Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04466488 |
| Other study ID # |
IRB00231219 |
| Secondary ID |
R01AI150432 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 15, 2021 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
June 2024 |
| Source |
Johns Hopkins University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
BACKGROUND
HIV associated mortality and TB disease in LMIC:
TB is the leading cause of death due to an infectious agent worldwide. Among PWH in low and
middle income countries (LMIC), TB represents the leading cause of mortality among PWH. South
Africa is particularly affected by the syndemic of HIV and TB with an estimated HIV
prevalence in 2017 of 7.2 million and TB incidence of 567/100,000 population with over 60% of
TB cases among PWH. There were an estimated 78,000 deaths from TB in South Africa in 2017;
56,000 of the deaths among PWH. Findings from the investigators' group suggest this is likely
an underestimate of true TB disease and TB related mortality.
TB preventive therapy reduces TB disease and mortality:
For the past 30 years isoniazid based TPT has been known to reduce the risk of TB among PWH.
Multiple studies have subsequently confirmed and strengthened this finding. Following cohort
studies conducted in South Africa and Brazil by the investigators' team that showed marked
reductions in TB incidence for PWH, clinical trials of isoniazid preventive therapy have
reported up to a 70% reduction in TB incidence among PWH.
Current delivery of TPT to PWH is anemic:
Despite the evidence and guidelines supporting TPT, current delivery of TPT is anemic.
Reports from South Africa (and preliminary data by members of this investigative team) have
observed between 14% and 35% of eligible patients are prescribed TPT. Other countries in
sub-Saharan Africa have similarly low initiation. In 2017, TPT initiation, as reported in the
2018 World Health Organization (WHO) Global TB Report ranged from 1 to 53% for high burden
African countries. South Africa reports higher rates of TPT initiation compared to the rest
of the continent, but progress has plateaued and current initiation levels are insufficient
for impact.
Current barriers to TPT delivery:
Key factors leading to low TPT initiation are (1) lack of provider confidence in definitively
ruling-out active TB, (2) concerns about increasing drug resistant TB, (3) understanding
appropriate screening for TB disease, (4) concerns for drug-induced liver injury (DILI), (5)
the complexity of prescribing guidelines, (6) misperceptions regarding which patients may
benefit, (7) not understanding the benefit of TPT, (8) assumption that patients will not
adhere to TPT, and (9) the increased work-load of TPT initiation. All of these factors
contribute to the cognitive load of TPT initiation, some also add to the workload. Drug
stock-outs in some settings have also posed a barrier to initiation.
Choice architecture and TPT delivery:
Choice architecture is a behavioral economics approach that is used to improve decision
making. Choice architecture involves deliberate consideration of how options are presented
and what follows from each option, including what happens if no active decision is made
(sometimes referred to as passive selection or the "default" setting). Choice architecture
can reduce time and complexity required for decision making leading to a reduction in the
cognitive load. Lower cognitive load can improve decisions; high cognitive load leads to
poorer decisions.
Currently TPT initiation requires an active process to select TPT and a passive (neglecting
to consider TPT) process for not initiating. The current active process required for TPT
initiation includes at least four steps: (1) consider TPT, (2) evaluate reasons for not
initiating, this includes potential concerns for undiagnosed TB and the presence of liver
disease, (3) weigh the risks and benefits of TPT, (4) consider patient adherence, and (5)
write the TPT prescription. These steps require consideration (cognitive load) and time. Both
cognitive load and time compete with other priorities of a complex clinical encounter. As a
result, clinicians may "defer" consideration to the "next" visit or turn to rules of thumb to
justify deferring or not initiating TPT. Given that the vast majority of ART patients in
South Africa would benefit from TPT, the use of choice architecture making TPT the "default"
could improve provider decision making and safely increase TPT initiation.
