The study is a pragmatic, single-centre, three-arm, parallel, open-label, stratified
cluster-randomized controlled trial with 1:1:1 allocation.
“Pragmatic” means the study (interventions) would occur in natural settings or real
live situations. A cluster is defined as a geographical community or village(s)/settlement(s)
(with at least 250 households or a population of 1,500 people) serving as the proximate catchment area for at least one public primary health facility
and one patent medicine vendor (PMV) within the study sites/strata in Ebonyi state.
A three-arm parallel design, with equal number of clusters in each arm and equal sample
size in each cluster, will be used to assess the effect of two interventions compared
Control Arm: No intervention. This arm involves the usual practice of provision of MRDT services
by individual health care providers (in public health facilities and PMVs) with basic
training in MRDT. Patent medicine vendors that have offered the MRDT service previously
but are not currently doing so will be re-supplied with MRDT kits to resume provision
of MRDT services for the study period.
Social Group Arm: Social group intervention. This arm involves control treatment plus the sensitization
and education of social groups about MRDT.
Social Group/Provider Arm: Social group/provider intervention. Control treatment, the sensitization and education
of social groups about MRDT plus the training of health care providers in health communication
with patients/caregivers (clients) about MRDT.
The trial protocol development was guided by the Standard Protocol Items: Recommendations
for Interventional Trials (SPIRIT) 2013 checklist (see Additional file 1).
The study is being conducted in three sites/strata in Ebonyi state, south-eastern
Nigeria. Ebonyi state is located in the south-east geopolitical zone of Nigeria between
latitude 50 40’ and 60 54’N and longitude 70 30’ and 80 30’E with land area of 5,953 sq. km.35 It shares borders with Benue state to the north, Enugu state to the west, Cross River
state to the east, Imo and Abia state to the south.35,36 The State lies in the Cross River plains with rainy/wet season from April to October
and dry/harmattan season from October to March.35 Floods often occur during the rainy season due to poor drainage systems, stagnant
rivers and ponds which expose the State to mosquito infestations and high malaria
burden.35 The vegetation of the state is mostly savannah in the drier northern part and forests
in the wetter southern part.35
The state’s projected population for 2016 was 2,897,401 (based on the 2006 national
census figure and a growth rate of 2.8 percent) with male making up 48.62 percent,
female is 51.38 percent and under-5 years age group is 20 percent.35 The people of Ebonyi are primarily of the Igbo language and ethnic extraction with
ten dialects/minor languages spoken across the state.36 English, especially its local variant, the pidgin, is a widely spoken language in
the state. People of other languages and ethnic groups in Nigeria also live in the
state especially in the capital and urban areas. Most inhabitants practice Christianity.36 The State is divided into 3 senatorial zones (Ebonyi north, Ebonyi central and Ebonyi
south), with 13 Local Government Areas (LGSs) (with Abakaliki LGA as the administrative
and political capital), 64 development centres, 138 autonomous communities and 215
political wards.35 Each autonomous community has a traditional ruler and consists of autonomous villages
each having a village head called chairman. Each autonomous village is made up of
smaller villages or settlements each having a village/settlement head.
The public sector is the main driver of the State economy and agriculture is the major
occupation.36 The state has several solid mineral resources (including lead), crude oil and natural
gas36 but there are few large-scale commercial mines and industries.35,36 The state is called "the salt of the nation" because of huge salt deposit at the
Okposi and Uburu Salt Lakes.36 Traditional industries and works of art include blacksmithing, pottery works and
wood works (carved doors, stools, walking sticks, traditional flutes, wooden mortars
Health care in Ebonyi state (like other states in Nigeria) is provided by the public
and private sectors under the overall guidance of the federal government through the
federal ministry of health (and its agencies) and the national council on health.
The federal government (through the federal ministry of health – FMoH) provides health
services in the state through tertiary health
facilities. The state government (through state ministry of health – SMoH) provides health care
through secondary health
facilities (general hospitals). The state government also supports the local governments in
providing primary health care (PHC) through PHC
facilities. The Ebonyi state Malaria Elimination Program (SMEP), within the department of public
health in the state ministry of health, coordinates the efforts to combat malaria
in the state.
