Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04428385 |
| Other study ID # |
Pro00105072 |
| Secondary ID |
5R01AI141444-02 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 15, 2021 |
| Est. completion date |
February 28, 2023 |
Study information
| Verified date |
May 2024 |
| Source |
Duke University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Highly subsidized first-line antimalarials (artemisinin combination therapy or ACT) are
available over the counter in the private retail sector in most malaria-endemic countries.
Overconsumption of ACTs purchased over the counter is rampant due to their low price, high
perceived efficacy, and absence of diagnostic tools to guide drug use. The ultimate goal of
the proposed work is to improve antimalarial stewardship in the retail sector, which is
responsible for distributing the majority of antimalarials in sub-Saharan Africa. Through a
combination of diagnosis and treatment subsidies and provider-directed incentives, this
approach will align provider and customer incentives with appropriate case management and
thereby improve health outcomes.
The main objective of this study (Aim 2) is to test two key interventions in a random sample
of private medicine retail outlets in Nigeria. This will be a cluster-randomized controlled
trial where the cluster is a private retail outlet that stocks and sells WHO quality-assured
ACTs. This two-arm study will test 1) a provider-directed incentive for testing and reporting
in combination with a consumer-directed intervention in the form of a diagnosis-dependent ACT
subsidy against 2) a comparison arm. Outlets in both arms will offer malaria diagnostic
testing to customers who wish to purchase one. Information for the primary and secondary
outcomes will be collected during exit interviews with eligible customers. The primary
outcome will be the proportion of ACTs sold to customers with a positive diagnostic test. The
main secondary outcome will be the proportion of suspected malaria cases presenting to the
retail outlet that are tested. Other secondary outcomes include adherence to the RDT result
amongst those tested (defined as taking a quality-assured ACT following a positive test and
refraining from taking an ACT following a negative test) and appropriate case management for
all suspected malaria cases (proportion tested and adhered among all suspected cases).
Description:
RATIONALE:
The investigators hypothesize that decision-making in the retail sector is influenced
primarily by price (or profit) supplemented by individual beliefs or preferences. Information
from a diagnostic test, when available, plays only a minor role in the decision-making
landscape. In response to this, the investigators propose to test a scalable, policy-relevant
strategy that integrates testing and treatment subsidies and makes ACT subsidies available
only to customers with a positive malaria test. Differential pricing based on the results of
the diagnostic test will align consumer and provider incentives (price and profit) with
testing and appropriate ACT use. The investigators' approach will also ensure that public
subsidies are directed at confirmed malaria cases thereby enhancing the sustainability of
such programs. By allocating subsidy dollars across both testing and conditional treatment
(rather than universal, treatment-only subsidies), the investigators can reduce the cost of
subsidizing malaria treatment and improve targeting of ACTs without compromising access.
OBJECTIVES:
This goal of the proposed work is to improve antimalarial stewardship in the retail sector,
which has the largest market share of antimalarials in sub-Saharan Africa. In this study (Aim
2) the investigators will use a cluster randomized controlled trial to measure the impact of
two innovative interventions - a provider-directed incentive for offering malaria rapid
diagnostic tests to suspected malaria cases and a consumer-directed diagnosis-dependent ACT
subsidy (conditional ACT subsidy). The investigators will test both interventions in tandem
against control conditions. The unit of randomization will be the private medicine outlet
(cluster).
STUDY DESIGN:
The study will be a cluster-randomized controlled trial with two arms. See Section 4.4
Statistical Design and Power for complete details.
STUDY POPULATION:
The study will be conducted in Nigeria, a country with high malaria burden. Nigeria has the
programmatic goal of universal access to prompt parasitological confirmation before treatment
and have endorsed the use of malaria RDTs in the public health sector at all levels of care.
However, very high rates of treatment in the retail sector undermine the explicit policy that
all malaria cases should be confirmed by parasitological diagnosis. In Nigeria, the
government has recently permitted retail outlets to conduct RDTs in an effort to reduce
overuse of antimalarials, particularly publicly subsidized ACTs.
Specific study site will be Lagos, Nigeria.
STUDY PROCEDURES:
A complete sampling frame of eligible retail outlets will be made for the site. Outlets will
be eligible if they regularly carry quality-assured, subsidized ACTs. Participating retail
outlets will receive an initial small start-up stock of RDTs and will be given contact
information for RDT wholesalers who can provide replenishment stocks on demand. In addition,
all attendants will be trained to use a mobile reporting app that captures basic information
about suspected malaria cases. This app will not be used to assess outcomes, but will be an
important monitoring tool and serve as the conduit for all payments according to the arm
assignment.
