Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05236452 |
| Other study ID # |
353/2021 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2022 |
| Est. completion date |
December 30, 2023 |
Study information
| Verified date |
April 2023 |
| Source |
Bahir Dar University |
| Contact |
Desalegne Amare |
| Phone |
0929466624 |
| Email |
desalegnezelellw[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Although many interventions are implemented to increase TB case detection, decrease diagnosis
delay, and avoid catastrophic costs, there are no significant changes and the end TB goal
will not be achieved in 2035. Innovative intervention that considers indigenous knowledge and
unique culture and religious perspectives because many people go to traditional healers and
holy water for healing. Therefore, integrating traditional tuberculosis care with modern care
increase case detection, decrease diagnosis delay, and avoid catastrophic costs. There is no
literature clearly defining integrating traditional TB care with modern care, but for the
purpose of this study, integrating traditional care with modern care is defined as the
collaboration of two systems through referral linkage. TB screening and diagnosis services
will be done collaboratively in traditional and modern care services. A referral linkage
model will be used to detect TB cases in both traditional and modern care services. Health
care providers, traditional healers, priests, pastors, and imams will participate in the
integration process. TB detection or diagnosis services will be integrated through referral
linkage and strengthening capacity-building strategies. Traditional care centers and modern
health care services will work collaboratively to improve TB case detection, reduce care
costs, and avoid diagnosis delays. The standardized operational procedure of the full
interventional package is described below.
There are four steps of the intervention phases. These are the preliminary phase, preparation
for implementation and refinement on a small scale phase, administering the intervention, and
end-line assessment of outcomes. The intervention will be providing training for traditional
and modern care practitioners, patient education, TB screening, and bidirectional referral
linkage.
This study hypothesized that integrating traditional care with modern care at the primary
care level will increase the TB case detection rate by fifteen percentage points. Integrating
traditional care with modern care at the primary care level will decrease TB diagnosis delay
by fifteen percentage points. Integrating traditional care with modern care at the primary
care level also will decrease the cost of TB care by 15 percentages of points
Description:
Quantitative description Design: Both qualitative and quantitative methods will be used to
answer our research questions. Cluster randomized control trial study design will be used to
determine the effectiveness of integrating traditional care into modern care on case
detection rate (for the first, second, and third objectives). The explanatory sequential
design will be used to determine the effect of integrating traditional care and modern care
on patient satisfaction (fourth objective). This explanatory sequential design will follow to
obtain substantiate evidence from quantitative data which is used to determine whether it has
effects on patient satisfaction on integration between the traditional with modern care. In
this design, two phases will be involved. The first phase will be an initial quantitative
instrument phase, followed by a qualitative data collection phase, in which the qualitative
phase builds directly on the results from the quantitative phase. In this way, the
quantitative results will be explained in more detail through the qualitative data.
Study participants: Study participants will be TB suspected individuals (i.e., coughs for
more than two weeks, and other constitutional TB signs and symptoms such as fever, chills,
night sweats, anorexia, and weight loss).
Intervention: Integration is recognized as a multidimensional concept with no singular
purpose. Integrated service delivery can be defined as joining inputs, management,
organization, and distribution of health services related to diagnostics, treatment, care,
rehabilitation, and health promotion as a means of improving health status, access, quality,
and continuity of care, consumer satisfaction, and efficiency. There is no literature clearly
defining integrating traditional TB care with modern care, but for this study, integrating
traditional care with modern care is defined as the collaboration of two systems through
referral linkage. TB screening and diagnosis services will be done collaboratively in
traditional and modern care services. A referral linkage model will be used to detect TB
cases in both traditional and modern care services. Health care providers, traditional
healers, priests, pastors, and imams will participate in the integration process. TB
detection or diagnosis services will be integrated through referral linkage and strengthening
capacity-building strategies. Traditional care centers and modern health care services will
work collaboratively to improve TB case detection, reduce care costs, and avoid diagnosis
delays. The standardized operational procedure of the full interventional package is
described below.
