Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and Improve Adverse Event Identification Among Voluntary Medical Male Circumcision (VMMC) Clients in the Republic of South Africa
Phase: NA
Conditions: Voluntary Medical Male Circumcision
Sponsor: University of Washington

Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and 
Improve Adverse Event Identification Among Voluntary Medical Male 
Circumcision Clients in the Republic of South Africa 
 
NCT04327271 
 
Caryl Feldacker, Principal Investigator 
 
Study Protocol Version Date 7/27/20 

PROTOCOL
Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-up
and Improve Adverse Event Identification Among Voluntary Medical Male
Circumcision Clients in Republic of South Africa
Version 2.0 dated 27 July 2020
PI Feldacker and Co-PI Setswe and will provide joint oversight to the implementation
of the entire research plan.
Principal Investigator: Dr Caryl Feldacker will have primary responsibility for:
The study design, Drafting all SOPs and protocol, Conducting all quantitative and
qualitative data analysis, Management of sub-contract to Medic Mobile, providing
management and oversight including training on the technology, Medic Mobile toolkit
data review, quality assurance, All UW IRB applications, follow-up, reporting, etc, all
NIH communication and final publications approval
Co-Principal
Investigator:
Prof
Geoffrey
Setswe
will
have
primary
responsibility for:
All local staff hiring and management, all ground implementation and daily study
oversight, protocol adherence, randomization for RCT, clinical team training, DSMB
organization and liaising, WITS IRB application, follow-up, management, and
reporting,
Submission
of
progress
reports
to UW, Site administration, Data
coordination – cleaning, quality assurance, excel databases of non 2wT toolkit data,
Qualitative data collection, Clinical oversight, Capacity building of local research
staff, work closely with Medic Mobile to provide feedback for local optimization of the
technology and integration of user feedback for scale, Study implementation and
decision making will be managed with weekly investigator meetings led by co-PI and
submission of annual progress reports.
Joint roles and collaborative actions for PI and Co-PI:
SOP finalization, Staff training, Project oversight, Research output decisions, Study
governance, take specific mentoring responsibilities and support research team
members in conducting research, analysis, and manuscript preparation, Weekly or
monthly, depending on study status, one-on-one calls between the investigators;
Authorship on publications will be based on relative contributions with a key effort to
guide and develop writing among research team members.
Investigator Holeman – Medic Mobile – will be responsible for:
Technology delivery for the pilot, Modifications for the RCT, Optimization for the
Intensive phase, Delivery of timely databases for analysis of primary and secondary
outcomes and all daily technology management to ensure smooth application and
delivery of the intervention.
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CONTENTS
I. Investigator Affiliations, Roles and Responsibilities
4
2. Project summary
5
3. STUDY BACKGROUND, PURPOSE AND SUMMARY
5
4. GOAL AND OBJECTIVES
8
5. Study Design
9
Recruitment Sites:
10
Recruitment: Procedure
10
Eligibility Criteria:
11
6. Study Procedures:
12
Participant overview:
12
Recruitment and Informed Consent:
12
Study preparation:
12
Randomization process:
13
Participant eligibility and recruitment:
14
7. Training of Study Personnel:
18
8. Study Participants:
18
9. Data collection:
18
10. DATA ANALYSIS:
19
11. Information management and analysis software
20
Capacity Building and Sustainability:
20
Future plans:
21
Innovations
21
12. ETHICAL CONDUCT OF THE STUDY
21
13. Confidentiality:
24
14. CONSENT
25
COMPENSATION FOR TIME:
27
15. Data Management Plan (DMP):
27
16. LIMITATIONS AND UNCERTAINTIES:
28
17. INTENDED USE OF FINDINGS
28
18. Study Timeline
28
19. Budget
29
20. References
29
Appendices:
34
1.
Study Budget
34
2.
Consent form – men
34
3.
Consent form – clinicians
34
4.
SOP clinical team
34
5.
SOP data management
34
6.
SOP usability
34
7.
DSMB charter
34
8.
Recruiting flyer
34
9.
Recruiting script
34
10.
Clinician subject recruitment
34
11.
Study procedures – visits
34
12.
Texting flow chart
34
13.
Brief survey participant
34
14.
Follow up calls and texts scripts
34
15.
Qualitative interview clinicians
34
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16.
Usability survey
34
17.
MedicMobile Inbox example
34
18.
Enrollment Form
34
19.
Follow up Time and Motion Survey
34
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I. INVESTIGATOR AFFILIATIONS, ROLES AND RESPONSIBILITIES
1. Geoffrey Setswe, DrPH, MPH; The Aurum Institute, Johannesburg
Affiliation:
The Aurum Institute, Johannesburg
Role:
Co-Principal Investigator
Responsibility:
Dr. Setswe carries the overall end-responsibility of the
project, including oversight for the protocol development, implementation, and
assurance for the timely reporting and dissemination of study results.
2. Caryl Feldacker, PhD, MPH I-TECH, University of Washington
Affiliation:
I-TECH, University of Washington.
Role:
Co-Principle Investigator
Responsibility:
Dr. Feldacker carries the overall end-responsibility of the
project, including oversight for the protocol development, implementation, and
assurance for the timely reporting and dissemination of study results.
The Investigators and co-investigators report no conflict of interest or
competing interest in the submission, implementation, dissemination or publication of
this work.
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2. PROJECT SUMMARY
Because male circumcision (MC) reduces the risk of female-to-male HIV-1
transmission by up to 60%, nearly 10.4 million voluntary medical male circumcision
(VMMC) procedures were performed in sub-Saharan Africa where the HIV epidemic
is most concentrated. VMMC is safe: the average rate of moderate and severe
adverse events (AEs) at the country level is 0.8%, corresponding to 99% of men
healing without incident. To reach the global target of 20 million by 2018, VMMC
productivity needs to double in countries already plagued by severe healthcare
worker shortages like South Africa. Current VMMC care in South Africa strongly
suggests in-person, follow-up visits at post-operative days 2, 7, 14 and 21. Over 60%
adhere to multiple follow-up visits within 14 days of VMMC. South Africa’s program
has an overall AE rate of less than 2%; therefore, to reach its target of 2 million
additional VMMCs in RSA, there could be millions of unnecessary follow-up visits.
for VMMC clients without complications. High mobile phone ownership, severe
healthcare worker shortages, and rapid VMMC scale up make South Africa’s VMMC
program an ideal setting to test a mobile health (mHealth) intervention to reduce
provider workload while safeguarding patient safety. Through an un-blinded,
prospective, randomized, control trial (RCT) in high-volume facilities providing
VMMC, the Aurum Institute, a VMMC implementation partner, will implement an
interactive, two-way texting (2wT) intervention to identify men healing without
complication, allowing them to decline routine in-person follow up visits. 2wT will
simultaneously identify men with any sign of an adverse event, encouraging rapid
in-person follow-up when an AE is suspected on any day, reducing unnecessary
visits while maintaining quality care. We aim to 1) determine if 2wT can safely reduce
VMMC follow-up visits; 2) estimate the cost savings associated with 2wT over
routine VMMC follow-up; and 3) assess the acceptability and feasibility of 2wT for
further scale-up. It is expected that this intervention with be as safe as routine care
while providing distinct advantages in terms of efficiency, costs, and reduced
healthcare worker burden. This approach is innovative as it focuses on using a
low-cost mHealth intervention to reduce provider workload without deterioration in
quality care. The success of this intervention could lead to adoption of this
intervention at the national level, increasing efficiency of VMMC scale up and
reducing burdens on providers and patients. The international, interdisciplinary team
will build the capacity among local research colleagues and NDOH collaborators,
helping the South Africa team become future leaders in mHealth research.
