A Policy Relevant US Trauma Care System Pragmatic Trial for PTSD and Comorbidity
Phase: NA
Conditions: Posttraumatic Stress Disorder, Depression, Alcohol-Related Disorders, Suicidal Ideation, Substance-Related Disorders, Mild Cognitive Impairment, Quality of Life, Pain, Wounds and Injury, Brain Injuries, Chronic Disease
Sponsor: University of Washington

A Policy Relevant US Trauma Care System 
Pragmatic Trial for PTSD and Comorbidity (TSOS6) 
Study Protocol 
NCT02655354
Document Date: October 17, 2018
Douglas Zatzick, MD: Principal Investigator 

1 
1. Overview and Aims
The overarching goal of this UH2-UH3 proposal is to work with the NIH Health Care Systems Research 
Collaboratory to develop and implement a large scale, cluster randomized pragmatic clinical trial demonstration 
project that directly informs national trauma care system policy targeting injured patients with presentations of 
Posttraumatic Stress Disorder (PTSD) and related comorbidity. Each year in the United States (US), over 30 
million individuals present to trauma centers, emergency departments, and other acute care medical settings 
for the treatment of physical injuries. Multiple chronic conditions including enduring PTSD, depression and 
associated suicidal ideation, alcohol and drug use problems, pain and somatic symptom amplification, and 
chronic medical conditions (e.g., hypertension, coronary artery disease, diabetes, and pulmonary diseases) are 
endemic among physical trauma survivors with and without traumatic brain injuries (TBI). Evidence-based, 
collaborative care/care management treatment models for PTSD and related comorbidities exist. These care 
management models have the potential to be flexibly implemented in order to prevent the development of 
chronic PTSD and depressive symptoms, alcohol use problems, and enduring physical disability in survivors of 
both TBI and non-TBI injuries; care management models may also be effective in mitigating the impact of the 
acute injury event on symptom exacerbations in the large subpopulation of injury survivors who already carry a 
substantial pre-injury burden of multiple chronic medical conditions. 
Effective collaborative care/care management treatment models however, have yet to be broadly 
implemented throughout US Trauma Care Systems; prior investigation by members of the interdisciplinary 
study team suggest that less than 10% of US trauma centers routinely provide post-injury screening or 
integrated care management treatment targeting the chronic disease cluster of PTSD and related 
comorbidities. Injured patients presenting to trauma care systems are often from low income, ethnoculturally 
diverse backgrounds. These “safety net” patient populations face major challenges in care coordination from 
trauma care systems to primary care and community services. The enduring challenges presented by the 
chronic disease cluster of PTSD and comorbidities after injury require innovative research approaches that cut 
across the traditional domains of multiple NIH institutes. 
The primary aim of the UH3 period, years 2-5 of the project, is to conduct a pragmatic randomized 
effectiveness trial of a collaborative care intervention targeting PTSD and comorbid conditions after acute care 
injury hospitalization. The investigation aims to determine if injured patients receiving the collaborative care 
intervention demonstrate significant reductions in PTSD symptoms when compared to control patients 
receiving care as usual. The study also aims to determine if the intervention patients when compared to control 
patients will demonstrate significant reductions in depressive symptoms and alcohol use problems, and 
improvements in physical function. An exploratory aim of the investigation is to assess whether the intervention 
is effective in injury survivors with and without pre-existing chronic medical conditions and with and without 
TBI. Exploratory analyses will also assess whether the intervention successfully reduced enduring symptom 
development for other co-morbid presentations (e.g., suicidal ideation, physical pain, drug use problems). 
A second aim of the UH3 project is to understand the processes of pragmatic trial implementation. The 
study team will use the RE-AIM model to comprehensively assess factors related to intervention reach, 
effectiveness, adoption, implementation, and maintenance. An exploratory assessment of the impact of the 
intervention on post-injury health service utilization and costs will also be conducted. The RE-AIM and health 
economic analyses aim to further understand trial implementation experiences, in order to elucidate barriers to 
and facilitators of sustainable screening and intervention procedures for PTSD and comorbidities across US 
trauma care systems.  
A final project dissemination aim is to conduct a policy summit with the key study stakeholder, the 
American College of Surgeons in UH3 year 5. The policy summit targets the broader goal of further engaging 
trauma centers in the research process by integrating pragmatic trial results into mandates and clinical practice 
guidelines for screening and intervention for PTSD and related comorbidities across trauma care systems 
nationwide. 

2 
 
2. Significance 
 
A. Physical injury trauma occurs frequently in the US and constitutes both a substantial source of 
individual suffering and a significant public health burden.1-5 Each year in the US, over 30 million 
individuals present to acute care medical trauma center and emergency department settings for the treatment 
of traumatic physical injury.1-5 Injured trauma survivors present to acute care medical settings after both 
intentional (e.g., gunshots, stabbings, physical assaults) and unintentional (natural disasters, motor vehicle 
crashes) injury events.6 Annually 1.5-2.5 million Americans are so severely injured that they require inpatient 
hospitalization.1-5 Estimates suggest that approximately 1.5 million American youth and adults experience 
traumatic brain injury (TBI) annually.7,8 Physical injury with and without TBI, constitutes a major public health 
problem for both civilian and veteran trauma-exposed patient populations.9,10 Traumatic injury is a leading 
cause of death for individuals under the age of 45 and accounts for 12% of medical expenditures in the US.1-3,5 
In one nationwide US study, over 40% of injured trauma survivors reported they were unable to return to work 
12 months after their hospital admission.11 Globally, traumatic injury accounts for approximately 16% of the 
world’s burden of disease.12-14 
Multiple chronic conditions including PTSD and pre-existing medical co-morbidities (e.g., 
hypertension (HTN), coronary artery disease (CAD), diabetes, and pulmonary disease) are endemic in 
populations of injured trauma survivors.15-24 Recent commentary has defined chronic conditions as 
“conditions that last one year or more and require ongoing medical attention and/or limit activities of daily 
living”.25-27 Prior investigation suggests that complex comorbid conditions meeting these definitional criteria are 
endemic among injured patient populations treated at US trauma centers and their affiliated trauma care 
systems.21,28,29 Highly prevalent comorbidities include PTSD, depression and associated suicidal ideation, 
alcohol and drug use problems, enduring physical pain and somatic symptom amplification, and chronic 
medical conditions such as HTN, CAD, diabetes, and pulmonary disease.17,28,30 Initial studies suggest that 
enduring personality disturbances may also occur in some sub-populations of injured trauma survivors.31 
A series of US prospective cohort investigations suggest that between 20-40% of physically 
injured trauma survivors may go on to develop symptoms consistent with chronic PTSD after 
hospitalization for injury.21,32-36 Chronic PTSD symptoms develop between 3-12 months after exposure to a 
traumatic injury event. A recent Institute of Medicine Report articulates that a majority of individuals presenting 
with PTSD have one or more comorbid conditions.37 In injury survivors, chronic PTSD often occurs in 
conjunction with comorbid depressive symptoms.21,32-34,36,38-42  
PTSD and related comorbidity including depression, pain and somatic symptom amplification 
occur as a “cluster” among patients with TBI and non-TBI related injury.41,43-45 The constellation of 
enduring PTSD, depression, suicidal ideation, somatic symptom amplification post-injury pain, and TBI share 
common presentations and symptom overlap; prior study suggests that broad spectrum medication and 
psychotherapeutic treatments can target this constellation of chronic conditions and symptoms.45-51    
 
After injury, chronic PTSD and depression lasting 12 months or more are associated with a 
broad profile of functional impairments and costs, including diminished physical function and inability 
to return to work.34,35,52-54 In both TBI and non-TBI patient populations, PTSD and depression independently 
account for post-injury functional impairments.43,44 In one nationwide 69-site trauma center investigation, PTSD 
and depression made an independent “dose” related contribution to the inability to return to work after injury 
hospitalization;55 PTSD and comorbidity are associated with increased health care and societal costs.56-60 
 
Alcohol use problems and other high risk behaviors are also endemic among injured trauma 
survivors.6,17,61 In one study of 1118 consecutively admitted injured trauma survivors, the lifetime prevalence 
of alcohol abuse/dependence was 37% and 24% had a diagnosable alcohol abuse or dependence at the time 
of injury admission.17 Alcohol use problems in injured trauma survivors are associated with the occurrence of 
chronic recurrent traumatic life events.18,61 Multiple prior reports suggest that drug use problems may also be 
endemic among injured trauma survivors.17,30  
 
Pre-existing chronic medical conditions also occur frequently among injured trauma survivors. 
In a national US study of approximately 3000 injured trauma survivors admitted to 69 hospitals, approximately 
35% of injury survivors had one or more chronic medical conditions including HTN (20.4%), CAD (11.8%), and 
diabetes (7.4%).21,28,29 In a recent investigation by the study team that utilized automated electronic health 
record (EHR) International Classification of Diseases, 9th Revision, Clinical Modification (ICD)  code screening 
to recruit patients, approximately two thirds of patients had one or more chronic medical conditions including 

3 
 
HTN (36%), CAD (38%), diabetes (20%), pulmonary (17%), or other medical diagnoses (e.g., renal disease, 
liver disease, HIV, 21%).29 Table 1 below delineates medical and chronic condition comorbidity rates in the 
study team’s prior investigations. 
 
