Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS)
Phase: PHASE3
Conditions: Hypertension
Sponsor: Moi University

 Strengthening Referral Networks for Management of Hypertension Across the Health System 
(STRENGTHS): A Cluster Randomized Controlled Trial
Dr. Constantine Akwanalo (Contact-PI)
Moi University College of Health Sciences and Moi Teaching and Referral Hospital
3-30100, Eldoret, Kenya
Dr. Jemima Kamano (MPI)
Moi University College of Health Sciences and Moi Teaching and Referral Hospital
3-30100, Eldoret, Kenya
Josephine Kisato (Project Coordinator)
Academic Model Providing Access to Healthcare
4606-30100, Eldoret, Kenya
Sponsor:
The National Heart Lung and Blood Institute (NHLBI)
Grant Number: U01HL138636
Version: 9.0 – 2020-09-10
Version Date: 2020-09-10

Table of Contents
List of Tables.......................................................................................................................................................4
List of Figures.....................................................................................................................................................4
List of Abbreviations............................................................................................................................................4
1.
Synopsis......................................................................................................................................................0
2.
Study Flow...................................................................................................................................................1
3.
Background and Rationale...........................................................................................................................2
4.
Specific Objectives.......................................................................................................................................2
5.
Concise Statement of Design.......................................................................................................................3
6.
Participant Recruitment and Follow Up........................................................................................................4
Inclusion Criteria..............................................................................................................................................4
Exclusion Criteria............................................................................................................................................4
Recruitment Approach.....................................................................................................................................4
Randomization................................................................................................................................................4
Blinding........................................................................................................................................................5
Usual Care...................................................................................................................................................6
Intervention..................................................................................................................................................6
Participant Follow Up.......................................................................................................................................7
Study Withdrawal............................................................................................................................................7
7.
Study Outcomes..........................................................................................................................................7
Clinical Efficacy Outcomes..............................................................................................................................7
Process Outcomes..........................................................................................................................................8
Cost Effectiveness Outcomes..........................................................................................................................8
8.
Adverse Events and Serious Adverse Events..............................................................................................8
9.
Data Collection, Handling and Record Keeping...........................................................................................9
Data collection, handling and record keeping..................................................................................................9
Protections against risk to data......................................................................................................................10
10.
Data Analysis........................................................................................................................................11
Minimum detectable difference (MDD)..........................................................................................................12
Methods of Analysis......................................................................................................................................12
Approach to handle missing data..................................................................................................................12
11.
Protection of human subjects................................................................................................................13
Informed Consent..........................................................................................................................................13
Data Safety and Monitoring Board.................................................................................................................13
Ethical Approval............................................................................................................................................16
12.
Team Roster..........................................................................................................................................16
Policy on oral or written presentation of results.............................................................................................17
13.
Timeline.................................................................................................................................................17
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14.
References............................................................................................................................................19
15.
Appendix...............................................................................................................................................23
Appendix 1: Screening for eligibility tool........................................................................................................23
Appendix 2: Consent Form STRENGTHS.....................................................................................................26
Appendix 3: Process Evaluation Protocol......................................................................................................30
Appendix 4: Adverse Event and Serious Adverse Event Reporting Form......................................................38
Appendix 5: Protocol Deviation/Violation Log................................................................................................43
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List of Tables
Table 1: Estimated power over a range of ICC and MDD values......................................................................12
Table 2: STRENGTHS Team Roster................................................................................................................17
Table 3: Planned Enrollment by Sex.................................................................................................................18
List of Figures
Figure 1: STRENGTHS Study Flow....................................................................................................................1
Figure 2: The Integrated HIT and Peer-support intervention...............................................................................3
Figure 3: Referral Network Facilities in the STRENGTHS study.........................................................................5
Figure 4: Adverse Events and Serious Adverse Events Reporting Procedure....................................................9
Figure 5: Timeline for overall STRENGTHS Study............................................................................................18
List of Abbreviations
AE
Adverse event
AMPATH
Academic Model Providing Access to Healthcare
BP
Blood Pressure
CDM
Chronic disease management
CVD
Cardiovascular disease
DALY
Disability-adjusted life year
DCC
Data coordinating centre
DSMB
Data Safety and Monitoring Board
EMR
Electronic medical record
ES
Executive secretary
FGD
Focus group discussions
HIT
Health Information Technology
ICC
Intra-class correlation
KII
Key informant interviews
LMICs
Low and middle-income countries
Lower-MICs
Lower middle-income countries
MDD
Minimum detectable differences
mHealth
Mobile Health 
MTRH
Moi Teaching and Referral Hospital
NCD
Non-communicable disease
NHLBI
National Heart Lung and Blood Institute
PN
Peer navigator
RA
Research assistant
SAE
Serious adverse event
SD
Standard deviation
SBP
Systolic blood pressure
SOP
Standard operating procedure
UC
Usual care
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1.
Synopsis
 
 
Title
Strengthening Referral Networks for Management of Hypertension Across the Health 
System (STRENGTHS)
Lead Institutions
Moi University College of Health Sciences (MUCHS) and Moi Teaching and Referral 
Hospital (MTRH)
Investigators
Dr. Constantine Akwanalo (MUCHS & MTRH)
Dr. Jemima Kamano (MUCHS & MTRH)
Dr. Benson Ng’ang’a (MTRH)
Prof. Violet Naanyu (MUCHS)
Dr. Ann Mwangi (MUCHS)
Dr. Timothy Mercer (University of Texas, Austin)
Dr. Rajesh Vedanthan (New York University)
Dr. Sonak Pastakia (Purdue University)
Dr. Jonathan Dick (Indiana University)
Dr. Makeda Williams (NHLBI)
Study Sites
Primary, Secondary & Tertiary Health Facilities in Uasin Gishu County, Trans Nzoia 
County, Busia County, Bungoma County and Nandi County
Planned Study 
Period
2017 - 2022
Objective
This study aims to evaluate whether an integrated intervention composed of peer 
support and a health information technology tool can improve referral adherence and 
improve blood pressure among patients with complicated hypertension in a lower 
middle-income country setting
Study Design
This is a cluster randomized controlled trial that will compare:
Intervention: An integrated intervention composed of peer support and a health 
information technology tool to support referral services
Control: Usual referral service
A total of 8 clusters representing unique referral networks will be randomized equally 
at the level of the secondary health facility. 
Number of 
Participants
1600 patients with hypertension who are referred either to a higher or lower health 
facility
Inclusion Criteria
Age ≥ 18 years and either:
1.
Patients with complicated hypertension (meet criteria for referral up the 
network), defined as any of:
a.
Uncontrolled (SBP ≥ 140 or DBP ≥ 90) on 3 or more anti-hypertensive 
medications
b.
Have signs or symptoms of end-organ damage (dyspnea on exertion, 
leg edema, reduced urine output, focal weakness)
c.
Have suspected secondary causes of hypertension (age <35 years, 
HIV, or pregnancy)
d.
Any other concerning condition that the clinician suspects to be 
attributable to hypertension for which they would seek a higher level of 
care

        Or:
2.
Patients with stable, uncomplicated hypertension (meet criteria for referral 
down the network), defined as controlled BP (SBP < 140 and DBP < 90) for 3 
or more consecutive visits and no evidence of new end-organ damage
Exclusion Criteria
1.
Acute illness requiring immediate medical attention
2.
Terminal illness
3.
History of coronary artery disease or stroke
4.
Inability to provide informed consent
Primary Endpoint
One-year absolute mean change in SBP
Secondary 
Endpoints
One-year change in overall CVD risk as measured by the QRISK2 score
Process Metrics
Up-referral completion rate
Down-referral completion rate
Median referral completion time
Referral appropriateness
2.
Study Flow
 
 
Figure 1: STRENGTHS Study Flow
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3.
Background and Rationale
 
 
Hypertension: Burden and Implementation Gaps. Elevated blood pressure (BP) is the leading preventable 
cause of early death and disability globally,1,2 and 75% of patients with hypertension live in LMICs.3 In Kenya, 
prevalence of hypertension is nearly 25%.4 similar to. Despite many evidence-based interventions to manage 
hypertension, gaps in implementation persist, especially in LMICs.3,5,6 In lower-MICs, only 37% of known 
hypertensives were on treatment, with less than 10% of them being adequately controlled.5 
Referral Networks. The Kenya Health Referral Strategy 2014-2018 highlights an effective referral system as 
crucial to improving equitable access to essential health services.7 However, referral networks in Kenya8 and 
similar lower-MICs are characterized by referral non-adherence and delays in referral completion.9-11 Public 
sector health systems in lower-MICs often employ a multi-level system spanning a primary- to specialty-care 
continuum,12 with a tripartite system of primary, secondary, and tertiary care.13 Patients with complicated 
hypertension require referral up the network for specialty care, as well as advanced diagnostic and treatment 
modalities.13 Patients with stable, uncomplicated hypertension can be referred down the network where care is 
geographically decentralized and task-shifted to lower levels of providers, reducing costs and increasing 
access to care.7  Effective referral networks have improved outcomes in maternal and child health,13,14 HIV,15,16 
and CVD.17 Furthermore, in resource-limited settings, strong referral networks are essential to improve the 
efficiency of resource utilization and guarantee equitable provision of healthcare services.18 Therefore, strong 
referral networks provide an evidenced-based foundation upon which interventions for hypertension can be 
implemented and evaluated in lower-MICs. 
Multi-Level Factors Impacting Referral Networks for Hypertension. Rates of referral adherence in lower-
MICs is low. Successful referral completion was only 37% among patients found to have hypertension or at 
elevated CVD risk following community-based screening in Bangladesh, Guatemala, Mexico and South 
Africa.17 In Burkina Faso, referral adherence was 20% among patients referred for hypertension.9 The causes 
of referral non-adherence are multifactorial.7,17,19 Patient-related factors include lack of time, cost, transport 
distances, and limited understanding of the rationale.17,20-22 Provider-level factors include poor documentation 
and limited human resources for health.17 Health system-related factors include lack of integrated health 
records,23,24 long patient waiting times, and the complexity of navigating larger health facilities.17
Peer Support. Peer-based care approaches leverage unique patient-patient interactions built on shared 
disease experiences to influence behavior change.25 Peers have successfully been used to improve adherence 
to HIV medicines 26-29 and have effectively supported chronic disease management.7,30-33 Peer navigators have 
been used to improve linkage to and retention in care for patients with HIV,34,35 as well as improve healthcare 
utilization in mental health36 and cancer.37,38 To date, peer navigators have not been evaluated in the context of 
strengthening referral networks to improve hypertension control. 
HIT. HIT, including integrated EMRs and mHealth, are a key strategy in LMICs for NCD management,39-41 and 
can improve documentation and data capture, which are significant barriers to effective referral networks.13,23,42 
Our systematic review of mHealth for NCDs in sub-Saharan Africa highlights the use of HIT for patient follow-
up and peer networks among patients with NCDs.43 However, the evidence base is limited, with an urgent need 
for more rigorous implementation research of HIT interventions.43 Specifically, it is not well known if HIT, in 
combination with peer support, can strengthen referral networks for hypertension control. 
4.
Specific Objectives 
 
 
The objective of this research is to utilize the PRECEDE-PROCEED framework to conduct transdisciplinary, 
translational implementation research focused on strengthening referral networks for hypertension control. The 
central hypothesis is that HIT integrated with peer support will be effective and cost-effective in strengthening 
referral networks, improving BP control, and reducing CVD risk among patients with hypertension in western 
Kenya. We hypothesize that HIT and peer support will synergistically address barriers to hypertension control 
at the patient, provider and health system levels. We further hypothesize that changes in referral network 
characteristics may mediate the impact of the intervention on the primary outcome, and that baseline referral 
network characteristics may moderate the impact of the intervention. To test these hypotheses and achieve the 
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overall objective, we will conduct a two-arm cluster randomized trial comparing: 1) usual care vs. 2) referral 
networks strengthened with an integrated HIT and peer support intervention. We will pursue the following 
specific objectives:
1.
Evaluate the effectiveness of HIT and peer support on one-year change in SBP and CVD risk 
reduction.  
2.
Conduct mediation analysis to evaluate the influence of changes in referral network characteristics on 
intervention outcomes, and a moderation analysis to evaluate the influence of baseline referral network 
characteristics on the effectiveness of the intervention.
3.
Conduct a process evaluation using the Saunders framework, evaluating key implementation measures 
related to fidelity, dose delivered, dose received, recruitment, reach, and context. 
4.
Evaluate the incremental cost-effectiveness of the intervention, in terms of costs per unit decrease in 
SBP, per percent change in CVD risk score, and per DALY saved. 
5.
Concise Statement of Design 
 