3.
STUDY
BACKGROUND,
PURPOSE
AND
SUMMARY
Male circumcision (MC) reduces the risk of female-to-male HIV-1 transmission
by up to 60%
1-3. From 2008-2017, over 15 million voluntary medical male
circumcision (VMMC) procedures were performed4,5, falling far short of the 20 million
needed to reach the UNAIDS/ World Health Organization (WHO) target of 80%
coverage in 14 priority countries by 2016 6. Reaching the target could avert 3.4
million HIV infections and save $16.5 billion in HIV-related care through 2025 7.
Although
surgical
VMMC has been streamlined and made efficient through
operational optimization 8, current VMMC follow-up requires at least one in-person
visit within 14 days of MC 9-11. VMMC program guidelines often require multiple,
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additional visits over the 42-day healing period. Severe healthcare worker
shortages
12 combined with rapidly expanding VMMC programs threaten
already overburdened healthcare systems by recruiting workers away from
facilities or diverting their efforts from other competing patient care needs.
In pilot studies and controlled trials in sub-Saharan Africa, surgical adverse
event (AE) rates from combined moderate and severe AEs range from 0.5% to 8%
with few severe AEs resulting in permanent impairment 1-3,13-20. Although AE reporting
in field settings is challenging 21-23, AE rates averaged 0.8% (range: 0.4%-4.2%) in all
southern African countries from 2010-2012 24. These low AE rates correspond to
99% of men healing without incident, leading to millions of healthcare visits
conducted without cause and needlessly increasing the workload.
For men, these
unnecessary visits likely create barriers to care such as transportation costs, wait
times, and inconvenience
25-30, potentially reducing VMMC uptake. Empowering
men to seek in-person follow-up care only when needed or desired would
decrease the burden for both healthcare workers and patients, thereby
improving efficiency and reducing both direct and indirect costs for this
critical component of combination HIV prevention.
The spread of mobile telephones throughout sub-Saharan Africa affords an
important opportunity to address these inefficiencies and retain quality care. Text
messages show promise to positively influence health behavior and improve clinical
care 31-33.
Most short message service (SMS)-based health promotion efforts use
one-way
‘push’
messages,
blasting
pre-defined
messages
to
many
people
simultaneously 34-36. Among VMMC programs, a randomized control trial determined
that automated SMS modestly increased adherence to 7-day follow-up visits from
59.7% to 65.4% (RR 1.09, 95% CI 1.00–1.20; p = 0.04) but did not influence
resumption of sex during the 42-day healing period (relative risk=1.13, 95% CI
0.91-1.38, p=0.3) 30,37. An important weakness of these one-way, blast approaches is
the one-size-fits-all approach, removing patients’ ability to communicate back with
healthcare workers 38, potentially reducing patient engagement in care.
Two-way texting (2wT) between providers and patients shows promise to
provide quality interactive care. In Kenya, patients enrolled in a SMS study
significantly increased adherence and viral load suppression, but high-volume,
manual texting was time-consuming and not sustainable for healthcare workers 39.
Another Kenyan study engaged patients in important health-related conversations
and provided critical health information
40; however, this intervention tasked the
health
workers
to
respond
to
complicated,
open-ended questions, investing
considerable time. In 2008 members of this study team pioneered an alternative
approach to provide high-quality, efficient, coordinated service by enabling patients
or community health workers to exchange ad hoc messages with facility-based
nurses in Malawi 41,42. Use of interactive, mobile technology that improves both
care quality and care efficiency for providers and patients is warranted.
The Republic of South Africa (RSA) is primed for this type of mobile
intervention. RSA has a high burden of HIV and one of the highest rates of new
transmissions, making it a priority country to scale up VMMC to achieve the WHO
target of a circumcision coverage of 80% 43. As of December 2015, the number of
VMMCs reported in RSA was approximately 2.25 million, leaving slightly more than 2
million VMMCs to perform in order to achieve the national target (4.3 million males)
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44. Although some AE underreporting is possible especially among older men who
are less likely to return for follow-up13, South Africa’s VMMC program is safe with the
national VMMC program’s AE rate of less than 2%. Under the current VMMC
National Department of Health (NDOH) standards, men who receive surgical MC
return to the clinic at Days 2, 7, 21 and 6 weeks. Therefore, 2 million additional
VMMCs in RSA could translate to ~4 million unnecessary follow-up visits. As
each VMMC client likely passes through reception, observation, and examination,
the healthcare workload and time lost for VMMC clients healing without
complication is likely several times higher. Moreover, VMMC teams may perform
most VMMCs in outreach or mobile sites (tertiary clinics, schools, communities)
where clients must seek follow-up care in their local healthcare clinics, clinics that
may suffer from a chronic shortage of healthcare workers or a less than ideal
healthcare worker mix 45. Unnecessary follow-up in these smaller primary healthcare
sites results in additional days away from other clinic duties, stretching human
resources required for myriad other health needs. While healthcare is strained,
mobile technology is advancing rapidly: in 2017, 3G cellphone coverage in South
Africa was nearly universal while 4G networks reached almost 75% of the population
46. This setting with high, unnecessary in-person VMMC follow-up; healthcare worker
shortages; and high cell coverage is ideal to test and evaluate a better, low-cost
approach to minimizing the burden on both the healthcare system and VMMC
clients.
Building
upon
these
previous
mHealth
initiatives,
we
seek
to
implement
a
two-way
texting
(2wT)
intervention
that
combines
automated
and
interactive
text
messaging
to
maintain safety while dramatically
reducing the burden that in-person
VMMC follow-up places on weak
health
systems.
Automated
messaging during Days 1-14 after
circumcision could track men who
are healing without complication,
enabling a conservative estimate of
more than 80% of clients to avoid
unnecessary in-person follow-up at
post-operative Days 2, 7 and 21. When a patient responds to an automated prompt
message in a way that flags a potential AE, interactive messaging with a nurse
would encourage them to promptly seek in-person, follow-up care. 2wT would act as
active but efficient surveillance, improving care. By combining automated messaging
to screen out cases with no complications and interactive texting to identify potential
AEs, this intervention could make the care pathway far more efficient, reducing the
costs of VMMC care over time for both providers and patients. Reduced in-person
follow-up could also free these same healthcare workers to perform additional
VMMC surgeries.
As a national VMMC implementing partner, Aurum Institute, in partnership
with the National Department of Health (NDoH), works to implement VMMC services
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in 3 Provinces namely KwaZulu Natal, Eastern Cape and Western Cape across 7
PEPFAR priority districts. Aurum Institute began implementation of VMMC in 2010
and now works out of more 100 clinics across 3 provinces and has performed more
than 200 000 MCs with adverse events (AEs) of less than 2%. Adherence to
follow-up visits, another indicator of program quality 47, was good: The majority of
men attended at least one post-operative visit before Day 14. More than 40% also
had a Day 21 visit to verify complete healing. With such high follow-up visits, even if
20% of an expected annual 80,000 men were reviewed on Days 2 and 7 for high
sensitivity of AE detection, almost 74,000 in-person visits were unnecessary
and could potentially be replaced with 2wT interactions between patients and
providers (Figure 1). Aurum Institute continues to rapidly scale up. Greater
efficiency would enable more VMMCs.