   
B. Nationwide trauma care systems provide care for injured patients.1,62-64 The nation’s trauma care 
system is the service delivery sector in which injury victims receive their treatment. A trauma care system is an 
organized and coordinated effort in a defined geographic area that is designated to deliver the full spectrum of 
care to populations of injured trauma survivors. This care begins immediately after the injury and includes 
inpatient trauma center surgical hospitalization. 
 
Injured patients presenting to US trauma care systems are often from low-income diverse 
backgrounds and include a substantial proportion of uninsured/under-insured and dual 
Medicaid/Medicare recipients.21,65-71 Prior investigation suggests that a substantive majority of injured 
patients in trauma care systems receive insurance coverage either through public funding sources (e.g., 
Medicare, Medicaid) or are uninsured; the proportion of uninsured may continue to be high in states that have 
elected not to expand their Medicaid programs as part of health care reform.11,21,28,62,72 
 
Patients treated in trauma care systems often receive fragmented care that is not coordinated 
from emergency department and trauma centers to primary care and community settings.73,74 Recent 
commentary has suggested the extension of trauma care to include primary care and community linkages.63,75 
Quality of care improvements in trauma care systems could address issues of care coordination across acute 
care hospitalization, and primary care and community services.73,74,76-82 In particular, low-income, diverse 
“safety net” patient populations face major challenges in care coordination across trauma care system and 
primary care service delivery sectors.71 
 
Early intervention models that bridge supportive care and evidence-based treatment delivery 
are crucial elements in the prevention of chronic PTSD and related comorbidity.83-89 Epidemiologic data 
suggests that it may take years for trauma-exposed individuals with PTSD to enter treatment.90 Intervention 
models that serve to link acutely exposed individuals to evidence-based PTSD treatment services remain to be 
widely implemented and represent a crucial next step in the prevention of PTSD and the mitigation of 
symptoms for pre-injury medical comorbidity.25,83,84,86-88,91-94 
 
Currently, few patients treated in trauma care systems receive evaluations or evidence-based 
treatment for PTSD and related comorbidity.  Prior investigation by members of the interdisciplinary study 
Table 1. Characteristics of Patients with Multiple Chronic Conditions in Prior Studies 
 
 
Characteristic 
69 Site 
Cohort Study 
(N=2931) 
20 Site 
Alcohol R01 
RCT (N=878) 
Single Site  
PTSD R01 
RCT (N=207) 
 
Single Site PTSD IT 
Pilot (N=121) 
Mean (SD) of Chronic Conditions 
1.4 (2.0) 
2.0 (1.2) 
2.4 (1.8) 
3.8 (2.2) 
≥ 3 Multiple Chronic Conditions % 
12.9% (605) 
25.2% (221) 
44.0% (91) 
62.8% (76) 
Chronic Condition Breakdown % 
 
 
 
 
 - Chronic PTSD Symptoms % 
21.8% (602) 
14.1% (124) 
39.0% (60) 
43.8% (53) 
 - Chronic Depressive Symptoms % 
6.7% (175) 
14.7% (92) 
31.8% (49) 
41.3% (50) 
 - Chronic Alcohol Use Problems % 
17.1% (797) 
68.5% (600) 
52.7% (109) 
57.0% (69) 
 - Chronic Drug Use Problems % 
3.2% (146) 
37.0% (320) 
28.5% (59) 
28.1% (34) 
 - Traumatic Brain Injury % 
46.3% (2643) 
50.2% (441) 
38.2% (79) 
35.5% (43) 
 - ≥1 Chronic Medical Disorders % 
33.7% (2039) 
21.4% (137)  
41.1% (85) 
64.5% (78) 
   1) Hypertension (HTN) 
16.5% (984) 
12.0% (77) 
18.4% (38) 
35.5% (43) 
   2) Coronary Artery Disease  
       (CAD) 
11.8% (876) 
1.9% (12) 
16.9% (35) 
38.0% (46) 
   3) Diabetes 
7.4% (438) 
3.6% (23) 
3.9% (8) 
19.8% (24) 
   4) Pulmonary (Asthma, COPD) 
6.9% (379) 
7.3% (47) 
15.0% (31) 
17.4% (21) 
   5) Other Disorders (e.g., Renal,  
       HIV) 
6.1% (405) 
3.0% (19) 
12.6% (26) 
 20.7% (25) 
Insurance Status % 
 
 
 
 
 - Public (e.g., Medicaid, Medicare) 
20.9% (1252) 
22.5% (198) 
53.6% (111) 
62.8% (76) 
 - Uninsured 
28.2% (1130) 
26.9% (236) 
21.7% (45) 
15.7% (19) 
 - Private 
50.9% (2661) 
28.9% (254) 
24.6% (51) 
21.5% (26) 

4 
 
team suggest that less than 10% of US trauma centers routinely provide early post-trauma screening and 
intervention services for PTSD.95 
 
Health care reform including the introduction of accountable care organizations and the patient-
centered medical home present a series of potential opportunities for the incorporation of novel 
intervention strategies targeting injured patients with multiple chronic conditions who require hospital 
to primary care and community care transitions.96-102 Trauma care systems are currently grappling with the 
advent of health care reform.100,101,103-105 While much dialogue has occurred, few evidence-based intervention 
models have been widely implemented for injured patients with comorbid conditions including physical injury, 
mental health disorders and substance use problems, as well as pre-injury chronic medical conditions.50,51 The 
establishment of systematic trauma center to primary care and community linkages could potentially impact 
unplanned, costly, emergency department and trauma center readmissions.97,99,103-105   
 
The American College of Surgeons oversees the development of national policy mandates and 
clinical best practice guidelines that inform the integrated operation of US trauma centers and affiliated 
trauma care systems.63 The College has successfully linked trauma center funding to verification site visits 
and other quality indicators.63,106,107  
 
C. Trauma care systems constitute high volume integrated health care systems that are increasingly 
supported by sophisticated EHRs. Recent investigation by members of the interdisciplinary study team 
document that trauma care systems are increasingly integrating advanced EHR systems.108 The investigative 
team is aware that an overarching goal of the NIH Collaboratory is to integrate all aspects of the research 
including screening, enrollment, treatment assignment and monitoring of outcomes into routine practice 
workflows and data capture mechanisms.109 Although potential exists, currently most trauma care systems do 
not utilize information technology (IT) innovations to support real-time, workflow integrated, automated data 
screening, intervention, and quality documentation procedures.108 
EHR/
Institutional 
Databases
Diagnosis Codes
Utilization Data
Text Narrative
1) Institutional EMR & Administrative
Databases – Real-time Extract
2) Computerized Decision Support for PTSD & Cormobidity:
Workflow-integrated Screening & Intervention
3) Standardized Quality, Outcomes, 
& Research Outputs
Data
Extraction & Translation
Document Creation, Data Mapping,
Export of De-Identified Data
Inpatient
Admission
Quality, Outcomes, Research 
Data
Supervised Screening & 
Intervention
Data Standardization & 
Workflow Automation
Computerized
Decision
Support
Tool
Comprehensive Data
Capture & Organization
Figure 1. Comprehensive Trauma Center Screening, Intervention & Quality Documentation for PTSD & Comorbidity
American 
College of 
Surgeons’
Committee 
on Trauma
 
 
Members of the study team are implementing a series of IT care enhancements for patients 
treated in trauma care systems (Figure 1).110-113 These innovations include: 1) automated population-based 
EHR screening procedures for PTSD and comorbidity, 2) trauma center-based computerized decision support 
tools that facilitate the delivery of care management interventions, and 3) methods for documentation of high 
quality screening and intervention procedures.29,49 The investigative group is experienced in creating EHR-
linked screening tools that use generalized business-rules logic engines, both in locally constructed EHR 
systems and in nationally adopted EHR systems.108,110-113 Applying these principles, study team members have 
developed a PTSD risk prediction algorithm that uses 10 EHR domains to identify patients at high risk for 
PTSD.21,36,49,114-122 Novel applications developed by Dr. Van Eaton and colleagues also include a computerized 
decision support tool that targets study team care management of surgical, medical, mental health and 
substance related comorbidities.29,113 In addition, members of the study team are participating in American 
College of Surgeons’ policy workgroups that establish policy for US trauma care systems quality 
documentation. Finally, in the UH2 start-up phase of the protocol, study team collaborators, including Dr. Van 
Eaton, have developed and piloted an open-source method for automated de-identification and mapping of 
patient data to the National Trauma Data Bank (Appendix 9).123 The National Trauma Data Bank provides de-
identified data for nationwide trauma care systems quality benchmarking. An overarching goal of the study 
team is to work with the NIH Collaboratory and the American College of Surgeons’ to refine this constellation of 
IT innovations in order to develop real-time, workflow integrated, automated screening, intervention, and 

5 
 
quality documentation procedures for PTSD and related comorbidities that can be deployed across trauma 
care systems nationally (Figure 1).  
 