Phase 1: Preliminary phase A preliminary intervention package is developed by inviting TB
experts, and language professionals. The training manual is prepared and will deliver for
practitioners to increase their knowledge and skill. Based on the provision of training
contents, the knowledge gain and skill acquisition will be evaluated. The fidelity of the
intervention is developed to monitor the whole implementation activities of the training
manual as planned.
Phase 2: Preparation for implementation and refine on a small scale In this phase, numerous
activities related to the intervention will be performed. Experts who can implement the
intervention will be recruited based on experts' educational status (who have earned a BSc
degree and above in nursing or public health or medical doctor), and have research and
working experiences at TB clinic. A pilot test will be implemented outside the study area on
10% of the project sample size which is suggested by Connelly LM (2008)(287). Based on pilot
findings and experts' judgment, the intervention package will be refined and enriched. Before
the actual intervention is administered, a baseline data collection will be conducted on TB
case detection rate and diagnostic delay in both intervention and control sites.
Phase 3: Administering the intervention, feedback, and revision This phase is crucial that
the researchers are planning to administer intervention successfully. In this phase, a
full-blown intervention implementation will be conducted in the intervention areas.
Therefore, practitioners will screen all TB suspected cases at traditional care centers, and
every suspected case will be referred to modern TB care centers for further diagnosis and
treatment. Along with the administration of this intervention, the feasibility and
acceptability of the intervention will be assessed using standardized checklists (see annexed
checklist).
Phase 4: End line assessment of outcomes After the completion of the intervention period,
end-line data collection will be conducted on both intervention and control groups. The
outcomes of the intervention will be evaluated quarterly, half-year, and one year by trained
data collectors. The comparison will be done between the end-line and the baseline data in
both intervention and control groups.
Training on basic concepts of TB, causes of TB, signs, and symptoms, mode of transmission,
screening, diagnosis, case detection, treatment, the benefit of early detection,
complication, and prevention will be delivered to both traditional and modern care
practitioners. The training will also include topics about intergrading traditional and
modern health care systems. The training manual is prepared and annexed in this document (see
annex 7: Training manual). The training will be delivered at Bahir Dar University College of
Medicine and Health Sciences meeting hall. The training will be provided three times which
will be delivered every three months. In the first round, traditional practitioners will be
trained for 5 days. In this round, the training will be also delivered to modern health care
providers on how to communicate and work with traditional care providers for 2-day. Then, a
one-day interactive discussion session will be prepared for both traditional and modern care
providers. In the second round and third rounds, one-day training will be carried out at
three and six months. Training of the Trainer (TOT) will be given by researchers and those
experts who had TOT will provide training for traditional care providers (traditional
healers, priests, Imams, and pastors) and modern care providers (nurses, public health
officers, physicians, laboratory technicians/ laboratory technologists).
Furthermore, researchers will recruit traditional care providers (TCP) (traditional healers,
priests, pastors, and imams), and modern care providers (MCP) who can implement the
intervention. The traditional healers, priests, pastors, and imams will take a brief history
of patients' illnesses and complete the documentation properly. The suspected patients will
be referred to the nearby health facilities in the intervention district that fulfill the
inclusion criteria. Then, trained healthcare providers who are working in the selected health
facilities will screen and diagnose patients based on the national TB treatment guideline and
diagnostic algorithm. The intervention, content, duration, frequency, and dose are presented
in table 1 below.
The intervention of fidelity (IF) refers to the degree to which an intervention is delivered
as intended by researchers. The intervention fidelity is developed based on behavioral change
consortium treatment fidelity recommendations. The fidelity checklist is developed. This
fidelity will be used to monitor whether the intervention is applied exactly as we have
planned. The checklist depends on adherence, quality intervention delivery, dosage,
participant responsiveness, and compared between experimental and comparison groups. To
select the trainer, the authors will be select the trainer score more than 80% pass mark on
post-test to each content. The qualification of the trainee (practitioners) will be
considered after scoring more than 60% post-test to each content of the course. The content
of the training will be assured by recording and supervising each session (see annex table
3). The patient will be referred from traditional care centers to modern care centers using
the TB screening and referral form included in the annex (see TB screening and referral
form).