Following training, shops will be randomized to one of the two arms:
- Arm 1 (control): RDTs available at study-recommended price, providers trained on mobile
app
- Arm 2 (consumer-directed and provider-directed intervention): providers receive a small
reimbursement for each RDT that they perform and report on the mobile app, and consumers
with a positive test are eligible for a subsidy on a quality-assured ACT. RDTs are
available at study recommended price.
Customers who come to a participating outlet in either arm with fever or suspected malaria
are eligible for an RDT at the study-recommended price and, in arm 2, a conditional ACT
subsidy when the RDT is positive. Attendants will be trained to recognize danger signs and
refer those individuals to a health facility for immediate care. Customers purchasing
medicine on someone's behalf or those who have already had a malaria test will not be
eligible for RDT testing or conditional subsidies.
Study outcome measures will be collected by interviewing a random sample of customers leaving
participating shops (exit interviews). A team of field interviewers will be trained in each
site and will be assigned to participating outlets on random days in a month. Both the day of
the month and the interviewer assigned to the specific outlet will be randomized in order to
balance data collection across interviewers and arms and to minimize the observer effect.
Each outlet will be visited thrice in a month and the interviewer will enroll eligible
participants in succession until they have completed 3-4 interviews. Three customers per
month per outlet are needed to reach the sample size of 32 interviews per outlet over the
data collection time frame. Exit interviews will capture information about customer
demographics, symptoms of their current illness, whether they had a malaria diagnostic test
at the outlet or elsewhere, how much they paid for the test, the results of the test, and the
drug(s) they purchased. Customers will be eligible to participate in the exit interview if
s/he was seeking drugs for him/herself or their minor child older than one year of age and
the child is physically present, s/he had a febrile illness or suspected malaria, and s/he
agrees to be interviewed.
Study monitoring will be continuous throughout the study period using the mobile app. Study
staff will regularly review reporting data captured by the mobile app. In particular,
pictures of RDTs will be reviewed alongside results reported by outlet attendants to ensure
correct use and interpretation of the RDTs. In addition, exit interviews will be summarized
monthly by outlet and compared to the data submitted via the app. This monitoring step will
allow us to identify major discrepancies between actions reported by the shop and those
reported by the customers such as testing rates, RDT positivity rates, dispensing of
qualified ACTs and prices charged for RDTs and ACTs.
SAMPLE SIZE AND POWER:
The investigators calculated power based on a cluster randomized two-sample two-tailed t-test
for the comparison of two proportions using standard formulae. We calculated power for
differences in the primary outcome for the comparison of interest noted above. With a sample
of 32 exit interviews per outlet (48 outlets in Nigeria), we would have >90% power to detect
a minimum difference between Arms 1 (control) and 2 (combined interventions) in the primary
outcome of 12 percentage points.
While interview rates at some of the higher volume shops have been higher than expected,
interview rates at some of the lower volume shops are on pace to finish below the target of
32 interviews per shop. This higher than anticipated variation in cluster size could
negatively impact power, therefore sampling will be continued across all shops for the
duration of the study in an effort for each shop to meet or exceed the target number of
interviews, or at least to come as close as possible. With a revised mean of approximately 53
interviews per shop, the above power calculations will be maintained.
The sample size estimates correspond to a total of 2524 exit interviews with clients in
Nigeria. Since not everyone interviewed will have purchased an ACT, the estimates account for
the fact that only a subset will enter into the analysis for the primary outcome. The
investigators will have a team of data collectors (one team per site) and each team will
target 3 participants per outlet per month. Exit interviews conducted up until the study
design change was implemented (n = 1676) may be used for supplemental analyses.
See Section 4.4 Statistical Design and Power for comprehensive description of sample size,
power and statistical analysis.
SUBJECT CONFIDENTIALITY:
Customers leaving the shop will be approached by the field interviewer to ask if they are
interested in participating in a short interview. If they agree, then they will be taken to a
private area and the study will be explained to them. Once they provide consent, the
interviewer will record the details of their illness and treatment at the outlet. No
participant identifiers will be recorded in the electronic data collection form. This limits
the possibility of identifying the source of any health information (See Protection of Human
Subjects Section 3.3).
