Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04428307 |
| Other study ID # |
Pro00104256 |
| Secondary ID |
5R01AI141444-02 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 11, 2021 |
| Est. completion date |
August 31, 2022 |
Study information
| Verified date |
February 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 Kenya. 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 three-arm study will test 1) a consumer-directed intervention in the form of a
diagnosis-dependent ACT subsidy, 2) both a provider-directed incentive for testing and a
client-directed intervention in combination against 3) a comparison arm. Outlets in all three
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. This 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 unit of randomization will be the private medicine
outlet (cluster).
STUDY DESIGN:
The study will be a cluster-randomized controlled trial with three arms. The original study
design was for a four-arm trial (an additional arm that would have tested the
provider-directed incentive alone), however preliminary data from the study area indicated
that the study may not be powered to measure the effect of a four arm study. No participants
were enrolled prior to finalization of the study design, and all clusters will be randomized
to one of the three remaining study arms only (1) control, 2) client-directed intervention,
and 3) combined client- and provider-directed intervention). See Section 4.4 Statistical
Design and Power for complete detail.
STUDY POPULATION:
The study will be conducted in Kenya, a country with high malaria burden. Kenya 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 Kenya, retail outlets
currently do not conduct RDTs and emphasis has been placed on implementing community case
management for malaria through public-sector community health workers (including conducting
RDTs).
The specific study site will be western Kenya (Bungoma County and Trans Nzoia county).
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. Attendants who dispense
medicines at each outlet will be trained to correctly and safely perform RDTs. They 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 three arms:
- Arm 1 (control): RDTs available at study-recommended price, providers trained on mobile
app
- Arm 2 (client-directed intervention): ACT subsidy to client conditional on positive RDT,
RDTs available at study-recommended price
- Arm 3 (client-directed and provider-directed intervention): providers are reimbursed for
each RDT 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 any arm with fever or suspected malaria are
eligible for an RDT at the study-recommended price and, in arms 2 and 3, 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. Ten customers per month
per outlet are needed to reach a sample size of 170 interviews per outlet in 15 months of
data collection. 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. The investigators calculated power for differences in
the primary outcome for each of the two comparisons of interest noted above. With a sample of
170 exit interviews per outlet (40 outlets in Kenya), the investigators will have >90% power
to detect a minimum difference between Arms 1 (control) and 3 (combined interventions) in the
primary outcome of 16 percentage points. The investigators will also have >80% power to
detect a minimum difference of 11 percentage points for the main secondary comparison of
interest (testing uptake).
The sample size estimates correspond to a total of 6800 exit interviews with clients in
Kenya. Since not everyone interviewed will have purchased an ACT, 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 8 data collectors and each data collector will conduct
approximately 50-60 interviews per month. Exit interviews should take 15 months to complete.
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).