Other health care service providers recognized by the National Health Act 2014 include
the private healthcare providers, traditional healthcare providers and alternative
health care providers.37 These can be grouped as the private health sector and subdivided as: formal private
sector (private hospitals and clinics) and informal private sector (pharmacies, patent
medicine vendors (PMVs), traditional healers and alternative health care providers).4 Majority of febrile patients, especially from the lower socio-economic groups seek
care primarily in the informal private sector.14,16,18
The three study sites/strata consist of the three senatorial zones: Ebonyi north,
Ebonyi central and Ebonyi south. Ebonyi north consists of four local government areas
(LGAs) with a 2016 population of 998,473.38
Two of these LGAs, Abakaliki LGA (the state capital) and Ebonyi LGA, have contiguous
urban areas that jointly constitute the city/metropolis of Ebonyi state. However, Ebonyi north is a predominantly rural area. The vegetation is mostly savannah
and it is drier than the other sites. Ebonyi central consists of four local government
areas (LGAs) with a 2016 population of 861,55438 and is a predominantly rural area. The vegetation changes from savannah towards forests
and the weather become wetter as one move through this central zone southward towards
the southern zone. Ebonyi south consists of five local government areas (LGAs) with
a 2016 population of 1,037,37638 and is also predominantly rural. The three sites are all endemic for malaria with
year-round transmission and a high malaria burden.
Participants and participant timeline
that will be included to participate in the study include villages/settlements (a community) that have at least one eligible
public primary health care facility and one eligible patent medicine vendor (PMV)
(see below) and are easily accessible (close to a motorable road) even in the rainy
season. Clusters either participating in or that participated in any similar interventions
within the preceding one year will be excluded from
participating in the study. Clusters that are too close (less than 15kms apart), and not separated
by a buffer area or natural barrier, and urban clusters (in cities/towns) will be
participating in the study to minimize contamination between clusters within strata.39,40 Non-consenting clusters will also be excluded from
participating in the study.
Social groups are any set of persons within society with particular demographic, economic
or social characteristics.41 Examples of social groups include women associations/meetings, village meetings,
men associations, youth associations, market/trade unions, elders’ fora, parent-teacher
association etc. Social groups that are recognized by cluster heads/authorities will
be included to participate in the study and non-consenting social groups will be excluded. </p>
Primary health facilities and individual health care providers
Eligible public primary health facilities are those providing MRDT services, maternal
and child health care services including immunisation; attending to at least an average of four fever cases (or suspected cases of malaria)
per day and having at least two staff that are at least junior community health extension
workers (JCHEWs). Individual public health care providers involved in the diagnosis (and treatment) of malaria in these facilities are eligible. Eligible patent medicine vendors (PMVs) are those with basic training in MRDT services and either currently offering or previously offered
MRDT services. Non-consenting health facilities and individual providers will be excluded
from the study.
Households and community members
Households will be eligible to participate
in a population-based household survey if there is a report of any case of fever or suspected malaria among under-5 children,
5 years and above children, and adults (excluding pregnant women) in the household
in the preceding two weeks to the survey. For each household, consent will be obtained
from the mother of the house or the female primary care giver who will be the respondent
to the survey.
Non-consenting households will be excluded from the survey.
After the baseline household survey, community members that have resided in the community for at least two years will
be eligible to participate in a focus group discussion (FGD).
Non-consenting community members will be excluded from the FGD.
Informed consent to participate in the study will be obtained from the selected eligible
participants (clusters, social groups and providers) before clusters are randomly
allocated into the three study arms. The main study outcomes will then be measures through
a baseline household survey and an end-line household survey three months after the
end of intervention. The participant timeline is depicted below in accordance with
the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline
(see figure 1).
The interventions in this study include: (1) the sensitization and education of social
groups about MRDT (social group intervention) and (2) the sensitization and education
of social groups plus the training of health care providers in health communication
with client’s about MRDT (social group/provider intervention). Participants in the
control arm will not receive any of these interventions.
The sensitization and education of social groups
The social group intervention will involve the sensitization and education of social
groups within each cluster in the social group arm. There will be three episodes of
group discussion/interaction, one per month, with each social group during the intervention
period of three months. Health education messages designed to change wrong beliefs
and perceptions, promote right beliefs and perceptions, increase knowledge and promote
key actions will be communicated to social group members in an interactive session/group
discussion. The health education message is adopted from a national framework42 and modified for the study.
