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Prevent TB: Choice Architecture for TPT Delivery

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ClinicalTrials.gov Identifier: NCT04466488
Recruitment Status : Not yet recruiting
First Posted : July 10, 2020
Last Update Posted : July 10, 2020
Sponsor:
Collaborators:
University of Witwatersrand, South Africa
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

Background: Clinical guidelines and policies often fail to achieve high levels of delivery of intended clinical interventions. The difference in what the investigators know works and what is actually delivered at the clinic-level to patients, is known as the "science-to-service gap." In the realm of tuberculosis (TB) prevention, this gap is reflected in <20% of TB preventive therapy (TPT) -eligible persons living with HIV (PWH) being offered or initiated on isoniazid preventive therapy (IPT) in many settings. Recent innovation in TPT have brought new pharmacological options allowing for shorter courses, intermittent dosing, or both.

The overarching goal of this study is to identify a generalizable approach to overcome current barriers to delivery of TPT in order to achieve high levels of TPT delivery during routine care in public clinics. Multiple approaches are in standard use to change prescribing behavior including in service training, audit and feedback, clinical mentoring, the use of clinical decision aids, and "academic detailing." However, the overall change is generally modest. To achieve a substantial increase in TPT delivery (from current approximately 20% to 60-80%) will require a fundamental change in the approach to selecting patients for TPT - a redesign of the choice architecture of TPT prescribing.

Methods: The investigators are proposing a choice architecture that makes prescribing TPT the "default" or standard option and that for TPT not to be prescribed will require a choice by a clinician to "opt-out" of TPT for a specific patient.

The investigators are proposing a cluster randomized design to test the choice architecture approach to increasing delivery of TPT. Clinics will be randomized to one of two strategies: (1) standard implementation and (2) choice architecture default TPT. Because of the clinic-level nature of the implementation strategies, all PWH receiving care at a clinic will be exposed to the standard implementation or TPT routinization implementation. Clinical process data will be used to assess the effectiveness of each strategy to determine the proportion of PWH (1) screened for TPT, (2) eligible for TPT, and (3) prescribed TPT.

Significance: TB is the leading cause of death among PWH in South Africa and elsewhere on the continent. TPT is a proven intervention to reduce mortality among PWH but is not widely prescribed. This study seeks to identify an implementation strategy to reach optimal TPT prescribing.


Condition or disease Intervention/treatment Phase
HIV/AIDS Tuberculosis Behavioral: Choice Architecture Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The investigators will conduct a covariate-constrained randomization to balance, if an imbalance is detected, ensuring validity of the randomization process. Implementation will be staggered over time with each of two clinics from the intervention arms matched to control clinics for the purpose of contemporaneous study initiation. Randomization will occur either electronically or through drawing names with Department of Health representatives.
Masking: Single (Investigator)
Masking Description: The data identified by clinic allocation will be blinded to the PI and co-investigators and study statistician until completion of comparative analysis. There will be no other blinding.
Primary Purpose: Health Services Research
Official Title: Prevent TB: Application of Choice Architecture to Implement TB Preventive Therapy in South Africa
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Standard of care study arm
The standard TPT implementation is for a clinician to screen for TB and to consider TPT for those who do not have "presumptive TB". Clinicians in the study district (and most districts in South Africa) have received training and job aids to assist in appropriate application of the TPT initiation algorithm. Prescribing for TPT and ART is done by writing, by hand, the prescription in the patient's paper file. As part of this study, all study clinic providers will have access to standard Department of Health printed material and clinical training.
Experimental: Choice Architecture study arm

In the choice architecture implementation strategy, all opt-out clinic providers and pharmacists will be trained on the approach. The fundamental tenant of this approach is that TPT will be prescribed with any ART initiation and any ART re-prescribing for 3-12 months of TPT (adherent to current guidelines) if TPT has not been previously prescribed. This will be facilitated by co-prescribing ART and TPT. That is when ART is being prescribed TPT is meant to be prescribed at the same time of the clinic visit.

The simultaneous prescribing will be facilitated through the introduction of an ink stamp or pre-printed sticker to use for quick entry of the ART prescription along with TPT and cotrimoxazole. The stamp/sticker for ART prescription, the prescription for TPT and for cotrimoxazole will be "automatically" included. Active canceling of these prescriptions (and indicating the reasons) will be needed to not have TPT dispensed.

Behavioral: Choice Architecture
  1. Providers will receive general training on TPT benefits, indications, and contra-indications.
  2. Providers will be provided with updated ART and TPT prescribing approach, including an ink stamp or pre-printed sticker for quick entry of the ART prescription along with TPT and cotrimoxazole.
  3. The pharmacy or clinician (if the clinician dispenses) will dispense ART, cotrimoxazole, and TPT as prescribed




Primary Outcome Measures :
  1. Proportion of patients newly starting ART also initiating TPT [ Time Frame: Up to 12 months ]
    Comparing choice architecture and standard of care prescribing arms


Secondary Outcome Measures :
  1. Proportion of established ART patients also initiating TPT [ Time Frame: Up to 12 months ]
    Comparing choice architecture and standard of care prescribing arms

  2. Proportion of TPT-eligible patients newly starting ART also initiating TPT [ Time Frame: Up to 12 months ]
    Comparing choice architecture and standard of care prescribing arms

  3. Proportion of TPT-eligible established ART patients also initiating TPT [ Time Frame: Up to 12 months ]
    Comparing choice architecture and standard of care prescribing arms

  4. Proportion of patients started on TPT with subsequent discontinuation [ Time Frame: Up to 12 months ]
    Comparing choice architecture and standard of care prescribing arms

  5. Clinic implementation of choice architecture as assess by adoption [ Time Frame: Up to 12 months ]
    Adoption will be determined by the proportion of visits in which the choice architecture strategy was used (as measured by the use of the pre-printed/stamped prescription), regardless of the clinician's initiation decision.

