<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04428307</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00104256</org_study_id>
    <secondary_id>5R01AI141444-02</secondary_id>
    <nct_id>NCT04428307</nct_id>
  </id_info>
  <brief_title>Malaria Diagnostic Testing and Conditional Subsidies to Target ACTs in the Retail Sector: TESTsmART Aim 2 - Kenya</brief_title>
  <official_title>Malaria Diagnostic Testing and Conditional Subsidies to Target ACTs in the Retail Sector: the TESTsmART Trial Aim 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Moi University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinton Health Access Initiative Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Highly subsidized first-line antimalarials (artemisinin combination therapy or ACT) are&#xD;
      available over the counter in the private retail sector in most malaria-endemic countries.&#xD;
      Overconsumption of ACTs purchased over the counter is rampant due to their low price, high&#xD;
      perceived efficacy, and absence of diagnostic tools to guide drug use. The ultimate goal of&#xD;
      the proposed work is to improve antimalarial stewardship in the retail sector, which is&#xD;
      responsible for distributing the majority of antimalarials in sub-Saharan Africa. Through a&#xD;
      combination of diagnosis and treatment subsidies and provider-directed incentives, this&#xD;
      approach will align provider and customer incentives with appropriate case management and&#xD;
      thereby improve health outcomes.&#xD;
&#xD;
      The main objective of this study (Aim 2) is to test two key interventions in a random sample&#xD;
      of private medicine retail outlets in Kenya. This will be a cluster-randomized controlled&#xD;
      trial where the cluster is a private retail outlet that stocks and sells WHO quality-assured&#xD;
      ACTs. This three-arm study will test 1) a consumer-directed intervention in the form of a&#xD;
      diagnosis-dependent ACT subsidy, 2) both a provider-directed incentive for testing and a&#xD;
      client-directed intervention in combination against 3) a comparison arm. Outlets in all three&#xD;
      arms will offer malaria diagnostic testing to customers who wish to purchase one. Information&#xD;
      for the primary and secondary outcomes will be collected during exit interviews with eligible&#xD;
      customers. The primary outcome will be the proportion of ACTs sold to customers with a&#xD;
      positive diagnostic test. The main secondary outcome will be the proportion of suspected&#xD;
      malaria cases presenting to the retail outlet that are tested. Other secondary outcomes&#xD;
      include adherence to the RDT result amongst those tested (defined as taking a quality-assured&#xD;
      ACT following a positive test and refraining from taking an ACT following a negative test)&#xD;
      and appropriate case management for all suspected malaria cases (proportion tested and&#xD;
      adhered among all suspected cases).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RATIONALE:&#xD;
&#xD;
      The investigators hypothesize that decision-making in the retail sector is influenced&#xD;
      primarily by price (or profit) supplemented by individual beliefs or preferences. Information&#xD;
      from a diagnostic test, when available, plays only a minor role in the decision-making&#xD;
      landscape. In response to this, the investigators propose to test a scalable, policy-relevant&#xD;
      strategy that integrates testing and treatment subsidies and makes ACT subsidies available&#xD;
      only to customers with a positive malaria test. Differential pricing based on the results of&#xD;
      the diagnostic test will align consumer and provider incentives (price and profit) with&#xD;
      testing and appropriate ACT use. This approach will also ensure that public subsidies are&#xD;
      directed at confirmed malaria cases thereby enhancing the sustainability of such programs. By&#xD;
      allocating subsidy dollars across both testing and conditional treatment (rather than&#xD;
      universal, treatment-only subsidies), the investigators can reduce the cost of subsidizing&#xD;
      malaria treatment and improve targeting of ACTs without compromising access.&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
      This goal of the proposed work is to improve antimalarial stewardship in the retail sector,&#xD;
      which has the largest market share of antimalarials in sub-Saharan Africa. In this study (Aim&#xD;
      2) the investigators will use a cluster randomized controlled trial to measure the impact of&#xD;
      two innovative interventions - a provider-directed incentive for offering malaria rapid&#xD;
      diagnostic tests to suspected malaria cases and a consumer-directed diagnosis dependent ACT&#xD;
      subsidy (conditional ACT subsidy). The unit of randomization will be the private medicine&#xD;
      outlet (cluster).&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      The study will be a cluster-randomized controlled trial with three arms. The original study&#xD;
      design was for a four-arm trial (an additional arm that would have tested the&#xD;
      provider-directed incentive alone), however preliminary data from the study area indicated&#xD;
      that the study may not be powered to measure the effect of a four arm study. No participants&#xD;
      were enrolled prior to finalization of the study design, and all clusters will be randomized&#xD;
      to one of the three remaining study arms only (1) control, 2) client-directed intervention,&#xD;
      and 3) combined client- and provider-directed intervention). See Section 4.4 Statistical&#xD;
      Design and Power for complete detail.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      The study will be conducted in Kenya, a country with high malaria burden. Kenya has the&#xD;
      programmatic goal of universal access to prompt parasitological confirmation before treatment&#xD;
      and have endorsed the use of malaria RDTs in the public health sector at all levels of care.&#xD;
      However, very high rates of treatment in the retail sector undermine the explicit policy that&#xD;
      all malaria cases should be confirmed by parasitological diagnosis. In Kenya, retail outlets&#xD;
      currently do not conduct RDTs and emphasis has been placed on implementing community case&#xD;
      management for malaria through public-sector community health workers (including conducting&#xD;
      RDTs).&#xD;
&#xD;
      The specific study site will be western Kenya (Bungoma County and Trans Nzoia county).&#xD;
&#xD;
      STUDY PROCEDURES:&#xD;
&#xD;
      A complete sampling frame of eligible retail outlets will be made for the site. Outlets will&#xD;
      be eligible if they regularly carry quality-assured, subsidized ACTs. Attendants who dispense&#xD;
      medicines at each outlet will be trained to correctly and safely perform RDTs. They will&#xD;
      receive an initial small start-up stock of RDTs and will be given contact information for RDT&#xD;
      wholesalers who can provide replenishment stocks on demand. In addition, all attendants will&#xD;
      be trained to use a mobile reporting app that captures basic information about suspected&#xD;
      malaria cases. This app will not be used to assess outcomes, but will be an important&#xD;
      monitoring tool and serve as the conduit for all payments according to the arm assignment.&#xD;
&#xD;
      Following training, shops will be randomized to one of the three arms:&#xD;
&#xD;
        -  Arm 1 (control): RDTs available at study-recommended price, providers trained on mobile&#xD;
           app&#xD;
&#xD;
        -  Arm 2 (client-directed intervention): ACT subsidy to client conditional on positive RDT,&#xD;
           RDTs available at study-recommended price&#xD;
&#xD;
        -  Arm 3 (client-directed and provider-directed intervention): providers are reimbursed for&#xD;
           each RDT and consumers with a positive test are eligible for a subsidy on a&#xD;
           quality-assured ACT. RDTs are available at study recommended price.&#xD;
&#xD;
      Customers who come to a participating outlet in any arm with fever or suspected malaria are&#xD;
      eligible for an RDT at the study-recommended price and, in arms 2 and 3, a conditional ACT&#xD;
      subsidy when the RDT is positive. Attendants will be trained to recognize danger signs and&#xD;
      refer those individuals to a health facility for immediate care. Customers purchasing&#xD;
      medicine on someone's behalf or those who have already had a malaria test will not be&#xD;
      eligible for RDT testing or conditional subsidies.&#xD;
&#xD;
      Study outcome measures will be collected by interviewing a random sample of customers leaving&#xD;
      participating shops (exit interviews). A team of field interviewers will be trained in each&#xD;
      site and will be assigned to participating outlets on random days in a month. Both the day of&#xD;
      the month and the interviewer assigned to the specific outlet will be randomized in order to&#xD;
      balance data collection across interviewers and arms and to minimize the observer effect.&#xD;
      Each outlet will be visited thrice in a month and the interviewer will enroll eligible&#xD;
      participants in succession until they have completed 3-4 interviews. Ten customers per month&#xD;
      per outlet are needed to reach a sample size of 170 interviews per outlet in 15 months of&#xD;
      data collection. Exit interviews will capture information about customer demographics,&#xD;
      symptoms of their current illness, whether they had a malaria diagnostic test at the outlet&#xD;
      or elsewhere, how much they paid for the test, the results of the test, and the drug(s) they&#xD;
      purchased. Customers will be eligible to participate in the exit interview if s/he was&#xD;
      seeking drugs for him/herself or their minor child older than one year of age and the child&#xD;
      is physically present, s/he had a febrile illness or suspected malaria, and s/he agrees to be&#xD;
      interviewed.&#xD;
&#xD;
      Study monitoring will be continuous throughout the study period using the mobile app. Study&#xD;
      staff will regularly review reporting data captured by the mobile app. In particular,&#xD;
      pictures of RDTs will be reviewed alongside results reported by outlet attendants to ensure&#xD;
      correct use and interpretation of the RDTs. In addition, exit interviews will be summarized&#xD;
      monthly by outlet and compared to the data submitted via the app. This monitoring step will&#xD;
      allow us to identify major discrepancies between actions reported by the shop and those&#xD;
      reported by the customers such as testing rates, RDT positivity rates, dispensing of&#xD;
      qualified ACTs and prices charged for RDTs and ACTs.&#xD;
&#xD;