 
We will evaluate the effectiveness of HIT and peer support for strengthening referral networks for hyper-
tension control by conducting a non-blinded two-arm cluster randomized trial comparing: 1) usual care vs. 2) 
referral networks strengthened with an integrated HIT and peer support intervention (Figure 2). The primary 
outcome measure will be one-year change in systolic blood pressure (SBP) and a key secondary outcome will 
be change in CVD risk score.
Figure 2: The Integrated HIT and Peer-support intervention
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6.
Participant Recruitment and Follow Up
 
 
Inclusion Criteria
Adult patients (≥18 years) who are enrolled in AMPATH’s CDM program with hypertension, who meet criteria 
for referral up or down the network, will be eligible for inclusion in the trial.
For referral up, criteria are:

Patients with complicated hypertension, defined as any of:
a.
Uncontrolled (SBP ≥ 140 or DBP ≥ 90) on 3 or more anti-hypertensive medications
b.
Have signs or symptoms of end-organ damage (dyspnea on exertion, leg edema, reduced urine 
output, focal weakness)
c.
Have suspected secondary causes of hypertension (age <35 years, HIV, or pregnancy)

Any other concerning condition that the clinician suspects to be attributable to hypertension for which 
they would seek a higher level of care
       
For referral down, criteria is patients with stable, uncomplicated hypertension, defined as controlled BP (SBP < 
140 and DBP < 90) for 3 or more consecutive visits and no evidence of new end-organ damage
Exclusion Criteria

Acute illness requiring immediate medical attention

Terminal illness

History of coronary artery disease or stroke

Inability to provide informed consent
Recruitment Approach
The clinicians will be sensitized about the study and the eligibility criteria. They will then invite AMPATH CDM 
patients with hypertension and eligible for referral from the health facility to enroll in the study on the day of 
their routine clinic visit. On that day, research team members will briefly describe the research study to the 
potential participant. They will then perform a short interview using the screening for eligibility tool which 
documents the age of patient, type of referral and reason for referral (Appendix 1). Patients meeting eligibility 
criteria will then be asked their willingness to participate in the study, and if willing will proceed to the informed 
consenting stage. Patients not meeting eligibility or unwilling to participate further will be referred back to their 
clinician to continue with clinical care as per the clinician’s management plan. For referral networks 
randomized to the HIT and peer support intervention arm, participants will be informed of the HIT functionality 
and the availability of peer navigators who can assist them with the referral process.  Extreme care will be 
taken to fully explain the benefits and risks of the research study, before written consent is obtained. The 
consent will be written in lay terminology at approximately 6th grade (USA) level (Appendix 2). Individuals will 
be free to refuse to participate in the study at any time during the period of the study. A refusal will not impact 
the health care available to the individual in any manner. Access to care will not be impacted in any manner by 
an individual’s decision to opt out of this research project.  
Randomization
The unit of randomization will be a cluster, which consists of a geographically separate, distinct hypertension 
referral network within the overall AMPATH CDM program. There will be a total of eight clusters (referral 
networks), each of which will be centered around a secondary-level health facility:  Mosoriot, Kwanza, Kiminini, 
Webuye, Kocholya, Bunyala, Butula, and Nambale (Figure 3). Each of these secondary-level facilities 
constitute the last step in their respective referral network before reaching the common, tertiary level of MTRH, 
Busia County Referral Hospital, Kitale County Referral Hospital, or Bungoma County Referral Hospital. In 
addition, each secondary-level facility has a number of primary-level health facilities that feed into it. Four of 
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the clusters will be randomly assigned to the intervention arm, and four will be randomly assigned to the control 
arm. Randomization will be stratified by the size of the secondary-level health facility. 
Clusters*
Primary Level
Secondary Level
Tertiary Level
Mosoriot
Mogoget
Birbiriet
Itigo
Lelmokwo
Kokwet
Ngechek
Mosoriot Sub-county 
hospital
Moi Teaching and 
Referral Hospital 
Kitale County 
Referral Hospital
Bungoma County 
Referral Hospital
Busia County 
Referral Hospital
Kiminini
Bikele
Sister Fredah 
Matunda Sub-county 
hospital
Kwanza
Kaisagat
Namanjala
Kwanza Sub-county 
hospital
Webuye
Milo
Webuye County 
hospital
Kocholya
Angurai
Changara
Malaba
Kamolo
Akichelesit
Aboloi
Moding
Kocholya Sub-
county hospital
Bunyala
Budalangi
Bulwani
Busagwa
Mukhobola
Osieko
Rukala
Sirimba
Sisenye
Port Victoria Sub-
county hospital
Butula
Bumala A
Bumala B
Ikonzo
Sikarira
Khunyangu Sub-
county hospital
Nambale
Lwanyange
Madende
Musokoto
Nambale Sub-
county hospital
Figure 3: Referral Network Facilities in the STRENGTHS study
*Unit of randomization
Blinding
Trial participants, research assistants and the research coordinator will not be blinded. This is because the 
nature of the intervention, peer support, cannot be concealed from participants, or the research staff who will 
be doing enrollment and follow-up at the clinic sites and as such will be aware if there is a peer or not in the 
facility. The data analyst/biostatistician and co-investigators will be blinded, unaware which participant is 
assigned to which arm of the trial.  The PI’s (CA and JK) see patients at the cardiology and medical outpatient 
clinic at MTRH, and might interact with study participants during their clinical duties. They might therefore 
become aware, during the course of their clinical duties, of the trial arm to which a study participant has been 
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assigned. Should this happen, the PIs are expected to implement usual clinical care regardless of the patient’s 
participation in the trial. No further action will require to be taken.
Usual Care
Within the AMPATH CDM program, usual management at the primary and secondary levels involves an 
attempt to control BP with up to 3 anti-hypertensive medications before referral, under the supervision of a 
mentoring clinician who visits the lower level facility on a rotating basis. Frequency of clinical visits will depend 
on clinical circumstances and level of care, mimicking real-word conditions. The process for referrals will 
continue as it is currently practiced within the AMPATH CDM program and Kenyan MOH. For patients with 
complicated hypertension requiring referral up the network, the referring clinician writes a referral letter on a 
standardized, blank referral form, with demographic information of the patient and reason for referral. This 
referral letter is then given to the patient, who is responsible for presenting it to the receiving facility and 
arranging the referral visit. For patients with stable, uncomplicated hypertension requiring referral down the 
network, a counter-referral letter, and/or copies of clinical records, are given to the patient to take back to their 
primary facility, although this process is not consistently adhered to. There is no dedicated psychosocial or 
health system navigation support in the usual care arm.
Intervention
Those randomized to the intervention group will receive clinical care for hypertension in the same manner as 
those randomized to the usual care group. Reasons for referral will also be the same in the two groups. The 
change in referral process is the intervention which is an integrated HIT tool and peer support. 
HIT: AMPATH uses AMRS, a customized version of OpenMRS.44 AMRS is centrally hosted and accessed by 
tablet via the Internet with all data simultaneously available to all users of the system, independent of their 
location. This facilitates both real-time data collection and monitoring. Our HIT intervention will augment AMRS 
to support a referral system in four ways: 1) communication: facilitate data sharing by all providers and peer 
navigators across all levels of the health system; 2) decision support: provide clinical decision support to 
facilitate appropriate patient referrals; 3) tracking: generation and sharing of real-time patient referral lists; and 
4) dashboards: create a platform for monitoring key evaluation metrics. The system will prompt for referral if 
indicated but also allow the user to self-initiate a referral. Providers and peer-navigators will access the 
designed referral dashboard for a clinic to review patient referrals, identify patients who made their referral 
appointment, and track patients who have been referred back to the referring site. Key referral process metrics 
(described below under “Secondary Outcomes”) will be available in real-time for providers and peer navigators 
to monitor and act upon. 
Peer Support: The peer support component of the intervention will involve “peer navigators” at each level of the 
referral network – primary, secondary and tertiary, titled “Community Peer Navigators”, “Facility Peer 
Navigators”, and “Central Peer Navigators”, respectively. The Community Peer Navigators will cover a 
catchment area within the community surrounding each primary level health facility. The Facility Peer 
Navigators will be stationed at the secondary level health facilities in each referral network. The Central Peer 
Navigator will be stationed at the tertiary level, MTRH. The roles of the peer navigators will be drawn from 
those described in the HIV and oncology literature,45-50 but adapted and contextualized. The peer support 
intervention has three main functions: 1) referral adherence: link clinicians and patients to provide referral 
logistics support; 2) navigation: help patients navigate the complex health system;51 and 3) psychosocial 
support: leverage their shared disease experience to help patients overcome barriers to health seeking 
behavior. Referral adherence support entails ensuring patients know the “what, where, when, and how” of the 
referral process. The peer navigators will be equipped with an HIT tool, as described above, so they can see 
the same data as the clinicians in order to track and follow referred patients appropriately. When a clinician at 
the primary level refers a patient to a higher level of care, the Community Peer Navigator covering that 
patient’s community catchment area will automatically be alerted on their HIT tool so they can contact and 
meet the patient, and review referral logistics. The Community Peer Navigator will then complete a referral 
navigation form on the HIT tool, which will automatically trigger a notification to the clinician and Facility or 
Central Peer Navigator at the receiving facility, alerting them of the incoming referral. The second major role of 
the peer navigator is health system navigation, especially at the tertiary level. Here, the peer navigator can 
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personally and physically receive a referred patient and walk them through the complexities of registration, 
scheduling, triage, and diagnostic work-up in order to streamline the referral process and ensure patients are 
not lost in the complexity of the system.52 Furthermore, peer navigators will meet with patients after the clinic 
visit to provide any follow-up navigation between the pharmacy, laboratory, or imaging. Communication 
between the Central, Facility, and Community Peer Navigators will be automated via the HIT tool to ensure 
seamless communication and data-sharing. The third major role of the peer navigator is to provide 
psychosocial support to patients and their families, helping them overcome individual-level barriers to health 
seeking behaviors, drawing from the innate trust inherent in their shared disease experience.25 Peer navigators 
at all levels will be trained to provide education, motivational interviewing, and psychosocial support.
Participant Follow Up
Participants will have three visits for both study arms: a baseline visit upon enrollment, a six-month visit, and a 
12-month visit. In both arms of the trial, if the patient does not present to the clinic for the 6 month or 12-month 
visit, the patient will be traced by the research team. Missing data resulting from loss to follow up will be 
handled as detailed in section 10.  
Study Withdrawal
Individuals will be free to refuse to participate in the study and withdraw at any time during the period of the 
study. Withdrawal will not impact the health care available to the individual in any manner. Access to care will 
not be impacted in any manner by an individual’s decision to opt out of this research.  
7.
Study Outcomes
 
 
Clinical Efficacy Outcomes
Primary outcome
One year absolute change in mean BP
The systolic blood pressure at baseline will be compared to systolic blood pressure after 1 year of follow up.
Secondary outcomes
One-year change in overall CVD risk as measured by the QRISK2 score 
QRISK2 score is a computerized algorithm for predicting the ten-year risk of developing CVD events. The 
factors that enter into the calculation of the QRISK2 score include: Age 25-84 years, sex, ethnicity, smoking 
status, diabetes status, family history of coronary artery disease in first degree relatives below the age of 65 
years, chronic kidney disease stages 4 and 5, atrial fibrillation, rheumatoid arthritis, cholesterol / high density 
lipoprotein ratio, systolic blood pressure, body mass index. 
A score of 10% or more suggest a 10% risk of primary CVD events in ten years and warrants intervention to 
reduce the risk. It's not used among patients who already have a heart attack or a stroke.
One-year mortality rate
Death by the end of the 1 year follow-up 
Hospital admissions
Number of self-reported hospital admissions for any cause among participants over one year follow up
CVD complications
Any self-reported cardiovascular complications including hypertensive crises, heart failure, Stroke and Acute 
myocardial infarction
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Change in CVD risk factors and behaviors
Baseline risk factor profile compared to profile at 1 year of the various CVD risk factors as assessed using a 
standardized CVD risk factors and behaviors screening questionnaire
Medication adherence
Changes in self-reported adherence to hypertension medication at one year from baseline as assessed using 
the Voils adherence questionnaire53
Process Outcomes
Referral Process Metrics