Each discussion will be a one-hour event. One investigator will moderate each discussion
with a group discussion guide. In order to make the intervention more pragmatic and
to optimize adherence to trial intervention, the discussions will take place at the
usual meeting time of each social group, or at an agreed time, and at their usual
meeting point/venue or at a central location as is most convenient for the participants.
The intervention will be discontinued for a social group or cluster whenever such
request is made by the respective social group head/leader or cluster head/authority.
The first episode will be divided into seven sub-headings viz: (1) introduction (2)
individual beliefs and opinions (3) key facts about malaria (4) key facts about MRDT
(5) demonstration of testing with MRDT kit (6) key actions to practice and promote
(7) closing remark. The moderator will explain the research problem and objectives
to the participants and the broad role the participants (social group members) are
expected to play in addressing the problem. Each participant will then share his/her
beliefs and opinion about malaria with respect to cause, symptoms, complications/fatalities,
diagnosis, treatment, where to seek care and why, and prevention. The discussion will
explore the reasons for and against these views and there will be questions and answers
from participants. The moderator will then highlight the key facts about malaria.
Key facts about MRDTs will also be highlighted and discussed. Demonstration of MRDT
will be done on volunteer participants, the procedure will be explained, the results
interpreted to them and those that test positive will be treated with an ACT.
The moderator will then highlight and discuss the key actions that the participants
should exercise and promote as individuals, social group members, opinion leaders,
parents, heads of households, family members, friends and relatives, neighbours etc.
These actions include recognizing the symptoms of malaria especially in under-5 children;
promptly seeking care with providers that carry out MRDT (preferably in
the public primary health facilities) and requesting for the “simple test” for malaria (MRDT), receiving the test, asking
for the result, and receiving treatment for malaria (with ACTs) only when the test
is positive; making sure under-5 age children receives treatment within 24 hours
of on-set of fever; acquiring and giving the right ACTs, in the right dose, for the right number of days.
The moderator will then give a closing remark and thank the participants for their
The second and third episodes will take similar format as the first but will focus
more on re-emphasizing the key facts and actions to practice and promote so as to
reinforce participants’ knowledge and attitude. The participants will be encouraged
to share their experiences in the preceding four weeks for discussion and clarifications.
Visits to the social groups will end with the third episode of group discussion. However,
the cell phones of the investigators will be open to group members who might still
sought clarifications about malaria and MRDT during the subsequent months.
Other supportive interventions will include at least weekly reminder text messages
to social group members that have cell phones; regular phone calls to social group
heads (to urge them to remind and encourage the group members during meeting sessions)
and regular visits by a provider (PMV or public) to the scheduled meetings of each
social group for provision of MRDT services and ACTs for positive results.
The training of health care providers
The clusters in the social group/provider arm will also receive the social group treatment
as described above and in addition, will receive provider training in health communication
with clients. Health communication involves the use of communication strategies to
inform and influence individual and community decisions that enhance health and it
is a vital aspect of provider-patient relations.43 The provider training will involve a one-day sensitisation and training workshop
for the participating health care providers at the Abakaliki (the capital of Ebonyi
state). The research team will administer the workshop with the aid of a power point
projector, a provider training guide and a health communication guide. There will
be a pre-post-test to assess the knowledge of participants with respect to malaria,
MRDT and communication. The training will be divided into two parts with four sessions
in each. The first part will focus on sensitising the participants. The four sessions
include (1) Pre-test (2) Background information: on the research problem and aim (objectives)
and malaria (3) Demonstration of testing with MRDT kit (4) Key actions to practice
and promote. The facilitators of the training will use a power point presentation
to highlight the objectives of this part of the workshop and then to present an explanation
of the problem he research wants to address and how, the objectives it hopes to achieve
and the broad role the participants/providers are expected to play in this respect.
Volunteer participants will then perform and receive MRDT, explain the procedure and
interpret the results. This will be followed by a question and answer session on the
sensitivity and specificity of MRDT, adherence to test results and what to do if result
is negative, the benefits of universal testing and complete adherence to test results.
The facilitators will then highlight the key actions that need to be practiced and
promoted by providers. Questions and comments will be respectively answered and discussed.
