<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/NCT04428385</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00105072</org_study_id>
    <secondary_id>5R01AI141444-02</secondary_id>
    <nct_id>NCT04428385</nct_id>
  </id_info>
  <brief_title>Malaria Diagnostic Testing and Conditional Subsidies to Target ACTs in the Retail Sector: TESTsmART Aim 2 - Nigeria</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>Clinton Health Access Initiative Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Moi University</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 Nigeria. 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 two-arm study will test 1) a provider-directed incentive for testing and reporting&#xD;
      in combination with a consumer-directed intervention in the form of a diagnosis-dependent ACT&#xD;
      subsidy against 2) a comparison arm. Outlets in both arms will offer malaria diagnostic&#xD;
      testing to customers who wish to purchase one. Information for the primary and secondary&#xD;
      outcomes will be collected during exit interviews with eligible customers. The primary&#xD;
      outcome will be the proportion of ACTs sold to customers with a positive diagnostic test. The&#xD;
      main secondary outcome will be the proportion of suspected malaria cases presenting to the&#xD;
      retail outlet that are tested. Other secondary outcomes include adherence to the RDT result&#xD;
      amongst those tested (defined as taking a quality-assured ACT following a positive test and&#xD;
      refraining from taking an ACT following a negative test) and appropriate case management for&#xD;
      all suspected malaria cases (proportion tested and 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. The investigators' approach will also ensure that public&#xD;
      subsidies are directed at confirmed malaria cases thereby enhancing the sustainability of&#xD;
      such programs. By allocating subsidy dollars across both testing and conditional treatment&#xD;
      (rather than universal, treatment-only subsidies), the investigators can reduce the cost of&#xD;
      subsidizing 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 investigators will test both interventions in tandem&#xD;
      against control conditions. The unit of randomization will be the private medicine outlet&#xD;
      (cluster).&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      The study will be a cluster-randomized controlled trial with two arms. See Section 4.4&#xD;
      Statistical Design and Power for complete details.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      The study will be conducted in Nigeria, a country with high malaria burden. Nigeria 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 Nigeria, the&#xD;
      government has recently permitted retail outlets to conduct RDTs in an effort to reduce&#xD;
      overuse of antimalarials, particularly publicly subsidized ACTs.&#xD;
&#xD;
      Specific study site will be Lagos, Nigeria.&#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. Participating retail&#xD;
      outlets will receive an initial small start-up stock of RDTs and will be given contact&#xD;
      information for RDT wholesalers who can provide replenishment stocks on demand. In addition,&#xD;
      all attendants will be trained to use a mobile reporting app that captures basic information&#xD;
      about suspected malaria cases. This app will not be used to assess outcomes, but will be an&#xD;
      important monitoring tool and serve as the conduit for all payments according to the arm&#xD;
      assignment.&#xD;
&#xD;
      Following training, shops will be randomized to one of the two arms:&#xD;
&#xD;
        -  Arm 1 (control): RDTs available at study-recommended price, providers trained on mobile&#xD;
           app&#xD;
&#xD;
        -  Arm 2 (consumer-directed and provider-directed intervention): providers receive a small&#xD;
           reimbursement for each RDT that they perform and report on the mobile app, and consumers&#xD;
           with a positive test are eligible for a subsidy on a quality-assured ACT. RDTs are&#xD;
           available at study recommended price.&#xD;
&#xD;
      Customers who come to a participating outlet in either arm with fever or suspected malaria&#xD;
      are eligible for an RDT at the study-recommended price and, in arm 2, 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. Three customers per&#xD;
      month per outlet are needed to reach the sample size of 32 interviews per outlet over the&#xD;
      data collection time frame. Exit interviews will capture information about customer&#xD;
      demographics, symptoms of their current illness, whether they had a malaria diagnostic test&#xD;
      at the outlet or elsewhere, how much they paid for the test, the results of the test, and the&#xD;
      drug(s) they purchased. Customers will be eligible to participate in the exit interview if&#xD;
      s/he was seeking drugs for him/herself or their minor child older than one year of age and&#xD;
      the child is physically present, s/he had a febrile illness or suspected malaria, and s/he&#xD;
      agrees to be 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 using standard formulae. We calculated power for&#xD;
      differences in the primary outcome for the comparison of interest noted above. With a sample&#xD;
      of 32 exit interviews per outlet (48 outlets in Nigeria), we would have &gt;90% power to detect&#xD;
      a minimum difference between Arms 1 (control) and 2 (combined interventions) in the primary&#xD;
      outcome of 12 percentage points.&#xD;
&#xD;
      While interview rates at some of the higher volume shops have been higher than expected,&#xD;
      interview rates at some of the lower volume shops are on pace to finish below the target of&#xD;
      32 interviews per shop. This higher than anticipated variation in cluster size could&#xD;
      negatively impact power, therefore sampling will be continued across all shops for the&#xD;
      duration of the study in an effort for each shop to meet or exceed the target number of&#xD;
      interviews, or at least to come as close as possible. With a revised mean of approximately 53&#xD;
      interviews per shop, the above power calculations will be maintained.&#xD;
&#xD;
      The sample size estimates correspond to a total of 2524 exit interviews with clients in&#xD;
      Nigeria. Since not everyone interviewed will have purchased an ACT, the estimates account for&#xD;
      the fact that only a subset will enter into the analysis for the primary outcome. The&#xD;
      investigators will have a team of data collectors (one team per site) and each team will&#xD;
      target 3 participants per outlet per month. Exit interviews conducted up until the study&#xD;
      design change was implemented (n = 1676) may be used for supplemental analyses.&#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">March 15, 2021</start_date>
  <completion_date type="Actual">February 28, 2023</completion_date>
  <primary_completion_date type="Actual">February 28, 2023</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>
    <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>2</number_of_arms>
  <enrollment type="Actual">3881</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 (consumer-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>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 2 (consumer-directed and provider-directed intervention)</arm_group_label>
  </intervention>
  <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 (consumer-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>Clinton Health Access Initiative</name>
      <address>
        <city>Lagos</city>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nigeria</country>
  </location_countries>
  <verification_date>May 2023</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>May 18, 2023</last_update_submitted>
  <last_update_submitted_qc>May 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>treatment seeking in the informal (retail) 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>March 1, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04428385/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04428385
org study id: Pro00105072
secondary id: 5R01AI141444-02
nct id: NCT04428385
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 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).
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).
allocation: Randomized
intervention model: Parallel Assignment
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 (consumer-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: 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 2 (consumer-directed and provider-directed intervention)
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 (consumer-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: Nigeria
responsible party type: Sponsor
mesh term: Malaria
mesh term: Artemisinins
mesh term: Artemisinin
sharing ipd: No
provided document: 