4. GOAL AND OBJECTIVES
We propose to maintain patient safety while reducing the substantial
VMMC follow-up workload burden by using two-way mobile phone texts to provide
in-person review only for men who indicate a desire or need for follow-up. This
tailored approach to post-procedure VMMC care could reduce unnecessary visits
and remove barriers for VMMC clients without deterioration of quality care. I-TECH’s
diverse, expert team of researchers from the University of Washington, Seattle, USA;
Aurum Institute’s office in Johannesburg; and Medic Mobile, Nairobi, Kenya, will test
this mHealth intervention. We believe that bi-directional, interactive, text-based short
message service (SMS) during the most critical 14 days after circumcision will help
men identify and act on any sign of an adverse event, thereby seeking in-person
follow-up only when an AE is suspected and reducing unnecessary visits. Reduced
in-person follow-up could also free healthcare workers to perform additional
VMMC surgeries. Using a prospective, randomized control trial (RCT), our
intervention compares two groups of clients with cell phones: 1) standard care
(control group) and 2) clients who receive and respond to a daily text with in-person
follow-up only if desired or if an AE is suspected (intervention). Both arms complete
a study-specific, Day 14, in-person, follow-up review for verification of self-reports
(intervention) and comparison (control). Our specific objectives are to:
Objective 1: Determine if 2-way texting can safely reduce VMMC follow-up
visits
Approach:
Un-blinded,
prospective,
non-inferiority,
RCT
in high-volume
facilities providing VMMC. Two-way texting (2wT) will provide interactive, text-based
follow-up. 2wT men healing without complication could decline in-person follow-up;
those with suspected AEs will be referred to in-person care. We will compare the
safety outcome of combined moderate or severe AE rate ≤Day 14 post-VMMC and
the workload outcome of average number of in-person follow-up visits between
control and intervention arms.
Objective 2: Estimate the cost savings associated with 2wT over routine
VMMC follow-up
Approach: We will determine the programmatic costs of 2wT from a systems
perspective, including the technology
48, healthcare worker costs, and client
perspective (travel, text costs, missed work). We will estimate the incremental
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intervention costs relative to standard practice to quantify gains in healthcare
efficiency for scale-up and adoption.
Objective 3: Assess the acceptability and feasibility of 2wT for further scale-up
Approach: Qualitative interviews with VMMC healthcare workers and brief
quantitative interviews with 2wT clients inform intervention acceptance. Meetings
with local researchers and collaborators will further assess feasibility, adaptation,
open-source collaborative development, and system integration for replication and
sustainability in RSA and the region.
The
proposed
mHealth
study
will
establish
new,
low-cost,
technology-supported VMMC follow-up that will streamline in-person care, therefore
reducing provider workload and patient burden while maintaining the quality of care.
5. STUDY DESIGN
Study overview: Following usability testing with both healthcare workers and
2wT VMMC clients during a ~50-man pilot, we will test if two-way texting (2wT)
reduces unnecessary follow-up visits without compromising patient safety (Objective
1) using a randomized control trial in large, urban VMMC clinics. We will assess the
costs of 2wT from technology, healthcare worker, and client perspectives to
determine the costs incurred by NDoH if adopted for scale-up (Objective 2). We will
assess
acceptability
and
feasibility
working
towards
system
integration
and
sustainability in RSA and beyond (Objective 3).
Objective 1: Technology overview: Studies that demonstrate the impacts of
mHealth interventions too often have evaluated technologies that are made ‘from
scratch’ and as a result are not robust enough to merit widespread replication 41,49.By
partnering with a well-established non-profit mHealth organization, Medic Mobile
(http://medicmobile.org/), and integrating with their existing software platform,
open-source community and current efforts to integrate with existing health
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information systems (HIS) throughout sub-Saharan Africa, our team and proposed
intervention are well positioned to scale up and sustain any promising results. Since
2008, Medic Mobile has been a leader in the global mHealth community
50-52,
equipping more than 13,500 health workers serving over 8 million people across 23
countries. The Mobile Medic Toolkit is an Android-based application that supports
texting in any language and works with or without internet connectivity on basic
phones, smartphones, tablets, and computers
53. The existing, well-proven,
app-based Toolkit that will be the basis for 2wT provides an automated and
prioritized list of upcoming tasks, guiding health worker through actions (e.g.,
response waiting, referral). The Toolkit provides real-time progress indicators such
as texting delivery rates and response rates. Data from mobile users are replicated
to Medic Mobile web app and analytics tools for real-time response. The platform is
highly configurable, currently supporting evidence-backed workflows and program
implementation related to ensuring safe deliveries 54, tracking tuberculosis patients 55
, boosting immunization rates 56 and monitoring stocks of essential medicines 57.
These adaptable tools are free, open-source, and developed using human-centered
design with input from people delivering care in the hardest-to-reach communities.
This technology has been used effectively in an ongoing randomized control trial in
Zimbabwe, requiring adaptation, but not redesign, of the clinical content as the
existing 2wT software toolkit already contains the robust messaging features
discussed in this proposal (Figure 2). The software adaptation process to alter and
test alternative clinical content and the local specifications requires little additional
software development. The adaptation process will be completed by collaborator,
Holeman, with additional technical and training support provided by Nairobi-based
technical experts.
RECRUITMENT SITES:
Study sites and population: In RSA, the World Bank estimated that there were
126 cellular subscriptions per 100 people in 2014 58, indicating that the technology
infrastructure exists and uptake is high. 2wT will be implemented in existing VMMC
sites in Bojanala and Ekurhuleni Districts, districts purposefully selected for high
VMMC volume static clinic locations and previous outreach success.
RECRUITMENT: PROCEDURE
The City Health Director who manage the national VMMC program at the
Provincial level in conjunction with our implementing partners will facilitate access to
the clinics/hospitals where Aurum Institute provides ongoing support for VMMC. As
study sites are Aurum Institute static sites, permission will be granted as part of the
participatory study development process. It would be expected that demand creation
would happen in anticipation of the study implementation.
Each site will establish local recruitment and screening methods that
operationalize protocol-specified requirements for eligibility determination in a
manner that is tailored to and most efficient for the local study setting and target
study population. In brief, information about the study will be disseminated by Aurum
Institute at the selected sites. VMMC demand creation as part of routine Aurum
Institute program practice will support study recruitment. Aurum Institute-supported
HCW recruited for participation in the study will be reached at their workplaces (the
Aurum Institute health care facilities) following communication between the study
team and the site leadership. VMMC clients will be recruited in the VMMC clinic
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area. Recruitment will be managed by a specifically-trained research coordinator
who receive payment for their roles as part of routine or study work. This research
coordinator will meet with VMMC patients to sensitize them about the opportunity to
participate in a study of text-based follow-up; those meeting eligibility criteria will be
individually informed by 2wT staff (who are also part of Aurum Institute) about the
opportunity to participate in the study. Interested patients will be referred to the site
study coordinator for study enrollment and informed consent. This person will meet
with patients in a private setting, further explain the study, confirm study eligibility,
and seek informed consent. Participants who refuse to enroll in the study will be
asked to provide reason(s) for non-participation, noted on a 2WT checklist.
This activity is being conducted with cooperation from the NDOH, Aurum
Institute, and I-TECH. This activity will seek ethical approval from the University of
Witwatersrand Human Research Ethics Committee and the University of Washington
Internal Review Board, Seattle, Washington, USA.