Up-referral completion rate

Down-referral completion rate

Median referral completion time
Process Evaluation

Fidelity (quality of intervention delivery as assessed using a checklist-based field observation of peer 
navigators, written tests for peer navigators at baseline and six months, and separate focus group 
discussions for peer navigators, participants and clinicians, see Appendix 3 for full Process evaluation 
protocol)

Dose delivered (completeness)

Dose received (exposure and satisfaction)

Recruitment

Reach (participation rate)

Context
Cost Effectiveness Outcomes

Incremental cost effectiveness ratio
8.
Adverse Events and Serious Adverse Events
 
 
An AE is defined as any untoward or unfavourable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally 
associated with the subject’s participation in the research, whether or not considered related to the subject’s 
participation in the research. 
An SAE is a defined as any AE that: 

results in death;

is life-threatening (places the subject at immediate risk of death from the event as it occurred);

results in inpatient hospitalization or prolongation of existing hospitalization;

results in a persistent or significant disability/incapacity;

results in a congenital anomaly/birth defect; or

based upon appropriate medical judgment, may jeopardize  the subject’s health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition
The safety observation period extends from the time the signed informed consent is obtained through the 
completion of the final study visit. All patients enrolled in the trial who experience an SAE will be managed at 
their nearest health facility according to the Kenya MOH cardiovascular disease guidelines,54 with referral to 
higher levels of care if needed.
Reporting Procedures
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Given that peer navigators and research assistants are the study staff who will have direct contact with study 
participants, we anticipate that an AE or SAE will first be detected by the peer navigator or the research 
assistant. Should the PN be the first to detect a probable AE or SAE, they will be expected to report to the RA 
within 1 hour of detection. Once an RA is aware of an AE or SAE, they will fill out the electronic AE/SAE 
reporting form (Appendix 4), and inform the research coordinator via phone, both RA actions will be expected 
to be complete within 1 hour. The filed form will then be reviewed by one of the three clinical Kenyan 
investigators within four hours, who will then ascertain the AE/SAE. If ascertained as a true AE/SAE, the 
investigator will be expected to generate a report to NHLBI, IREC and the DSMB within 24 hours. All peer 
navigators and RAs will be trained on AEs and SAEs detection and reporting.  All SAEs and AEs will be 
captured on electronic CRF. The three Kenyan clinical investigators (a monthly rota will be created and 
maintained by the research coordinator) are responsible for continuing to follow all AE and SAE reports 
(whether or not related to study intervention) until resolution or until the event is considered chronic and/or 
stable by the investigator and/or other physician who has the responsibility for the patient’s medical care. All 
SAEs will require expedited reporting by the PI to the study's DSMB, IREC/IRB, and NHLBI. An expedited 
report of an SAE will be submitted by email and must be reported to the DSMB, IREC/IRB and the NHLBI  
within 24 hours of the event being reported to the Investigator. The expedited report will be followed by a  
detailed, written AE/SAE report  using the standard study AE/SAE reporting form (Appendix 4) as soon as 
possible.  Follow  up  information  will  be  availed  if  asked  for  by  DSMB  directly,  or  from  NHLBI  or  its 
representatives. A master log of all AE's/SAE's will be maintained and the PI will submit a statistical report from 
the log to the DSMB at least two weeks prior to all scheduled DSMB meetings. 
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Figure 4: Adverse Events and Serious Adverse 
Events Reporting Procedure

9.
Data Collection, Handling and Record Keeping
 
 
Data collection, handling and record keeping
For the primary and secondary clinical efficacy outcome, the baseline and 12-month assessments will be 
measured by trained study staff to ensure standardization and uniformity of measurement. Data will be 
collected on covariates we hypothesize may be related to our outcomes. These include patient demographics, 
socioeconomic and education status, clinical comorbidities, CVD risk factors, health behaviors, geographic 
location, referral level, and provider level of training.
For the process outcomes, data will be collected at whatever level of care the patient clinically requires, in 
order to mimic real-world practice and accurately map the patient wherever he or she falls within the referral 
network. Semi-quantitative and qualitative data for the process evaluation, including observation, surveys, 
interviews, and focus group discussions. Observational data will not contain any patient identifiers. These data 
include transcripts of mabaraza55 (traditional form of community assembly), focus group discussions, and 
interviews; completed clinician surveys; and observation notes (study activities preceding the trial portion). 
Mabaraza, focus group discussions, and interviews will be digitally audio-recorded and uploaded with a coded 
identification number (no identifying names) as an audio file to an electronically secure database. Similarly, the 
clinician surveys will be de-identified and coded, and the data extracted and stored in the same electronically 
secure database.  These research data will be stored in an electronically secure database protected by 
password that will be known only to key research team members and the Study Coordinator.  Once uploaded 
to the electronically secure database, the data will be deleted from the digital recording device and the original 
surveys containing identifying information will be destroyed. Electronically captured data will transfer to the 
research database at the time of entry into the handheld device through a secure connection tunnel. All data 
on mobile devices will be encrypted and stored on the device’s internal memory. All paper data collection forms 
will be reviewed by the Study Coordinator and Data Manager for completeness. Once validated, any sheets 
containing directly identifiable information and consent documentation will be separated and added to the site’s 
secure storage locker. The remaining, de-identified pages will then be placed in a separate storage locker prior 
to data entry.  Only key investigators and study personnel will have access to individually identifiable private 
information about human subjects. Transcription of the audio files will occur in Kenya and will be done by the 
trained research assistants.  These transcripts will also be stored in an electronically secure database on a 
password-protected computer.
For the cost-effectiveness outcomes, cost data will be obtained during the implementation of the intervention 
and health service utilization data will be obtained from the AMRS. These data will be collected during the 
course of the project implementation by research staff. Two sets of costing instruments will be used, one 
completed by study participants, and the other completed by research staff. The instruments completed by 
participants capture healthcare utilization and expenditures, work loss, and transportation costs and can be 
used to quantify cost offsets from intervention participation. The instruments completed by research staff 
capture all relevant labor, materials, supplies, and contracted services costs for all activities required to deliver 
the intervention. All data collected on paper forms will be transferred to the research database using double 
data entry. 
Electronically captured data on REDCAP will transfer to the research database at the time of entry into the 
handheld device through a secure connection tunnel. All data on mobile devices will be encrypted and stored 
on the device’s internal memory. All paper data collection forms will be reviewed by the Study Coordinator and 
Data Manager for completeness and the presence of pre-specified “danger” values. Once validated, any 
sheets containing directly identifiable information and consent documentation will be separated and added to 
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the site’s secure storage locker. The remaining, de-identified pages will then be placed in a separate storage 
locker prior to data entry.  Only key investigators and study personnel will have access to individually 
identifiable private information about human subjects. 
 
Protections against risk to data 
The following principles and procedures for data collection will be followed at the research site in order to 
minimize risk and protect confidentiality: 

Data will be collected on coded forms, which do not include other personal identifiers 

Only the tracking form will have the participant’s name and identifiable information

Study records will be stored in locked cabinets in a locked room

Only the study personnel will have access to the data and the codes 

All computerized information will be protected by access codes known only to key investigators and 
certain designated staff members

No data will be published with participant names

Data that are contained on a digital audio recording device will be PGP-encrypted

All staff members will be trained to keep participants' information confidential, and will be informed of 
the penalty for breach of confidentiality
The consent form signed by the participant will provide written assurance that all individual data collected in the 
study will be kept confidential to the extent provided by the Privacy Act of 1974.  AMPATH will provide file 
security so that confidential data are not released.  Specifically, participants will be informed that: (1) the only 
people who will know that they are research participants are members of the research team and, if appropriate, 
their physicians or health care providers; (2) no individual identifying information about them will be disclosed 
to others, except if required by law; and (3) when the results of the study are published or discussed in 
conferences, no information will be included that would reveal their identity.   
 
Any material that is digitally audio-recorded will be uploaded with a coded identification number (no identifying 
names) as an audio file to an electronically secure database. These research data will be stored in an 
electronically secure database protected by password that will be known only to the Principal Investigator and 
the Study Coordinator. Once uploaded to the electronically secure database, the data will be deleted from the 
digital recording device. Transcription of the audio files will occur in Kenya. These files will also be stored in an 
electronically secure database on a password-protected computer. 
 
All clinical patient-level data will be entered into the AMRS as per AMPATH’s standard operating procedures. A 
separate, password-protected research database will retrieve data from AMRS via access that will be 
controlled through user authentication. All data collected on paper forms will be transferred to the research 
database using double data entry. Electronically captured data will transfer to the research database at the 
time of entry into the handheld device through a secure connection tunnel. All data on mobile devices will be 
encrypted and stored on the device’s internal memory.  
 
All data management will be carried out by CITI-certified research staff members, and all data will be stored on 
dedicated, password-protected computers. Any data stored on portable media will be PGP-encrypted, in order 
to ensure security of the data. Paper forms will be stored for the duration of the study, and for one year 
following in order to allow verification of any data as needed for reporting and publication purposes.  The paper 
forms will then be shredded.  The electronic data with a coded identification number only (and no identifying 
names) may be kept indefinitely, in a secure manner as described above.  
 
To prevent inadvertent disclosures and ensure subject confidentiality, data entry and document storage for 
materials containing directly identifiable information (i.e., coversheets) will be handled by key investigators or 
the Study Coordinator. The Study Coordinator will be responsible for the secure handling and storage of 
survey documents for the duration of research activity at the study site. Once activities have been completed, 
coversheets will be collected and forwarded to the AMPATH research office, where they will be stored in a 
secure, locked cabinet within a secure, locked room. To minimize the number of people with access to the 
STRENGTHS Protocol v 9.0. 2020-09-10

coversheet data, all data entry will be conducted under the direct supervision of the Study Coordinator. Once 
identifiable data has been entered as described, paper-based documents will be returned to secure storage.
10. Data Analysis
 
 
We will quantify the effectiveness of an integrated HIT and peer support intervention for strengthening referral 
networks to improve BP control and reduce CVD risk. The primary outcome measure is one-year absolute 
mean change in SBP. A key secondary outcome measure is one-year change in overall CVD risk as measured 
by the QRISK2 score, which has been validated for calculating 10-year CVD event risk for Black Africans.146-154
For the cost-effectiveness analysis, only net incremental costs, after factoring in cost offsets that may result 
from improved health, will be included as the numerator in the CE analysis as these are the relevant costs for 
decision makers. As part of the costing analysis, we will also identify which activities drive the overall costs, 
and how costs would change if specific activities are added or eliminated.
 