The second Part of the training will focus on improving the health communication skills
of participants with the aid of a health communication guide. The four sessions in
this part include (1) Background information on health communication (2) Practical
session (including simulation) on health communication with clients (3) Closing session
and filling of assessment forms (4) Post-test. The facilitators will use power point
presentation to highlight the objectives of this part of the workshop and to talk
about communication and health communication with regards to definitions, communication
components, process, channels/media, types, aids etc. This will be followed by a practical
session and simulation of real life situation. The facilitators will then divide the
participants into two groups – public provider group and private provider group. Each
group will be sub-divided into clients and providers. Each client/patient sub-group
will visit their respective providers with malaria-like illness. Their providers will
then engage them in health communication about malaria and MRDT (with or without the
use of a self-written/improvised guide). The strengths and weaknesses of each group’s
communication techniques during the simulation will be noted by the other group. These
will be read out by a facilitator for discussion by all parties.
The facilitators will then introduce the participants to a health communication guide
on how to effectively educate their clients during the discharge of their duties.
They will be educated on how to use the guide in communicating with all categories
of clients including those that requested for MRDT or freely accepted providers’ suggestion
of a test or initially declined from doing the test. The participants will then apply
the guide in another round of simulation exercise. Participants will then fill an
assessment form on which they will rate the training process and logistics, state
what they believe or know previously that has now been corroborated, what they believe
or know previously that has now been contradicted, what they just learnt for the first
time, any additional key actions that can be taken or promoted to increase the use
of MRDT and adherence to test results. The participants will be encouraged to use
the health communication guide to effectively communicate with their clients (suspected
malaria cases) about MRDT at the course of their regular duties. A facilitator will
then give the closing remark and implore the participants to develop their communication
skills by putting it to practice immediately.
The training workshop will be followed by a twice weekly reminder text messages and
a monthly visit to each of the participating provider for supportive supervision (on-the-job
training) and monitoring throughout the rest of the three month intervention period.
Each support visit will aim at assessing providers’ performance, exploring their experiences
in the previous weeks and addressing their challenges in health communication with
their clients. The on-the-job training will make the intervention more pragmatic and
will optimise adherence to the trial intervention. The intervention will be discontinued
for a health care provider whenever such request is made by the respective provider.
The trained providers will also be subjected to mystery client monitoring. The mystery
client assessment of providers' performance will guide the researchers in properly
identifying those that require more attention and in what specific areas during the
support visits. Mystery clients will be trained on how to interact with providers
and how to fill the assessment form thereafter. A mystery client will visit a participating
provider/health facility and claim he has malaria based on familiar symptoms. If proposed
by provider, he will freely accept MRDT otherwise, he will request for MRDT. He will
all the while note whether the provider engaged him in health communication with basic
standard techniques. He will then fill the assessment form after leaving the provider.
Each provider/health facility will be visited by a mystery client at least twice.
The primary objectives include:
To evaluate the effectiveness of the sensitization/education of social groups about
MRDT (social group intervention) in increasing the demand (use and/or request) for
MRDT compared to usual practice (control)
To evaluate the effectiveness of the sensitization/education of social groups about
MRDT and training of providers in health communication with patients/caregivers about
MRDT (social group/provider intervention) in increasing the demand for MRDT compared
to usual practice (control)
To evaluate the effectiveness of the social group/provider intervention in increasing
the demand for MRDT compared to the social group intervention
The secondary objectives include:
To evaluate the effect of the interventions on the care seeking practices and anti-malarial
drug use pattern among community members
To assess the effect of the interventions on the knowledge and opinion of respondent
female heads of households (female primary care givers) about malaria and malaria
To evaluate the effect of the interventions on the number of suspected malaria cases
visiting the public primary health centres
To assess the effect of the interventions on the knowledge and opinion of health care
providers and their practice of health communication about malaria and malaria diagnosis
To evaluate the cost-effectiveness of the interventions
To assess the level of demand (use and/or request) for MRDT, care seeking practices
and anti-malarial drug use pattern among community members with fever or malaria-like
To assess the knowledge and opinion level of female head of households (female primary
care givers) and of health care providers about malaria and malaria diagnosis
To ascertain the factors that influence the demand for MRDT among community members
The social group intervention is more effective (and more cost-effective) in increasing
the demand (use and/or request) for MRDT compared to control.