ELIGIBILITY CRITERIA:
For VMMC clients (Objective 1):
Inclusion criteria for VMMC clients are:
1) 18 years or older;
2) Possession of own phone at enrollment;
3) Provides contact details (phone, physical location);
4) Receives surgical VMMC;
5) Willing to follow NDOH VMMC protocols;
6) Willing to come in Day 14;
7) Able and willing to respond to a questionnaire administered by phone 21
days after circumcision;
8) No intraoperative adverse event during routine VMMC.
Exclusion criteria:
1) Not willing to participate
2) Men without cell phones and
3) Those who chose VMMC devices, when applicable, as
devices require a
removal visit 7 days after placement and have distinctly different follow-up
protocols.
For health care workers (Objective 3):
Inclusion criteria are:
Within the RCT study site, health care workers (HCW) will be eligible to
participate in the individual interviews if they:
a) Are employees posted at the Aurum Institute site;
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b) Are at least 18 years of age or over;
c) Provide health care services to patients as part of the VMMC programs;
and
d) Are able to provide written informed consent.
Exclusion Criteria:
•
Not willing to participate
•
Not willing to be recorded
6. STUDY PROCEDURES:
PARTICIPANT OVERVIEW:
●
Based on prior experience in Zimbabwe, up to 50 men will be needed for the
pilot depending to reach maximum system stability (after making adaptations)
and to reach healthcare worker efficiency and comfort. This increases the
quality of the full study. Not randomized. Enrolled into texting. Not included in
outcome analysis.
●
1104 men in the full study randomized in a 1:1 ratio of texting and control for
552 men in texting and 552 in control (routine care).
●
Same recruitment, consent, and follow-up procedures in pilot and intervention
as outlined, per group, below
RECRUITMENT AND INFORMED CONSENT:
Each site will establish local recruitment and screening methods that
operationalize protocol-specified requirements for eligibility determination in a
manner that is tailored to and most efficient for the local study setting and target
study population. In brief, information about the study will be disseminated through
Aurum Institute at the selected sites. VMMC demand creation as part of routine
Aurum Institute program practice will support study recruitment. HCW recruited for
participation in the study will be reached at their workplaces (the health care
facilities) following communication between the study team and the site leadership.
VMMC clients will be recruited in the VMMC clinic area. Recruitment will be
managed
by
a
specifically-trained
Aurum
Institute research coordinator and
supported by Aurum Institute interns and fellows. This research coordinator will meet
with VMMC patients to sensitize them about the opportunity to participate in a study
of text-based follow-up; those meeting eligibility criteria will be individually informed
by Aurum Institute staff about the opportunity to participate in the study. Interested
patients will be referred to the site 2WT study coordinator for study enrollment and
informed consent. This person will meet with patients in a private setting, further
explain the study, confirm study eligibility, and seek informed consent. Participants
who refuse to enroll in the study will be asked to provide a brief reason(s) for
non-participation.
STUDY PREPARATION:
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We will conduct a rapid situation analysis with healthcare workers, VMMC
clients, and stakeholders to assess suitable responses to VMMC client texts, setting
standards for text responses and in-person follow-up. We will modify existing
usability surveys for this public health context. A small pilot with 50 VMMC clients
who will be enrolled in the texting intervention will include usability testing with both
2wT
clients
and
nurses
implementing
the 2wT system, illuminating system
experiences from both perspectives. Usability results will inform in-box modification,
message format preferences and optimal message delivery (timing, frequency,
language preferences). Experience from study coordinator and other team members
will add detail to inform 2wT adaptation and modification of Standard Operating
Procedures before implementation. We will examine local infrastructure (e.g.
electricity and cell network), and explore 2wT cost reduction options (e.g., text
bundling, free-call back numbers) and adapt accordingly
RANDOMIZATION PROCESS:
We will conduct randomization using a randomized block design, ensuring
that each group of 20 envelopes has 10 intervention and 10 control per block,
shuffling each block to ensure a near random order. The full set of 1104 will be
numbered before distribution to sites. Each group assignment envelope will be
selected by the coordinator and then opened by the participant and shown to the
coordinator or 2WT enrollment coordinator. Security envelopes will be used to help
prevent selection of assigned group. Subjects within each block are randomly
assigned to treatment conditions. This design reduces variability within treatment
conditions and potential confounding, allowing for more interim analysis with near
equal size groups and more certain randomization within sites.
Standard VMMC care (Control arm): For the 552 men randomized into the
control arm, Aurum Institute follows all NDOH protocols based on WHO guidelines 9
including routine surgical VMMC follow-up on post-surgery days 2, 7 and 21 (Table
1) 59. Patients may seek care outside scheduled visits for suspicion of AEs at any
healthcare facility at any time but most often return to their VMMC site. Referral
cards for VMMC clients provide local numbers for patients to text, call, or request a
call back for emergencies. A standardized approach is used to assess, identify, and
record the severity of AEs 47. All VMMC care, from assessment of all AEs through
complete healing, is provided free to clients from NDoH. Clients who do not return to
the clinic for follow-up on Day 2 or Day 7 are traced: 3 attempts by phone and then 1
attempt at in-person tracking after which they are considered lost to follow-up
(LTFU). There is no tracing for Day 21 visits. For the purposes of this study, control
arm VMMC clients will be asked to come in on Day 14 for an additional follow-up
visit. Active follow-up by phone call is provided at Day 14.
VMMC care procedures (2wT arm): We will conduct a prospective, un-blinded,
randomized control trial (RCT) among VMMC clients in a 1:1 ratio of control to
intervention. Study participants and clinic staff are not masked to treatment. For the
552 men randomized into the intervention arm, men in the 2wT will receive routine
VMMC surgical care and counseling, including referral cards for emergencies. 2wT
clients will receive automated daily texts from days 1-14 (Table 1 and Figure 3). It is
free to receive call and texts; it costs approximately R0.20 to send a SMS in RSA 60.
If they respond that they suspect no adverse event, no immediate follow-up action
will be taken. If a 2wT VMMC client responds affirmatively to any daily text that he
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suspects an AE, a VMMC nurse will exchange modifiable, scripted texts with the
client to determine the symptoms, frequency, and severity. Then, if deemed
necessary, the client will be asked to return to clinic the following day or earlier if an
emergency is suspected. AE management will adhere to NDOH standard care. If
2wT patients do not respond to texts on Day 2 or Day 7, the same NDOH tracing
process will be activated on Day 14, after which they will be considered LTFU. All
study participants will be asked to come to the clinic for study-specific, Day 14
follow-up to review healing and verify adverse event reporting. Day 14 was chosen
for verification because 95% of all AEs within a similar VMMC program in Zimbabwe
are reported Day 14 or earlier 61, suggesting that most AEs have occurred by this
time point. In a previous field study of AEs, the most common AEs of bleeding and
infection were found a mean of 6.7 and 9.0 days, respectively, after VMMC 21, further
supporting the 14 day period used in this and a previous study14. The Day 14 review
will be conducted by routine VMMC providers according to NDOH review guidelines.
At Day 21, we will implement a brief text-based survey with 2wT clients to ascertain
complete healing, providing stronger inferences at study completion.