      SAMPLE SIZE AND POWER:&#xD;
&#xD;
      The investigators calculated power based on a cluster randomized two-sample two-tailed t-test&#xD;
      for the comparison of two proportions. The investigators calculated power for differences in&#xD;
      the primary outcome for each of the two comparisons of interest noted above. With a sample of&#xD;
      170 exit interviews per outlet (40 outlets in Kenya), the investigators will have &gt;90% power&#xD;
      to detect a minimum difference between Arms 1 (control) and 3 (combined interventions) in the&#xD;
      primary outcome of 16 percentage points. The investigators will also have &gt;80% power to&#xD;
      detect a minimum difference of 11 percentage points for the main secondary comparison of&#xD;
      interest (testing uptake).&#xD;
&#xD;
      The sample size estimates correspond to a total of 6800 exit interviews with clients in&#xD;
      Kenya. Since not everyone interviewed will have purchased an ACT, estimates account for the&#xD;
      fact that only a subset will enter into the analysis for the primary outcome. The&#xD;
      investigators will have a team of 8 data collectors and each data collector will conduct&#xD;
      approximately 50-60 interviews per month. Exit interviews should take 15 months to complete.&#xD;
&#xD;
      See Section 4.4 Statistical Design and Power for comprehensive description of sample size,&#xD;
      power and statistical analysis.&#xD;
&#xD;
      SUBJECT CONFIDENTIALITY:&#xD;
&#xD;
      Customers leaving the shop will be approached by the field interviewer to ask if they are&#xD;
      interested in participating in a short interview. If they agree, then they will be taken to a&#xD;
      private area and the study will be explained to them. Once they provide consent, the&#xD;
      interviewer will record the details of their illness and treatment at the outlet. No&#xD;
      participant identifiers will be recorded in the electronic data collection form. This limits&#xD;
      the possibility of identifying the source of any health information (See Protection of Human&#xD;
      Subjects Section 3.3).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2021</start_date>
  <completion_date type="Actual">August 31, 2022</completion_date>
  <primary_completion_date type="Actual">August 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>three-arm parallel cluster randomized trial</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Interviewers assessing outcomes and statisticians will be blinded to arm assignment</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>ACT consumption by true malaria cases</measure>
    <time_frame>Cross-sectional, day of enrollment</time_frame>
    <description>The primary outcome is the proportion of all ACTs that are sold to malaria test-positive clients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Use of malaria rapid diagnostic test</measure>
    <time_frame>Cross-sectional, day of enrollment</time_frame>
    <description>Proportion of suspected malaria cases presenting to the retail outlet that are tested</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to the RDT result among all those tested in the shop</measure>
    <time_frame>Cross-sectional, day of enrollment</time_frame>
    <description>The proportion of tested participants who are adherent where adherence to the test result is defined as taking a quality-assured ACT if the RDT is positive or taking another drug (or no drug) if the test is negative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appropriate case management</measure>
    <time_frame>Cross-sectional, day of enrollment</time_frame>
    <description>Proportion of all suspected malaria cases that are managed appropriately (tested for malaria, and use ACT following a positive test and do not purchase an ACT after a negative test)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACT use among untested clients</measure>
    <time_frame>Cross-sectional, day of enrollment</time_frame>
    <description>Proportion of clients who are not tested for malaria and purchased an ACT, among those who did not test in the shop, do not have documentation of a test, and purchased any antimalarial at the shop.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">5754</enrollment>
  <condition>Malaria</condition>
  <condition>Febrile Illness</condition>
  <arm_group>
    <arm_group_label>Arm 1 (control)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>RDTs available at study-recommended price, providers trained on mobile reporting app</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 (client-directed intervention)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ACT subsidy to client conditional on positive RDT, RDTs available at study-recommended price</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3 (client-directed and provider-directed intervention)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>providers receive a small payment for each RDT that they perform and consumers with a positive test are eligible for a subsidy on a quality-assured ACT, RDTs are available at study recommended price</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conditional artemisinin combination therapy subsidy</intervention_name>
    <description>An additional discount on WHO-approved quality assured ACTs will be offered to individuals with a positive RDT.</description>
    <arm_group_label>Arm 2 (client-directed intervention)</arm_group_label>