D. Collaborative care/care management treatment models that combine effective intervention elements 
and incorporate IT innovations have the potential to enhance the prevention and management of 
multiple chronic conditions; these models have the capacity to maximize flexibility and integration of 
approaches to addressing the chronic disease cluster of PTSD and comorbidity after injury (Table 2 
and Figure 2).124,125 Derived from the chronic care mode, collaborative care/care management interventions 
hold promise for the integration of treatment for patients with multiple chronic conditions within trauma care 
systems.51,126-129 A large body of research now has established the effectiveness of integrated care delivery 
models such as “collaborative care” in reducing depressive, anxiety, pain and other somatic symptom 
presentations in conjunction with comorbid medical conditions in primary care settings.51,128-145 Collaborative 
care treatments bring together efficacious medication and psychotherapeutic intervention elements with care 
management strategies that target reductions in care fragmentation and enhanced care coordination for 
patients with multiple chronic conditions (Table 2). The novel application of collaborative care models for injury 
survivors at risk for PTSD and comorbidity has the potential to address myriad aspects of the “Multiple Chronic 
Conditions Strategic Framework” (Table 2).25,91,92  
 
Medication coordination and reconciliation can improve care transitions for patients with 
chronic medical conditions.146-149 Previous investigation has documented high rates of errors in chronic 
condition pharmacotherapy during acute care to primary care and community care transitions. Interventions 
targeting care transition pharmacotherapy for patients with chronic medical conditions have been developed; 
these interventions include care management care coordination, obtaining accurate inpatient medication 
histories, reconciliation of medication discrepancies and careful and ongoing medication coordination with 
primary care and other community providers.146-149  
 
Medication interventions are effective in the management of PTSD and comorbidities.48,150-162 
The Selective Serotonin Reuptake Inhibitor (SSRI) class of medications is efficacious in the treatment of PTSD 
and depression.153,154,163-165 Medication treatment targeting trauma-related insomnia may be effective in 
reducing global PTSD symptoms and associated somatic symptom presentations.51,128,145,159-161,166,167 Clinical 
practice guidelines based on these research studies have been formulated.89,150-152,168 
 
Table 2. Core Elements of Intervention Targeting Multiple Chronic Conditions (MCC) After Injury 91 
Essential Element 
Which of multiple (≥ 3) MCC Targeted 
MCC strategic framework goals addressed* 
Population-based EHR 
PTSD & comorbidity risk 
prediction 
PTSD, depression, alcohol & drug use 
problems, pain and somatic symptoms, & 
chronic medical conditions after acute injury 
Goal 1 Objective D, Implement and efficiently use 
health information technology; Automated 
screening efficiently identifies constellation of PTSD 
and comorbidity in injured populations 
Care management with 
trauma center to primary 
care linkage 
Coordination of acute injury mental health and 
pre-existing chronic medical condition care 
Goal 2 Facilitate use of community based services 
and self-care management 
Early post-injury medication 
history, reconciliation, and 
care coordination 
PTSD, depression, pain, somatic symptom 
amplification & TBI symptoms prevention. 
Chronic medical condition (e.g. HTN, CAD, 
Diabetes) reconciliation and coordination 
Goal 1 Objective E Prevent occurrence of new 
chronic conditions and mitigate the consequences 
of existing conditions & Goal 2 Objective C, 
Provide tools for medication management 
Evidence-based MI 
embedded within care 
management   
Targets alcohol and drug use problems and 
enhanced patient engagement 
Goal 1 Objective E Prevent occurrence of new 
chronic conditions and mitigate the consequences 
of existing conditions 
Evidence-based CBT 
embedded within care 
management  
Targets PTSD, depression, pain, somatic 
symptom amplification and TBI sequelae. Also 
targets enhanced patient self-efficacy 
Goal 1 Objective E Prevent occurrence of new 
chronic conditions and mitigate the consequences 
of existing conditions, & Goal 2 Objective A 
Facilitate self-care management 
Patient and caregiver-
centered posttraumatic 
concern elicitation and 
improvement 
Patient-centered concerns elicitation and 
improvement targets patient and family 
engagement in care of full MCC constellation 
Goal 2 Optimize self-care management and 
coordinated use of services by patient and 
caregivers 
Caseload supervision & 
stepped measurement-
based care implementation 
PTSD, depression & associated suicidal 
ideation, alcohol & drug use problems, chronic 
medical conditions & acute physical injury 
Goal 3 Provide better information and education 
on treatment of MCCs to health-care workers 
* All study elements address MCC Goal 4 of Enhancing Research Knowledge on MCCs 

6 
 
 
 
Flexibly delivered Cognitive Behavioral Therapy (CBT) interventions have been used to 
successfully target PTSD.24,136,169-171 A series of investigations have described the feasibility, acceptability, 
and effectiveness of telephone and care management based CBT intervention strategies targeting PTSD and 
depression; these interventions can also enhance chronic disease management self-efficacy.129,170,172,173  
 
A body of evidence supports the effectiveness of brief Motivational Interviewing (MI) 
interventions targeting alcohol use problems.18,129,174-183 A series of randomized clinical trials (RCTs) 
support MI as an evidence-based treatment for alcohol use problems in the acute care inpatient setting.18,129,175-
179 
 
Recent investigations document the effectiveness of stepped care management treatment 
models targeting PTSD and related comorbidities for injured patients treated within trauma care 
systems (Figure 2). Two recent trials have demonstrated the effectiveness of care management models 
targeting PTSD and related comorbidity.129,172 The collaborative care treatment models begin with population-
based PTSD screening.129,172 Next, care managers elicit patient and family member post-injury concerns and 
target these concerns for amelioration. Early supervised psychopharmacologic intervention elements including 
SSRI antidepressants and other related agents target the constellation of overlapping PTSD, depressive, 
somatic and TBI symptom presentations.29,50,51 Prior investigation demonstrates enhanced post-injury quality of 
care for multiple chronic conditions as documented by increased rates of primary care linkage and adherence 
to pharmacotherapy regimes.51,172 Simultaneously, care managers deliver evidence-based MI and CBT 
elements during routine post-injury patient encounters in trauma wards and emergency departments, in 
outpatient clinics, in community settings, and over the telephone. Finally, care managers work to link injured 
patients’ care from inpatient and emergency department settings to primary care and community services. 
 
These collaborative care models show promise both in preventing the development of chronic 
PTSD symptoms and associated enduring disability after acute injury episodes, and in mitigating the 
impact of the injury event in the large subpopulation of injury survivors who already carry a substantial 
pre-injury burden of ≥ 3 chronic medical, mental health, and substance related conditions. In the 
proposed pragmatic trial, early CBT and pharmacological interventions target high early acute symptoms of 
PTSD and other mental health, substance related comorbidity and chronic medical condition exacerbation. 
Early medication history and reconciliation can comprehensively address the need to continue/restart 
medications targeting pre-existing chronic medical conditions. Sustained pharmacotherapy intervention and 
treatment linkage target more chronic presentations of PTSD and comorbidity while simultaneously bolstering 
early treatment gains. 
 