The social group/provider intervention is more effective (and more cost-effective)
in increasing the demand for MRDT compared to control and compared to social group
The social group intervention is expected to enhance the knowledge and opinion of
community members about malaria and malaria diagnosis as well as their preference
for MRDT. This will lead to a moderate increase in their demand for MRDT compared
to community members in the control arm. The social groups/provider intervention is
expected to (to a greater extent) enhance the knowledge and opinion of the community
members and their preference for MRDT. This intervention will also enhance the knowledge
and opinion of health care providers about malaria and malaria diagnosis as well as
their preference for MRDT. These will lead to a large increase in the demand for MRDT
among community members compared to community members in the control arm. The summary
of the study’s logical framework is shown in Figure 2.
primary outcome is the proportion of under-5 children with fever or malaria-like illness in the preceding
two weeks to a population-based household survey that received MRDT.
co-primary outcome is the proportion of 5 years and above children and adults (excluding pregnant women)
with fever or malaria-like illness in the preceding two weeks to a population-based
household survey that received MRDT.
The main secondary outcomes at the community level include:
The proportion of these under-5 children, that received MRDT, whose caregivers requested
for the MRDT
The proportion of these 5 years and above children and adults, that received MRDT,
that requested for or whose caregivers requested for the MRDT
The proportion of under-5 children with fever or malaria-like illness in the preceding
two weeks to a population-based household survey whose caregivers sought care with
a provider, those that sought care the same or next day and among those for whom care
was sought, type of provider with whom care was sought.
The proportion of these under-5 children that took any anti-malarial drug and those
that took ACTs.
The proportion of 5 years and above children and adults (excluding pregnant women)
with fever or malaria-like illness in the preceding two weeks to a population-based
household survey that sought care with a provider, those that sought care the same
or next day and among those that sought care, the type of provider with whom care
The proportion of these children and adults that took any anti-malarial drug and those
that took ACTs.
The proportion of respondent female heads of households (female primary care givers)
that have good knowledge and opinion about malaria and malaria diagnosis.
The secondary outcomes at the provider level include:
The number of suspected malaria cases visiting the public primary health facilities
(monthly) measured using patients’ register
The proportion of providers that have good knowledge and opinion and practice of health
communication about malaria and malaria diagnosis.
Total cost of the social group and social group/provider interventions, average cost
who participated in the provider training and average cost per social group member
who participated in the social group sensitization/education.
Measurement of study outcomes
Population-based household survey
Survey questionnaire adopted from the 2015 Nigeria Malaria Indicator Survey (NMIS)15 woman’s questionnaire, and modified to collect data on both the primary and community
level secondary outcomes will be pre-tested in non-participating clusters before the
survey. Interviewers will be recruited and trained over a one-week period to administer
the questionnaire. The training of the interviewers will include a detailed review
and explanation of the questionnaire items, interview techniques, how to provide information
to household respondents about the survey, how to obtain consent, the translation
of key words in the questionnaire to local language and how to administer the questionnaire.
Baseline survey will be carried out before intervention (see figure 1) to collect
data for the assessment of the level of demand (use and/or request) for MRDT among
community members with fever or malaria-like illness in Ebonyi state. A section of
the questionnaire will collect data on the determinants of the demand for MRDT. End-line
survey will be carried out three months after the end of intervention (see figure
1) to collect data for the evaluation of the effects of the interventions on the demand
for MRDT among community members.
The interviewers will be accompanied by research supervisors at the start of the baseline
survey for monitoring and supportive supervision. This will be followed by at least
once weekly visit for monitoring and supportive supervision. The household survey
questionnaire is designed to collect data about the following items from the respondent
female head of household (the mother of the house or female primary care giver):
Basic socio-demographic characteristics (of the respondent and of eligible household
members reported to have had fever/malaria in preceding two weeks)
Fever/malaria-like illness management including care seeking and demand for MRDT
Respondent’s knowledge and opinion about malaria and malaria diagnosis
The determinants of the demand for MRDT
Focus group discussion (FGD)
Focus group discussions (FGDs) will be conducted at baseline to collect data on the
factors that influence the demand (use and or request) for MRDT in the communities.
Nine (9) focus group discussions (FGDs) will be carried out across the three study
sites/strata. Participants will be purposively selected from among providers, male
and female community members (who have resided in the community for at least two years).