    <arm_group_label>Arm 3 (client-directed and provider-directed intervention)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Testing incentive</intervention_name>
    <description>A small incentive will be paid to the provider each time they perform a malaria rapid diagnostic test.</description>
    <arm_group_label>Arm 3 (client-directed and provider-directed intervention)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All clients attending a participating outlet on the day selected for exit interviews will&#xD;
        be eligible to be screened for inclusion into the interview sample.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with fever, or history of fever in the last 48 hours, or suspects they&#xD;
             may have malaria&#xD;
&#xD;
          -  Individual with malaria-like illness must be present at recruitment&#xD;
&#xD;
          -  Older than one year of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any individual with signs of severe illness requiring immediate referral&#xD;
&#xD;
          -  Individuals who have taken an antimalarial in the last seven days, including for the&#xD;
             current illness&#xD;
&#xD;
          -  Patients &lt;18 years without a parent or legal guardian present&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wendy P O'Meara, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moi University</name>
      <address>
        <city>Eldoret</city>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Kenya</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>treatment seeking in the informal (retail) health sector</keyword>
  <keyword>malaria diagnostic testing</keyword>
  <keyword>rational drug use</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Artemisinins</mesh_term>
    <mesh_term>Artemisinin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 24, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT04428307/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>August 31, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04428307
org study id: Pro00104256
secondary id: 5R01AI141444-02
nct id: NCT04428307
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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).
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).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: three-arm parallel cluster randomized trial
primary purpose: Health Services Research
masking: Single (Outcomes Assessor)
masking description: Interviewers assessing outcomes and statisticians will be blinded to arm assignment
measure: ACT consumption by true malaria cases
time frame: Cross-sectional, day of enrollment
description: The primary outcome is the proportion of all ACTs that are sold to malaria test-positive clients.
measure: Use of malaria rapid diagnostic test
time frame: Cross-sectional, day of enrollment
description: Proportion of suspected malaria cases presenting to the retail outlet that are tested
measure: Adherence to the RDT result among all those tested in the shop
time frame: Cross-sectional, day of enrollment
description: The proportion of tested participants who are adherent where adherence to the test result is defined as taking a quality-assured ACT if the RDT is positive or taking another drug (or no drug) if the test is negative
measure: Appropriate case management
time frame: Cross-sectional, day of enrollment
description: Proportion of all suspected malaria cases that are managed appropriately (tested for malaria, and use ACT following a positive test and do not purchase an ACT after a negative test)
measure: ACT use among untested clients
time frame: Cross-sectional, day of enrollment
description: Proportion of clients who are not tested for malaria and purchased an ACT, among those who did not test in the shop, do not have documentation of a test, and purchased any antimalarial at the shop.
arm group label: Arm 1 (control)
arm group type: No Intervention
description: RDTs available at study-recommended price, providers trained on mobile reporting app
arm group label: Arm 2 (client-directed intervention)
arm group type: Experimental
description: ACT subsidy to client conditional on positive RDT, RDTs available at study-recommended price
arm group label: Arm 3 (client-directed and provider-directed intervention)
arm group type: Experimental
description: providers receive a small payment for each RDT that they perform and consumers with a positive test are eligible for a subsidy on a quality-assured ACT, RDTs are available at study recommended price
intervention type: Other
intervention name: Conditional artemisinin combination therapy subsidy
description: An additional discount on WHO-approved quality assured ACTs will be offered to individuals with a positive RDT.
arm group label: Arm 2 (client-directed intervention)
arm group label: Arm 3 (client-directed and provider-directed intervention)
intervention type: Other
intervention name: Testing incentive
description: A small incentive will be paid to the provider each time they perform a malaria rapid diagnostic test.
arm group label: Arm 3 (client-directed and provider-directed intervention)
criteria: 
gender: All
minimum age: 1 Year
maximum age: N/A
healthy volunteers: No
last name: Wendy P O'Meara, PhD
role: Principal Investigator
affiliation: Duke University
facility: 
country: Kenya
responsible party type: Sponsor
mesh term: Malaria
mesh term: Artemisinins
mesh term: Artemisinin
sharing ipd: No
provided document: 
submitted: August 31, 2023