STUDY OBJECTIVES
The overarching goals of this proposal are to test a low-cost and context appropriate
approach to translating TPT policy into on-the-ground TPT delivery. The investigators are
proposing a cluster-randomized trial (CRT) to measure the effectiveness of a choice
architecture-based TPT initiation strategy versus usual prescribing. The investigators
anticipate a substantial increase in TPT initiating, potentially increasing from
approximately 35% to 60-80% of ART initiators. This can be achieved through choice
architecture and a decrease in cognitive load. The investigators will assess the
effectiveness, implementation measures, and patient-level delivery and acceptability to
providers.
The primary objectives of this study are:
1. To compare the proportion of patients newly starting ART also initiating TPT between the
choice architecture and usual prescribing arms
2. To characterize the processes of TPT implementation by study arm including:
- Provider adoption
- Fidelity
- Provider acceptability
- Intervention maintenance
- Provider cognitive load of TPT prescribing
- Clinic workflow integration
3. To describe patient-level characteristics associated with initiating TPT and adhering to
TPT
The secondary objectives of this study are:
1. The proportion of patients already on ART initiating TPT
2. The proportion of eligible patients newly starting ART also initiating TPT
3. The proportion of eligible patients already on ART initiating TPT
4. The proportion of patients who initiate TPT and discontinue TPT prior to completion
SIGNIFICANCE
TB is the leading cause of death among people with HIV in South Africa and much of the world.
TPT is a proven approach to reduce mortality. This study has the potential of identifying an
approach to markedly increase TPT prescribing.
METHODS
Study design:
This is a clinic-level cluster randomized trial of a strategy to increase the delivery of
evidence-based care. Clinics will be randomized to the novel choice architecture strategy arm
or usual prescribing arm with analysis based on the clinic-level proportion of TPT initiated.
This study will further assess implementation outcomes, the underlying theory of change (the
effect of choice architecture on cognitive load), provider experiences with the novel
strategy, and patient experiences with TPT by study arm.
Study setting:
The research will be conducted by the Perinatal HIV Research Unit (PHRU) in two districts:
the Kenneth Kaunda district in the North West Province of South Africa and Mangaung District
in the Free State Province. Kenneth Kaunda district has a population of 742,000 and is served
by 36 public-sector clinics (primary care clinics and community health centers) providing HIV
care (ART, TPT, TB treatment). Mangaung District has a population of 747,431 and is served by
45 public clinics. Both districts have urban, peri-urban, and large rural areas. Both
districts are also settings with high HIV and TB prevalence with which the team is very
familiar, has a working relationship with the local Department of Health, and has completed
prior research on TB and TPT delivery.
The proposed study will be conducted in 36 public clinics that provide antiretroviral therapy
(ART). Clinics will be located in rural and peri-urban areas in Kenneth Kaunda and urban and
rural areas of Mangaung, especially around Botshabelo. The investigators selected these two
areas based on a long-standing working relationship between the team and the Department of
Health in these locations and established PHRU research infrastructure in both locations.
Study population:
The study is a cluster-randomized trial with the randomization at the clinic level and the
primary outcome at the clinic level. The strategy arm seeks to improve delivery of
guideline-mandated services to the clinic population. Thus the strategy clinics may have
greater prescribing of TPT and anticipated improved health outcomes, but clinic patients will
not perceive any differences in care nor will any individual randomization or patient-level
consent occur for the primary outcome of the proportion of patients who receive TPT.
Clinic selection:
Baseline data collection will be completed for a stratified randomization. Key clinic
characteristics used for stratification will be measured during a pre-study initiation
baseline assessment in the study clinics prior to randomization and will include clinic-level
characteristics of patient volume, staffing, and monthly ART initiation.
Prior to randomization, data on TPT prescribing, ART initiation, ART maintenance, and clinic
staffing will be obtained for the prior 12 months. These data will be abstracted as monthly
aggregates from electric and paper clinic reporting systems. No patient level data or
identifiers will be abstracted.
Randomization:
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.
Standard of care 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.
Implementation 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. This stamp/sticker will be available in the consulting rooms and will be
pre-stamped/applied by file clerks to files when retrieved. 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.