PARTICIPANT ELIGIBILITY AND RECRUITMENT:
VMMC client recruitment, voluntary consent, and enrollment will be managed
by the on-site 2wT study coordinator before VMMC surgery. Eligibility criteria for
VMMC clients are: 1) 18 years or older; 2) possession of own phone at enrollment;
3) provides contact details (phone, address, next of kin); 4) requests surgical VMMC;
5) willing to follow NDOH VMMC protocols; 6) willing to come in Day 14; 7) willing to
respond to a questionnaire administered by phone 21 days after circumcision. Men
without cell phones and those who chose an MC device will be excluded as devices
require a device-removal visit 7 days after placement and have distinctly different
follow-up protocols. As phone sharing practices are common, informed consent will
ascertain whether eligible men have consistent access to a phone to receive
messages about AEs. Participants who refuse enrollment will be asked to provide
informed consent for data collection about reasons for non-participation. We expect
to enroll and randomize
men into a 1:1 ratio of intervention and control within 6
months, allowing observation of the primary outcome by end of year 1. On Day 14,
all men in both arms who return for follow-up will receive a Rand 100 airtime credit.
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7. TRAINING OF STUDY PERSONNEL:
VMMC staff at Aurum Institute study sites will be informed of the study and
briefed on study protocols. A 2wT study coordinator will be trained in confidentiality,
protection of human subjects, enrollment, and data collection methods, working to
not interfere with routine VMMC flow. For technology training, an experienced Medic
Mobile trainer from Nairobi will work with the local study coordinator and team
members in-person to implement and learn to maintain the Medic Mobile toolkit
independently. We believe that achieving local maintenance and ownership of the
system is feasible because of Medic Mobile’s considerable investments in open
source collaboration and in designing software that is user friendly and intuitive
enough to be adapted and maintained by local staff. As part of 2wT, one experienced
Aurum Institute VMMC nurse will serve as Study Coordinator in Pietermaritzburg and
will manage the texting database, including text and voice follow-up communication
with
intervention
clients.
RSA-based
co-investigators
and
interested
partner
organization researchers will also be invited for Medic Mobile training.
8. STUDY PARTICIPANTS:
Group
name/description
Data
collection
method
Age
range
of
subjects
Target
number
of
individuals
Men
in
the
intervention
pilot
(texting):
Assigned texting
Usability
survey,
routine
VMMC
clinical
review
18-6
5
50
Men
in
intervention
group
(texting):
Randomized into group
Interview
, routine VMMC
clinical review
18-6
5
552(100
selected
for
the satisfaction
and
acceptability
questionnaires
)
Men in control group
(routine care): Randomized
into group
Routine
VMMC
clinical
review
18-6
5
552
Healthcare
workers
(VMMC clinicians)
Interview
18-6
5
~10
9. DATA COLLECTION:
Sample size:
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10. DATA ANALYSIS:
For Objective 1, the 2wT safety outcome of interest is cumulative AE rate
(moderate or severe) ≤Day 14. In RSA, and similar to other countries in the region,
moderate AEs are those which include symptoms requiring modification of activity,
but not resulting in loss of work or cancellation of social activities while severe AEs
are those with incapacitating symptoms, requiring bed rest and loss of work
66.
Incidence of AEs before Day 14 will be extracted from routine VMMC data for both
2wT and control. Incident AEs on Day 14 will be identified, classified, and graded for
severity using routine NDOH protocols 10 and recorded on routine VMMC AE forms.
We will compare cumulative rates of any moderate or severe AE ≤Day 14 between
groups using Fisher’s exact test as the expected number of AEs is low. The rates will
be calculated per arm as: (# moderate + severe AEs)/ (total # VMMC clients who
attend/responded to 2, 7 or 14 Day follow-up visits or texts). Multivariate logistic
regression models (any AE v none) will quantify the magnitude of difference,
adjusting for any potential confounders. To determine follow-up visit reduction, we
will compare the mean number of in-person visits for intervention and control using a
t-test. A multivariate linear regression model will further quantify the effect of
intervention on visit reduction, adjusting for potential confounders. Secondary
outcomes include: AE rates on Day 14, texting response rate, time between 2wT AE
text reporting and follow-up, severity of AEs. We will perform appropriate summaries
of missing data and LTFU, testing for systematic differences in response by study
arm. We hypothesize that 1) 2wT is non-inferior to routine follow-up for patient safety
and that 2) 2wT will reduce unnecessary follow-up over standard care.
For Objective 2, 2wT costs, we will calculate the relative costs and outcomes
(effects) of intervention versus control, including costs for technology, healthcare
worker time, and client considerations (travel, text costs, missed work). We will
conduct both activity-based costing from the implementation perspective and from
the technology perspective to extrapolate our results as costs that would be incurred
by the NDOH should they elect widespread scale up of 2wT. Approach for costing.
First we quantify the total direct and indirect costs of 2wT deployment, a method
previously used for technology cost assessment in Malawi
48, which includes
comprehensive costs from installation and training, routine maintenance, healthcare
worker time associated with 2wT, and staff efficiency gains/losses in addition to the
direct cost of technology. Second, we will estimate incremental costs (incremental
relative to standard practice) for the intervention. This component entails a
micro-costing study using activity-based approaches for costs incurred (trainings,
VMMC service provision, follow-up) and costs averted (health costs for providers and
patients saved by reducing visits), adapting previous VMMC costing estimates 67 for
2017 dollars when appropriate. Cost data will also be collected from the study
budget, public health clinic budgets, published government reports, and the health
economics literature. Lastly, to estimate the cost savings associated with 2wT over
routine VMMC follow-up, we will conduct a time-motion study 68,69 to quantify time
spent for VMMC follow-up, indicating potential time savings for providers and VMMC
clients. One trained observer will record VMMC client/provider follow-up interactions
for 5-10 days, or approximately 100 reviews, recording times and activities using a
pre-established checklist and timing system. During these same 5-10 days, client
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time from registration through visit completion will be recorded by a second observer.
Data will be exported into STATA 12.0 for analysis. The combined, overall costs for
the delivery of 2wT in public health clinics will be estimated and compared to
standard follow-up.
We hypothesize that 2wT will reduce the costs associated with
VMMC patient follow-up over standard care.
For Objective 3, 2wT acceptability, using study recruitment and enrollment
logs in addition to the texting database, we will describe levels of acceptance,
participation, refusal and drop-out. We will carry out key informant interviews (KIIs)
with up to 10 health care workers to gauge acceptability, satisfaction, identify
facilitators
and
barriers
to
program
success, and ascertain suggestions for
intervention improvement. KIIs will be audio recorded and transcribed. Atlas.Ti
software will be used to create a spreadsheet of key themes, perceived barriers, and
suggested
facilitators
to
the
program
from
KIIs.
We
will
also
implement
questionnaires at the Day 14 visit with a subset of 100 2wT VMMC clients in the
main study who were randomized to texting to gauge satisfaction, estimate direct
and indirect costs (time away from work, transportation costs), and ascertain
suggestions
for
intervention
improvement.
Responses
from
these
brief,
self-administered, quantitative surveys with VMMC clients will be entered in Excel
and frequencies explored in STATA 12.0. For feasibility, costing data will be
combined with usability and acceptability information. These comprehensive data will
be discussed at a final stakeholder meeting to disseminate study results, validate
interpretations and refine recommendations for future scale up and modification of
2wT in RSA and beyond. Additional meetings between local researchers and the
NDOH will further determine feasibility for replication and scale-up. We hypothesize
that acceptability, usability, and feasibility will be high, aiding program scalability.