CARE MANAGEMENT INTERVENTION FOR PTSD & COMORBIDITY
I) Screening for PTSD and 
Comorbidity
II) Care-Management for PTSD and Comorbidity
A) Posttraumatic Concern Elicitation & Improvement
B) CBT Elements Targeting PTSD & Comorbidity
C) Motivational Interview Targeting Risk Behaviors
III) Medication Consultation
IV) Trauma Center Linkage
A) Primary Care
B) Community Services
Traumatic Event:
Inpatient Surgical Hospitalization
Outpatient Surgical Clinics
Primary Care/Community Services
Improved 
Outcomes
1. Patient 
2. Provider
3. Organization
IT Innovation: I) EHR Screening
II) Computerized Decision Support & Supervision
III) National Trauma Data Harmonization
Figure 2. Essential Elements of Trauma Center Screening & Intervention Targeting PTSD & Comorbidity
 
E. Conceptual framework informing pragmatic trial design and implementation.  
Overview. By necessity, multiple theoretical and applied perspectives inform the conceptual framework 
underlying the Trauma Survivors Outcomes and Support (TSOS) study design and implementation. The 
conceptual framework for implementation incorporates collaborative care intervention models targeting the 
PTSD and comorbidity cluster that includes PTSD, depression and associated suicidal ideation, alcohol and 
drug use problems, enduring physical pain and somatic symptom amplification, and chronic medical conditions 
in patients with TBI and non-TBI related injury. The conceptual framework also must incorporate key features 
of pragmatic trial design and implementation captured in the pragmatic-explanatory continuum indicator 
summary or PRECIS model.184 
The PRECIS model and the TSOS trial.184 Gold standards for pragmatic trial design and 
implementation include broad participant eligibility criteria, flexible intervention delivery, application by the full 

7 
 
range of practitioners, and incorporation of rigorous prospective controls, preferably by randomization. Usual 
practice comparison conditions are frequently used in pragmatic trials.184-189 The optimal pragmatic trial is 
characterized by an intent-to-treat data analytic approach that includes all patients regardless of adherence.184 
The TSOS trial encompasses these pragmatic trial attributes by fielding a readily implementable collaborative 
care intervention that targets injured patients with the full spectrum of PTSD and related comorbidity with 
minimal exclusionary criteria.  
 
Pragmatic trial outcomes are often centrally measured, clinically meaningful, and require minimal 
adjudication.184-189 With regard to pragmatic trials in US trauma care systems no one or even multiple 
administrative databases can be used to track outcomes among injured trauma survivors; thus for trauma care 
system pragmatic trials, outcome assessments may by necessity occur as an addition to naturalistic follow-up. 
The PRECIS framework suggests that for some trials, outcome assessments must by necessity be obtained 
through contact with participants.184 Similarly the PRECIS framework takes into consideration the observation 
that in some trials that rely heavily on patient reported outcomes, some training in the assessment and 
adjudication may be desirable.184 
 
The “Robust, Sustainable, Rapid Pragmatic Trials Framework,” that includes the RE-AIM model 
as a central component, is a conceptual framework that can guide the synergistic work of the TSOS 
study team and NIH Health Care Systems Research Collaboratory in the implementation of the UH3 
trial (Figure 3).185,190 This framework outlines a series of pragmatic trial approaches including the reach, 
effectiveness, adoption, implementation and maintenance model as a systematic method for understanding the 
processes of pragmatic trial implementation. To enhance trial impact, the Robust, Sustainable, Pragmatic 
Trials Framework encourages trial policy relevance and the collection of policy relevant cost-effectiveness 
data. The use of mixed quantitative and qualitative methods that comprehensively assess the potential for 
pragmatic trial/health care system sustainability are also encouraged. Deriving from this framework, the TSOS 
study pragmatic cluster randomized trial may be best characterized as an hybrid effectiveness-implementation 
RCT.29,50,51,191 The TSOS trial simultaneously aims to determine the effectiveness of the stepped collaborative 
care intervention model while also assessing the potential utility of the implementation strategy for trauma care 
systems nationally.185,190 
 
Core Elements of Evidence-Based 
Program
Targeting PTSD & Comorbidity After Injury
1) PTSD & comorbidity screening
2) Care management
a) Posttraumatic concerns
b) CBT & MI elements
3) Medication consultation targets PTSD & 
medical comorbidity
4) Trauma center to primary care linkage
Interdisciplinary TSOS Study Team Working 
Synergistically With 
NIH HCS Research Collaboratory 
1) Biostatistical & IT/EHR methods development
2) RE-AIM process evaluation
3) Study team-Collaboratory Cores ongoing 
dialogues
Policy Relevant Large Scale 
Randomized Multisite Pragmatic 
Trial Targeting PTSD & 
Comorbidity
American College of Surgeons’ Policy for 
US Trauma Care Systems
1) Population of US Level I trauma centers
2) 24 trauma centers optimally engaged in trial 
3) Potential for policy targeting integration of 
real-time screening and intervention for 
PTSD & comorbidity nationally
Design 
Appropriate 
For Question
Stakeholder Partnership
Fit
Figure 3. Integration of Large-Scale Pragmatic Trials, Robust Implementation, & Policy Relevance 
Conceptual Frameworks for Trauma Care Systems
 
 
F. A series of innovative methodological approaches are suggested by the combined application of the 
PRECIS and RE-AIM frameworks in a single pragmatic trial demonstration project targeting PTSD and 
related comorbid conditions (Figure 3). RE-AIM provides additional pragmatic domains that corroborate and 

8 
 
enhance the PRECIS framework.192,193 The RE-AIM framework provides a model for the integration of 
pragmatic trial results into routine trauma center practice.190 RE-AIM pragmatic trial criteria include: can the 
program reach those most often in need and most often left out of health care systems interventions? RE-AIM 
adoption criteria ask the question: can the intervention program be adopted by low-resource settings and by 
front-line staff serving high risk populations? RE-AIM maintenance criteria include the question: can the 
settings sustain the program over time without added resources and leadership? By targeting low income, 
ethnoculturally diverse injured trauma survivors treated in trauma care systems, and by including an American 
College of Surgeons’ policy component, the TSOS study incorporates these RE-AIM pragmatic trial domains. 
 
Implementation science investigation can also inform a better understanding of the processes of 
pragmatic trial implementation and ultimately pragmatic trial sustainability. Organizational behavior and 
process research can provide insight into trauma center implementation and maintenance of interventions for 
PTSD and comorbidity.107,194-202 Prior study suggests that training workshops, plus feedback and coaching are 
the optimal procedures for training in evidence-based interventions.203-208 An emerging body of research 
suggests that mixed method investigations can also inform transparency and understanding of the manner in 
which multiple stakeholders can work collaboratively to understand implementation processes and translate 
research findings into policy.209-214  
 
Policy relevant cost-effectiveness analyses are key methodological approaches for optimizing 
pragmatic injury trial public health impact.11,215-220 At trauma centers, both general cost-effectiveness 
approaches and approaches relevant to specific acute care issues, such as injured trauma survivors returning 
to work, are germane.11,219,220 Members of the investigative group have previously conducted cost-
effectiveness and analyses related to the impact of mental health and substance abuse care management 
interventions in acute, primary care, and general medical settings.11,219-224 The integration of mixed, quantitative 
and qualitative research methods can optimally inform the results and policy implications of pragmatic trials.225-
229 
 
G. The potential for the project to develop transformative methods and reusable resources. The 
significance of the TSOS study extends beyond specific investigative aims to the potential development of 
transformative research approaches for the multiple chronic condition framework and reusable pragmatic trial 
resources for US health care systems. The investigation brings to the Collaboratory a unique American College 
of Surgeons-TSOS study team stakeholder partnership. This partnership has been cultivated over the past 
decade and has the potential to directly translate UH3 pragmatic trial results into American College of 
Surgeons’ policy targeting real-time workflow integrated screening and intervention procedures for PTSD and 
related comorbidity for US trauma care systems. The American College of Surgeons’ stakeholder partnership 
can potentially generate a novel model for the dissemination and sustainability of Collaboratory research 
results; the TSOS study team policy arm is poised to advocate for American College of Surgeons’ best practice 
recommendations that incorporate theoretical and applied research products including information technology 
innovations. 
 
With regard to the generation of innovative and reusable research methods, the TSOS pragmatic trial 
employs a novel cluster randomized stepped wedge design that begins with control phase recruitment and 
then “switches on” the intervention; this design addresses study implementation challenges raised by the 
inclusion of 24 diverse trauma center sites in the trial. The stepped wedge design also optimizes 
implementation science approaches to training at 24 US level I trauma center sites that may wish to 
incorporate PTSD screening and intervention procedures as part of future American College of Surgeons’ 
policy. The study introduces across 24 US level I trauma center hospitals with diverse electronic health record 
(EHR) capacity, a novel EHR screening procedure for PTSD and related comorbidity. The procedure is 
designed to be flexibly implemented at sites that can either automate the screen or apply the screen in a 
manual chart review fashion. The TSOS stepped screening and intervention procedures target a multiple 
chronic condition/comorbidity cluster that includes PTSD and associated mental health comorbidity such as 
depression and suicidal ideation, alcohol and drug use comorbidity, pain and somatic symptom amplification, 
TBI and non-TBI injury, as well as a heterogeneous clustering of chronic medical comorbidities. The 
investigation addresses complex challenges raised by the introduction of the need to screen for multiple 
chronic conditions within the EHR and complexities related to accurate diagnoses of patients with mental 
health conditions. A single care management based intervention program targets this heterogeneous 
comorbidity cluster with minimal exclusions. 
 