The control sites will be followed the existing passive case-findings system (self-referral
patients to nearby health facilities that use the same national guidelines to treat TB). The
baseline information will be assessed in both intervention and control groups at the same
time. The findings obtained from the control groups will be compared with the intervention
groups. Finally, changes among the two groups will be assessed and concluded.
Sample size determination: To estimate the effect of integrating traditional care with modern
care on TB case detection, cost of TB care, diagnosis delay, and patient satisfaction, the
sample size is calculated by using the two-sample comparison of proportions formula using
STATA version 16. Fisher's exact test for two independent groups is used to calculate the
final sample size.
By considering, the previous study conducted in the Amhara region with the proportion of
59.9% and 0.05 two-tailed alpha, power 80% by assuming that the effect of the intervention on
diagnosis delay decreased by 15% in the intervention group as compared to the control. Adding
10% contingency, the final sample size is 814 (407 in each arm). Since the study is a
multicenter individually randomized trial, a design effect is used. According to the
multicenter design effect formula, design effect formula is design effect=(σe^2)/(σe^2+σB^2 )
= 1-ρ. The majority of formulas applied on multicenter design with better accuracy relative
difference (ICC lesser than 0.052) for designs including more than 10 centers. Assuming that
randomized is balanced and stratified on centers that have equal group sizes. Assuming the
variation between the centers is 0.05, the design effect = 1-ρ=0.95. Therefore, the sample
size is taken as the final sample size is calculated as sample size* design effect
814*0.95=774 (387 per group).
Participant recruitment and randomization: Randomization is stratified by the district. Based
on the list obtained from the zone, two Woredas and two town administrations will be selected
by random sampling methods using a random.org website. Of these, one district and one town
administration were assigned in the intervention group, and another district and town
administration were assigned in the control group. All health facilities and traditional care
centers will be allocated to intervention or control arms using random.org. Allocation will
be carried out by a trial statistician before the intervention or patient recruitment. Using
the rule of thumb assumption, about 20% of districts in the South Gondar Zone will be
selected randomly for this study. For the cluster, randomized control trial, the
intervention, and control districts have been randomly selected. Based on the random sampling
approach Dera woreda and Debre Tabor were selected as intervention sites and Libokemkem
woreda and Woreta town were selected as control sites. The intervention and control sites
have almost similar baseline TB case detection rates. In addition, health facilities to
population ratio, traditional care providers, and socio-culturally aspects of both
intervention and control sites are almost similar. The random allocation process, enrolling
participants and participants assigned in the intervention group will be done by
statisticians who will not have awareness about the characteristics of the intervention and
control groups using the computer random.org website. The study subjects will be unaware of
the intervention they received. Laboratory personnel who will be involved in the tuberculosis
diagnosis and a person who will assess the outcomes of intervention will be unaware of the
group assignment. Intervention outcomes will be assessed by research assistants who are not
participating in participant recruitment and they are masked. The study participants,
caretakers/attendants, and healthcare providers will be masked at any point.
Trial safety and adverse effects monitoring: Integrating traditional care with modern care is
the trial-tested by this study. This trial will not directly involve any procedures or drugs
that affect the study participants and there has no known risk of any adverse event. A
multi-disciplinary group of specialists i.e. Data Monitoring Committee (DMC) will be formed
that makes recommendations to those in charge of the overall management of the trial. Also,
interim analyses will be conducted based on the pre-specified trial protocol to minimize bias
from unplanned analyses. DMC recommendations will be included either: continuing the trial as
planned; stopping early for hazard; stopping because efficacy is unequivocally established,
or stopping because continuing the trial is futile.
Trial adherence and compliance monitoring: Ongoing process evaluation of the intervention
will be carried out. Regular monitoring of intervention and control groups will be taken
place by trained assessors. Overall adherence of intervention and control of study
participants in trials will be assessed using self-report and direct observation by trained
field supervisors.
Participant retention strategies: Once TB suspected individuals are enrolled in this study,
trained traditional healers and clergy will provide health promotion and avocation to the
patients who go to modern care centers (health facilities) with referral letters. Regular
communication and feedback will be made between the supervisors and modern and traditional
care practitioners to minimize the attrition rate of intervention participants from the
study.