There will be three focus group discussions (FGDs) with providers, one per stratum;
three FGDs with male community members, one per stratum; three FGDs with female community
members, one per stratum.
Investigators will administer the focus group discussions (FGDs) using a focus group
discussion question guide prepared in English and pre-tested in non-participating
clusters. The focus group discussion question guide will consist of both very open-ended and more
targeted questions designed to explore the providers’ and community members’ knowledge
and practice concerning MRDT and their perceptions on the determinants of the demand
for MRDT in their communities/villages. The more targeted focus group questions are
based on the proximal determinants in the study’s logical framework. The more targeted
questions are combined with the very open-ended questions to identify additional determinants.
Before commencement of each focus group discussions (FGD), the investigators will
collect background data of participants such as age, sex, level of education, occupation,
years of experience with use of MRDT (for providers). Each FGD will consist of 8-10
participants and will last for about one hour. The FGD will be audio-recorded and
later transcribed (and translated) verbatim into English before analysis.
Provider survey will be conducted at baseline and end-line (three months after the
end of intervention) to collect data for the assessment of the effect of the interventions
on the knowledge and opinion of health care providers and their practice of health
communication about malaria and malaria diagnosis. The provider survey questionnaire
is similar to the household questionnaire and is modified to collect data about the
following items from the health care providers:
Basic socio-demographic characteristics
Knowledge and opinion about malaria and malaria diagnosis
The practice of health communication about malaria and malaria diagnosis
The determinants of the demand for MRDT
Review of patient register
and personal medical records
Patient registers are routinely kept by public primary health facilities. The following
relevant data are contained in the registers: patient’s biodata (name, age, sex, address
etc), date, symptoms, type of test done, test result, type of drug given. The participating
patent medicine vendors (PMVs) will be asked to keep similar records. The registers
will be used by the research team for monitoring, supportive supervision and evaluation.
The investigators will review the patient registers for the nine months pre-intervention
and nine months post-end-of-intervention records. The document review will provide
data for evaluating the effect of the interventions on the number of suspected malaria
cases visiting the public primary health centres.
Documentations of the implementation/intervention process
The process of implementation of the study will be documented including challenges
encountered and how these were addressed. The social group and provider intervention
processes will be documented and/or recorded with respect to the name of the participants,
participants’ phone number/contact, individual contributions, participants’ observations
and evaluation of the intervention logistics and suggestions etc. The study personnel
and the organisers of the interventions will also record their experience on challenges
and possible solutions. These data will be used for monitoring and to guide the implementation
of similar interventions in the future.
Costing of the intervention process
Direct and indirect costs of the intervention process will be assessed from the perspective
of the implementer of intervention and that of the recipient of intervention (the
societal perspective) using standard economic evaluation methods. Cost data will be
estimated primarily from the documentation of the implementation/intervention process
and the project financial accounts. The costing will be guided by the research budget.
Data management plan and quality assurance
During the household surveys, the research supervisors will revisit an average of
thirty households in each participating cluster with a specially designed questionnaire
to double check on responses and coverage. The supervisors will collect completed
questionnaires from the interviewers weekly and crosscheck/review for internal consistency
and completeness. Questionnaires with internal inconsistencies and or missing data
will be returned to the respective field staff for correction with the respective
respondent. The questionnaires will be serially (and uniquely) numbered and data will
be double-entered using Microsoft Excel 2007 (Microsoft Inc., Redmond, Washington)
and will be verified using Stata version 15 (Stata Corp, College Station, TX, USA).
The datasets compare utility in Stata will be used to verify the datasets and any
discrepancies identified will be crosschecked against the corresponding original questionnaire
and corrected before analysis. The variables and data in the dataset will also be
examined in details and range checks will be done to ensure the data entry was done
correctly and appropriately.
The audio recordings of the focus group discussions (FGDs) will be transcribed (verbatim)
within 24 hours of recording and translated into English before analysis. The questionnaires,
the audio recordings and the verbatim transcript of the focus group discussions (FGDs)
will be stored in secure area while the electronic data file will have a back-up file.
Access to study materials and data files by unauthorized persons will be prevented.