9 
 
3. Study Design 
 
A. Design Overview 
The pragmatic trial demonstration project is designed to test the implementation of efficient, high quality 
screening and intervention for PTSD and comorbidities across 24 US level I trauma center sites. The 
investigation will employ a stepped wedge cluster randomized design. In the stepped wedge design, level I 
trauma center sites are randomized sequentially to initiate the intervention. In the UH3 implementation phase, 
after IRB approval is obtained, each of the 24 trauma center sites will be randomized to one of four waves. All 
sites will begin with control patient recruitment and each wave is assigned a specific proportion of control and 
intervention patient recruitment. Wave one recruits 8 control and 32 intervention patients, wave two recruits 16 
control and 24 intervention, wave three recruits 24 control and 16 intervention, and wave four recruits 32 
control and 8 intervention patients. The demonstration project aims to recruit 960 patients, 40 at each trauma 
center site.  
A routine trauma center provider, the site PTSD intervention champion, will be selected to orchestrate 
screening and intervention procedures. All sites will work with the study team to implement an EHR initial 
PTSD risk evaluation. Patients identified by EHR evaluation as at-risk for high early PTSD symptom levels (i.e., 
a score of ≥ 3 risk domains positive) will then be formally screened for study entry with the patient reported 
outcome measure, the PTSD Checklist. Formal study cohort definition occurs with the PTSD Checklist; 
patients scoring ≥ 35 on the PTSD Checklist will be followed in the longitudinal portion of the investigation.  
Patients in the control condition will receive enhanced trauma center care as usual. Enhanced trauma 
center care as usual consists of nurse notification of control patients who screen into the study with high PTSD 
symptom levels. Patients in the intervention condition will receive a stepped collaborative care intervention 
targeting PTSD and related comorbidities. The intervention phase will begin with a one-day workshop training 
in care management, medication, MI, and CBT elements targeting PTSD and related comorbidity. These 
workshop trainings will occur on site at each of the 24 level I trauma center sites. The site PTSD intervention 
champion, as well as trauma surgical, nursing, psychiatric, social work, and other allied mental health providers 
who are already routinely delivering care at each of the sites will be invited to attend the workshop training. 
After the one-day workshop, the site will receive ongoing decision support facilitated supervision from the 
University of Washington study team.  
Intent-to-treat outcome analyses will incorporate baseline patient reported outcome and trauma registry 
derived EHR data, as well as patient reported outcome assessment data from the 3-, 6-, and 12-months post-
injury patient interviews. The investigation aims to determine if injured patients receiving the collaborative care 
intervention demonstrate significant reductions in PTSD symptoms when compared to control patients 
receiving care as usual. The study also aims to determine if the intervention patients, when compared to 
control patients, will demonstrate significant reductions in depressive symptoms and alcohol use problems, and 
improvements in physical function. The investigation is designed as an effectiveness-implementation hybrid 
that simultaneously aims to determine the effectiveness of the care management intervention while also 
assessing the potential utility of the implementation strategy.191 Thus, the investigative team will also use the 
RE-AIM framework and exploratory health economic analyses to better understand the processes of 
intervention implementation, as well as the resource implications for trauma care systems nationwide. 
In the UH3 year 5 of the proposal, the results of the pragmatic trial will be presented at an American 
College of Surgeons’ policy summit. A key focus of the summit will be discussion of the implications of trial 
results for screening and intervention for PTSD and comorbidity, clinical practice guidelines, and policy 
mandates. In particular, the study team will discuss findings that facilitate the implementation of real-time 
workflow integrated screening and intervention procedures for PTSD and comorbidity across trauma care 
systems nationally. The summit will be timed to optimally impact the next version of trauma center guidelines 
for PTSD and comorbidity.  
 
B. Study Phases (see Figure 4) 
Phase 1: Planning and start-up. In the start-up phase, the University of Washington (UW) study team has 
identified the 24 participating trauma center sites; potential wait list or “back-up sites” that could participate in 
the trial should initially contacted sites drop from the study have also been identified. At each potential site, the 
study team has identified three different types of “Champions”, or individuals who have the background and 
experience at a trauma center to advocate for a particular component or element of the study protocol. The 

10 
 
three identified champions at each site are the trauma surgical champion, PTSD intervention champion and 
information technology champion. Also during the start-up phase, each site will be asked to assess their 
capacity for automated versus manual health record PTSD screening and to characterize their potential 
method for identifying injured patient cohorts and implementing the 10 domain PTSD risk factor screening 
elements.  
 
 
 
Phase 2: Start-Up/Pre-randomization. Appropriate regulatory approvals (e.g., IRB, DSMB) will be obtained 
prior to initiation of this phase. Ten provider subjects will be consented and will complete a baseline 
organizational survey to assess their views and experiences of working in their respective trauma centers. 
Data quality assessments (e.g., whether 10 domain PTSD risk factor screening items are identified in the 
health record or from ward observation) will also begin during this phase. 
 
Phase 3: Randomization. Randomization of the 24 trauma centers occurs during this phase.  
 
Phase 4: Control phase initiation. Sites will be trained in the study protocol, recruitment procedure, consent 
process, and how to use the decision support tool recruitment modules. Recruitment of control patient subjects 
will begin following this training. Data quality assessment procedures and baseline standardized patient 
interviews with care manager provider subjects will also occur in this phase. 
  
Phase 5: Follow-up outcome assessments. Follow-up interviewer training will begin prior to the initiation of 
this phase. The 3-, 6- and 12-month, blinded follow-up interviews will begin and continue ongoing throughout 
this phase. 
 
Phase 6: Intervention phase initiation. Recruitment of control patient subjects will end at each site based 
upon the wave they are assigned in the stepped wedge design. The UW intervention study team members will 
conduct a one-day intervention training workshop at each site at this time. Following this training, each site 
begins recruitment of intervention patient subjects and their care manager subjects begin charting notes in the 
decision support tool and have regular supervision with the UW study team. Intervention feedback and 
coaching will occur during this phase. Standardized patient sessions continue during this phase. Data quality 
assessment procedures will also continue at each site in this phase. All provider subjects will be asked to 
complete another organizational survey, after this phase is completed. 
 
Phase 7: Final study procedures. Final data cleaning and analyses will be conducted in this phase. 
Manuscript preparation and the end of study policy summit will occur in this phase. The UW study team will 
coordinate with the American College of Surgeons’ Committee on Trauma, as well as other stakeholders to 
hold a policy summit. 
 
 

11 
 
 
C. Site Eligibility and Recruitment 
Over the course of the start-up phase, the TSOS study team has recruited the 24 trauma center sites that will 
participate in the trial. The goal of the selection process 
was to recruit 24 level I trauma centers nationally that 
would be capable of efficiently implementing the study 
procedures. The study team sent notification emails and/or 
contacted by telephone all US level I trauma centers 
(Figure 5). Responding centers were asked questions 
about current PTSD screening and intervention practices; 
the study excluded the less than 10% of sites nationally 
that were already routinely screening and intervening for 
PTSD and related comorbidity. Pediatric specialty trauma 
centers were also excluded from the investigation, as 
elements of the intervention (e.g., the administration of 
psychopharmacological agents targeting PTSD) are less 
well established for patients under the age of 18. 
With the exception of pediatric trauma center 
specialty status, the organizational characteristics of the 24 
participating sites does not substantially differ from the 
characteristics of all US level I trauma centers potentially 
eligible for the study (Table 3). Site level 
generalizability/reach is an important aim of the 
investigation as it aims to influence American College of 
Surgeons’ policy for PTSD and comorbidity screening and 
intervention for all trauma centers nationwide (see the RE-
AIM investigation implementation assessments in the 
Statistical and Data Analysis Plan section). Potential sites 
were also required to identify three champions to assist 
with study implementation; the trauma surgical champion, 
the PTSD intervention champion, and the information 
technology champion (Table 4).  
 