Participant withdrawal criteria: At any time, a subject can voluntarily withdraw from
participation in some or all components of a study for which the subject previously consented
to participate, the researchers may terminate a subject from some or all study components at
any time at his or her discretion. The subject will be terminated from the study by the
investigators that are believed the subjects' safety is compromised or feeling of
discontinuation described by the subject. When the research team decided to withdraw the
subject from the study, the reason will be informed to them. The data will be handled by
obtaining additional identifiable private information from any source such as medical
records, or any laboratory samples that have not yet been analyzed. In addition, retaining
and analyzing previously collected data.
Study variables: Outcome variables of this study are case detection rate, diagnostic delay,
cost of TB care, and client satisfaction. On the other hand, the independent variables are
socio-demographic variables such as gender, age, educational status, marital status,
occupational status, religion and income and stigma related to TB infection, patients
knowledge on TB, health-seeking practice, contact history, accessibility of facilities for TB
diagnosis, transportation access, presence of treatment support and distance.
The outcome variables will be measured based on their outcome interest. Case detection rate
will be calculated as the number of cases notified divided by the number of cases estimated
for that year, expressed as a percentage. The WHO estimator for the year 2020 was 140 per
100,000. To estimate the number of TB cases for that year will be computed by using
X/100,100* total population of the catchment area equal to Z. Where "X" is given by the WHO
for that year, it is varied across the countries and "Z" is several cases estimated for that
year. Thus, CDR=number of cases notified divided the number of cases estimated multiplied by
100 or (notified cases/Z)* 100, expressed as a percentage.
To assess patient satisfaction a short form patient satisfaction questionnaire (PSQ-18) which
is a validated tool adapted from a previous study. In addition, the tool is adapted from
patient satisfaction literature. Patient satisfaction with the latest visit will be assessed
using five items on a five-point Likert scale ranging from strongly disagree (1) to strongly
agree (5). The patient will be considered satisfied when the individual scores above the
mean.
These are payments made directly by the patient or their household member. Direct medical
payments will include payments for formal medical professionals, informal traditional or
alternative practitioners, clinics, health centers, pharmacies, and hospitals for medical
services and products. This will exclude prepayment for health services for example health
insurance payments and where relevant, net of any reimbursements to the individual who made
the payments. The other will be non-medical direct costs including travel, accommodation,
food, or other non-medical payments that are incurred by the patient, their household member,
or caregiver/guardian while picking up medication or during the visit/hospital stay for TB
care. The sum of the direct medical and non-medical costs for the different phases/entire
episode is used as the numerator.
Indirect costs can be estimated using two alternative methods: self-reported household income
loss net of welfare or social assistance payments. This includes the cost that the caregivers
bear by contributing their time and in-kind services. Any gain or loss of income reported
during each phase or for the entire episode is considered the total indirect cost. The
opportunity cost of time spent away from the daily productive routine. Participants are asked
to self-report time spent seeking and receiving care as well as the average number of hours,
they work each day if this changed since the last interview, and if so, by how much. The time
total period of absence (in hours) is multiplied by the hourly wage rate of the absent
worker. The hourly wage can be estimated from directly reported data, household asset
ownership, or national statistics. Indirect costs for the different phases/entire episode
will be used as the numerator in the catastrophic total cost equation. The indirect cost will
include productivity loss of the patients and caregivers during TB care. The catastrophic
cost will be a total cost of tuberculosis care (including the direct and indirect cost)
exceeding 20% of the annual income of the household. Costs will describe using quartiles and
expressed as the median and 25-75th interquartile range. Patients with costs >75th quartile
will consider having high expenditure and costs <75th quartile will consider as a low-cost
expenditure.
Sampling procedure and technique Study areas and subjects will be selected randomly. For the
first objective, all forms of TB cases in the health facilities will be taken from patients
in the health facilities. For the second, third, and fourth objectives a proportional
allocation will be done for each health facility and participants will be selected randomly.
All health facilities providing TB diagnosis and treatment service will be identified.
Data collection methods: A structured questionnaire will be adapted from previous literature.
