparison Routine practice
Outcome 1. Adherence to treatment (or treatment interruption
because of nonadherence)
Conventional TB treatment outcomes: cured/
completed, failure, relapse, survival/death
2. Adverse reactions from TB drugs (severity, type,
organ class)
Study Design(s) Randomized clinical trials and Quasi-experimental studies

Screening and data extraction

Initial screening of studies will be based on the information contained in their titles and abstracts and will be conducted
by two independent investigators. When the reviewers disagreed, the article will be re-evaluated and, if the
disagreement persisted, a third reviewer will make a final decision. Full-paper screening will be conducted by the
same independent investigators. Cohen’s kappa will be used to measure inter-coder agreement in each screening phase.
Data will be extracted using a previously proposed tool,(18) including four domains: (1) identification of the study
(article title; journal-title; impact factor of the journal; authors; country of the study; language; publication year; host
institution of the study (the hospital; university; research center; single institution; multicentre study)); (2)

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IOSR Journal of Nursing and Health Science (IOSR-JNHS)
e-ISSN: 2320–1959.p- ISSN: 2320–1940 Volume 11, Issue 1 Ser. I (Jan. – Feb. 2022), PP e12-e17

methodological characteristics (study design; study objective or research question or hypothesis; sample
characteristics, e.g. sample size, sex; age, race; acute and/or chronic diagnoses; groups and controls; stated length of
follow-up; validated measures; statistical analyses, adjustments; (3) main findings and (4) conclusions. If the outcome
data in the original article were unclear, the corresponding author will be contacted via email for clarification. For
data extraction, two independent Microsoft Excel spreadsheets will be elaborated for two reviewers to summarise the
data from the included studies. Then, the spreadsheets were combined into one. Disagreements will be resolved by a
third investigator.
Quality assessment
The methodological quality of the RCTs will be assessed using the Jadad Scale,(18) a widely used tool for
classification of the quality of the evidence from RCTs. The Jadad Scale scores range from 0 to 5, with studies scoring
<3 considered as low quality and studies that score ≥3 are classified as high quality.Error! Bookmark not defined.
The internal validity and risk of bias for RCTs will be assessed with the appraisal tool from the Cochrane Handbook
for Systematic Reviews of Interventions V.5.1.0,46 which assesses the following study-level aspects: (1)
randomization sequence allocation; (2) allocation concealment; (3) blinding; (4) completeness of outcome data and
(5) selective outcome reporting; and classifies studies into low, high or unclear risk of bias. For assessing NRCT, the
ROBINS-I, a recently developed tool, will be used.(18) ROBINS-I is particularly useful to those undertaking
systematic reviews that include non-randomized studies of interventions. This tool is guided through seven
chronologically arranged bias domains (pre-intervention, at intervention and post-intervention), and the interpretations
of domain-level and overall risk of bias judgement in ROBINS-I are classified in low, moderate, serious or critical
risk of bias.Error! Bookmark not defined. Two independent reviewers will assess the methodological quality of
eligible trials. Two independent reviewers will score the selected studies and disagreements will be resolved by a third
reviewer. The risk of bias for each outcome across individual studies will be summarized as a narrative statement and
supported by a risk of bias table. A review-level narrative summary of the risk of bias will also be provided.
3. CONCLUSION
This systematic review will provide evidence in support or against the hypothesis that treatment adherence leads to
better treatment outcomes in tuberculosis. This conclusion will stem from the reported outcomes of TB treatment
among persons undergoing TB treatment in Low and middle-income countries. Where sufficient data are available, A
meta-analysis will be conducted to confirm the relationship between treatment adherence and treatment outcomes.
Overall, the review will complement the evidence on the benefits of treatment adherence in the control of tuberculosis.

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