11. INFORMATION MANAGEMENT AND ANALYSIS SOFTWARE
During informed consent, participants will be asked to give permission to use
data from their routine VMMC medical records, including the VMMC register and
client record form (CRF). Data from paper CIFs includes VMMC number, age,
circumcision type, eligibility criteria, pre-procedure assessment, and adverse events
during the procedure. Variables of interest from CIFs and register will also be
entered using Medic Mobile software and verified through data checks, easing
merging with the SMS database and smoothing data management. De-identified,
coded data will be shared between researchers via secure networks.
Qualitative data will be entered, coded and analyzed as text documents in
Atlas.ti 6. The first-line data quality assurance will be the responsibility of the I-TECH
investigators. These files will also be sent to the team in Seattle, USA for secondary
data quality assurance and analysis. The recordings of the interviews will be
destroyed one year after the activity ends. However, the transcriptions will be kept
for five years in compliance with University of Washington policy.
CAPACITY BUILDING AND SUSTAINABILITY:
Aurum Institute is a local organization and the lead on the research
implementation, lending to the goal of capacity building. Aurum Institute and NDOH
partnership also enhances local ownership and buy-in, helping ensure replication of
the mHealth intervention if successful. Frequent communication and team-based
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decision making among all members of the multinational, multidisciplinary team will
help strengthen mHealth research capacity at I-TECH/RSA and local NGO partner,
Aurum Institute. By working closely with researchers from the UW and Medic Mobile,
investigators from Aurum Institute will gain mHealth research and implementation
capacity, helping translate findings to public health policy. Through their leadership in
this research, they will become mHealth leaders in RSA, creating a local team of
researchers for scale-up and evaluation. Partnering with Medic Mobile in Nairobi,
integrating with their existing software platform and building an expanded, local open
source community will afford distinctive advantages for long-term maintenance and
expansion.
FUTURE PLANS:
If texting with VMMC clients is found to be superior to routine, in-person
follow-up for detection of AEs, scale up could dramatically reduce time spent on
unnecessary VMMC follow-up visits by healthcare personnel and decrease the
burden on VMMC clients. Future funding could enable scale-up of the intervention in
other high volume VMMC sites with high mobile phone coverage, conducting
additional rigorous evaluation in diverse field and clinical contexts. We would seek
funding to test 2wT among rural populations or smaller urban areas. Lastly, we will
explore how 2wT could be integrated into DHIS2, or other national health information
system, to improve and ease reporting.
INNOVATIONS
●
Replace in-person follow-up visits with 2wT interaction between patients and
providers holds potential to dramatically reduce the burden on the health
system at low cost while maintaining patient safety. This rigorous research
involving local researchers is needed to test and optimize the approach.
●
Implement 2wT within an existing VMMC program structure that will
greatly improve the likelihood of program scalability and sustainability.
●
Quantify expected Aurum Institute/NDOH cost savings provided by 2wT
scale-up
●
Set a precedent by employing digital technology to identify cases of
uncomplicated healing and thereby to reduce the burden of unnecessary
VMMC clinic visits for both providers and patients - thus opening use of
mHealth
in
post-operative
care
or
other
contexts
with
low
rates
of
complications, potentially even long-term antiretroviral therapy use.
●
As the rate of unnecessary, in-person care in VMMC programs is likely high,
potential gains in efficiency identified through this low-cost digital innovation
are large, increasing the likelihood of scale-up and replication in the region.
12. ETHICAL CONDUCT OF THE STUDY
This study will be conducted in compliance with the protocol after approval by
the CDC, the Human Science Research Council Research Ethics Committee (REC),
and the University of Washington IRB. No deviations from the protocol after approval
will be implemented without prior approved amendment by these IRBs except where
it may be necessary to eliminate any immediate hazard to study participants. In such
case, the deviation will be reported to the IRBs as soon as possible.
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Risks: For VMMC clients, male circumcision comes with some risk, but this
study protocol does not cover the procedure which has its own consent. The VMMC
procedure is not included in this study. As a routine medical preventive procedure,
VMMC includes standard risks which are minimized and managed via NDOH
standard care and follow-up. All routine VMMC surgical procedures will be followed
for this study.
Any additional MC-related risk that may be incurred by participants by virtue
of their text-based follow-up will be monitored closely and managed as described
above. Participants will be reminded that they may seek in-person follow-up if they
suspect an AE or if they desire in-person follow-up without repercussion, confirming
that participants understand that they may decline in-person care if they wish but are
also welcome to seek it as per NDOH guidelines. Referral cards for after hours and
emergency care will be provided for 2wT participants as per routine care patients.
Adverse event (AE) management will be conducted according to NDOH guidelines,
including assessment of the severity, type, and treatment plan. The Adverse Event
guide is attached in an appendix.
Participants will be allowed to seek in-person
follow-up at any time, as with the control arm, as per NDOH guidelines. Participants
will also be informed that they can withdraw from the study at any time with no
repercussions.
This study carries some small risk of social harms for VMMC clients. VMMC
clients face a risk of stigma from circumcision as their circumcision status may be
inadvertently revealed to others outside the study as a result of their participation or
as a result of the texting intervention. VMMC clients who participate in surveys may
feel uncomfortable answering questions about service quality and their opinions
about the intervention.
Risks for HCW: This study carries minimal risk for HCW. Risks in this study
are low relative to the potential for improvement in health and quality of healthcare
services that could arise from the research. HCW will be informed that there is
limited risk associated with the intervention and data collection procedures. Some
HCW participating in interviews may feel uncomfortable answering questions about
quality of health care services, HCW responsibilities, intervention quality, or other
areas of inquiry.
Injury/side effects/adverse events: All routine VMMC surgical procedures will
be followed for this study. Any additional MC-related risk that may be incurred by
participants by virtue of their text-based follow-up will be monitored closely and
managed as described above. Adverse event (AE) management will be conducted
according to NDOH guidelines, including assessment of the severity, type, and
treatment plan. Participants will be allowed to seek in-person follow-up at any time,
as with the control arm, as per NDOH guidelines. Participants will also be informed
that they can withdraw from the study at any time with no repercussions.
Discomfort/stress: Individuals who consent to participate may experience mild
discomfort or stress as they will be asked to discuss topics that may be sensitive,
including their VMMC method choice and rationale. We will prevent undue influence
by stressing the voluntary nature of this study and each person’s ability to decline
without any risk to their VMMC service quality.
Procedures for minimizing risk to participants include:
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1. For AE management, AEs will be managed according to NDOH guidelines.
The 2wT study nurse will urge in-person follow-up for any 2wT intervention
arm participant who is concerned about any possible AE. The participant will
be instructed to return to the study site or the nearest hospital in case of any
unexpected event, for example if there is severe discoloration of the penis,
signs of infection (purulence), severe or increasing pain, wound opening, or
any other significant concern that they may have. In the event of a
complication meeting the case definition for a clinical AE associated with the
VMMC, the provider will document the complication in the VMMC register and
client record form according to the guidelines. Mild post-operative infections
will be managed with wound cleansing and dressing, and antibiotics will be
prescribed where clinically indicated.