After comparing the required sample size for each of the primary objectives, the largest
sample size will be used. This is based on the primary objective to evaluate the effectiveness
of the social group/provider intervention compared to the social group intervention
in increasing the demand for MRDT in the communities. The sample size is estimated
using the methods recommended for stratified cluster randomized trial39,40 and will be based on the primary outcome of the proportion of under-5 children with
fever or malaria-like illness in the preceding two weeks to a population-based household
survey that received MRDT. A plausible estimate of the primary outcome of 11% in the
control arm, based on the reported value for the South-East zone (that includes Ebonyi
state) in the Nigeria Malaria Indicator Survey (NMIS) 201515, will be used.
Assuming a coefficient of variation between clusters within strata of 0.16, a sample
size per cluster of 40 eligible under-5 children, 80% power at 5% probability of type
I error, the trial will require 6 clusters per arm to detect a difference of 20%
in the primary outcome between the control arm and the social group arm (an increase
from 11% to 31%) and a difference of 20% between the social group arm and the socio
group/provider arm (an increase from 31% to 51%). A sample size per cluster (cluster
size) of 40 subjects with 6 clusters per arm gives a total cluster number of 18, with
240 subjects per arm and a total sample size of 720 subjects. The sample size per
cluster (of 40) will be
increased by 20% (to 50) to compensate for any probable invalid records and other field eventualities. This
gives a final cluster size of 50 subjects with 300 subjects per arm and a total sample
size of 900 subjects.
The same sample size will be used to assess the
co-primary outcome of the proportion of 5 years and above children and adults (excluding pregnant
women) with fever or malaria-like illness in the preceding two weeks to a population-based
household survey that received MRDT. Equal number of clusters (6) will be allocated
to each arm and to each stratum and, despite variations in population size of clusters,
equal number of fixed sample size (of 50 for each target population) per cluster will
be used to optimize statistical efficiency.39,40
Sample size is estimated for the provider survey to give the expected level of precision
(at 95% confidence level) for determining the proportion of providers that have good
knowledge and opinion about malaria and malaria diagnosis. Based on the number of
clusters (6) allocated to each arm and about 7-8 individual providers per cluster
who consented to participate in the study, we expect to survey 42 providers per arm
(7 per cluster). Assuming the outcome measure of 50% in each of the control and social
group arms and 70% in the social group/provider arm, with an intracluster correlation
coefficient (ICC) of 0.01, we can estimate the true outcome measure with ± 15.6% precision in each of the control and social group arms and ± 14.3% precision in the social group/provider arm.
Sampling technique (recruitment)
Stratified multistage (cluster) sampling will be employed. Eighteen clusters will
be randomly selected from a list of eligible clusters across three strata (6 in each
stratum) using the “sample” command in Stata. To enhance reproducibility, random-number
seed will be set using the “set seed” command before running the “sample” command.
If written consent is not provided by any of the selected cluster(s) before randomization,
replacement cluster(s) will be randomly selected from the remaining list of eligible
clusters using same technique. The summary of the trial profile is shown in figure
Within the selected clusters, an average of four eligible social groups per cluster
will be purposively selected and non-consenting social group(s) prior to randomization
will be replaced. All eligible and consenting health facilities
and the individual providers involved in the diagnosis and treatment of suspected
malaria cases will be selected across clusters before randomization. A number of eligible individual providers and community members, who have resided
in the community for at least two years, will be purposively selected for the focus
group discussion. All the households in the selected clusters will be enumerated and
screened for inclusion during the pre- and post-intervention surveys. If the required
sample size is not reached after the interviewers have reached the end of the enumerated
households, non-eligible households will be revisited and re-assessed to see whether
they have become eligible.
Randomization will be done using Stata version 12 (Stata Corp, College Station, TX,
USA). Stratified randomisation technique will be used to assign the 18 clusters across
the three strata to the three treatment arms, after written consent is obtained from
all recruited participants, by a statistician that will not otherwise take part in
the study. The 6 clusters within each stratum will be randomly allocated to the three
study arms in the ratio of 2:2:2 using a programme written in Stata. To ensure the
desired balance in cluster number in the study arms, restricted randomization technique
will be employed for the within strata allocation. The summary of the trial profile
is shown in figure 3.
It will not be possible to blind the interviewers that will administer questionnaires
in the household survey and the respondent female heads of households because of the
pragmatic nature of the trial as they could acquire treatment knowledge from informal
sources or grapevine. Some of the respondents could also be social group members or
providers. It will also not be possible to blind the investigators that will administer
intervention or participants that will receive intervention (social groups and providers).
