<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/NCT04468789</url>
  </required_header>
  <id_info>
    <org_study_id>H-40512</org_study_id>
    <secondary_id>OPP1192640</secondary_id>
    <nct_id>NCT04468789</nct_id>
  </id_info>
  <brief_title>Evaluation of Six-month HIV Treatment Dispensing in South Africa</brief_title>
  <official_title>Evaluation of the National Department of Health's Six-month Antiretroviral Treatment Dispensing Demonstration Pilot in Primary Health Care Clinics in the Context of the COVID-19 Pandemic and Response in South Africa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bill and Melinda Gates Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many countries in sub-Saharan Africa are implementing a policy of six-month dispensing of&#xD;
      antiretroviral (ARV) medications for HIV. Under the new guidelines, stable patients can&#xD;
      receive a six-month supply of ARV medications at once, reducing the number of clinic visits&#xD;
      required for medication refills. South Africa is considering this policy but has not yet&#xD;
      adopted it and has requested evidence of its feasibility, effectiveness, and costs to the&#xD;
      healthcare system and to patients. The decision on whether to implement a six-month&#xD;
      dispensing policy has become urgent due to the SARS-Cov-2 epidemic, as clinic visits to&#xD;
      refill prescriptions pose COVID-19 transmission risks to both patients and providers.&#xD;
&#xD;
      To generate the required evidence, South Africa is implementing a pilot program that will&#xD;
      allow for a cluster-randomized evaluation of 6-month dispensing. This protocol is for that&#xD;
      evaluation. It aims to provide supporting evidence to inform future policy and procurement&#xD;
      decisions by the National Department of Health (NDOH). All interventions will be conducted as&#xD;
      part of routine care by Department of Health staff.&#xD;
&#xD;
      In the pilot program, the NDOH will randomize 28 clinics in two provinces 1:1 to receive the&#xD;
      six month dispensing intervention or continue standard of care, which currently allows for&#xD;
      2-3 month dispensing. The researchers will assess the patient outcomes of six month&#xD;
      dispensing, administer a cross-sectional patient questionnaire, conduct semi-structured&#xD;
      in-depth interviews with care providers and implementers, and estimate the costs to NDOH and&#xD;
      to patients of six month dispensing. A maximum of 150,545 patients will be followed through&#xD;
      their medical records and 400 patients and providers will be consented to be interviewed at&#xD;
      baseline and after 6 months (total maximum sample size = 150,945).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall aims of this study are to assess the uptake and impact of six-month medication&#xD;
      dispensing (6MMD) on HIV patients' treatment outcomes at public-sector clinics; estimate the&#xD;
      costs of the intervention; and assess patients' and providers' perspectives on 6MMD. All&#xD;
      implementation of the interventions and generation of data will be done by the National&#xD;
      Department of Health and its support partners; this study will evaluate the outcomes.&#xD;
&#xD;
      The specific objectives of the evaluation are to:&#xD;
&#xD;
      Objective 1: Among HIV infected patients on antiretroviral therapy who are newly eligible for&#xD;
      6MMD, assess the uptake of 6MMD among eligible patients, stratified by repeat prescription&#xD;
      refill strategy. Evaluation questions:&#xD;
&#xD;
        -  What proportion of patients is eligible for 6MMD?&#xD;
&#xD;
        -  What proportion of eligible patients choose to enrol in 6MMD?&#xD;
&#xD;
        -  What proportion of enrolled patients receive more than one consecutive 6-month refill?&#xD;
&#xD;
      Objective 2: Is six-month dispensing non-inferior to standard of care (two- or three-month&#xD;
      dispensing) in terms of retention in care and viral suppression? Evaluation questions:&#xD;
&#xD;
        -  What is the effect of 6MMD on retention compared to standard of care for patients&#xD;
           eligible for 6MMD?&#xD;
&#xD;
        -  What is the effect of 6MMD on viral suppression within 6 and 12 months of intervention&#xD;
           enrollment (intervention patients) or eligibility (comparison patients), compared to&#xD;
           standard of care for patients eligible for 6MMD?&#xD;
&#xD;
        -  What is the effect of 6MMD on retention and suppression among all ART patients in a&#xD;
           clinic, regardless of whether they were eligible for or received 6MMD?&#xD;
&#xD;
      Objective 3: Is 6MMD more or less acceptable to patients and providers than standard of care?&#xD;
      Evaluation questions:&#xD;
&#xD;
        -  What factors influence patient choice to enrol in 6MMD?&#xD;
&#xD;
        -  To what extent does the risk of COVID-19 influence a patient's decision to enrol in&#xD;
           6MMD?&#xD;
&#xD;
        -  What are the barriers and facilitators to implementing 6MMD from the perspective of&#xD;
           providers?&#xD;
&#xD;
        -  How has COVID-19 impacted the implementation of 6MMD?&#xD;
&#xD;
        -  Has there been any task shifting as a result of the implementation of 6MMD?&#xD;
&#xD;
        -  What was the level of fidelity to the standard operating procedures (SOP) for 6MMD&#xD;
           implementation?&#xD;
&#xD;
      Objective 4: What is the cost of 6MMD to providers and patients compared to standard of care.&#xD;
      Evaluation questions:&#xD;
&#xD;
        -  How often do 6MMD patients return to facilities for HIV or other health care or to&#xD;