Table 3. Organizational Characteristics of TSOS study versus all US level I trauma centers 
Characteristic  
UH3 TC N=24 N(%) 
Other TCs N=198 N(%) 
P 
Region of country   
            0.40 
    Midwest  
  7(29.2) 
  64(32.3) 
 
    South / Southeast 
  4(16.7) 
  30(15.2) 
 
    Northeast /East 
  5(20.8) 
  63(31.8) 
 
    West  
  4(16.7) 
  28(14.1) 
 
    Central 
  4(16.7) 
  13(6.6) 
 
Rural status  
  3(12.5) 
  24(12.1) 
1.0 
Population  served   
             0.03 
    Adult  
  7(29.2) 
  92(46.5) 
 
    Adult & pediatrics  
17(70.8) 
  82(41.4) 
 
    Pediatrics  
  0(0.0) 
  23(11.6) 
 
    Missing 
  0(0.0) 
    1(0.5) 
 
Teaching hospital 
23(95.8) 
162(81.8)    
0.14 
Council of teaching hospitals 
22(91.7) 
143(72.2)    
0.04 
University affiliation  
24(100.0) 
189(95.5)    
0.60 
                  Median(IQR) 
Number of interns/residents 
    327(282) 
    224(297)  
0.11 
Number of hospital beds  
    575(296) 
    534(318)       
0.40 
Number of inpatient admits  
26971(16311) 
25699(14978) 
0.28 
224 US Level I Trauma 
Centers Contacted
Assessed for 
Participation = 88
Excluded, eg PTSD 
Innovator = 13
Enrolled = 24
Declined Assessment = 105
Declined After 
Assessment = 22
Waitlisted = 29
Excluded = 31
- 19 Children’s Hospitals
- 12 Prior Pragmatic Trial
Figure 5. Site Recruitment CONSORT

12 
 
A champion is an individual who has the background and experience at a trauma center to advocate for 
a particular component or element of the study protocol. For example, a trauma surgeon champion is a 
surgeon opinion leader at the trauma center who can advocate with other surgical staff regarding the 
importance of PTSD screening and intervention. The champion at the trauma center site will interface with 
study personnel (e.g., trauma surgeon champion at each study site interfaces with study trauma surgery policy 
lead/co-investigator, Gregory Jurkovich, MD). 
Senior trauma surgical co-investigator, Dr. Jurkovich will be in contact with the trauma surgeons-in-
chief at all sites to coordinate investigative activities and to insure data is collected in a timely manner. All 
trauma centers will receive $20,000-$25,000 in payments and equipment/supplies (e.g., a laptop computer) 
over the course of the study in order to offset costs incurred by the requisite study research and information 
technology implementation activities. Also, as a further incentive for study participation all trauma centers may 
receive American College of Surgeons’ research participation credit; centers residing in College verified states 
will receive a waiver on alcohol screening and brief intervention verification documentation criteria (Appendix 
2). 
 
Table 4. Site Champions 
Site 
Trauma Surgeon 
Champion 
PTSD Intervention 
Champion 
IT Champion 
Baylor 
Michael Foreman 
Ann Marie Warren 
Inga Gerard 
Cedars-Sinai 
Dan Margulies 
Heidi Hotz 
Meaghan Harada 
Georgia Regents 
Steven Holsten 
Cassie Alexander 
David Fallaw 
Hartford 
D’Andrea Joseph 
Colleen Mulkerin 
Marc Palter 
Iowa 
Patrick Kealey 
Dionne Skeete 
Dwight Barnes 
L.S.U. 
Alan Marr 
Erich Conrad 
Alan Marr 
Madison 
Suresh Agarwal 
Becky Turpin 
Jeff Burnett 
North Memorial 
Greg Beilman 
Patty Reicks 
Amina Baha 
Ohio State 
David Evans 
Ken Yeager 
Jeremy Harper 
Regions 
Michael McGonigal 
Jen Gabbey 
Kurt Isenberger 
Santa Clara 
John Sherck 
Vickie Pham 
Michael Hwa 
Scott & White 
Alex Thompson 
Alex Thompson 
Jeana O’Brien 
Scottsdale 
Charles Hu 
Linda Sinwell 
Nicole Reyes 
Strong Memorial 
Paul Bankey 
Ray McLean 
David Krusc 
U.C. Davis 
Joseph Galante 
Bonnie McCracken 
Kent Anderson 
Wake Forest 
Preston Miller 
Laura Veach 
Dee Emon 
Wishard 
Michelle Laughlin 
Wendy St. John 
Seth Brooks 
UT Galveston 
Bill Mileski 
Lance Griffin 
Paolo Mangahas 
Cincinnati 
Bryce Robinson 
Dina Gomaa  
Brett Hartnett 
Vermont 
Bill Charash 
Jennifer Gratton 
Matt Price 
U. Kentucky Chandler Hospital 
Andrew Bernard 
David Maynard 
Joe Bobadilla 
Inova FairFax 
Maggie Griffith 
Anna Bradford 
Alex Solorzano 
Jacobi Medical Center 
Sheldon Teperman 
Melvin Stone 
Janet Cucuzzo 
U.T. Southwestern 
Joseph Minei 
Jessica Mitchell 
Garrett Hall 
U.C.L.A. Harbor 
Dennis Kim 
Nicole Perez 
Dr. Moazzez 
Utah 
Giavonni Lewis 
Amy Vincent 
Shay Taylor 
 
All 24 level I trauma center sites have completed subcontract agreements that are included with this UH3 
transition request (see Table 5 and budget documents). The Western IRB (WIRB) approved the UH3 on March 
16, 2015; the five sites that cede to WIRB have approved the UH3 protocol (Table 4). As of May 26, 2015, all 
of the 19 sites that have elected an individual IRB review had submitted the protocol to their respective IRBs; 
7/19 sites had obtained IRB approval (Table 5). 
 
 
 
 
 
 

13 
 
 
D. Provider Subject Eligibility and Recruitment 
All provider recruitment procedures described below were successfully piloted during the UH2 start-up phase 
of the project. There is no formal screening for providers aside from a recommendation by another trauma 
center provider at a site or a search of the site’s public website. No study activities will begin with providers 
until consent is obtained. 
 
Providers participating in the study at each site will be consented into the study as provider subjects, as 
they will complete interviews in addition to their roles working with patient subjects. At the beginning of the 
study prior to randomization, all provider subjects, staff and care managers, will fill out an online organizational 
survey to assess their opinions of their work environment, experiences with trauma and traumatic stress, and 
potential for job turnover (see Measures and Assessments: Provider assessments section and  provider 
measures in Appendix 11). Providers will be asked to complete this survey again after termination of 
recruitment/intervention activity at their respective sites. To compensate them for their time spent completing 
these surveys, provider subjects will be paid $35 at each time point.  
 
For the roughly one to five PTSD interventionist care manager subjects at each site, there are 
additional study procedures. Throughout the study, a member of the UW study team will conduct standardized 
patient interviews (see also Treatment Conditions: Fidelity Assessments section and Appendix 12) with the 
care manager subjects.  These standardized patient interviews will assess the care manager subject's skill set 
in interviewing patient subjects and will be tape recorded and later coded by study team members. A 
standardized patient interview consists of the UW study team member trained in conducting these interviews 
calling the care manager subject, introducing a mock patient situation, and running through an approximately 
15-20 minute roll play in which the care manager subject addresses the mock patient’s presenting issues (e.g., 
symptoms of PTSD, depression, alcohol use, etc.). These sessions are recorded and later reviewed by the UW 
intervention supervision team to incorporate in regular intervention supervision calls. These four standardized 
patient interviews occur at baseline prior to stepped wedge randomization, approximately just before training in 
the intervention, after intervention workshop training has taken place, and at the end of recruitment. The care 
manager subject(s) will be paid $50 for their time for each standardized patient interview.  
 
At the end of the study, one or more care manager subject(s) at each site may be asked to take part in 
a semi-structured qualitative interview that will be audio-recorded (see also the discussion of RE-AIM 
investigation implementation assessments in the Statistical and Data Analysis section and Appendix 12). This 
Table 5. Regulatory Documentation Status 
Site/State 
Subcontract Complete 
IRB Authority 
IRB Status 
Baylor/Texas 
Yes 
Institutional IRB 
Approved 
Cedars-Sinai/California 
Yes 
Institutional IRB 
Submitted 
Georgia Regents/Georgia 
Yes 
WIRB 
Approved 
Hartford/Connecticut 
Yes 
Institutional IRB 
Submitted 
University of Iowa/Iowa 
Yes 
WIRB 
Approved 
L.S.U./Louisiana 
Yes 
Institutional IRB 
Revision, Post-Review 
UW Madison/Wisconsin 
Yes 
Institutional IRB 
Submitted 
Ohio State University/Ohio  
Yes 
Institutional IRB 
Revision, Post-Review 
Regions/Minnesota 
Yes 
Institutional IRB 
Submitted 
Scott & White/Texas 
Yes 
Institutional IRB 
Approved 
Scottsdale/Arizona 
Yes 
Institutional IRB 
Submitted 
Strong Memorial/New York 
Yes 
Institutional IRB 
Submitted 
U.C. Davis/California 
Yes 
Institutional IRB 
Approved 
Wake Forest/Virginia 
Yes 
Institutional IRB 
Approved 
Wishard/Indiana 
Yes 
Institutional IRB 
Revision, Post-Review 
U.T. Galveston/Texas 
Yes 
Institutional IRB 
Approved 
Cincinnati/ Ohio 
Yes 
WIRB 
Approved 
University Hospital/Vermont 
Yes 
Institutional IRB 
Submitted 
    Chandler Hospital/Kentucky 
Yes 
Institutional IRB 
Revision, Post-Review 
Inova FairFax/Virginia 
Yes 
WIRB  
Approved 
Jacobi Medical Center/ New York 
Yes 
WIRB 
Approved 
U.T. Southwestern/ Texas 
Yes 
Institutional IRB 
Approved 
U.C.L.A. Harbor/ California 
Yes 
Institutional IRB 
Submitted 
University Hospital/Utah 
Yes 
Institutional IRB 
Submitted 
Santa Clara/California 
Pending Final Signatures 
Institutional IRB 
Approved 
North Memorial/Minnesota 
Pending Final Signatures 
Institutional IRB 
Submitted 

14 
 
qualitative interview will be conducted by a member of the UW study team. This assessment will elicit 
perspectives on participation in the study as a whole. They will be paid $50 for their time. Care manager 
subjects will be allowed to withdraw from the assessment portion of the study and still continue in their 
respective roles in the study at their site without any further interviews. 
 