The structured questionnaire was composed of socio-demographic and socioeconomic,
perceptions, patient knowledge, service accessibility, stigma, contact history, patients'
satisfaction, cost of TB (catastrophic cost), diagnosis delay, and healthcare-seeking
practices. The questionnaire will be translated into the national language (Amharic) spoken
by almost all residents in the study area. The data will be collected using face-to-face
interview questionnaires. The data will be collected by BSc nurses or public health officers
who had data collection experiences. Nurses or public health officers who had MSc/MPH degrees
will be selected for data collector supervisors. The data will be collected at baseline and
the end of one year of the intervention.
Data quality assurance: Data collectors will be recruited from BSc nurses and health
officers. The data collection will be supervised by experienced MSc nurses or MPH experts who
have sufficient experience in supervision. Training which comprised of the aim, methodology,
sampling technique, ethical issues, and data collection instrument and data collection
procedure will be prepared and delivered for implementers, data collectors, and supervisors.
The training will be done by researchers. Professional and language experts will invite to
validate the tools, training guidelines, and intervention manuals. Then, the tool will be
examined by conducting a pretest among 5% of study participants in non-selected woredas. The
intervention will be conducted by experts who have certificates in TB training. The necessary
amendment will take place based on the pretest findings. The researcher will be in regular
contact with the data collectors with scheduled meetings and other communication channels as
needed to maintain the quality of data. To minimize data entry errors, a double data entry
method will be used. Buffering zone will be considered between the intervention and control
areas to avoid information contamination. All potentially eligible populations in the
selected areas will be included in the study. The primary outcome assessors will be unaware
of the intervention. The primary assessor will be a trained TB expert who has no information
about the intervention group and control group. Additional outcome measurements will be
performed in the same manner in both arms. The data will be analyzed using intention-to-treat
principles. To ensure the quality of methodological components, a Consolidated Standards of
Reporting Trials 2010 statement extension to cluster randomized control trial study guideline
will be used and to ensure better reporting of the intervention Template for Intervention
Description and Replication (TIDieR) checklist will be used.
Data processing and management: In the field, data will be checked for consistency and
completeness every day by supervisors and the principal investigator. Then, a data entry
template will be created on EpiData version 3.1 based on coded responses. Data clerks will
enter the data of which 10% will be randomly double-checked by the principal investigator.
The data will be then exported to STATA version 16 where further recoding and cleaning will
be done to check for inconsistencies, outliers, and missing values. Finally, the cleaned data
will process and analyzed using STATA. Before further processing of the data, numeric data
will be checked for normality using normality plots (Q-Q plots and/or histograms) or
normality tests. Internal consistency (Cronbach's Alpha (α) =0.75) will be also checked for
the reliability of the items.
Description analysis: The data will be described using frequency, proportions, mean, median,
standard deviation, interquartile range, tables, and graphs. Comparisons of proportions among
categorical variables will be made using the Chi-squared test. Also, associations between
numeric variables will be examined using simple correlation analysis. For those variables
which have a normal distribution, a comparison of mean among different categories will be
made using independent t-test, paired t-test, and one-way Analysis of variance (ANOVA). For
non-normal distributions, median across categories will be compared using a nonparametric
test. In all the tests statistical significance will be judged at p<0.05. Generalized
Estimating Equation (GEE) with a binary logit function will be used to examine the change
difference of outcome between the intervention and control groups. GEE will be run to
accommodate the correlation of observations within subjects. The correlation matrix test will
be assessed and the fit model will be selected. The effects of potential confounding factors
will be accounted for. The change difference between independent and dependent variables will
be analyzed. The effect of the intervention on the TB case detection rate will be assessed at
the end of one year. Odds ratios and respective 95% confidence intervals will be calculated
and p values < 0.05 will be considered statistically significant.
Generalized linear mixed models (GLMM) will be used to assess the impact of the intervention
on the change of cost of TB care over time and diagnosis delay. This GLMM enables to
accommodate the correlation of observations due to the pre and post-intervention measurements
and clustering individuals within randomly selected clusters. Model fitting will be checked
before the analysis is done. The effects of potential confounding factors will be controlled.
The variance of the cluster-level residual errors will be computed using the intercept-only
model. The variation between and within the groups will be analyzed.