Minimum detectable difference (MDD)
The study is powered to detect improvement in SBP in the intervention arm compared to usual care. We 
expect that each of the eight referral networks will enroll at least 200 participants. Based on other studies in the 
region we expect a difference of 4 to 10-mmHg56 between the two groups at month 12. The power calculations 
summarize MDD in the primary outcome for the comparison between the two groups. Using a two sided test 
with a Type I error rate at 5% (alpha = 0.05), and a standard deviation of 15mmHg (SD values for change in 
SBP found in the literature ranges from 10 to 20).57,58 Table 1 presents power for the comparison across 
different combinations of ICC ranging from 0.02 to 0.08, consistent with prior studies using SBP as the 
outcome58-60 for a range of MDD of 4 to 10 mmHg. We assume that up to 15% of enrolled participants will be 
lost to follow up.
Table 1: Estimated power over a range of ICC and MDD values
 
Methods of Analysis
Our analyses for both the primary and secondary outcome will be conducted according to the principle of 
intention to treat, in which every cluster is analyzed according to the assigned intervention, regardless of the 
treatment actually received. We will use a repeated measures mixed-effects model for SBP, with fixed effects 
for time and intervention arm, and random effects for cluster and individual. The model specification is:
E (Y itk)=α +β1I (t=6)+β2I (t=12)+β3I (t=6,intervention)+β4 I (t=12,intervention)
where Yitk is SBP for the ith individual at the tth time in the kth cluster and I() represents the indicator of the event 
in (). The hypothesis test for the coefficient β4 will be a test of whether SBP after 1 year differs for those in the 
intervention compared to those in the usual care condition.
STRENGTHS Protocol v 9.0. 2020-09-10
MDD 
ICC 
0.02 
0.04 
0.06 
0.08
4 
52 
32
24
20
6 
85
61
46
37
8 
98
84
70
58
10 
99
96
87
77

We will compare key independent variables across the trial arms to ensure balance of the randomization 
process,  and  assess  whether  adjustments  for  any  baseline  characteristics  is  necessary  and  make 
adjustments  in  the  model  to  estimate  treatment  effects  as  needed.  The  analysis  will  be  stratified  by 
predefined strata of referral up and referral down. For modeling QRISK2, we will use the transformation log (-
log(QRISK2)) because the risk score ranges from 0% to 100%. The model will be fit using maximum 
likelihood with the software package R.  
Approach to handle missing data
Individuals who are missing outcome data at 12 months will be traced by the research team to ascertain and 
alleviate dropout bias in our trial.61-63 The follow-up sample will enable us to form an imputation model for the 
missing outcomes. Using the subset of individuals who dropped out but whose SBP was ascertained after 
tracing, we will fit a regression using 12-month outcome as the dependent variable, and baseline covariates 
and the most recently observed outcome at month 6 as the independent variables, and use the model to 
generate predicted (imputed) values of outcomes for those not traced. We will account for uncertainty using 
multiple imputation.64 In addition, the generalized linear mixed models proposed for the primary and secondary 
analyses incorporate an assumption of data that are missing at random, meaning that the likelihood of a value 
being missing depends on observable characteristics.  We will employ sensitivity analyses via pattern mixture 
modeling65-67 to examine potential for systematic bias attributable to missing values that cannot be ascertained 
by tracing participants (expected to be up to 15% of the sample, as above).
11. Protection of human subjects
 
 
Informed Consent
The proposed study will be conducted following strict guidelines for the protection of the rights of participants.  
Informed consent will be signed by all participants following screening. Extreme care will be taken to fully 
explain the benefits and risks of the research study, before consent is obtained.  Written informed consent will 
be obtained from all participants. The consent form (Appendix 2) will be written in lay terminology at 
approximately 6th grade level. Participation in the study will be discontinued if the participant chooses to stop 
participating in the study and notifies the study team. Participants will be allowed to withdraw from the study, 
should they choose to, without risk of any discrimination, or any risk of impact on their clinical care and they 
can choose to seek clinical care at any facility (AMPATH, other public sector or private sector) that they wish. 
The residents of study site areas may come from economically disadvantaged backgrounds.  We will continue 
the policy of AMPATH of not providing excessive monetary compensation for study subjects beyond 
reimbursement to cover travel expenses and time. This policy will be followed in order to ensure that consent is 
freely given without risk of “monetary coercion.” Vulnerable populations such as children, neonates, human 
fetuses, and any individuals <18 years old will not be included in the study. Pregnant women who are 
hypertensive will be eligible for participation in the trial but their clinical management will remain per the usual 
clinical care. Within each referral network cluster, the relevant MOH facilities will be contacted and receive 
information on the different study procedures anticipated through completion of this project.
Data Safety and Monitoring Board
An independent DSMB has been established for this study to ensure the safety of trial participants. This DSMB 
is composed of independent faculty members from the Moi University College of Health Sciences, Aga Khan 
University Hospital (Kenya), and the MOH, who are not otherwise involved with the project. Membership of the 
DSMB includes the following expertise: Clinical Cardiology, Clinical Trials, Community-Based Research, 
Implementation Science, and Ethics. All members are independent and free of any project-related financial 
interest. 
After constitution, the DSMB formulated a charter to guide DSMB operations, a living document that can be 
reviewed  at regular intervals to determine whether any changes in procedure are needed, but cover the areas 
described below. 
STRENGTHS Protocol v 9.0. 2020-09-10

Responsibilities of the DSMB
The DSMB is responsible for safeguarding the interests of study participants, assessing the safety and efficacy 
of study procedures, and monitoring the overall conduct of the study.  The DSMB is an independent group and 
is required to provide recommendations about starting, continuing, and stopping the study. In addition, the 
DSMB can be asked to make recommendations, as appropriate, to the NHLBI and/or the appropriate 
institutional review board (IRB) about:
•
Efficacy of the study intervention (DSMB only)
•
Benefit/risk ratio of procedures and participant burden
•
Selection, recruitment, and retention of participants
•
Adherence to protocol requirements
•
Completeness, quality, and analysis of measurements 
•
Amendments to the study protocol and consent forms
•
Performance of individual centers and core labs
•
Participant safety
•
Notification of and referral for abnormal findings 
The DSMB will also be expected to coordinate with the TREIN/Hy-TREC consortium coordinating centre for 
preparing regular DSMB reports. 
Organization and Interactions
Communication between the study staff and DSMB members is primarily through the DSMB administrator 
(ES). It is expected that study investigators will not communicate with DSMB members about the study directly, 
except when making presentations or responding to questions at open DSMB meetings. The DSMB ES will 
provide an unbiased staff interface for the DSMB, especially during executive sessions. The ES is responsible 
for assuring the accuracy and timely transmission of the final recommendations and DSMB minutes.
Scheduling, Timing, and Organization of Meetings
The DSMB convened prior to initiation of the trial portion of the study to review the study protocol and give 
approval of the study trial. They will also convene during the period of trial implementation when interim data 
analysis is available, and when the final data analysis for the study is available. We will schedule three DSMB 
meetings a year, with the provision for cancellation should there be nothing to report. The DSMB chair will also 
decide if additional meetings are required in addition to these minimum meetings. Scheduled analyses will be 
performed by the study biostatisticians and supplied to the DSMB for review prior to each meeting. If the 
difference in the primary outcome (change in systolic blood pressure) between any of the intervention arms 
exceeds the a priori limits defined by the study biostatisticians and the DSMB, the project steering committee 
has the authority and obligation to consider termination of the study. The DSMB will also receive all Serious 
Adverse Event (SAE) Reports and may request additional information, as needed. If the DSMB chair deems 
that an unexpected number of SAEs have been reported they may choose to meet off cycle to assess the 
events and determine what action should be taken. In addition, on-site monitoring visits from a qualified 
research monitor (Edwin Sang) will be scheduled quarterly until data quality is deemed acceptable and then 
will be scheduled six monthly for the remainder of the study.
DSMB meetings are held by teleconference and or video conference as appropriate. The purpose of the first 
meeting was to review and discuss the DSMB charter, to provide an overview of study activities, to review and 
make recommendations about the protocol(s), and to determine the frequency of interim analyses and whether 
data will or will not be masked to identity of randomized groups. 
The agenda for DSMB meetings is drafted by the ES. The agenda and meeting materials are distributed to the 
DSMB at least two weeks in advance of the meeting. Before each meeting, when the agenda is sent out, the 
Chair asks all DSMB members to state whether they have developed any new conflicts of interest since the 
last formal annual report to NHLBI.  If a new conflict is reported, the Chair and staff determine if the conflict 
STRENGTHS Protocol v 9.0. 2020-09-10

limits the ability of the DSMB member to participate in the discussion. The DSMB also reviews adverse event 
data, other safety data, quality and completeness of study data, and enrollment data at each meeting to ensure 
proper trial conduct. At intervals, as noted above, the DSMB also reviews formal interim analyses of the 
primary end point.
It is expected that all DSMB members will attend every meeting.  However, it is recognized that this may not 
always be possible. Quorum for voting is considered to be half the number of standing members plus one, that 
is, 3 members for this proposed DSMB. The DSMB may however wish to decide if particular expertise is 
needed within the quorum for the meeting to be valid. All standing DSMB members are voting members. The 
Board may also wish to decide in advance whether ad hoc members can vote. 
In the case of the STRENGTHS trial, the decision as to whether to recommend early discontinuation of 
recruitment should be the responsibility of the DSMB based on all available evidence. Unlike trials where 
toxicity or inferiority of efficacy is readily demonstrable, the STRENGTHS trial is not expected to be stopped 
early. Safety and efficacy boundaries, however, have been created for the rare situation of unexpected benefit 
or harm.
Discussion of Confidential Material
DSMB meetings and calls are organized into open, closed, and executive sessions.
•
During the open sessions, information is presented to the DSMB by the STRENGTHS study 
investigators and NHLBI staff (as appropriate), with time for discussion.  
•
During the closed sessions, the DSMB and NHLBI program staff will discuss confidential data from the 
study, including information on efficacy and safety by treatment arm. If the closed session occurs on a 
conference call, steps will be taken to ensure that only the appropriate participants are on the call, and to invite 
others to re-join the call only at the conclusion of the closed session.
•
The DSMB may elect to hold an executive session in which only the DSMB members and NHLBI 
Program staff are present in order to discuss study issues independently. Voting on recommendations will 
follow Roberts’ Rules of Order (Robert's Rules of Order Newly Revised (11th Edition) RONR by Henry M. 
Robert III, William J. Evans (Editor), Daniel H. Honemann (Editor), Thomas J. Balch (Editor), Sarah Corbin 
Robert, Henry M. Robert III, General Henry M. Robert). If the executive session occurs on a conference call, 
steps will be taken to ensure that only the appropriate participants are on the call, and to invite others to re-join 
the call only at the conclusion of the executive session.
At the conclusion of the closed and executive sessions, the participants will be re-convened at the discretion of 
the Chair, so that the DSMB Chair can provide a summary of the DSMB’s recommendations. This provides an 
opportunity for study investigators, the STRENGTHS DCC, and NHLBI to ask questions to clarify the 
recommendations before adjournment. Alternatively, the DMSB’s recommendations will be communicated by 
the Chair to the Study PI after the meeting, at the discretion of the Chair.
Reports of DSMB Deliberations
Rapid Communication: The DSMB Secretary will convey to the PI, and the NHLBI staff the immediate 
outcome of the DSMB meeting in regards to continuation of the study within 24 hours via personal 
communication, telephone or email. 
Formal minutes:  The DSMB Chair is responsible for the accuracy and transmission of the formal 
DSMB minutes within 14 days of each meeting or call. These minutes will summarize the key points of the 
discussion and debate, requests for additional information, response of the investigators to previous 
recommendations, and the recommendations from the current meeting.  The DSMB Chair may sign the 
minutes or indicate approval electronically via email.  Then, the minutes are sent to the Principal investigator, 
who will be responsible for sending the document to all relevant institutional review boards, the consortium 
coordinating centre, and the NHLBI program and clinical trials staff. Subsequently, recommendations of the 
STRENGTHS Protocol v 9.0. 2020-09-10

Board are sent to the STRENGTHS primary study investigator(s); and included in the materials for the 
subsequent DSMB meeting to be approved by voice vote at that meeting. Once they have been voted and 
approved by the Board, they will be considered final.
Reports to the DSMB
For each meeting, the ES will prepare summary reports to facilitate the oversight role of the DSMB. The DSMB 
should discuss at the first or subsequent meetings what data they wish to review and how it should be 
presented. 
Statistical Monitoring Guidelines 
At the first meeting, review of the protocol will include review of the statistical analysis plan. The DSMB should 
discuss the adequacy of that plan. The final plan, whether part of a research protocol or separate document, 
will be maintained as an appendix in the formulated DSMB charter. The DSMB should discuss the statistical 
monitoring procedures they propose to follow, in order to guide their recommendations about termination or 
continuation of the trial.  These procedures could include guidelines for early termination for benefit, 
termination for futility, and termination for safety reasons.  
Protocol Violations and Protocol Deviations 
Protocol deviations are accidental or unintentional changes to, or non-compliance with the research study 
protocol that does not increase risk or decrease benefit; or does not have a significant effect on the subject's 
rights, safety or welfare; and/or on the integrity of the data. Deviations may result from the action of the subject, 
researcher, or research staff. Protocol violations on the other hand are accidental or unintentional changes to, 
or non-compliance with the IREC-approved protocol without prior sponsor and IREC approval. Violations 
generally increase risk or decrease benefit, affects the subject's rights, safety, or welfare, or the integrity of the 
data. In the event of a protocol deviation/violation, the PI or designee will report it to NHLBI, IREC and the 
DSMB as soon as possible after becoming aware, but no later than seven (7) days for protocol violations and 
15 days for protocol deviations, including a ‘Corrective Action Plan’ for review. In addition, the RC will add the 
protocol deviation/violation to a log of all protocol deviations/violations, which will be maintained in the 
regulatory binder (Appendix 5).
Safety and Efficacy Boundaries
The DSMB should plan to conduct one major interim analysis at approximately 15 months after initiation of 
recruitment; the exact time being at the DSMB Chair’s discretion. This is to allow for sufficient accrual of 
primary outcome data for a meaningful number of study participants to reasonably assess safety and efficacy 
of the intervention. This review will not only look at the usual safety data, but will specifically review the 
hypertension data in light of clinical events such as strokes, myocardial infarctions and deaths.
If an unexpectedly favorable mean change in blood pressure is noted, defined as a decrease of ≥30 mm Hg, 
this will be considered an unequivocal sign of benefit, and the DSMB may consider advising stopping the study 
for overwhelming benefit. This decision will also take into account the data regarding clinical events, especially 
mortality.
If an unexpectedly unfavorable mean change in blood pressure is noted, defined as an increase of ≥20 mm 
Hg, this will be considered as an unequivocal sign of harm and the DSMB may consider advising stopping the 
study for overwhelming harm. This decision will also take into account the data regarding clinical events, 
especially mortality.
There are no futility boundaries being set for this study given the short/intermediate term follow-up.
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Should the DSMB recommend early stopping or modification of the protocol the following steps will be 
undertaken:
•
A meeting will be held between the Principal Investigator and the DSMB to discuss the issues.  
•
The Principal Investigator will call a meeting with the Steering Committee, as well as the NHLBI 
program staff representatives.  Discussions should be limited to blinded data whenever possible.  This 
discussion should result in agreed actions based on DSMB recommendations.
Ethical Approval
The protocol for this study, data collection tools, and any subsequent amendments will receive approval from 
the Moi/MTRH IREC.
12. Team Roster
 
 
Table 2: STRENGTHS Team Roster
Name
Role
Dr. Constantine Akwanalo
PI
Dr. Jemima Kamano
Co-PI
Josephine Andesia Kisato
Project coordinator
Dr. Benson Njuguna
Co-investigator
Prof. Violet Naanyu 
Co-investigator
Dr. Ann Mwangi
Co-investigator
Dr. Timothy Mercer 
Co-investigator
Dr. Rajesh Vedanthan 
Co-investigator
Dr. Sonak Pastakia 
Co-investigator
Dr. Jonathan Dick 
Co-investigator
Dr. Makeda Williams
Co-investigator
Dr. Gerald Bloomfield
Consultant
Tom Valente
Consultant
Eric Finkelstein
Consultant
Juliet Miheso
Research Assistant
Agneta Pkassan
Research Assistant
Eunice Njoki
Research Assistant
Monica Nyambura
Data Manager
Esther Matini Lotokho
Research Assistant
Florence Kiwunja Njulu
Research Assistant
Godfrey Kutwa
Research Assistant
Sally Asere Ekirapa
Research Assistant
Policy on oral or written presentation of results
A written policy guiding oral or written presentation of results will be developed.
13. Timeline
 
 
Table 3: Planned Enrollment by Sex
Targeted/Planned Enrollment 
Males 
Females 
Total 
990 
660 
1650 
 
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STRENGTHS Protocol v 9.0. 2020-09-10
Figure 5: Timeline for overall STRENGTHS Study

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14. References
 
 
1.
Forouzanfar MH, Alexander L, Anderson HR, et al. Global, regional, and national comparative risk 
assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 
countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London, 
England) 2015;386:2287-323.
2.
Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury 
attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the 
Global Burden of Disease Study 2010. Lancet (London, England) 2012;380:2224-60.
3.
Mills KT, Bundy JD, Kelly TN, et al. Global Disparities of Hypertension Prevalence and Control: A 
Systematic Analysis of Population-Based Studies From 90 Countries. Circulation 2016;134:441-50.
4.
Kenya STEPwise survey for non-communicable diseases risk factors 2015 report: Ministry of Health
Kenya Nation Bureau of Statistics
World Health Organisation; 2015.
5.
Chow CK, Teo KK, Rangarajan S, et al. Prevalence, awareness, treatment, and control of hypertension 
in rural and urban communities in high-, middle-, and low-income countries. JAMA : the journal of the American 
Medical Association 2013;310:959-68.
6.
Irazola VE, Gutierrez L, Bloomfield G, et al. Hypertension Prevalence, Awareness, Treatment, and 
Control in Selected LMIC Communities. Global Heart;11:47-59.
7.
Dale J, Caramlau IO, Lindenmeyer A, Williams SM. Peer support telephone calls for improving health. 
The Cochrane database of systematic reviews 2008:Cd006903.
8.
The State of the Health Referral System in Kenya: Results from a Baseline Study on the Functionality 
of the Health Referral System in Eight Counties. Ministry of Health. 2013.
9.
Ilboudo TP, Chou YJ, Huang N. Compliance with referral for curative care in rural Burkina Faso. Health 
policy and planning 2012;27:256-64.
10.
Uwemedimo OT, Arpadi SM, Chhagan MK, et al. Compliance with referrals for non-acute child health 
conditions: evidence from the longitudinal ASENZE study in KwaZulu Natal, South Africa. BMC health services 
research 2014;14:242.
11.
Kallander K, Tomson G, Nsungwa-Sabiiti J, Senyonjo Y, Pariyo G, Peterson S. Community referral in 
home management of malaria in western Uganda: a case series study. BMC international health and human 
rights 2006;6:2.
12.
WHO. World Health Report 2000, health systems: improving performance: Geneva: World Health 
Organization.; 2000.
13.
Murray SF, Pearson SC. Maternity referral systems in developing countries: current knowledge and 
future research needs. Social science & medicine (1982) 2006;62:2205-15.
14.
Josyula S, Taylor KK, Murphy BM, Rodas D, Kamath-Rayne BD. Obstetric referrals from a rural clinic to 
a community hospital in Honduras. Midwifery 2015;31:1054-9.
15.
Brennan AT, Long L, Maskew M, et al. Outcomes of stable HIV-positive patients down-referred from a 
doctor-managed antiretroviral therapy clinic to a nurse-managed primary health clinic for monitoring and 
treatment. AIDS (London, England) 2011;25:2027-36.
16.
UNICEF. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. 
Progress Report 2009.  Towards universal access: scaling up priority HIV/AIDS interventions in the health 
sector Progress report 2009: OMS; 2009.
17.
Levitt NS, Puoane T, Denman CA, et al. Referral outcomes of individuals identified at high risk of 
cardiovascular disease by community health workers in Bangladesh, Guatemala, Mexico, and South Africa. 
Global health action 2015;8:26318.
18.
Backman G, Hunt P, Khosla R, et al. Health systems and the right to health: an assessment of 194 
countries. The Lancet;372:2047-85.
19.
Levitt NS, Puoane T, Denman CA, et al. Referral outcomes of individuals identified at high risk of 
cardiovascular disease by community health workers in Bangladesh, Guatemala, Mexico, and South Africa. 
Global health action 2015;8.
20.
Kowalewski M, Jahn A, Kimatta SS. Why do at-risk mothers fail to reach referral level? Barriers beyond 
distance and cost. African journal of reproductive health 2000;4:100-9.
STRENGTHS Protocol v 9.0. 2020-09-10

21.
Pembe AB, Urassa DP, Darj E, Carlsted A, Olsson P. Qualitative study on maternal referrals in rural 
Tanzania: decision making and acceptance of referral advice. African journal of reproductive health 
2008;12:120-31.
22.
Pembe AB, Carlstedt A, Urassa DP, Lindmark G, Nystrom L, Darj E. Effectiveness of maternal referral 
system in a rural setting: a case study from Rufiji district, Tanzania. BMC health services research 
2010;10:326.
23.
Bahous MC, Shadmi E. Health information exchange and information gaps in referrals to a pediatric 
emergency department. International journal of medical informatics 2016;87:68-74.
24.
Orimadegun AE, Akinbami FO, Akinsola AK, Okereke JO. Contents of referral letters to the children 
emergency unit of a teaching hospital, southwest of Nigeria. Pediatric emergency care 2008;24:153-6.
25.
Funnell MM. Peer-based behavioural strategies to improve chronic disease self-management and 
clinical outcomes: evidence, logistics, evaluation considerations and needs for future research. Family Practice 
2010;27:i17-22.
26.
Chang LW, Kagaayi J, Nakigozi G, et al. Effect of peer health workers on AIDS care in Rakai, Uganda: 
a cluster-randomized trial. PloS one 2010;5:e10923.
27.
Deering KN, Shannon K, Sinclair H, Parsad D, Gilbert E, Tyndall MW. Piloting a peer-driven 
intervention model to increase access and adherence to antiretroviral therapy and HIV care among street-
entrenched HIV-positive women in Vancouver. AIDS patient care and STDs 2009;23:603-9.
28.
Gusdal AK, Obua C, Andualem T, Wahlstrom R, Chalker J, Fochsen G. Peer counselors' role in 
supporting patients' adherence to ART in Ethiopia and Uganda. AIDS care 2011;23:657-62.
29.
Medley A, Kennedy C, O'Reilly K, Sweat M. Effectiveness of peer education interventions for HIV 
prevention in developing countries: a systematic review and meta-analysis. AIDS education and prevention : 
official publication of the International Society for AIDS Education 2009;21:181-206.
30.
Wu CJ, Chang AM, Courtney M, Kostner K. Peer supporters for cardiac patients with diabetes: a 
randomized controlled trial. International nursing review 2012;59:345-52.
31.
Funnell MM. Peer-based behavioural strategies to improve chronic disease self-management and 
clinical outcomes: evidence, logistics, evaluation considerations and needs for future research. Family practice 
2010;27 Suppl 1:i17-22.
32.
Smith SM, Paul G, Kelly A, Whitford DL, O'Shea E, O'Dowd T. Peer support for patients with type 2 
diabetes: cluster randomised controlled trial. BMJ (Clinical research ed) 2011;342:d715.
33.
Cabassa LJ, Camacho D, Velez-Grau CM, Stefancic A. Peer-based health interventions for people with 
serious mental illness: A systematic literature review. Journal of psychiatric research 2016;84:80-9.
34.
Hatcher AM, Turan JM, Leslie HH, et al. Predictors of linkage to care following community-based HIV 
counseling and testing in rural Kenya. AIDS and behavior 2012;16:1295-307.
35.
Okeke NL, Ostermann J, Thielman NM. Enhancing linkage and retention in HIV care: a review of 
interventions for highly resourced and resource-poor settings. Current HIV/AIDS reports 2014;11:376-92.
36.
Kelly E, Fulginiti A, Pahwa R, Tallen L, Duan L, Brekke JS. A pilot test of a peer navigator intervention 
for improving the health of individuals with serious mental illness. Community mental health journal 
2014;50:435-46.
37.
Gabitova G, Burke NJ. Improving healthcare empowerment through breast cancer patient navigation: a 
mixed methods evaluation in a safety-net setting. BMC health services research 2014;14:407.
38.
Maxwell AE, Jo AM, Crespi CM, Sudan M, Bastani R. Peer navigation improves diagnostic follow-up 
after breast cancer screening among Korean American women: results of a randomized trial. Cancer causes & 
control : CCC 2010;21:1931-40.
39.
Thorogood M, Connor MD, Lewando-Hundt G, Tollman S, Ngoma B. Secondary prevention of stroke--
results from the Southern Africa Stroke Prevention Initiative (SASPI) study. Bull World Health Organ 
2004;82:503-8.
40.
Standards of medical care in diabetes--2013. Diabetes care 2013;36 Suppl 1:S11-66.
41.
Kim JW, Bosworth HB, Voils CI, et al. How well do clinic-based blood pressure measurements agree 
with the mercury standard? Journal of general internal medicine 2005;20:647-9.
STRENGTHS Protocol v 9.0. 2020-09-10

42.
Nsanzimana S, Ruton H, Lowrance DW, et al. Cell phone-based and internet-based monitoring and 
evaluation of the National Antiretroviral Treatment Program during rapid scale-up in Rwanda: TRACnet, 2004-
2010. Journal of acquired immune deficiency syndromes (1999) 2012;59:e17-23.
43.
Bloomfield GS, Vedanthan R, Vasudevan L, Kithei A, Were M, Velazquez EJ. Mobile health for non-
communicable diseases in Sub-Saharan Africa: a systematic review of the literature and strategic framework 
for research. Globalization and health 2014;10:49.
44.
Mamlin BW, Biondich PG, Wolfe BA, et al. Cooking Up An Open Source EMR For Developing 
Countries: OpenMRS – A Recipe For Successful Collaboration. AMIA Annual Symposium Proceedings 
2006;2006:529-33.
45.
Genberg BL, Shangani S, Sabatino K, et al. Improving Engagement in the HIV Care Cascade: A 
Systematic Review of Interventions Involving People Living with HIV/AIDS as Peers. AIDS and behavior 
2016;20:2452-63.
46.
Raut A, Thapa P, Citrin D, et al. Design and implementation of a patient navigation system in rural 
Nepal: Improving patient experience in resource-constrained settings. Healthcare (Amsterdam, Netherlands) 
2015;3:251-7.
47.
Hendren S, Fiscella K. Patient navigation improves the care experience for patients with newly 
diagnosed cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 
2014;32:3-4.
48.
Freeman HP. The origin, evolution, and principles of patient navigation. Cancer epidemiology, 
biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the 
American Society of Preventive Oncology 2012;21:1614-7.
49.
Hopkins J, Mumber MP. Patient navigation through the cancer care continuum: an overview. Journal of 
oncology practice 2009;5:150-2.
50.
Fillon M. Can patient navigation help resolve gaps in cancer care? Journal of the National Cancer 
Institute 2011;103:1815-7.
51.
Park PH, Wambui CK, Atieno S, et al. Improving Diabetes Management and Cardiovascular Risk 
Factors Through Peer-Led Self-management Support Groups in Western Kenya. Diabetes care 2015;38:e110-
1.
52.
Rakhi Karwa, Tim Mercer, Mercy Maina, et al. Leveraging HIV peer based support to facilitate 
healthcare system transitions. UNPUBLISHED.
53.
Voils CI, Maciejewski ML, Hoyle RH, et al. Initial validation of a self-report measure of the extent of and 
reasons for medication nonadherence. Medical care 2012;50:1013-9.
54. Division Of Non-Communicable Diseases, Ministry Of Health. Kenya National Guidelines For 
Cardiovascular Diseases Management. 2018 
55. Naanyu V, Sidle JE, Frankel RM, Ayuku D, Nyandiko WM, Inui TS. Rooting inquiry in tradition: the health
baraza as a tool for social research in Kenya. Qualitative health research 2011;21:14-26.
56.
Collins GS, Altman DG. An independent external validation and evaluation of QRISK cardiovascular 
risk prediction: a prospective open cohort study. BMJ (Clinical research ed) 2009;339:b2584.
57.
Kengne AP, Awah PK, Fezeu LL, Sobngwi E, Mbanya JC. Primary health care for hypertension by 
nurses in rural and urban sub-Saharan Africa. J Clin Hypertens (Greenwich) 2009;11:564-72.
58.
Mendis S, Johnston SC, Fan W, Oladapo O, Cameron A, Faramawi MF. Cardiovascular risk 
management and its impact on hypertension control in primary care in low-resource settings: a cluster-
randomized trial. Bull World Health Organ 2010;88:412-9.
59.
He J, Irazola V, Mills KT, et al. Effect of a Community Health Worker-Led Multicomponent Intervention 
on Blood Pressure Control in Low-Income Patients in Argentina: A Randomized Clinical Trial. JAMA : the 
journal of the American Medical Association 2017;318:1016-25.
60.
Ogedegbe G, Plange-Rhule J, Gyamfi J, et al. Health insurance coverage with or without a nurse-led 
task shifting strategy for hypertension control: A pragmatic cluster randomized trial in Ghana. PLoS medicine 
2018;15:e1002561.
61.
Little RJ, D'Agostino R, Cohen ML, et al. The prevention and treatment of missing data in clinical trials. 
The New England journal of medicine 2012;367:1355-60.
STRENGTHS Protocol v 9.0. 2020-09-10

62.
Panel on Handling Missing Data in Clinical Trials. The Prevention and Treatment of Missing Data in 
Clinical Trials. Washington, DC: National Academies Press; 2010.
63.
Li T, Huftless S, Dickersin K, et al. Minimal standards in the prevention and handling of missing data in 
observational and experimental patient-centered outcomes research.  : Guidance document prepared for 
Patient Centered Outcomes Research Institute (PCORI); 2012.
64.
Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: Wiley &  Sons; 2004.
65.
Daniels MJ, Hogan JW. Missing Data in Longitudinal Studies: Strategies for Bayesian Modeling and 
Sensitivity Analysis. Boca Raton: Chapman & Hall / CRC Press; 2008.
66.
Hogan JW, Laird NM. Mixture models for the joint distribution of repeated measures and event times. 
Statistics in medicine 1997;16:239-57.
67.
Hogan JW, Roy J, Korkontzelou C. Handling drop-out in longitudinal studies. Statistics in medicine 
2004;23:1455-97.
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15. Appendix
 
 
Appendix 1: Screening for eligibility tool
STRENGTHS
SCREENING/ELIGIBILITY TOOL
Inclusion Criteria 
Questions
Response
Code
QA-1
Participant ID
Participant ID
__ __ __ __ __
QA-2
Encounter Date
Date of Encounter
__ __ / __ __ / __ __ __ __
Day/Month/Year
QA-3
Name of the Interviewer
Kisato J.
Miheso J.
Parklea A.
Mwangi Njoki E.
Njuguna B.
Akwanalo C.
Kamano J.
Vedanthan R.
Other.
1
2
3
4
5
6
7
8
____________
QA-4
Is patient at least 18 years of 
age or older?
Yes
No [Do no continue-ineligible]
1
0
QA-5
Enrolled in AMPATH CDM 
program with hypertension.
Yes
No
1
2
If referred up, confirm (must meet at least one of the following criteria):
Questions
Response
Code
QB-1
Uncontrolled blood pressure 
(SBP ≥ 140 or DBP ≥ 90) on 
3 or more anti-hypertensive 
medication?
Yes
No
1
0
QB-2
Have signs or symptoms of 
end-organ damage 
(dyspnoea on exertion, leg 
edema, reduced urine output, 
focal weakness)
Yes
No [Go to QB-4]
1
0
QB-3
[If QB-2=1] Please state the 
sign(s) or symptom(s) of end-
organ damage (check all 
that apply):
Dyspnea on Exertion
Leg Edema
Reduced Urine Output
Focal Weakness
1
2
3
4
QB-4
Have suspected secondary 
causes of hypertension (age 
<35 years, HIV, or 
Yes
No [Go to QB-6]
1
0
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pregnancy)?
QB-5
[If QB-4=1] Please state the 
suspected secondary causes 
(check all that apply):
Ag <35 years
HIV
Pregnancy
1
2
3
QB-6
Any other concerning 
condition that the clinician 
suspects to be attributable to 
hypertension for which they 
would seek a higher level of 
care
Yes
No
1
0
QB-7
Referral up criteria confirmed 
(if yes to at least one of the 
previous questions).
Yes
No
1
0
Go to QD-1
 If referred down, confirm (must meet at least one of the following criteria):
Questions
Response
Code
QC-
1
Patient has stable, 
uncomplicated hypertension, 
defined as controlled BP 
(SBP <140 and DBP < 90) for 
3 or more consecutive visits 
and has no evidence of new 
end-organ damage
Yes
No
1
0
QC-
2
The treating clinician 
recommends care at a lower 
level 
Yes
No
1
0
QC-
3
If Q2= 0, explain clinician’s 
reason.
Clinician’s reason
____________
QC-
4
Referral down confirmed (if 
yes to at least one of the 
questions).
Yes
No
1
0
Exclusion Criteria (if patient meets any of the following):
Questions
Response
Code
QD-
1
Patient has an acute illness 
requiring immediate medical 
attention?
Yes
No
1
0
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QD-
2
End stage disease?
Yes
No
1
0
QD-
3
Terminal illness?
Yes
No
1
0
QD-
4
Inability to provide informed 
consent (determined by 
interviewer)?
Yes
No
1
0
QD-
5
[If QD-4=Yes] Please explain. 
Explain
_____________
QD-
6
Did the participant answer 
ALL of the following 
questions correctly?
1.
Who is the current 
president?
2.
Where are we 
located?
Yes
No
1
0
QD-
7
Eligible?
Eligible
Not Eligible
1
0
QD-
8
Would you be willing to join 
the STRENGTHS study?
Yes
No
1
0
QD-
9
Please give reason for 
declining.
Reason Declined
_______________
QD-
10
Consent?
Yes
No
1
0
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Appendix 2: Consent Form STRENGTHS
INFORMED CONSENT FOR STRENGTHS TRIAL
IREC Study ID #: 0001936
Participant ID #: _________
Consenting start time: ___________
Principal Investigators: Constantine Akwanalo and Jemimah Kamano
Protocol Title: Strengthening Referral Networks for Management of Hypertension across the Health Systems 
(STRENGTHS)
Purpose of this Research Study
The purpose of this study is to find ways to improve success of referrals for hypertension care in rural Kenya. AMPATH and 
the Kenya Ministry of Health have implemented a referral network for the care of hypertensive patients in this area across 
different levels (that is, from dispensary, to health center, sub-county, county and national referral hospitals). AMPATH is 
planning to evaluate the impact of health information technology (health IT) combined with peer support (trained patients 
with hypertension) on successful referral for hypertension care and control of blood pressure among patients. We therefore 
plan to compare the impact of the combined intervention (that is, health IT and peer support) on blood pressure control 
versus the usual standard clinical care. The results of this study are not only designed to improve hypertension care in 
Kenya, but will also be applicable to the management of other chronic diseases in Kenya and other developing countries. 
You are eligible to take part in this research study because you are hypertensive, enrolled in the AMPATH Chronic Disease 
Management Program and have been referred to another health facility for further care.
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Duration of Participation and Number of People Expected to Participate
Participation Duration: One year
Anticipated Number of Subjects: 1600
Description of Procedure
If you agree to participate in this research study, the following information explains what may be involved.
To evaluate the impact of combining health IT and peer support on the quality of hypertension care, we are dividing the 
community into two random groups, one with usual clinical care and the other with our referral support intervention 
(combined health IT with peer support). Depending on the community unit you live in, you might be approached to receive 
our referral support intervention to help direct your referrals, or have your referral conducted as per the usual care (with no 
referral support intervention). If you receive the referral support intervention, a peer (patient with hypertension who is trained 
in supporting other patients with hypertension) will sit with you and clarify any questions you may have about your referral, 
and provide education and counseling about hypertension. In addition, in planning for your referral visit, the peer will assist 
you to plan e.g. provide you with information of anticipated costs for the referral, and help with booking an appointment in 
the facility you’ve been referred to. On the day of your visit, a different peer stationed at the receiving facility will be waiting 
to receive you and assist you to navigate through the facility. At the end of your referral visit, the peer will again clarify any 
questions you may have. Throughout your participation in the study, the peer may call you or even visit you at home to offer 
you furthur support for your referral.
The clinicians and the services offered will be the same regardless of the community you are coming from. The fees paid, 
which have been agreed upon by AMPATH and the Ministry of Health, will also remain the same.
At the beginning of the study we will ask you questions concerning your high blood pressure, medications you take, diet, 
physical activity level and other lifestyle related questions. We will measure your blood pressure and conduct blood tests to 
measure your lipid (“fat in blood”) levels, and how well your kidneys are working using a test called the creatinine test. To do 
this, we will need to prick you to withdraw blood using a small needle. About 10 mls of blood will be taken and fed into a 
portable machine that can determine the results of these tests, or transported back to a health facility laboratory for testing. 
All the blood test results will be immediately made available to you and we will share the results with your clinician. Taken 
together, the tests conducted will help us determine your risk for future complications of hypertension such as heart disease. 
We also wish to study the costs and expenses related to your medical care, to see if there is any difference in costs in the 
two different groups, therefore, we will ask you questions regarding how much you spend for your hypertension care. 
We will repeat the above procedures at the end of the one-year period in which you’ll be in the study, so that we can see if 
there has been any change in these results. The one-year results will also be shared immediately with you and your 
clinician. If we cannot find you at the end of the 1-year period, we will contact you or your relative by phone.
Confidentiality of Study Data
We will not use your name or any other identifying information when we use this information that you are giving us. The only 
people who will know that you are a research participant are members of the research team who are trained to keep your 
information confidential and if appropriate, your health care providers and study clinical monitor. No individual identifying 
information about you will be disclosed to others, except if required by law. 
Study records will be stored in locked cabinets in a locked room. Only the study personnel will have access to the 
information. All computerized information will be protected by access codes known only to the lead researcher and certain 
designated staff members. 
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Potential Benefits
The referral support intervention might lead to more successful referral completion for you, and improved health. In addition, 
the information gathered during this research study will help AMPATH improve the implementation of this program. You, 
your family, and your community may therefore benefit from this research. 
Potential Risks or Discomforts
We will only be collecting personal health information that is a routine part of clinical care, as well as the cost information. 
This information will be shared only with your clinicians, in order to provide you the best clinical care possible. 
Risks associated with blood pressure testing are minimal and may include minor pain discomfort, and swelling at the 
location of the needle prick, small risk of dizziness, light headedness, and fainting. The risk is however no more than what 
you may experience during your usual routine clinical care visit. 
Voluntary Participation and Right to Discontinuation
It is completely voluntary for you to take part in this study. If you choose to take part, you can refuse to answer any question 
or ask us to stop at any time with no penalty. This will not affect in any manner your ability to receive medical care at any 
health facility (private/public), or to receive any benefits to which you are otherwise entitled.
Compensation 
Participants will get transport reimbursement at the 6 month and 12 month follow up visit, however, the initial visit, or any 
costs associated with completing a referral or any usual clinical care will not be provided. A snack will be provided during 
the consenting and interview procedures as these will take away time from you. 
Future Contact
We would like to follow you up after six and twelve months. We therefore request for your permission to contact you or any 
other person (if unavailable) as provided in the demographic data form.
Disclosure of Financial Interests
Funding for conducting this research is provided by the National Institutes of Health, USA, and Grant number: 
U01HL138636.  There are no financial interests to disclose.
Contact Information:
In case of any questions/complaints regarding this study, please contact:
Dr. Constantine Akwanalo
Moi University College of Health Sciences
Eldoret, Kenya
cakwanalo@gmail.com
0722862968
Is it okay for you to participate in this research study?
PARTICIPANT’S  INFORMED CONSENT
I  Mr/Mrs/Ms/Dr………………………………………………………..have read/ have had the document read to me, all my 
questions have been answered and I have understood the information contained in the consent form above. I agree to 
voluntarily take part in the study. I acknowledge receipt of a copy of the informed consent statement.
             PARTICIPANT’S SIGNATURE:                                                                                  Date____________ 
             (Must be dated by the participant if literate)       
STRENGTHS Protocol v 9.0. 2020-09-10

      
             NAME OF WITNESS: ………………………………………………………………………………………        
             SIGNATURE OF WITNESS: ____________________________________Date: ____________
               (Impartial witness)                                                        (Must be dated by witness) 
            NAME OF PERSON OBTAINING CONSENT: ______________________________________
             SIGNATURE OF PERSON OBTAINING CONSENT:                                                Date: ____________            
Consenting stop time: _________
Appendix 3: Process Evaluation Protocol
STRENGTHS Process Evaluation 
Protocol
Last Modified: October 9, 2019
Overview of STRENGTHS Process Evaluation
The purpose of the process evaluation is to identify and correct problems in study 
implementation during the trial as well as help explain the results of the trial after the fact. 
The process evaluation for the STRENGTHS project is based on the Saunders framework1 
and will consist of several components: fidelity (quality), dose delivered (completeness), 
dose received (exposure), dose received (satisfaction), recruitment, reach (participation 
rate), and context, as demonstrated in the graphic below.
 
1 Saunders RP, Evans MH, Joshi P. Developing a process-evaluation plan for assessing health promotion program implementation: a 
how-to guide. Health Promotion Practice. 2005; Apr; 6(2): 134-47.
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Each process evaluation component will be assessed using several data collection tools. The protocol 
below goes over each of the individual data collection tools in detail. 
A Process Evaluation REDCAP will be utilized for the management of all quantitative data. Data will be 
entered by research assistants, verified by the research coordinators and data manager, and analyzed 
by the statistics team. Qualitative data will be transcribed by the research assistants and analyzed by 
the research coordinators using NVivo software. 
Acronyms: 
BP – Blood Pressure
CDM – Chronic Disease Management
FGD – Focus Group Discussions
HIT – Health Information Technology
KII – Key Informant Interviews
PN – Peer Navigators
RA – Research Assistant
SOP – Standard Operating Procedures
UC – Usual Care
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1. Fidelity (Quality)
Aim: To assess how well the trial was implemented as planned
Specific aims: To assess the fidelity of a) data collection and entry and b) the intervention delivery 
a) Fidelity of Data Collection and Entry:
Data Collection Observation
Participants:
All members of the research staff that will be collecting data from participants will be observed.
Methods:
A study investigator and the research coordinator will observe research staff at the beginning of the 
study or at the point of hiring (for new staff). Additional observation will be conducted at 3 and 12 
months if determined to be needed. The principal investigator and research coordinator will be provided 
with a checklist of expected behaviors and actions and will check off items as they are completed. The 
checklist items will be based on the study protocol procedures. The checklist will assess: 
Measurement taking: BP, height, weight, waist circumference, using point of care machine (fasting 
blood sugar, lipid profile)
Survey conduct and connection to participant during survey administration (observe each surveyor 3-4 
times and give feedback). Includes Costing Questionnaire and Social Network Survey.
Informed consent procedure (includes eligibility and consent forms, proper use of REDCap, and study 
explanation)
Outcomes and Analysis:
The statistics team will summarize adherence for each checklist item, and each research staff 
member’s score will be calculated as percent completion. The principal investigator and research 
coordinator will identify problem areas and provide individual feedback and follow-up training as 
necessary. 
Data Entry
Participants:
All members of the research staff that will be entering data from participants at baseline and/or 3 or 12 
months will be observed.
Methods:
The data manager and research coordinator will ensure that the following data entry checks are being 
utilized per the Data Management SOP: double data entry of paper forms for critical fields built into the 
data management system and out of range checks built into the data management system. 
Outcomes and Analysis:
The data manager and research coordinator will determine the adherence to the Data Management 
SOP to assess if the double data entry and out of range checks were implemented as intended. Data 
manager will utilize quality control feature of REDCAP to determine how many validation errors are 
made per research assistant, as defined in the Data Management SOP. 
b) Fidelity of Intervention Delivery:
Field Observation:
STRENGTHS Protocol v 9.0. 2020-09-10

Participants:
All PNs and clinicians enrolled in the study will be observed. 
Methods:
Trained research staff will observe PN actions and interactions by month 3 of the intervention during a site 
visit. The research staff will be provided with a checklist of expected behaviors and actions and will check 
off actions as they are completed. The checklist items will be based on the PN guides and designed to 
assess whether or not their role is being implemented as intended. If needed based on performance (on a 
case-by-case basis based on results reported on the field observation checklist), additional field 
observation can be conducted subsequently. 
Trained research staff will also observe clinician actions and interactions by month 3 of the intervention 
during a site visit. If needed based on performance, additional field observation can be conducted 
subsequently. The research staff will be provided with a checklist of expected behaviors and actions and 
will check off actions as they are completed. The checklist items will be based on the clinician guides and 
designed to assess whether or not their role is being implemented as intended. 
Outcomes and Analysis:
The statistics team will summarize adherence for each checklist item, and each PN’s score will be 
calculated as percent completion. Adherence will be compared by arm (as applicable), age, gender, and 
geographical region. The research staff will identify problem areas based on items not conducted (as per 
the field observation checklist) and will provide individual feedback and follow-up training as necessary. 
Should certain PNs not meet the expectations after additional training, they will be replaced with another 
PN from the same community unit.
Written Test:
Participants: 
Every PN will be given written tests.
Methods:
Separate written tests will be given to the PNs assessing knowledge of hypertension care, understanding 
of the referral system, as well as psychosocial support and patient communication
The test will be translated into Kiswahili and will be administered at baseline (following training) and 6 
months. 
Outcomes and Analysis:
The statistics team will summarize the results from the written test and do comparisons by groups 
(geographical region, age, gender, and intervention arm). PN ID numbers will be recorded on the test form 
to link the baseline and follow-up tests. Each PN’s score will be calculated as percent completion. The 
research staff will identify problem areas and provide individual feedback and follow-up training as 
necessary based on preliminary analysis of the baseline test. A score lower than 80% will be flagged for 
review by the principal investigator and/or the research coordinator, and will be evaluated on a case-by-
case basis to determine if additional training/feedback is necessary. 
Focus Group Discussions:
Participants:
FGDs will be conducted amongst consenting trial participants who have been retained in the trial, 
participants who dropped out of the trial (based on the clinical definition of a drop-out as someone who has 
not returned for care in 3 months since the last scheduled appointment), and among PNs. Two clusters 
from the intervention arm and two clusters in the UC arm will be randomly selected in which one FGD will 
STRENGTHS Protocol v 9.0. 2020-09-10

be conducted in each consisting of 8-10 randomly selected participants from the intervention arm (for a 
total of 4 FGDs). UC participants will be recruited from different health facilities in the applicable cluster.
Retained Participants
Participants that 
dropped out
Peer 
Navigator
Cluster 1
Cluster 2
Cluster 3
Cluster 4
All Clusters
All Clusters
All Clusters
HIT + 
peer support
HIT +
peer support
UC
UC
HIT + peer 
support
UC
HIT + peer 
support
Method:
FGDs will be conducted at approximately 8 months. Data collected through focus group discussions will be 
used to evaluate fidelity as well as other components of the framework as noted throughout this protocol. A 
summary of all data collected through FGDs is noted below.
Participant FGD will:
•
Assess participant perceptions of the different intervention components, including the PN and rural 
clinician activities
•
Determine if the intervention is acceptable to participants 
•
Identify barriers to use and points of successful use of the intervention
•
Elicit suggestions from participants about improving the intervention effectiveness
PN FGD will: 
•
Assess if they think peer navigation is helpful for participant care 
•
Assess perceptions of participant engagement
•
Determine if the intervention is acceptable to the providers
•
Identify barriers to use and points of successful use of the intervention
•
Ascertain if interventions are meeting trial arms and objectives
•
Elicit suggestion for improvement
Outcomes and Analysis:
Content analysis of the FGD data from transcripts of the audio-recordings and notes taken by facilitators 
during the discussion will be performed using NVivo software. For the participant FGD, the following a priori 
codes will be used: perceptions of PN and rural physicians, perceptions of intervention activities, 
importance of hypertension care, importance of referral pathways, and quality of referral services. For the 
PN FGD, the following a priori codes will be used: perceptions and concerns related to HIT and peer 
support, cognitive issues around patient interaction (perceived benefit, participant receptivity), emotional 
elements (frustrations, fears, expectations), and the impact of gender dynamics. Significant inductive 
(emerging) codes will be identified. 
Semi-structured interviews with clinicians
Participants:
Approximately 18 clinicians will be interviewed at 8 months (at least one from the primary and secondary 
level from each cluster, and at least 2 from the tertiary level; Moi Teaching and Referral Hospital)
Methods:
Trained research staff will conduct semi-structured interviews with the rural clinicians using a structured 
question guide with the following goals:
•
Assess if they think the intervention (use of HIT and peer support) is helpful for participant care
•
Determine if the intervention is acceptable to the providers
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•
Identify barriers to use and points of successful use of the intervention
•
Ascertain if interventions are meeting trial arms and objectives
•
Elicit suggestion for improvement
•
Assess how HIT and peer support impacts patient-clinic interaction 
Outcomes and Analysis:
Content analysis of the interviews from transcripts of the audio-recordings and notes taken by interviewers 
will be performed using NVivo software. The following a priori codes will be used: perceptions and 
concerns related to managing the HIT and peer support, cognitive issues around intervention (perceived 
benefit, participant receptivity), emotional elements (frustrations, fears, expectations), and impact of gender 
dynamics. Significant inductive (emerging) codes will be identified. 
2. Dose Delivered (Completeness)
Aim: To determine the number of units of each intervention delivered and if they included the necessary 
components
Specific aims: To determine if the referral services were provided to participants and in accordance with the 
components as outlined in the training manuals 
Participant Self-Reports
Methods:
At the conclusion of 6-month and 12-month visits, 5 randomly selected participants will fill out a brief 
checklist of tasks completed during the meeting. The checklist will include items assessing PN referral 
services provided during the visit. These sheets, which will be available in both English and Swahili, will be 
collected approximately every 3 months when research staff conduct site visits. 
Outcomes and Analysis:
The statistics team will summarize task completion by individual facility and by arm over the 12 months.
3. Dose Received (Exposure)
Aim: To assess to what extent participants were actively engaged with and receptive to the intervention, 
including initial use and continued use.
Specific aims: To assess participant engagement with the intervention as well as UC, both from the participant 
and PN perspectives.
Focus Group Discussions 
Conducted as outlined in 1. b) III.
Semi-structured interviews with rural clinicians 
Conducted as outlined in 1. b) IV.
Field Observation
Conducted as outlined in Section 1. B) I. 
Outcomes and Analysis:
Descriptive statistics will be performed with stratified analysis by relevant demographic characteristics as 
appropriate.
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4. Dose Received (Satisfaction)
Aim: To assess the level of participant and provider satisfaction both with the intervention and with their 
interactions with project staff
Specific aims: To assess the level of participant and provider satisfaction with the implementation of the 
intervention, as well as UC.
Focus Group Discussions 
Conducted as outlined in Section 3a) with focus on participant and provider satisfaction with the 
intervention components
Semi-structured interviews with rural clinicians
Conducted as outlined in Section 3b) with focus on provider satisfaction with the intervention components.
5. Reach (participation rate)
Aim: To determine what percentage of the enrolled participants that participated in the intervention.
Specific Aim: To determine the percentage of patients being referred who met with both the PN at their 
referring facility, as well as the PN at their receiving facility. This will thereby assess retention. Barriers to 
participation will also be assessed.
Clinic Attendance in Usual Care
Participants:
Every study participant in the UC arm.
Methods:
Every study participant in the UC arm will have their clinical attendance data extracted. Clinic attendance is 
defined as the completion of a CDM form. The data team will extract dates of CDM clinic attendance from 
the AMRS for each study participant at 12 months.
Outcomes and Analysis:
The statistics team will summarize the number of clinic appointments over 12 months by arm.
Peer Navigator Encounter in Intervention Arm
Participants:
All patient encounter data will also be extracted from the research database for each participant in the 
intervention. A patient encounter is defined as the completion of a patient encounter form by the PN. 
Methods:
Every study participant in the intervention arm (receiving HIT and peer support) will also have their 
encounter data extracted as defined above.
Outcomes and Analysis:
The statistics team will summarize the number of encounters over 12 months by arm.
Focus Group Discussions
Conducted as outlined in Section 3a). Specifically, the drop-out focus groups will help assess why certain 
participants stopped participating.
6. Recruitment
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Aim: To assess what procedures were used to attract participants and what percentage of eligible participants 
were enrolled out of the total number recorded as eligible during screening.
Specific Aim: To determine which enrollment procedures were utilized to screen patients eligible for enrollment, 
and monitor enrollment procedures.
Field built into eligibility form
Participants: 
Research staff involved in enrolling participants will be prompted by the screening and eligibility form on the 
data management software
Methods:
The screening and eligibility form on the project REDCap will prompt research staff to type in a reason 
when eligible participants choose not to enroll. For patients that do enroll, research staff will indicate which 
enrollment procedures were utilized. The data management program will also log the attempts to contact 
and enroll participants and the statuses of these attempts through the scheduling module. 
Outcomes and Analysis:
Reports generated by the data management system will be used to evaluate recruitment strategies and 
improve as necessary. In order to determine what percentage of eligible participants were enrolled, we will 
first determine how many participants were eligible from each recruitment pathway. From this, the data 
team can calculate what percentage of eligible patients were enrolled per pathway and in total.
Semi-structured interviews with research staff 
Participants:
Key members of the research staff in Kenya who were most directly responsible for STRENGTHS 
participant recruitment will be interviewed at 6 months.
Methods:
Trained research staff who were not directly involved with participant recruitment will conduct semi-
structured interviews with the research staff responsible for recruitment using a structured question guide 
with the following goals:

Determine what planned and actual recruitment procedures were used to recruit participants

Identify barriers in recruitment and successful strategies 
Outcomes and Analysis:
A content analysis of the interviews from transcripts of the audio-recordings and notes taken by 
interviewers will be performed using NVivo software. The following a priori codes will be used: recruitment 
procedures, barriers in recruitment, successful recruitment strategies. Significant inductive (emerging) 
codes will be identified.
7. Context
Aim: To assess the aspects of the environment that may influence intervention implementation or study 
outcomes, including contamination or the extent to which the control group was exposed to the program. 
Specific aim: To assess the barriers and facilitators to the two intervention arms, from the participant, provider, 
and staff perspectives 
a) Focus Group Discussions:
Conducted as outlined in Section 3a) with focus on barriers and facilitators to implementing the intervention. 
b) Semi-structured interviews with clinicians and research staff:
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Conducted as outlined in Sections 3b) and 6b) with focus on barriers and facilitators to implementing the 
intervention.  
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Appendix 4: Adverse Event and Serious Adverse Event Reporting Form
STRENGTHS 
ADVERSE EVENT AND SERIOUS ADVERSE EVENT REPORTING 
NOTE: Complete this report within 24 hours of knowledge of an adverse event occurring or 
worsening after consent. This report must be filled together/reviewed by the principal 
investigator or delegated co-investigator. All SAEs will require expedited reporting by the PI to 
the study's DSMB, IREC/IRB, and NHLBI. An expedited report of an SAE will be submitted by email 
and must be reported to the DSMB, IREC/IRB and the NHLBI within 24 hours of the event being 
reported to the Investigator. The expedited report will be followed by a detailed, written AE/SAE 
report as soon as possible.
Causal Relationship
The assessment of the causal relationship is a clinical decision based on all available information 
at the time of the completion of the CRF. The assessment is based on whether there was a 
"reasonable causal relationship" to the study interventions. An assessment of "No" would include 
the existence of a clear alternative explanation or non-plausibility. An assessment of "Yes" 
indicates that there is a reasonable suspicion that the event is associated with the subject’s 
participation in the study. Factors to be considered in assessing the relationship of the event to 
study treatment include:

The temporal sequence from study intervention procedures: The event should occur after 
the intervention is delivered. The length of time from exposure to event should be 
evaluated in the clinical context of the event

Recovery on intervention discontinuation, recurrence on intervention re-introduction: 
Participant’s response after discontinuation should be considered in the view of the usual 
clinical course of the event in question

Underlying, concomitant, intercurrent diseases: Each event should be evaluated in the 
context of the natural history and course of the disease being treated and any other 
disease the participant may have

Concomitant medication or treatment: Drugs the participant is taking or the treatment the 
participant receives should be examined to determine whether any of them may be 
suspected to cause the event in question
Alternative possible explanations 

Concomitant disease: any illness participant has at time of entering the study, 
excluding the indication for study intervention

Concomitant drug: any medication the participant was receiving at time of event onset

Intercurrent disease: any illness the participant may develop during the study 

Underlying disease: the indication the intervention is being tested for
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SECTION A – INTRODUCTION
Question
Response
Code
QA-1
Participant ID
Participant ID
_ _ _ _ _ 
QA-2
Start Date of Event
Start Date
Don’t Know
__ __ / __ __ / __ __ __ __
Day/Month/Year
99
QA-3
End Date of Event
Stop Date
Ongoing
Don’t Know
__ __ / __ __ / __ __ __ __
Day/Month/Year
88
99
QA-3
Date and time investigator 
became aware of this event
Date
Time (in 12-hr clock)
__ __ / __ __ / __ __ __ __
Day/Month/Year
_ _--_ _. _ _
hr—min. pm/am
QA-4
Does this event associated 
with any of the following 
seriousness criteria? (Select 
all that are appropriate)
Results in death
Is life threatening
Results in hospitalisation or 
prolongation of hospitalisation
Results in persistent or significant 
disability or capacity
(If any of the above are selected, Go 
to section B)
None of the above (Go to section c)
1
2
3
4
5
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SECTION B – SERIOUS ADVERSE EVENT
Question
Response
Code
QB-1
Serious Adverse Event, please fill out the 
details of the event and give specific 
diagnosis if possible e.g. heart failure, death 
etc 
QB-2
What was the intensity of the SAE 
Mild (transient in nature and not interfering 
with normal activities)
No [Sufficiently discomforting to interfere 
with normal activities]
Severe [prevents normal activities]
Don’t know 
1
2
3
99
QB-3
Is there a reasonable causal relationship to 
any of the study interventions? (see 
definitions on page 1)
Yes
No
1
2
QB-4
What action was taken with the study 
intervention?
Study intervention withdrawn (Go to QB-5)
Study intervention temporary interrupted (Go 
to QB-5)
No action (Go to QB-7)
1
2
3
QB-5
Did event disappear after stopping study 
interventions?
Yes
No
Unknown
1
2
99
QB-6
Did event reappear after reintroducing 
study interventions?
Yes
No
Study interventions not reintroduced
Unknown
1
2
3
99
QB-7
Are there any alternative possible 
explanations for this event? (see definitions 
on page 1)
Concomitant disease
Concomitant drug
Intercurrent disease
Underlying disease
Unknown
1
2
3
4
99
QB-8
What was the outcome of this event?
Recovered/Resolved
Not Recovered/Not Resolved
Recovering/Resolving
Fatal
Recovered/resolved with sequelae
Unknown
1
2
3
4
5
99
SECTION C – NON-SERIOUS ADVERSE EVENT
Question
Response
Code
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QC-1
Non-Serious Adverse Event, please fill out 
the details of the event and give specific 
diagnosis if possible e.g. heart failure, death 
etc 
QC-2
What was the intensity of the non-serious 
AE 
Mild (transient in nature and not interfering 
with normal activities)
No [Sufficiently discomforting to interfere 
with normal activities]
Severe [prevents normal activities]
Don’t know 
1
2
3
99
QC-3
Is there a reasonable causal relationship to 
any of the study interventions? (see 
definitions on page 1)
Yes
No
1
2
QC-4
What action was taken with the study 
intervention?
Study intervention withdrawn (Go to QC-5)
Study intervention temporary interrupted (Go 
to QC-5)
No action (Go to QC-7)
1
2
3
QC-5
Did event disappear after stopping study 
interventions?
Yes
No
Unknown
1
2
99
QC-6
Did event reappear after reintroducing 
study interventions?
Yes
No
Study interventions not reintroduced
Unknown
1
2
3
99
QC-7
Are there any alternative possible 
explanations for this event? (see definitions 
on page 1)
Concomitant disease
Concomitant drug
Intercurrent disease
Underlying disease
Unknown
1
2
3
4
99
QC-8
What was the outcome of this event?
Recovered/Resolved
Not Recovered/Not Resolved
Recovering/Resolving
Recovered/resolved with sequelae
Unknown
1
2
3
4
99
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SECTION D – CONCLUSION
Question
Response
Code
QD-1
Name of the Interviewer/Research Assistant
________________________________________
QD-2
Date of documentation
__ __ / __ __ / __ __ __ __
Day/Month/Year
QD-3
Name of the Investigator reviewing this 
information
________________________________________ 
QD-4
Date of Investigator review
__ __ / __ __ / __ __ __ __
Day/Month/Year
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Appendix 5: Protocol Deviation/Violation Log
Protocol Deviation/Violation Log
Description of 
Protocol 
Deviation:
Deviation 
Category*
Deviation 
Code**
Date Deviation
Occurred:
(dd/mm/yyyy)
Date IREC/
IRB 
Notified
Principal
Investigator’s 
Signature
Date Signed
(dd/mm/yyyy)
*DEVIATION CATEGORIES:
A. Safety 
B. Informed Consent 
C. Eligibility
D. Protocol implementation 
E. Other, specify in log
**DEVIATION CODES: Numbers listed by the 
sample protocol deviations
Safety (Category A)
1.
Not reporting an SAE within 24 hours
2.
Laboratory tests not done
3.
AE/SAE is not reported to IRB
4.
Other, specify in log
Informed Consent (Category B)
5.
Failure to obtain informed consent
6.
Consent form used was not current IRB-
approved version 
7.
Consent form does not include updates or 
information required by IRB
8.
Consent form missing
9.
Consent form not signed and dated by participant
10. Consent form does not contain all required 
signatures
11. Other, specify in log
Eligibility (Category C)
12. Participant did not meet eligibility criterion
13. Randomization of an ineligible participant
14. Participant randomized prior to completing Baseline 
Assessment, etc.
15. Randomization and/or treatment of participant prior 
to IRB approval of protocol
16. Other, specify in log
Protocol implementation (Category D)
17. Failure to keep IRB approval up to date
18. Participant receives wrong treatment
19. Participant seen outside visit window
20. Use of unallowable concomitant treatments
21. Prescribed dosing outside protocol guidelines
22. Missed assessment
23. Missed visit
24. Other, specify in log
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