E. Patient Subject Eligibility, Recruitment, and Follow-up (Figure 6 & Appendices 5-6) 
Patient identification and recruitment procedures described below were successfully piloted during the the UH2 
start-up phase of the project. PTSD interventionist and other providers will identify potential patient subjects by 
reviewing inpatient rosters and identifying individuals who are most likely to have PTSD using the UW study 
team’s validated PTSD screening algorithm further described below. Care manager subjects will then approach 
potential patient subjects about the study.  
1. Potential patient subjects are identified by searching health records at each site for inpatients brought 
into the hospital for a traumatic injury. In order to review those records for this purpose, the study team 
will apply for and receive a waiver of consent and a waiver of HIPAA authorization. 
2. In order to enhance the efficiency of 
trauma care system PTSD case finding, the 
study team has developed and implemented 
a 10 domain PTSD risk factor screen 
(Appendix 5).49 The 10 domains used for 
screening are: 1) Female gender, 2) Non-
white race/ethnicity, 3) Intentional injury, 4) 
Public or Veterans insurance status, 5) 
Intensive Care Unit (ICU) admission, 6) 
Previous hospitalizations 7) Substance use, 
8) Tobacco use, 9) Evidence of PTSD 
diagnosis, 10) Other mental health diagnosis. 
3. The PTSD screening evaluation can 
either be applied in an automated or manual 
format. The automated form of the evaluation 
can be programmed into the hospital 
computing system, while the manual form of 
the evaluation involves screening individual 
health records for the 10 PTSD risk factor 
domains. At both automated and manual 
sites that select the manual screening, UW 
study team members will train PTSD 
intervention care manager subjects to adhere 
to the chart abstraction checklists developed 
and validated by the UW study team (see 
also the Data Quality Assurance and 
Harmonization section). 
4. Each day the PTSD interventionist will 
oversee a hospital-based review for admitted 
injured patients. The review will aggregate 
data from the 10 PTSD risk factor domains. 
Patients with higher scores on the evaluation 
(i.e., more positive risk elements) will be 
prioritized for approach for formal PTSD 
symptom assessment with the PTSD 
Checklist. Providers will identify potential 
patient subjects who meet the criteria of 
having ≥ 3 PTSD risk factor domains positive. Once a patient is approached for the investigation, in 
order to be eligible for this study and move on to the consent process, the provider will inform the 
potential patient subject that they must be able to provide at least two pieces of contact information that 

15 
 
consists of at least one phone number and a second alternate contact (e.g., another phone number, 
email address). This requirement helps ensure that the patient subject has a better likelihood of being 
able to be contacted for future interviews. During the approach and prior to the consent process, the 
provider will review this with a potential patient subject and will not enroll someone if they do not have 
at least two contacts. This is being done because the internal validity of the study relies on adequate 
follow-up rates. The study team has employed this procedure before and obtained greater than 70-80% 
6-12 month follow-up rates of nationwide studies with low income, ethnically diverse, acute care 
medical patients. 
5. The recruitment process will vary at sites depending on a number of factors including the ability of sites 
to automate screening procedures, the number of patients selected for recruitment each day and the 
availability of health record data. Any of the exclusions (e.g., 18 > age, acute psychosis, prisoner) or 
any of the 10 PTSD risk factor domains may be obtained from the health record, ward observation, or 
patient approach. 
 
F. Patient Follow-up Contact 
The study team will ask patient subjects for at least two pieces of contact information. One piece will need to 
be a phone number, while the second piece of contact information could include the patient’s address, email 
address or any of the previous contacts for a relative or friend. In the event that the patient subject changes 
residence (a common event after injury admission), the follow-up team may use these alternate sources.  
 
Over the 12 months after the injury, the follow-up team may perform check in phone calls with patient 
subjects to insure that the contact information on file is up-to-date; at the 9-month follow-up time point this 
phone check-in may be performed in order to remind subjects that their final follow-up interview will be coming 
in about three months. Patient subjects at this time will have all contact information on file confirmed and asked 
for any new information. 
After a trauma, patient subjects sometimes relocate temporarily in order to receive better care, such as 
movement from independent living to a skilled nursing facility.  Therefore, in addition to contacting patient 
subjects through the information they provide during the initial interview, the follow-up team will utilize several 
approaches to try and stay in touch with patient subjects across the study window. These approaches are: 
1. Contacting other people in the patient subject’s life. At recruitment, patient subjects will be asked for phone 
numbers/addresses of at least two contact sources (for example friends or relatives).  In the event that a 
patient subject is no longer at their residence, the alternative follow-up numbers listed will be another way of 
contacting them.   
2. Looking at hospital records. If the follow-up team is unable to reach a patient subject after repeatedly trying 
to contact them through the information provided, they may have the UW research coordinator contact the 
respective hospital sites to review their hospital records for any updated contact information. 
3. Conduct a public records search. The follow-up team may also conduct a public records search to find new 
contact information. Examples of public records searches conducted may include the Yellow Pages, or using a 
Google search to find additional contact information. The follow-up team will search for records or information 
on forums that are open to the public either for free or at a cost. Patient subjects will not incur this charge; it will 
come from the study budget. 
4. Contact through a social media page. If the follow-up team finds a social media page (e.g., Myspace, 
Facebook, Google+, etc.), they may attempt to contact a patient subject on these sites via private message. 
They will only send this message if they are able to match at least three identifiers with information the patient 
subject already provided, including: first name, last name and middle initial, date of birth, address, hometown, 
phone number or photo identification. This information will be sent to the patient subject’s inbox and will not be 
viewable to the public. No information identifying the study or its purpose will be included in this message. 
5. Sending an interview in the mail, email or other means (e.g., FAX). If the follow-up team cannot reach a 
patient they may send the interview through the mail, by email or by other means such as FAX. The interview 
form would not include a name or any identifying information. Patient subjects will be reminded they should 
complete the interview in a confidential space where no one else can have access or see the interview. 

16 
 
4. Treatment Conditions 
 
A. Enhanced Usual Care Control Condition 
The control patient subjects will receive enhanced usual trauma center care from the care manager subjects. 
Prior investigation suggests that usual posttraumatic care includes routine surgical, primary care, and 
emergency department visits, as well as the occasional use of specialty mental health services. The enhanced 
portion of the usual care will consist of the recruiting provider informing the ward nurse currently covering the 
patient subject’s care of any distress they are experiencing as identified by a PTSD Checklist score of ≥ 35 or 
Patient Health Questionnaire (PHQ-9) item 9 ≥ 1 administered during the baseline interview (Appendix 10). 
During the control phase of the protocol, providers who are recruiting will utilize components of the decision 
support tool to document screening activity, but will not receive any study team supervision in the application of 
the tool intervention elements; these elements will be kept “blinded” from the recruiters during the control 
phase. Data quality procedures for the usual care control training include assessment of PTSD risk factor 
domain screening, PTSD Checklist interview reliability assessments, and decision support tool data 
documentation checks.  
 