           collect other chronic medications between scheduled ARV dispensing visits?&#xD;
&#xD;
        -  What is the average cost to the provider (DOH) per 6MMD patient and for all ART patients&#xD;
           at the study clinics?&#xD;
&#xD;
        -  What is the patient cost of ART for those receiving 6MMD compared to standard of care?&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The South African government decided not to implement the pilot project for which this protocol&#xD;
    was the evaluation. It was not approved by the IRB and never started.&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Uptake of 6MMD</measure>
    <time_frame>Baseline</time_frame>
    <description>Proportion of patients eligible for 6 multi-month dispensing (6MMD) who enroll in 6MMD at intervention sites</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Retention in care</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients eligible for 6MMD who are retained in care at 6 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Viral suppression</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of patients eligible for 6MMD who are virally suppressed at 12 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Provider acceptability of 6MMD before intervention</measure>
    <time_frame>Baseline</time_frame>
    <description>Acceptability of 6MMD to healthcare providers, based on interview responses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Provider acceptability of 6MMD after intervention</measure>
    <time_frame>6 months</time_frame>
    <description>Acceptability of 6MMD to healthcare providers, based on interview responses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient acceptability at baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Acceptability of 6MMD to patients, based on survey responses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient acceptability at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Acceptability of 6MMD to patients, based on survey responses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Provider costs</measure>
    <time_frame>12-months</time_frame>
    <description>Costs to healthcare provider (study clinics) of 6MMD, compared to standard of care</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Comparison group</arm_group_label>
    <description>Patients eligible for six-month dispensing receiving care at comparison sites.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <description>Patients eligible for six-month dispensing receiving care at intervention sites.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Six-month ARV dispensing</intervention_name>
    <description>Patients in the intervention group who meet eligibility criteria will receive a six-month supply of antiretroviral medications, rather than the standard of care supply which is typically 2-3 months.</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Objective 1: All adult, HIV-positive patients who have initiated antiretroviral therapy at&#xD;
        the study sites Objective 2: All adult, HIV-positive patients who have initiated&#xD;
        antiretroviral therapy at the study sites Objective 3: Adult, HIV-positive adults eligible&#xD;
        for six-month dispensing at the intervention sites; and providers at the intervention sites&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Objectives 1 and 2: On same ART treatment regimen for at least 6 months; most recent&#xD;
             viral load taken in the past 6 months; and last viral load undetectable (&lt;50&#xD;
             copies/ml3)&#xD;
&#xD;
          -  Objective 3: Patient at an intervention site who meets the eligibility criteria for&#xD;
             6MMD; or provider at an intervention site&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Objectives 1 and 2: Not resident in the facility's catchment area; recorded intention&#xD;
             to transfer care to a different facility within 12 months; or pregnant and eligible&#xD;
             for PMTCT&#xD;
&#xD;
          -  Objective 3: Not resident in the facility's catchment area; recorded intention to&#xD;
             transfer care to a different facility within 12 months; pregnant and eligible for&#xD;
             PMTCT; unable to communicate in one of the language into which the consent documents&#xD;
             and questionnaire have been translated&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sydney Rosen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Health Economics and Epidemiology Research Office</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>November 10, 2022</last_update_submitted>
  <last_update_submitted_qc>November 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>antiretroviral therapy</keyword>
  <keyword>multi-month dispensing</keyword>
  <keyword>South Africa</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04468789
org study id: H-40512
secondary id: OPP1192640
nct id: NCT04468789
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Many countries in sub-Saharan Africa are implementing a policy of six-month dispensing of
      antiretroviral (ARV) medications for HIV. Under the new guidelines, stable patients can
      receive a six-month supply of ARV medications at once, reducing the number of clinic visits
      required for medication refills. South Africa is considering this policy but has not yet
      adopted it and has requested evidence of its feasibility, effectiveness, and costs to the
      healthcare system and to patients. The decision on whether to implement a six-month
      dispensing policy has become urgent due to the SARS-Cov-2 epidemic, as clinic visits to
      refill prescriptions pose COVID-19 transmission risks to both patients and providers.