Data will be double-entered using Microsoft Excel 2007 (Microsoft Inc., Redmond, Washington)
and analyzed using Stata version 15 (Stata Corp, College Station, TX, USA). Since
the number of subjects/household members about whom data will be collected is expected
to vary across clusters (due to the method employed for household survey), the “sample”
command will be used to randomly select equal number of subjects across clusters for
the analysis. All analyses will be by intention-to-treat.
The effect of the interventions on the primary outcomes will be analyzed using cluster-level
stratified cluster randomized trials with small number of clusters per treatment arm.39,40 Point estimates of the intervention effects (risk difference) in each intervention
arm compared to control and in both intervention arms compared to each other, will
be computed from the unweighted mean of cluster-level summaries (proportions) of the
outcome measures in each study arm. But since the cluster size (sample size across
clusters) is constant, this point estimate will be identical to that obtained from
the weighted average of individual values.39,40 Also, since the number of clusters across strata is constant, the estimated risk
difference will be identical to the weighted average of stratum-specific risk difference.
An overall test of the null hypothesis of no difference between any of the study arms
will be conducted in a two-way analysis of variance (2-way ANOVA) of the cluster-level
proportion on stratum and treatment arm. This overall test is to guide the interpretation
of any subsequent significant findings in pair-wise comparisons. If the distribution
of the cluster summaries in each study arm is markedly skewed, logarithmic transformation
may be considered before analysis. Before conducting pair-wise significance testing
and computing a confidence interval, an estimate of the within-stratum between-cluster
variance will be obtained as the residual mean square from a two-way analysis of variance
of the cluster-level proportions on stratum and treatment arm, including interaction
terms. The within-stratum between-cluster variance will then be used in a stratified
t-test to tests the null hypotheses of no difference in the primary outcomes between
each intervention arm and the control and between both intervention arms. It will
also be used in computing the corresponding 95% confidence interval of each risk difference.
Adjusted analysis based on cluster summaries will be done in a two-staged procedure.
In the first stage, covariate-adjusted residual will be obtained for each cluster
using standard multiple linear regression analysis, incorporating the stratum (as
a fixed effect) and all baseline cluster-level covariates of interest but excluding
the intervention effect. The potential baseline covariates of interest will include
cluster-level summaries of the primary outcome measures, mean knowledge and opinion
score of respondents (about malaria and malaria diagnosis) and other baseline variables
found to differ between the study arms and which can be determinants of a particular
outcome. Only cluster-level summaries of baseline covariates will be used in the adjusted
analysis because baseline and follow-up data will be on different individuals since
the study employed a repeated cross-sectional design.39,40 The difference-residual for each cluster will be obtained as the difference between
the observed outcome in each cluster and the predicted outcome in the absence of intervention
effect. The covariate-adjusted residuals will replace the cluster-level proportions
in the second stage in estimating the intervention effects which are thus adjusted
for the covariates in the first stage.
The same cluster-level methods will be used to evaluate the effect of the interventions
on the secondary outcomes. Comparative analysis of baseline data will be used to assess
the balance between the treatment arms and potential baseline variables that will
be reported include the cluster-level and individual-level summaries of the primary
and secondary outcome measures, the age and sex of individual subjects, the respondent
female head of household’s age, educational level, occupation, knowledge and opinion
level about malaria and malaria diagnosis, and average knowledge and opinion score.
Summary statistics of baseline data will be used to assess the level of demand for
MRDT, care seeking practices and anti-malarial drug use pattern among community members
with fever or malaria-like illness; the knowledge and opinion level of female head
of households about malaria and malaria diagnosis; the knowledge and opinion level
of health care providers about malaria and malaria diagnosis.
To ascertain the factors that influence the demand for MRDT in the communities, a
thematic analysis of the focus group discussions (FGDs) will be done using the method
recommended by Braun and Clarke.44 The audio recordings of the focus group discussions (FGDs) will be transcribed (and
translated) verbatim into English and the transcript will be compared with the original
recording to check for ‘accuracy’ before conducting the analysis. Exact and meaning-based
translation will be used. QDA Miner Lite 2 (by Provalis Research) will be used to
manage the coding and analysis process.