2. We will form an independent Data Safety and Monitoring Board (DSMB), see
attached additional information. The DSMB will be available to review and
advise on any concerning findings, such as social harms or other adverse
events linked to the study, distress evoked among participants that might
outweigh the potential benefits of the study, difficulties in recruitment,
difficulties in study site participation, or any other issues that threaten the
scientific or ethical foundation of the study. The DSMB will have the power to
stop the study at any time. The investigators will also reach out to the UW IRB
and members of the Human Science Research Council REC, in the event of
concerns related to participant well-being or study validity, to consult on
whether study procedures need to be modified or halted. There are likely no
direct benefits to the participants for participation in this study. It is possible
that the opinions expressed may inform future program changes.
3. Careful selection, training, and supervision of study personnel and site-level
study liaisons, together with the systematic preparation of other HCW involved
in study operations. Study personnel are selected for past training and ability
to work with participants in this target population. All site-based study
personnel (project site coordinator, data clerk) will be working specifically for
this
study
from
partner
organization,
Aurum
Institute,
and
trained in
procedures to ensure confidentiality in research settings. They will also be
trained in research ethics and human subjects’ issues via the Collaborative
Institutional Training Initiative (CITI) training. At each site, there will be a
site-level study liaison (a VMMC provider) who is a regular staff member at
the health facility who will be informed on study recruitment procedures,
confidentiality protection, and documenting study operations. Dr. Feldacker
will also take the Clinical Research Training On-Line Course for Principal
Investigators
and
any
additional
courses
suggested
by
University
of
Washington or NIH to further her understanding of ethical conduct of clinical
research.
4. Study team members leading interviews and surveys are instructed to answer
questions that may arise, and to refer all medical questions from patients to
their health care providers.
Study team members are skilled in dealing with
anxiety or upset resulting from the collection of sensitive information. In the
rare case that a participant becomes distressed during an interview or survey,
the interviewer will reiterate the voluntary nature of participating in the
research study and the rights of the participant to decline to respond to any
question.
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Benefits: There are limited or no direct benefits to participating in the study for
HCW. However, if the intervention proves successful, future healthcare works could
save invaluable time though the reduction of in-person VMMC review visits, freeing
HCWs do perform VMMC or other duties. There are no direct benefits to the VMMC
client. However, future clients could save time and money by only attending the
reviews that were desired and forgoing compulsory reviews. This would ensure their
safety and peace of mind while avoiding unnecessary follow-up. Information
obtained in this study will be used by the NDOH and its partners to inform follow-up
visit schedules, potentially reducing in-person visits, which may lead to improving
VMMC coverage and thus HIV prevention among uncircumcised men.
Invasion of privacy: HCW will be informed that there are limited physical risks
and
psychological
risk
associated
with
the
intervention
and data collection
procedures.
Some
HCW
participating
in
interviews
may
feel
uncomfortable
answering questions about quality of health care services, HCW responsibilities,
intervention quality, or other areas of inquiry.
13. CONFIDENTIALITY:
Patients’ routine VMMC data from VMMC registers and client record forms will
be examined to extract data on patient demographics, clinical characteristics at
baseline and during follow-up period, VMMC procedure notes, and adverse events
reporting. This data will be entered into the study-specific database,
For the study specific database for analysis, only the study team will have
access to participant identities for healthcare workers (HCW) and VMMC clients
participating in interviews and surveys. Confidentiality will be maintained by
assigning a unique study-specific identifying alphanumeric code to each participant’s
data, for all interview and survey data collected as part of the study.
During the course of the study, study team members will review existing
paper-based records at the site with identified patient data, including VMMC register
and client record forms as compared to data in the study data system for purposes of
data quality assurance. Data will be abstracted only from the study database.
Any forms with identifying information, such as the informed consent forms
and participant list with study-assigned identification numbers, will be kept separately
from interview and survey data in locked cabinets or on password-protected,
encrypted computers. Encryption will also be used wherever data are transferred.
Implementation strategies for data management will take full consideration of
regulations on confidentiality and security of electronic data transmission and
storage. Upon completion of this study and exhaustion of the data retention period,
all study identifiers will be deleted. In addition to the research staff’s maintenance of
confidentiality, healthcare workers involved in the study will be oriented to the
importance of confidentiality and their own roles in maintaining confidentiality.
The
study
database
with
study-specific
data
will
include only coded
information and no names or identifying numbers which could be used for individual
identification of participants. Safeguarding confidentiality of personal data reported
on study surveys and questionnaires will be achieved through identifier codes
instead of full names on all research materials. The list referencing code number to
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name will be kept in a locked file cabinet in the research manager’s private office and
coded data will be stored in computers in locked offices to which only project staff
have access. The list relating names to number codes will be destroyed at the end of
the study.
Secondary data containing identifying information will be used to match
records for patients who specifically consent to use of their health records, between
the routine VMMC data and the study-specific database. Following the matching of
data sing names and codes, the identifying information within the dataset abstracted
from the secondary data sources will be destroyed and only the study-specific coded
identifiers will be preserved.
No individually identifiable information from VMMC
clients or HCW will be published.
No individual identifiers will be recorded on notes or within the transcripts for
HCW interviews. Only study personnel will have access to the consents, notes, and
tapes. Tapes, when transcribed, will not have any identifying information other than a
location number.
14. CONSENT
Subject recruitment and consent will be in English and Zulu (forthcoming
based on comments on English version). All staff are fluent in both English and local
languages for translation and transcription of activity materials. Consent forms,
advertisements, and study information materials will be translated by the local study
team. Interviewer-administered forms will be used in English, as used in previous
studies under the RSA protocol. Trained interviewers translate orally from English to
Zulu and complete forms in English. All study forms will be completed in English by
study staff. Literacy in RSA is high and the study team is well versed is use of
acceptable language level for VMMC clients.
Informed consent: The informed consent process is initiated prior to an
individual agreeing to enroll in the cohort and continues throughout the individual’s
participation in the cohort. Men who choose to enroll in the study will be provided
with the enrollment informed consent, which describes in detail the study procedures
and risks. Upon reviewing the document, the site staff member explains the research
study to the subject and answers any questions that may arise. Extensive discussion
of risks and possible benefits of study participation will be provided. The participant
signs the informed consent document prior to the conduct of any study procedures.
A copy of the enrollment consent form is given to the subjects for their records.
In obtaining informed consent, the study member enrolling patients will follow
a strict script that emphasizes: 1) participation in the study is completely voluntary; 2)
whether or not they participate will in no way adversely affect they care they receive.
Consent procedures will occur before enrollment in the intervention study and before
any interview or survey is administered. Participants in interviews or surveys will be
informed
of
all
study
procedures,
including
audio
recording
and
interview
format/timings. Patients who seek VMMC services at the selected sites will not be
consented unless they are being recruited to participate in the study. Participants in
the study, whether HCW or VMMC client, may quit the study at any time without
providing a reason. The amount of financial remuneration for the study participants
(cell phone airtime R100) is regarded as compensation for time and travel and not
considered an unfair enticement. HCWs will not be compensated.
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Protection against Risk: Procedures for minimizing risk to participants include
the careful selection, training, and supervision of study personnel and site-level study
liaisons, together with the systematic preparation of other HCW involved in study
operations. Study personnel are selected for past training and ability to work with
participants in this target population. All site-based study personnel (project site
coordinator, data clerk) will be working specifically for this study from partner
organization, Aurum Institute, and trained in procedures to ensure confidentiality in
research settings. They will also be trained in research ethics and human subjects’
issues via the Collaborative Institutional Training Initiative (CITI) training. At each
site, there will be a site-level study liaison (a VMMC provider) who is a regular staff
member at the health facility who will be informed on study recruitment procedures,
confidentiality protection, and documenting study operations. Dr. Feldacker will also
take the Clinical Research Training On-Line Course for Principal Investigators and
any additional courses suggested by University of Washington or NIH to further her
understanding of ethical conduct of clinical research.