      To generate the required evidence, South Africa is implementing a pilot program that will
      allow for a cluster-randomized evaluation of 6-month dispensing. This protocol is for that
      evaluation. It aims to provide supporting evidence to inform future policy and procurement
      decisions by the National Department of Health (NDOH). All interventions will be conducted as
      part of routine care by Department of Health staff.

      In the pilot program, the NDOH will randomize 28 clinics in two provinces 1:1 to receive the
      six month dispensing intervention or continue standard of care, which currently allows for
      2-3 month dispensing. The researchers will assess the patient outcomes of six month
      dispensing, administer a cross-sectional patient questionnaire, conduct semi-structured
      in-depth interviews with care providers and implementers, and estimate the costs to NDOH and
      to patients of six month dispensing. A maximum of 150,545 patients will be followed through
      their medical records and 400 patients and providers will be consented to be interviewed at
      baseline and after 6 months (total maximum sample size = 150,945).
The overall aims of this study are to assess the uptake and impact of six-month medication
      dispensing (6MMD) on HIV patients' treatment outcomes at public-sector clinics; estimate the
      costs of the intervention; and assess patients' and providers' perspectives on 6MMD. All
      implementation of the interventions and generation of data will be done by the National
      Department of Health and its support partners; this study will evaluate the outcomes.

      The specific objectives of the evaluation are to:

      Objective 1: Among HIV infected patients on antiretroviral therapy who are newly eligible for
      6MMD, assess the uptake of 6MMD among eligible patients, stratified by repeat prescription
      refill strategy. Evaluation questions:

        -  What proportion of patients is eligible for 6MMD?

        -  What proportion of eligible patients choose to enrol in 6MMD?

        -  What proportion of enrolled patients receive more than one consecutive 6-month refill?

      Objective 2: Is six-month dispensing non-inferior to standard of care (two- or three-month
      dispensing) in terms of retention in care and viral suppression? Evaluation questions:

        -  What is the effect of 6MMD on retention compared to standard of care for patients
           eligible for 6MMD?

        -  What is the effect of 6MMD on viral suppression within 6 and 12 months of intervention
           enrollment (intervention patients) or eligibility (comparison patients), compared to
           standard of care for patients eligible for 6MMD?

        -  What is the effect of 6MMD on retention and suppression among all ART patients in a
           clinic, regardless of whether they were eligible for or received 6MMD?

      Objective 3: Is 6MMD more or less acceptable to patients and providers than standard of care?
      Evaluation questions:

        -  What factors influence patient choice to enrol in 6MMD?

        -  To what extent does the risk of COVID-19 influence a patient's decision to enrol in
           6MMD?

        -  What are the barriers and facilitators to implementing 6MMD from the perspective of
           providers?

        -  How has COVID-19 impacted the implementation of 6MMD?

        -  Has there been any task shifting as a result of the implementation of 6MMD?

        -  What was the level of fidelity to the standard operating procedures (SOP) for 6MMD
           implementation?

      Objective 4: What is the cost of 6MMD to providers and patients compared to standard of care.
      Evaluation questions:

        -  How often do 6MMD patients return to facilities for HIV or other health care or to
           collect other chronic medications between scheduled ARV dispensing visits?

        -  What is the average cost to the provider (DOH) per 6MMD patient and for all ART patients
           at the study clinics?

        -  What is the patient cost of ART for those receiving 6MMD compared to standard of care?
observational model: Cohort
time perspective: Prospective
measure: Uptake of 6MMD
time frame: Baseline
description: Proportion of patients eligible for 6 multi-month dispensing (6MMD) who enroll in 6MMD at intervention sites
measure: Retention in care
time frame: 6 months
description: Proportion of patients eligible for 6MMD who are retained in care at 6 months
measure: Viral suppression
time frame: 12 months
description: Proportion of patients eligible for 6MMD who are virally suppressed at 12 months
measure: Provider acceptability of 6MMD before intervention
time frame: Baseline
description: Acceptability of 6MMD to healthcare providers, based on interview responses
measure: Provider acceptability of 6MMD after intervention
time frame: 6 months
description: Acceptability of 6MMD to healthcare providers, based on interview responses
measure: Patient acceptability at baseline
time frame: Baseline
description: Acceptability of 6MMD to patients, based on survey responses
measure: Patient acceptability at 6 months
time frame: 6 months
description: Acceptability of 6MMD to patients, based on survey responses
measure: Provider costs
time frame: 12-months
description: Costs to healthcare provider (study clinics) of 6MMD, compared to standard of care
arm group label: Comparison group
description: Patients eligible for six-month dispensing receiving care at comparison sites.
arm group label: Intervention group
description: Patients eligible for six-month dispensing receiving care at intervention sites.
intervention type: Other
intervention name: Six-month ARV dispensing
description: Patients in the intervention group who meet eligibility criteria will receive a six-month supply of antiretroviral medications, rather than the standard of care supply which is typically 2-3 months.
arm group label: Intervention group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sydney Rosen
role: Principal Investigator
affiliation: Boston University
facility: 
country: South Africa
responsible party type: Sponsor
sharing ipd: No