Patient satisfaction-related data will be analyzed using STATA software V.16.0. Owing to the
ordinal nature of the outcome variable (low, medium, and high satisfaction), a typical
approach will be used to use the standard ordered logit. The assumption will be checked.
Independent variables will be checked as continuous, categorical, or ordinal. The
Multi-collinearity test will be checked whether two or more independent variables are highly
correlated with each other. In addition, proportional odds will test that each independent
variable has an identical effect at each cumulative split of the ordinal dependent variable.
Statistical significance for the final model was set at p<0.05.
Qualitative methods Regional, zonal, and district TB focal persons, traditional healers,
religious leaders (clergy), Pastors and Imams as well as health care providers will be
participated in in-depth interviews (IDI) and focus group discussions (FGDs). The purposive
sampling method will be used to identify and select information-rich subjects for the most
effective use of limited resources. Tentatively the sample size will be 60 (10 focuses group
discussions (FGDs)) each group will contain 6 members), 50 In-Depth Interviews (IDI).
Qualitative data collection methods: To obtain more evidence that is detailed linked to the
study, both FGD & in-depth interview data collection methods will be applied. Interview
guiding questions will be developed from similar literature. Question guides for FGDs and IDI
will be prepared based on the context of the study participants. The interview guide will be
prepared in English. The IDI or FGDs will be conducted by the local language Amharic. The
data will be collected by the researcher. All conversations will be captured by audiotape
recorder. Data will be collected until saturation of response is assumed to be maintained.
The saturation of the response will be decided based on the adequacy of information,
completeness of the information, and little new information coming from the interviewees and
discussants. The interview will take place at a convenient place and time. Ten FGDs each
consist of at least six members. According to scholars' suggestions, 50 participants will be
adequate for IDI. The IDI will be conducted among health workers, TB focal persons,
traditional healers, Imams and clergy, and traditional healers. In addition, FGDs will be
conducted among TB patients. The IDI and FGDs guiding questions will be checked by language
experts, professionals, and senior consultants to maintain the quality of the tool. The
guiding questions were translated into the official language, Amharic to easy understanding
by the interviewees. Then, it will be translated back into the English language to maintain
consistency. Before FGDs and IDI are conducted, quiet rooms or settings will be arranged in
the field.
The data will be analyzed using sequences of steps. First, the data will be prepared and
organized. The recorded interview will be transcribed all data from voice to text verbatim.
Then, the data will be printed out the transcripts, gather your notes, and documents. Data
transcription will be done by the researcher to assure the dependability of the
transcription. The transcribed data will be checked for its consistency. When there is
variation in transcription between the transcribers, the discussion will be made by the
researchers. The transcribed data will be translated to the English language for the
subsequent analysis. Secondly, the data will be reviewed and explored. Thirdly, after
repeated reading, the researcher will create initial codes using highlighters, notes in the
margins, sticky pads, concept maps, or anything else that helps the researcher to connect
with the data. Fourthly, review those codes and revise or combine them into themes. Finally,
themes will be presented cohesively. Thematic analysis will be used to describe the data
obtained with interviews and focused group discussions. In vivo Software will be used for
data analysis and the result will be explained after the consensus is reached.
Ethics: The study will be approved by an institutional review board (IRB) of Bahir Dar
University, college of medicine and health sciences. Informed consent for adult participants
and assent for pediatrics participants will be obtained before data collection started. The
purpose of the study will be communicated and permission will be obtained from the respected
officials; the regional health bureau, respected zonal, words health offices, and health
facilities.
Participation of the study subjects will depend voluntarily. Hence, informed consent will be
taken from the study subjects. The information sheet, adult informed consent, and written
assent forms are prepared (Annex 1-3). The information included the purposes of the study,
the rights of participants, potential benefits, and harms of the study. The study will not
consider any financial compensation for participation. Participants will not enforce in any
way by anybody to take part in the study. To ensure the confidentiality of the information
provided by the participants, personal identifiers will not be included. In addition,
questionnaires will be kept in a locked cabinet and data in a password-protected computer
accessible to the principal investigators. The study will not have any harm to participants
and effort will be made to maximize the benefit to the participants.