Study team members leading interviews and surveys are instructed to answer
questions that may arise, and to refer all medical questions from patients to their
health care providers.
Study team members are skilled in dealing with anxiety or
upset resulting from the collection of sensitive information. In the rare case that a
participant becomes distressed during an interview or survey, the interviewer will
reiterate the voluntary nature of participating in the research study and the rights of
the participant to decline to respond to any question.
The
study
database
with
study-specific
data
will
include only coded
information and no names or identifying numbers which could be used for individual
identification of participants. Safeguarding confidentiality of personal data reported
on study surveys and questionnaires will be achieved through identifier codes
instead of full names on all research materials. The list referencing code number to
name will be kept in a locked file cabinet in the research manager’s private office and
coded data will be stored in computers in locked offices to which only project staff
have access. The list relating names to number codes will be destroyed at the end of
the study.
Secondary data containing identifying information will be used to match
records for patients who specifically consent to use of their health records, between
the routine VMMC data and the study-specific database. Following the matching of
data sing names and codes, the identifying information within the dataset abstracted
from the secondary data sources will be destroyed and only the study-specific coded
identifiers will be preserved.
No individually identifiable information from VMMC
clients or HCW will be published.
For AE management, AEs will be managed according to NDOH guidelines.
The 2wT study nurse will urge in-person follow-up for any 2wT intervention arm
participant who is concerned about any possible AE.
The participant will be
instructed to return to the study site or the nearest hospital (in the case of
dislodgement or severe pain) in case of any unexpected event, for example if there
is severe discoloration of the penis, signs of infection (purulence), severe or
increasing pain, wound opening, or any other significant concern that they may have.
In the event of a complication meeting the case definition for a clinical AE associated
with the VMMC, the provider will document the complication in the VMMC register
according to the guidelines. Mild post-operative infections will be managed with
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wound cleansing and dressing, and antibiotics will be prescribed (see medications
list) where clinically indicated.
COMPENSATION FOR TIME:
No compensation will be provided for HCWs. R100 cell phone credit for both
control and intervention arm on Day 14 visit.
15. DATA MANAGEMENT PLAN (DMP):
A. We will develop a Data Monitoring Plan (DMP). The DMP will include a list
of included data from routine, paper-based VMMC sources: Register, and client
reporting forms (CRFs); study-specific data from the texting database; routine AE
reports. We will establish best practices for collection and extraction of data from
source forms. All study team members will complete training on confidentiality of
data. We have solid plans for secure storage of data with limited data access as
implemented in previous clinical and research studies in South Africa conducted by
members of this team. The data clerks and data analysts will develop and adhere to
processes for Quality control (QC) of data, including identification and correction of
invalid data. Data will be entered into the Medic Mobile application and transformed
into a .csv for import into STATA for analysis. Costing data will be collected and
analyzed in Excel.
Data
Entry
frequency
Review
frequency
Person
responsible
Paper-base
d VMMC register
and CRFs
Daily
Weekly
Data
analyst
Texting
database
Daily
Weekly
Data
analyst and study
coordinator
AE reports
Monthly
for
moderate
or
as
needed for severe
AEs
Monthly
Data
analyst
with
co-investigator
oversight
B. Quality Control will be ensured through the timely review of all study data to
verify accuracy and validity. QC will take place on a weekly basis, allowing for swift
review and correction if needed. Validation review will also happen weekly. Revisions
will not override original data but be maintained in sequentially numbered and dated
databases. The study database with study-specific data will include only coded
information and no names. Safeguarding confidentiality of personal data reported on
study surveys and questionnaires will be achieved through identifier codes instead of
full names on all research materials. The list referencing code number to name will
be kept in a locked file cabinet in the research manager’s private office and coded
data will be stored in computers in locked offices to which only project staff have
access. The list relating names to number codes will be destroyed at the end of the
study.
Secondary data containing identifying information will be used to match
records for patients who specifically consent to use of their health records, between
the routine VMMC data and the study-specific database. Following the matching of
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data, the identifying information within the dataset abstracted from the secondary
data sources will be destroyed and only the study-specific numeric identifiers will be
preserved.
No individually identifiable information from VMMC clients or HCW will
be published. Databases will be password protected and shared through encrypted
file sharing services.
2WT assures its stakeholders and donor of the quality of the data collected.
Above outlines data collection details which shall be routinely reviewed for data
quality standards. De-identified data can be made available to CDC or other
research partners with data sharing agreements after all potential identifiers have
been removed. A specific public dataset can also be created to share via
dissemination and publication. The final versions of any de-identified data collected
and/or generated will be made publicly available within 30 months after the end of
the data collection period.
16. LIMITATIONS AND UNCERTAINTIES:
Men undergoing device VMMC are excluded, limiting generalizability to
surgical VMMC. Phone ownership in RSA’s urban areas is high, but there is a small
possibility that the population who undergoes VMMC has lower than estimated
phone access, reducing the potential efficiency of a texting approach to follow-up.
While evidence from Kenya and elsewhere suggests that patients are likely to
interact with health professionals via SMS, it is possible that a higher than estimated
percentage of clients will not respond to SMS, increasing the need for follow- up by
voice calls, thus reducing the efficiency and cost gains afforded by the intervention.
Lastly, we anticipate some challenges in program implementation such as network
outages (though these are increasingly fewer and shorter) and user error, but
previous Medic Mobile experience and the expert local team will enable swift
identification of bottlenecks and appropriate, real-time, solutions.
17. INTENDED USE OF FINDINGS
This project will evaluate the effectiveness, feasibility, and acceptability of a
promising intervention to improve VMMC efficiency while maintaining patient safety.
If successful, both providers and patients would neither perform nor attend
unnecessary visits, providing distinct advantages to both groups. These advantages
could
be
scaled
up
if
the
approach
is
adopted
by
the NDOH, providing
population-levels gains to millions of providers and patients of the VMMC program.
18. STUDY TIMELINE
We expect the study to start immediately after the IRB approvals, technology
adaptation, and pilot-driven modification. We aim to complete recruitment by June,
2021 in order to compete primary data analysis in July 2021. Objectives 2 and 3, as
well as much of the statistical analyses will be conducted in years 1 and 2.
19. BUDGET
This project will cost approximately $500,000.
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APPENDICES:
1. STUDY BUDGET
2. CONSENT FORM – MEN
3. CONSENT FORM – CLINICIANS
4. SOP CLINICAL TEAM
5. SOP DATA MANAGEMENT
6. SOP USABILITY
7. DSMB CHARTER
8. RECRUITING FLYER
9. RECRUITING SCRIPT
10.
CLINICIAN SUBJECT RECRUITMENT
11.
STUDY PROCEDURES – VISITS
12.
TEXTING FLOW CHART
13.
BRIEF SURVEY PARTICIPANT
14.
FOLLOW UP CALLS AND TEXTS SCRIPTS
15.
QUALITATIVE INTERVIEW CLINICIANS
16.
USABILITY SURVEY
17.
MEDIC MOBILE INBOX EXAMPLE
18.
ENROLLMENT FORM
19.
FOLLOW UP TIME AND MOTION SURVEY
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