  6. Clinic implementation of choice architecture as assessed by fidelity [ Time Frame: Up to 12 months ]
    Fidelity will be determined by the proportion of visits for which the clinician opts not to prescribe and has indicated a reason for not initiating.

  7. Acceptability of choice architecture approach as assessed by an acceptability questionnaire [ Time Frame: Up to 52 weeks after study initiation ]
    Acceptability will be assessed among providers in the choice architecture strategy arm using an acceptability questionnaire based on the theoretical framework of acceptability developed by Sekhon et al. which has 7 constructs with responses on Likert scale. Acceptability will be scored as a mean (if normally distributed, otherwise median) per domain with 95% confidence intervals (if normally distributed, otherwise inter-quartile range). Hypothesis testing will be used to compare the score to a neutral (4 on a 7-point Likert scale) response. Scores will be interpreted with a general threshold for acceptability if mean or median score favors acceptability (greater than 4).

  8. Cognitive load as assessed by the Paas scale [ Time Frame: 9-12 months after study initiation ]
    The Paas scale uses a Likert scale with a single question with a 9-point scale to assess cognitive load ranging from a low score of 1 (very, very low mental effort) to a high score of 9 (very, very high mental effort). Composite scores by study arm will be compared using either the Kruskal-Wallis test, a non-parametric method, or t-test if the results are normally distributed.

  9. Cognitive load as assessed by the Klepsch scale [ Time Frame: 9-12 months after study initiation ]
    The Klepsch scale uses 7 items, each with a 7-point Likert scale ranging from 1 (completely wrong) to 7 (absolutely right), to assess cognitive load. Composite scores by study arm will be compared using either the Kruskal-Wallis test, a non-parametric method, or t-test if the results are normally distributed.

  10. Cognitive load as assessed by the National Aeronautics and Space Administration (NASA) Task Load Index [ Time Frame: 9-12 months after study initiation ]
    The NASA Task Load Index (TLX) has six questions and is focused on task complexity and difficulty in completing. Participants will place an 'x' on a ruler scale with 21 vertical tick marks. The tick marks divide the ruler from 0 to 100 by 5 point intervals, ranging from low to high or good to poor. Composite scores by study arm will be compared using either the Kruskal-Wallis test, a non-parametric method, or t-test if the results are normally distributed.

  11. Patient characteristics associated with initiating and adhering to TPT as assessed by clinical record review [ Time Frame: 3-9 months after a patient could have initiated TPT ]
    The clinical records for 600 participants (300 per arm) will be abstracted for key clinical characteristics as a single cross-sectional assessment. Mixed effects logistic regression will be used to assess for differences between those who did and did not receive TPT, including clinic allocation. Random effects modeling will be used to adjust for the cluster level. Mixed effects logistic regression will be used to compare self-reported and clinical record documented side effects by study arm and other key characteristics, including age group and sex.

  12. Patient characteristics associated with initiating and adhering to TPT as assessed by a structured quantitative interview [ Time Frame: 3-9 months after a patient could have initiated TPT ]
    A structured quantitative patient interview with closed-ended questions will be used with 600 participants (300 per arm). Mixed effects logistic regression will be used to assess for differences between those who did and did not receive TPT, including clinic allocation. Random effects modeling will be used to adjust for the cluster level. Mixed effects logistic regression will be used to compare self-reported and clinical record documented side effects by study arm and other key characteristics, including age group and sex.

  13. Patient understanding and experience with TPT as assessed by an in-depth interview [ Time Frame: 3-9 months after a patient could have initiated TPT ]
    A subset of 30-45 patients among the 600 recruited for TPT assessment will be invited for participation in an in-depth interview to explore understanding and experience with TPT.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult (≥18 years old) patients initiating ART
  • Adult (≥18 years old) patients already on ART and coming for ART re-prescribing

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04466488


Contacts
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Contact: Christopher Hoffmann, MD, MPH 410-614-4257 choffmann@jhmi.edu

Locations
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South Africa
Perinatal HIV Research Unit
Soweto, Gauteng, South Africa, 1864
Contact: Minja Milovanovic, MA    +27 11 989 9793    milovanovicm@phru.co.za   
Contact: Neil Martinson, MD, MPH    +27 11 989 9836    martinson@phru.co.za   
Sponsors and Collaborators
Johns Hopkins University
University of Witwatersrand, South Africa
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Christopher Hoffmann, MD, MPH Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04466488    
Other Study ID Numbers: IRB00231219
R01AI150432 ( U.S. NIH Grant/Contract )
First Posted: July 10, 2020    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified trial data will be made available one year after completion of all study activities.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: One year after completion of study activities
Access Criteria: Contact PI

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
TB preventive therapy
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections