Digital Treatments for Opioids and Other Substance Use Disorders (DIGITS) in Primary Care: A Hybrid Type-III Implementation Trial
Phase: NA
Conditions: Drug Use Disorders, Illicit Drug Use, Alcohol-Related Disorders, Opioid Use Disorder
Sponsor: Kaiser Permanente

 
 
Digital treatments for opioids and other substance use 
disorders (DIGITS) in primary care: A hybrid type-III 
implementation trial 
  
ClinicalTrials.gov Identifier: NCT05160233 
 
 
STUDY PROTOCOL 
 
 
Principal Investigator: 
Joseph E. Glass, PhD, MSW 
 
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Project Abstract 
The DIGITS Trial addresses a critical knowledge gap: How to best implement digital treatments for 
substance use disorders (SUD) in primary care. We will study implementation of the reSET® and reSET-
O® digital therapeutic platforms into primary care to potentially improve care for people with SUD, and 
as a model for how to sustainably implement digital treatments into real-world healthcare. Digital 
treatments could extend the reach of SUD therapy to more people and could address a significant 
barrier to buprenorphine prescribing in primary care: the lack of access to psychosocial treatment. Prior 
implementation trials found that a digital SUD treatment in primary care was not sustained in part 
because of workflow and cost burdens so our study design and analytic plans focus on these issues. Our 
delivery system partners in Kaiser Permanente Washington are committed to collaborating with us to 
study strategies for implementing reSET and reSET-O throughout the region (approximately 30 primary 
care clinics in Washington State) to address prior implementation challenges documented in the 
literature. After piloting in 3 clinics, we will randomize clinics in a 2x2 factorial design to four 
approaches: (1) “standard implementation,” which is an evidence-based implementation strategy 
previously used by our delivery system partners; (2) “standard implementation with practice 
facilitation,” a clinician-facing implementation strategy; (3) “standard implementation with health 
coach,” a patient-facing implementation strategy using medical assistants to support patient adoption 
and engagement; and (4) “standard implementation with both.” These implementation strategies have 
some evidence in primary care, but their impact on real-world implementation of a digital treatment has 
not been evaluated. Specific Aims are to (1) Estimate the effect of clinician-facing (external facilitation) 
and patient-facing (health coach) implementation strategies in increasing the reach and fidelity of a 
digital treatment in primary care clinics, and (2) compare the population-level cost-effectiveness of each 
implementation strategy in increasing reach, fidelity, and abstinence by patients. IMPACT: Researchers 
and health systems do not know how to reach large numbers of patients with opioid and other SUD. 
Digital treatments are promising, but health systems lack evidence to guide implementation of digital 
therapies. This study will estimate and compare the effectiveness of clinician-facing and patient-facing 
implementation strategies, providing health system leaders with data on how to best implement digital 
treatments. 
Study Phases 
The DIGITS Study includes four phases. This protocol outlines the last two phases; piloting procedures 
are available in a separate document. 
1. A 3-month quality improvement (QI) pilot (henceforth “QI Pilot”) with the goal of evaluating the 
implementation and use of reSET/reSET-O in KPWA primary care (2 clinics) 
2. A 3-month DIGITS Trial Pilot with the goal of refining the implementation strategies that we will 
test experimentally in the DIGITS trial and evaluating the feasibility of the research design. The 
original plan was to carry out the Trial Pilot at 3 clinics. However, we reduced this to the same 
two clinics as the QI pilot due to LICSW staff departures. 
3. A 12-month implementation trial, where implementation strategies are randomized with a 
factorial design (30 clinics) 
4. We planned to complete a 12-month sustainment period, where research funding and support 
for implementation is scaled back to study sustainment and institutionalization of reSET/reSET-

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O. However, the digital treatment vendor filed for bankruptcy early in the sustainment period, 
so this goal was not accomplished.  
Study Background 
Implementation context: Kaiser Permanente Washington (KPWA) delivery system 
 
Partnership history. Our trial builds on a partnership of researchers at KPWA Health Research Institute 
and KPWA delivery system leaders. The partnership solidified in 2015 during integration of behavioral 
health care in primary care. In collaboration with researchers, KPWA leaders implemented care for 
cannabis, other drugs, and depression in primary care. Several other studies have followed, including 
two projects led by the PI to study the design of workflows for offering digital therapeutics in primary 
care. 
General overview of KPWA. KPWA is an integrated health coverage and care system that serves a 
population of privately insured patients as well as those insured by Medicaid and Medicare. KPWA 
provides care in urban, rural, and suburban communities. Patient populations of the primary care clinics 
vary. Approximately 340,000 unique patients visit these clinics annually. Current care for SUD at KPWA. 
Approximately 90% of KPWA primary care patients are screened annually for alcohol, cannabis, and 
other drug use. Clinics employ licensed independent social workers (LICSWs) who are embedded in 
primary care teams as mental health and SUD specialists. Many clinics have primary care providers who 
are buprenorphine prescribers. While many healthcare services are internalized, specialist addiction 
treatment services, or “rehab programs”, are provided through an external contracted care network.  
Beginning in May 2020, KPWA began offering a new web and smartphone-based app to all members as 
a health plan benefit. This app is designed for the management of multiple health behaviors and 
includes several modules for alcohol and drug use. Since 2017, KPWA has offered another digital 
treatment for depression to all patients.  
DIGITS Trial Summary Overview 
The DIGITS Trial will:  
(1) conduct a 2x2 factorial trial randomizing KPWA primary care clinics to four implementation 
approaches for digital treatments in primary care: (a) standard implementation, an evidence-based 
implementation strategy developed by our delivery system partners to implement a digital depression 
treatment; (b) standard with practice facilitation, adding a clinician-facing implementation strategy; (c) 
standard with health coaching, adding a patient-facing implementation strategy to support reSET/reSET-
O delivery, and (d) standard with both, adding both the clinician-facing and patient-facing 
implementation strategies. We will assess impact on two primary implementation outcomes: reach and 
fidelity. A secondary effectiveness outcome is substance use. We will formatively evaluate 
implementation and use our Steering Committee to promote sustainability. We will monitor 
sustainability as we transfer responsibility of implementation to the delivery system and use mixed 
methods to evaluate the impact of the intervention, setting, and ecological system on sustainability.  
(2) We will compare the population-level cost-effectiveness of each approach in increasing reach, 
fidelity, and abstinence.  
 
Specific Aims 

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1. Estimate the effect of clinician-facing (practice facilitation) and patient-facing (health coaching) 
implementation strategies in increasing the reach and fidelity of a digital therapeutic for SUD in 
primary care clinics 
2. Compare the population-level cost-effectiveness of each implementation strategy in increasing 
reach, fidelity, and abstinence by patients. 
 
 
Actual Timeline (overlapping timelines for Pilot and Trial activities are shown) 
 
 
Implementation Strategies 
 
Standard Implementation 
The research team/delivery system partnership will oversee all implementation strategies, with all 
clinics receiving standard implementation of reSET/reSET-O led by the delivery system. Our delivery 
system partners developed standard implementation, which combines several efficacious 
implementation strategies. First, delivery system leaders will provide 2.5 total hours of mandated 
training to all LICSWs, by videoconference over two days. Training will cover: current standard of care 
for SUD and use of health apps, research evidence for reSET/reSET-O, a reSET/reSET-O demo by Pear 
Therapeutics, description of the implementation toolkit and clinical procedures for using reSET/reSET-O 
in Primary Care (PC) (35 mins), and general Q&A (10 mins). 
 
After training, LICSWs will receive an implementation toolkit with (1) a job aid with major steps of 
reSET/reSET-O delivery with the “what”, “how”, and “why” of each step; (2) patient pamphlets to 
promote reSET/reSET-O and describe steps for getting started; (3) scripts to help clinicians introduce and 
enroll patients in reSET/reSET-O, and set expectations for use; and (4) EHR tools including 
documentation/charting templates and “after-visit-summaries” that reinforce instructions for getting 
started, summarize the rationale for reSET/reSET-O, describe risks/benefits, and communicate privacy 
information about reSET/reSET-O (e.g., HIPAA compliance, third-party data hosting). These toolkit items 
were used successfully for the previous implementation of a digital depression treatment and will 

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require minor adaptations for reSET/reSET-O. New for this study is (5) an EHR order set so LICSWs can 
easily access a standing reSET/reSET-O prescription.  
 
Delivery system leaders offer continued support to LICSWs. Leaders review monthly, four-page, text-
based performance reports of reSET/reSET-O usage data to help them decide whether to offer 1:1 
supervision visits with select clinicians who want additional assistance or who fail to initiate patients in 
reSET/reSET-O. 
 
 
 
Practice Facilitation (Clinician-Facing) 
Clinics randomized to receive practice facilitation will be offered 12 sessions with a trained facilitator.   
Practice Facilitation is a clinician-facing implementation strategy designed to overcome workflow 
challenges by supporting clinicians in tailoring implementation to their local context. It is both a process 
and a set of strategies designed to build relationships, identify and overcome barriers, and help the 
clinical team implement the innovation in their clinic. The first facilitation session will take place within 
the first month after randomization); all visits will be offered by video- or tele-conference.   
The facilitators will support the LICSWs in these clinics using four intervention strategies in the context 
of a supportive relationship:  
1.  Education to augment standard implementation training. The focus of education will be tailored 
to the needs identified, and may include evidence for the digital treatment, enhanced training on 
the procedures, or how to communicate with team members about this option for care. 
2. Audit and feedback strategies to prompt change in practice based on measurable performance 
goals, and clinic-specific, normed graphical reporting with actionable data and supporting text.  
The facilitator will share an anonymized report ranking each clinician's performance on reach and 
fidelity in comparison to others. 
3. Plan-Do-Study-Act (PDSA) cycles: The facilitator and LICSWs will collaboratively review audit and 
feedback data, develop an improvement plan for the LICSWs to implement, study the results, 
and adjust activities for continuous improvement. 
4. Engage others in change: The facilitator will help the LICSWs identify and engage other clinic 
stakeholders for the implementation effort, such as leaders, primary care providers, other clinic 
staff. 
 
Health Coaching (Patient-Facing) 
Health coaching is assigned at the clinic level, but the intervention is delivered directly to patients who 
are enrolled in reSET/reSET-O. The health coach will be responsible for cadenced telephone calls and/or 
Table 2. Clinical Procedures for Using reSET/reSET-O in PC 
Initiating a patient on reSET/reSET-O 
Support for use of reSET/reSET-O 
• 
Offer via shared decision making (a standard 
clinical skill) 
• 
Enter an electronic order for reSET/reSET-O in the 
EHR  
• 
Provide an enrollment code and patient 
instructions 
• 
Schedule 3 monthly visits during 12-week 
reSET/reSET-O prescription 
• 
Encourage 4 modules per week 
• 
Monitor use of reSET/reSET-O with the 
clinician dashboard  
• 
Identify barriers to using reSET/reSET-O 
• 
Review content learned  
• 
Encourage practice of skills learned 
• 
Consolidate what patients learn and 
discuss next steps 

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secure messages to reinforce use of the reSET/reSET-O, encourage skill practice, monitor reSET/reSET-O 
dashboard, conduct outreach to patients not engaging in reSET/reSET-O, and to monitor patient 
adherence to visits with LICSWs and encourage patients to see their LICSW. This role is to support 
people in their use of this digital intervention.  
Our trial will employ credentialed medical assistants (MAs) as health coaches (other trials have used a 
variety of professional roles, credentialed or not). The health coach will be trained in the use of an 
intervention manual that will act to structure and guide their patient contacts. There are two main 
sections to the health coach intervention manual; a structured breakdown of support sessions (phone 
and secure messaging) and conversation guides based on the core lesson within reSET/reSET-O a patient 
is working on.  
At the end of each support session, the manual has a stepped process for handling concerns that may 
come up during the session (safety, substance use, technical).  
The health coach will maintain contact with patients (via telephone and/or secure messaging in the 
medical record) for the length of the 12-week prescription.  
Table 3: Comparison of Standard Implementation to Health Coaching and Practice Facilitation 
Standard Implementation (all clinics) Standard Implementation plus 
Facilitation (50% of clinics)  
Standard Implementation plus 
Health Coaching (50% of clinics)
reSET/reSET-O Implementation Toolkit
• 
Pamphlet for patients 
• 
Scripting for offering the digital 
treatment 
• 
Step-by-step instructions for 
offering reSET/reSET-O 
• 
Step-by-step instructions for 
ongoing management of patients 
prescribed reSET/reSET-O 
• 
Huddle cards 
 
Training 
• 
2.5-hour LICSW training. 3 virtual 
trainings offered. Video recorded 
trainings available for those who 
missed the live trainings.  
• 
Evidence for reSET/reSET-O 
• 
Demo of reSET/reSET-O 
• 
Introduction to procedures and 
implementation toolkit for reSET 
• 
Enrollment via reSET/reSET-O 
dashboard 
Ongoing support 
• 
Performance report provided to 
LICSW leadership 
Facilitation Strategies 
1. Education: augment standard 
implementation training (evidence,
procedures for delivering the 
treatment) and how to market to 
patients and primary care team. 
2. Audit and feedback: prompts to 
change practice based on 
measurable performance goals, 
clinic-specific, normed graphical 
report with actionable data and 
supporting text. This feedback will 
be provided monthly to the LICSWs
at clinics receiving practice 
facilitation. Will provide 
opportunity for self-assessment, 
ranking individual performance 
against either aggregate 
performance at the clinic level or 
anonymously.   
3. Plan-Do-Study-Act cycles: The 
facilitator and LICSW will review 
audit and feedback data, make an 
improvement plan for the LICSW to
implement, and study the results 
Health Coaching 
• 
The health coaching is an 
augment to treatment 
provided by the LICSW. The 
goal is to encourage and 
support patient engagement
in their use of the 
reSET/reSET-O digital 
intervention (rather than to 
support them in dealing 
with their substance use). 
Structure 
• 
Health coaching is a patient-
facing centralized outreach 
service, located in and 
supervised by Mental Health
and Wellness Services  
• 
Delivered remotely (via 
telephone or secure 
messages in the Electronic 
Medical Record). 
• 
Structured (weekly or 
monthly) 
• 
Scripts and templates for 
outreach, plus “conversation

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• 
Discuss reSET/reSET-O 
implementation in staff meetings 
• 
Delivery-system leaders offer 1:1 
help to clinicians as needed 
 
Epic (Electronic Health Record) 
Integration 
• 
Electronic standing order 
• 
Templates for documentation and 
communication with patients about 
the program 
• 
Reporting Workbench: population 
management tool.  Lists all the 
patients with active reSET/reSET-O 
prescriptions.  Primarily used to 
identify and prompt outreach to 
patients due/overdue for required 
30-day SUD treatment visits.  
Performance Feedback Report 
• 
Referrals, enrollments by month 
and week 
• 
Visits by month 
• 
Patient-reported outcome data 
(baseline/most recent) 
• 
Detailed aggregate and individual 
clinician activity 
 
Basic Technical Support 
• 
As needed (passive) technical 
assistance if LICSWs request it 
• 
Patients and clinicians will have 
phone # to call Pear patient 
support center for technical 
support if needed 
  
and adjust activities for continuous 
improvement. 
4. Engage others in change: The 
facilitator will help the LICSW 
identify and engage other clinic 
stakeholders for the 
implementation effort, such as 
leaders, primary care providers, 
other clinic staff, and the health 
coach.   
 
Initial virtual visit with randomized 
clinics - Month 1 of implementation 
• 
Relationship-building 
• 
Meet with stakeholders 
• 
Education beyond initial standard 
implementation training 
• 
Needs assessment 
• 
Identify barriers/facilitators 
• 
Site-specific adaptations (post visit 
planning item, not likely to adapt at 
that 1st visit) 
• 
Introduce/discuss audit/feedback 
report 
 
Month 2-11 virtual meetings 
• 
Ongoing rapport 
• 
Feedback: review audit/feedback 
report  
• 
Identify barriers/facilitators 
• 
PDSA improvement cycles: work 
collectively with LICSWs to develop 
action plans and evaluate those plans 
• 
Enhanced technical support: Assess
for technical barriers, problem-solve 
using available resources and practice 
facilitation knowledge about 
reSET/reSET-O.  
 
guide” to support specific 
reSET/reSET-O modules. 
Health Coach activities include 
• 
Monitoring the reSET/reSET-
O dashboard and reaching 
out to patients not engaging
in reSET/reSET-O modules. 
• 
Reinforce use of the 
reSET/reSET-O digital 
intervention. 
• 
Encourage skill practice  
• 
Monitor adherence to 
required follow-up and 
encourage patients to 
follow-up with their LICSW 
as recommended.  
 
 
Combined: Practice Facilitation and Health Coaching  
Approximately 25% of Trial clinics will be randomized to receive both practice facilitation and health 
coaching. This strategy does not incorporate any unique activities, but some components of the two 
strategies may interact (e.g., the practice facilitator may involve the health coach in facilitation 
meetings). Combined clinics received components from all three columns of Table 3 above. 

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Randomization Assignment Procedures 
A factorial design (Table 4) will allow us to estimate the main effect of the implementation strategies, 
compare their effectiveness, and evaluate their interactions. Cluster randomization will be at the clinic 
level because the implementation approaches target clinics. Details about randomization (e.g., 
stratification, concealment) are contained in the trial’s Statistical Analysis Plan.   
Table 4: Random Assignment of PC Clinics to 4 Implementation Approaches (2x2 Factorial Design) 
Implementation 
Strategy 
Approach 1 
 Standard Only 
Approach 2  
Standard + Practice 
Facilitation 
Approach 3 
 Standard + Health 
Coach 
Approach 4 
Standard + 
Both 
Standard 
YES 
YES 
YES 
YES 
Practice Facilitation 
NO 
YES 
NO 
YES 
Health Coach 
NO 
NO 
YES 
YES 
 
Quantitative Evaluation: 
The Statistical Analysis Plan is available as a separate document.  
 
Formative Evaluation of Implementation 
The purpose of the formative evaluation is to monitor and assess the implementation of the reSET and 
reSET-O digital treatment for SUD in primary care clinics across Kaiser Permanente Washington. The 
formative evaluation includes qualitative assessments documented elsewhere. 
Economic Evaluation 
Aim 2 of the DIGITS Trial was to examine the population-level cost-effectiveness of each implementation 
strategy in increasing reach, fidelity, and abstinence by patients. Because of the low numbers of patients 
reached during the trial period we are instead reporting out on implementation, intervention, and 
operations costs, and we will not do a cost effectiveness analysis.  
The economic analysis will draw on several data sources: (1) KPWA’s Epic® Clarity® databases for EHR 
data, (2) KPWA’s insurance claims databases, (3) KPWA’s Cost Management Database, (4) Pear 
Therapeutics reSET databases, (5) study records of implementation activities, and (6) public use data on 
average salaries by occupation. Access to both EHR and claims databases allows us to capture 
healthcare within and outside the KPWA delivery system. EHR and claims databases log visit 
characteristics such as patient, provider type, visit type, visit department, procedures, ICD code sets, lab, 
pharmacy, enrollment, and patient sociodemographic data. The EHR databases specifically include PC 
clinic, clinician, prescriptions, and screening and assessment results. Claims databases cover contracted 
care such as emergency, hospital, and specialty addiction treatment visits. The Cost Management 
Database captures the cost of producing all services used by members incurred by KPWA. 
Implementation Costs are defined as the monetary value of time and resources needed to roll out 
reSET/reSET-O to patients. We will prospectively collect data during piloting, implementation, and 
sustainment. To derive implementation costs, we will use an activity-based approach to calculate the 
opportunity cost of time devoted to activities related to reSET/reSET-O implementation. This approach 
uses microcosting, applying unit costs to the amount of time spent by multiplying the number of hours 
devoted to activities by the estimated wage rate of a participant.   Implementation costs also include the 

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direct cost of resources to implement reSET/reSET-O (e.g., printing cost of materials to support 
adoption). We will sum costs associated with activities and resources needed to execute external 
facilitation, patient coach, and standard implementation strategies, respectively. 
Implementation activities will be collected for all participants involved in implementation including 
delivery system leaders, practice facilitators, health coaches, LICSWs and other personnel involved at 
the implementation sites. Activities by members of the delivery system will include development of 
training materials, construction of implementation toolkits, preparation of performance feedback and 
training sessions, meetings, conference calls, emails, and 1:1 supervision visits. Activities by health 
coaches will include training, providing phone calls/secure messages to patients and tracking clinician 
dashboards, conducting patient outreach, monitoring patient visits and communicating with LICSWs.  
Using previously employed methods, designated implementation staff will track the date and duration 
of each implementation activity, the mode of communication (in person, videoconference, phone), and 
names of individuals involved using structured Excel spreadsheets used in prior research.  To reduce 
documentation burden, we will create a reporting hierarchy so that only one person needs to document 
activities when multiple individuals are involved. For meetings, duration will be divided into preparation 
time, travel time, and meeting time. In addition, study staff will collect completed spreadsheets from 
delivery system leaders following bi-weekly operations meetings and reviewing research specialist notes 
of organized activities (e.g., initial training).  
To estimate time needed for LICSWs to conduct implementation activities outside of meetings (e.g. 
implementation toolkit use, interpreting performance reports), LICSWs across the KPWA system will be 
randomized to discrete data collection periods. Specifically, we will survey LICSWs throughout the 
implementation phase by contacting each LICSW during a random week in the study for a short email-
survey followed by a Teams message when necessary to reduce non-response.   
To monetize time on implementation activities, we will multiply hours of participation by opportunity 
cost of time, measured as participant’s estimate hourly wage rates. We will inflation-adjust all costs to 
2020 constant dollars using the Personal Health Care Index. To calculate hourly wages for all 
participating staff, we will use aggregate data from the Bureau of Labor Statistics on average wages by 
area and occupation. In addition to the time spent traveling, we will include direct costs of travel for 
implementation activities.  
Implementation costs will also include the direct costs of materials and resources required to support 
implementation of reSET/reSET-O. Examples include the printing cost of patient pamphlets, guides and 
training materials. These direct costs will be ascertained from study budget records.  
Operating Costs. Operating costs are dollars spent on regular operation of reSET/reSET-O incurred by 
the delivery system and patients. Costs include infrastructure/technical resources and staff support such 
as IT support, reSET/reSET-O fees, and capital equipment. 
Direct Intervention Costs. Patient receipt of reSET/reSET-O is expected to affect clinical service costs. 
Intervention costs include encounters with LICSWs related to the initiation and continued use of 
reSET/reSET-O. We will identify patient visits with LICSWs during the 12-week reSET/reSET-O 
prescription period, using EHR data. We will count encounters on the day of and in 12-weeks after the 
reSET-specific “after-visit-summary” is entered.  

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Using patient-level encounter records, we will use a KPWA internal cost model that measures actual 
production costs incurred by KPWA in providing care to members. KPWA’s automated information 
systems capture all services used by members within its integrated practice and contract providers for 
whom claims are submitted. To determine and allocate costs, KPWA’s Decision Information Support 
Center (DISC) has a model that captures and allocates utilization and costs from the health plan’s 
general ledger for all services. DISC enables standardization of costing data across KPWA and allows for 
determination of costs for specific encounters and aggregation of costs for individuals over time. All 
encounter-level costs are identified as a direct care cost (e.g., nurse salaries) or an overhead cost (e.g. 
facilities). Costs excluded from allocation include those not directly related to delivering health services 
(e.g., insurance) and patient out-of-pocket costs. Cost data are available to researchers through KPWA 
Cost Management Database and have been used previously. Other Indirect Health Care Costs. We will 
measure potential change in indirect health care costs attributable to reSET/reSET-O by defining total 
health care costs at the patient level as the sum of costs for all outpatient encounters (including PC, 
specialty mental health, specialty medical, ancillary) and dispensed medications expected in this 
population. We will calculate a patient-level measure of SUD-specific costs (screening, assessment, brief 
interventions, visits with a SUD diagnosis, SUD medications). We will measure costs of care delivered by 
KPWA, contracted care, and out-of-network providers recorded in insurance claims data. 
Limitations and Strengths 
We considered providing smartphones with data plans to ensure that all patients could benefit from the 
intervention even if they did not own a smartphone (77% of US adults own a smartphone—most but not 
all). But this would significantly increase costs and therefore could limit adoption and sustainability, as 
seen in a previous study,[4] and could limit generalizability. Our secondary abstinence outcome will be 
available only for some patients, because our measures come from EHR data. This is because we based 
the trial on pragmatic principles which offer an efficient design and avoids a biased sample limited to 
patients who consent to research.[5] We also considered conducting this study in another health 
system, but strengths of this system are that we have high universal screening rates for alcohol and 
drugs (most systems have alcohol only), and we can also capture patient data from inside and outside 
the delivery system (EHR and claims). This provides a natural laboratory to study the implementation of 
a digital SUD treatment. 
Safety Parameters 
IRB Monitoring 
The KPWA IRB reviewed and approved all research activities before the beginning of Active 
Implementation. The IRB will maintain ongoing oversight of the risks and benefits of the study, including 
annual review of the study and prior review and approval of any changes to the study protocol and 
materials. 
Data and Safety Monitoring 
Refer to separate DSMP file dated 08/30/2021  
Adverse Event (AE) and Serious Adverse Events (SAE) and Reporting 
Refer to IRB files: 1556080, 1743121 and 1794767 for information about how these events will be 
recorded and reported.  
Unanticipated Problems and Reporting 

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Refer to IRB files: 1556080, 1743121 and 1794767 for information about how these events will be 
recorded and reported. 
Ethics and Protection of Human Subjects 
Refer to IRB files: 1556080, 1743121 and 1794767 for information about ethics and protection of human 
subjects.  
Potential Risks and Benefits 
Refer to IRB files: 1556080, 1743121 and 1794767 for information about potential risks and benefits.  
Inclusion of Populations 
Refer to PHS Human Subjects and Clinical Trials Information sections of grant application. 
Protocol Violations and Deviations 
Refer to IRB files: 1556080, 1743121 and 1794767 for information about how protocol violations and 
deviations will be recorded.  
IRBNet ID 
Title 
1556080 
 
DIGITS Secondary Data Analysis 
1743121 
 
DIGITS Primary Data Collection for Economic Analysis of Implementation 
Strategies and Time 
1794767 
DIGITS Trial Implementation 
 
Overview of Main Protocol Changes 
 
 
 
Topic 
Date 
Details of Change 
Changes to 
provision of 
reSET/O 
4/28/2022 
Non-social work clinicians began offering reSET and reSET-O. 
Changes to 
provision of 
reSET/O 
7/1/2022 
Began allowing reSET and reSET-O prescriptions without requiring 
follow-up visits. 
Changes to 
provision of 
reSET/O 
8/9/2022 
Centralized the administrative tasks of prescribing reSET/reSET-O 
by allowing clinicians to hand-off the responsibility of creating 
patient accounts to an administrator. 
Economic 
analysis 
plans 
February 
2023 
Removed plans for population level cost effectiveness analysis due 
to the low number of patients reached during the Trial period. 
Early end to 
sustainment 
phase 
4/7/2023 
Removed plans for analysis of sustainment phase. Due to the 
bankruptcy of Pear Therapeutics, sustainment ended early, and we 
could not study this phase. 

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Key Roles and Contact Information 
Study Team: 
Refer to Team Directory located in the KPWHRI G drive: G:\CTRHS\DIGITS\ADMIN\DIGITS Team 
Directory 
Steering Committee: 
Refer to Steering Committee tab in Team Directory located in the KPWHRI G drive: 
G:\CTRHS\DIGITS\ADMIN\DIGITS Team Directory 
 
Appendix A:  
DIGITS Data Safety Monitory Plan is available as a separate file in the KPWHRI study G drive Protocol 
folder. (DIGITS_DSMP_2021-08-30) 
Appendix B:  
DIGITS Trial Formative Evaluation Plan is available as a separate file in the KPWHRI study G drive 
Protocol folder. (Formative evaluation plan_5.23.2022) 
 
References 
1. 
Fortney JC, Pyne JM, Burgess JF, Jr. Population-level cost-effectiveness of implementing 
evidence-based practices into routine care. Health Serv Res. 2014 Dec;49(6):1832-51. PMID: 25328029. 
doi: 10.1111/1475-6773.12247. 
2. 
Liu CF, Rubenstein LV, Kirchner JE, Fortney JC, Perkins MW, Ober SK, et al. Organizational cost of 
quality improvement for depression care. Health Serv Res. 2009 Feb;44(1):225-44. PMID: 19146566. doi: 
10.1111/j.1475-6773.2008.00911.x. 
3. 
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