B. Stepped Collaborative Care Intervention Condition (Appendix 7)51,129 
As with control patients, intervention patients will receive nurse notification of PTSD Checklist scores of ≥ 35 
and/or PHQ-9 item 9 scores of ≥ 1 (Appendix 7). Dr. Zatzick and potentially other UW study staff (e.g., Dr. 
Darnell) will visit the trauma center sites in order to perform a one-day intervention workshop training. The 
workshop will provide an overview of the core elements of the PTSD and comorbidity intervention (Appendix 
7). The workshop will begin with a review of the experiences of the control phase. Front-line providers at each 
site will be asked to review control phase cases and consider what potential interventions may have been 
appropriate to deliver had they had adequate time and supervision. Next, the trainers will review the 
intervention elements including care management, medications, MI and CBT elements and community linkage. 
An in-depth review of the decision support tool modules that support the intervention will also occur. Finally, 
the ongoing plan for caseload staffing and supervision will be discussed with each site. Aspects of each 
training workshop may be audio-recorded and rated to assess fidelity to the intervention model.  
After the one-day workshop training, Drs. Zatzick and Darnell will initiate between 1-4 care 
management supervisory calls each month (e.g., weekly calls) for the duration of the intervention period at 
each site. Utilizing the computerized decision support tool, the care managers will present cases to the 
supervisory team. These regular meetings may range between approximately 15 minutes and 2 hours 
depending on the number of patient subjects and symptomatic intensity of caseloads. These sessions will 
include coaching in concern elicitation, CBT and MI techniques, as well as problem-solving surrounding 
organizational obstacles to screening and intervention implementation for PTSD and related comorbidity. 
These calls will also include coaching on evidence-based medication prescription for PTSD and comorbidity. 
The computerized decision support tool will also be used to assess fidelity to specific care management, 
behavioral therapy, and pharmacotherapy elements of the clinical treatment protocol. The care managers will 
be able to contact Drs. Zatzick and Darnell by phone if specific questions regarding patients arise; of particular 
note, Drs. Zatzick and Darnell, will provide written feedback on questions via the staffing notes function in the 
decision support tool. With care manager subject permission, elements of any training/supervision procedures 
may be audio-recorded for educational or fidelity purposes.  
 
The care management intervention elements are distilled from manualized procedures derived from the 
study team’s previous intervention trials (Appendix 7). The delivery of specific elements will be dependent on 
care manager time allocation and patient subject intensity of symptoms. In the protocol, care management will 
occur up to six months after the injury. It is anticipated that the care manager will spend approximately 2-4 
hours working on intervention and treatment linkage for each intervention patient. The care manager will 
attempt to meet all intervention patients during their trauma center or emergency department stay. During this 
meeting, the care manager will begin to elicit and target for improvement each patient’s unique constellation of 
posttraumatic concerns. This will help to enhance initial treatment engagement and therapeutic alliance. The 
care manager will give the patients their hospital contact number and encourage calls for spontaneous 
questions and concerns. The care manager will also elicit treatment preferences (e.g., CBT only, medication 
only, combined treatment) for PTSD and comorbidity and will schedule ongoing times to meet/call the patients 
during the initial days and weeks post-injury. Whenever possible, patients’ family members will be integrated 

17 
 
into treatment planning and longitudinal care. The care manager will elicit information regarding patients’ plans 
for physical and mental health care follow-up, and will inquire about whether or not the patients have a primary 
care provider (PCP). During caseload supervision, this information will be relayed back to the supervising UW 
study team members. After team discussion, the care manager subject will discuss treatment options with the 
patient and come to a shared decision about the initial treatment plan with the patient, their family members, 
and providers. 
The elements and progression of the MI, CBT, and medication modules are described below. The 
intervention includes a MI psychotherapy element embedded within care management that targets both 
treatment engagement and high risk behaviors, such as alcohol and drug use problems that risk recurrent 
injury. The MI intervention element consists of a graded sequence of clinical tasks including: a) eliciting from 
patient subjects their views of the importance of changing and of their confidence in being able to change, b) 
giving patient subjects personalized feedback, and c) clarifying the patient subject’s behavior change goals and 
action plans.230 The MI intervention component has been successfully developed and implemented by the UW 
group over the past decade in single and multi-site pragmatic clinical trials targeting alcohol use problems. By 
empathically exploring ambivalent feelings about alcohol use, MI approaches encourage movement in the 
direction of reductions in at-risk drinking behaviors. 
 
The CBT intervention component builds upon the engagement and therapeutic alliance developed with 
concern elicitations and MI. The intervention team has embedded aspects of evidence-based CBT within 
routine care management. The PTSD interventionist will utilize a non-demanding, MI interpersonal style when 
discussing possible behavioral interventions to target symptoms of PTSD, depression, and other comorbidities. 
The care manager subject will work to gauge patient subject willingness and ability to complete CBT exercises 
and adjust recommendations to match patient subject readiness to change current ineffective behaviors. 
Consistent with CBT principles and the principles of chronic condition self-management, the PTSD 
interventionist will incrementally increase sophistication and difficulty of behavioral tasks in order to help the 
patient subject achieve early successes and increase self-efficacy.  
 
CBT approaches also have proven efficacious in the reduction of PTSD, depression, and related 
comorbid presentations such as suicidality; CBT elements will be embedded within care management to target 
PTSD, depressive, and other related (e.g., insomnia, pain) symptoms during trauma center inpatient, acute 
care outpatient, and telephone follow-up contact with patient subjects. Specific elements targeting PTSD 
include psychoeducation, problem-solving, breathing exercises, and behavioral activation homework 
assignments. Specific elements targeting depression include psychoeducation, problem-solving, activities 
scheduling, attention to experience, and behavioral activation homework assignments. For patient subjects 
who demonstrate adequate CBT readiness and motivation, homework assignments are given. 
In prior single site investigations, the study team has developed pharmacotherapy protocols that 
simultaneously target prevention of PTSD and comorbidity, and mitigation of symptom exacerbations among 
injury survivors with pre-existing chronic medical conditions. As in previous trials, the medication element will 
coordinate pre-injury medication prescriptions for chronic medical conditions with post-injury medication 
decisions. Due to high documented rates of medication errors in the acute care to primary care transition, the 
initial step in the care coordination intervention for chronic medical conditions will be taking an accurate 
medication history from the patient subject; next the study team may reconcile any discrepancies between the 
patient subject, hospital, and outpatient provider medication records. 
 
The medication intervention element also aims to initiate and insure adequate follow-up of 
pharmacologic treatment targeting PTSD and related comorbid presentations. The investigative team will train 
the site teams in preventive pharmacotherapy targeting PTSD and comorbidity. A series of placebo-controlled 
blinded RCTs have established the SSRI class of anti-depressants as efficacious in treating PTSD and 
depression. Recent guidelines endorse these agents as the first line medication treatment for PTSD and 
depression. Other trials in adults suggest that psychopharmacological agents may also be effective in treating 
sleep, pain, TBI and somatic symptom amplification disturbances that occur concurrently with PTSD and 
depressive symptoms. In terms of treatment, symptomatic intervention patient subjects electing PTSD 
pharmacotherapy will be recommended to begin, advanced to, and maintained on guideline-level therapeutic 
doses of SSRI anti-depressant agents (e.g., Sertraline 50-200mg) either as surgical patients or through 
primary care linkage and consultation.  
 
The site team will potentially perform psychotropic medication evaluations and medication prescriptions 
in a number of settings including trauma inpatient wards, emergency departments, trauma surgery outpatient 

18 
 
clinics, over the telephone, and in the community. For all psychotropic medication prescriptions, the 
intervention team will attempt to consult with inpatient, outpatient, or primary care teams with regard to 
medication recommendations. Medication recommendations will preferably derive from team discussions and 
staffing with the study principal investigator and psychiatric supervisor Douglas Zatzick, MD. These 
discussions will be recorded in the study clinical decision support tool and may be documented in the health 
record by non-research clinical staff. The team will not become the primary prescriber of psychotropic 
medications. However, in the transitional care period between hospitalization and the solidification of outpatient 
follow-up, the study team may temporarily prescribe medications.  On occasion, when patient subjects have 
demonstrated symptomatic need/distress and cannot obtain timely prescriptions from a non-study team 
provider, a study team member may provide psychotropic medication prescriptions to patient subjects. Study 
team members in this role are likely to vary and could include psychiatrists, nurse practitioners, or other 
surgical or medical providers (e.g., trauma surgeon, PCPs). All study team prescriptions will be reviewed by Dr. 
Zatzick. 
 
A key role for the PTSD interventionist care manager is to insure that high quality trauma center-to-
community linkages occur.49,129,231  Prior investigation by the study team has documented that approximately 
40% of injured trauma survivors do not have a PCP at the time of injury admission. The care coordination 
component will include a series of intervention elements that have previously improved acute care to primary 
care and community transitions.146-149 Intervention elements will include hospital to primary care medication 
reconciliation, clear care manager-to-patient communication regarding discharge instructions and follow-up, MI 
and CBT intervention elements targeting the promotion of patient self-efficacy regarding acute care to 
community transition, engaging the help of family members and other patient subject social support (when 
available), ensuring appropriate PCP follow-up, and ongoing coordination and monitoring of care during and 
after the transition with the patient subject, family members, and inpatient/outpatient care providers. In 
coordinating care with other health care providers or a patient subject’s family or friends, care manager 
subjects may speak with individuals in person, over the telephone, or communicate by text, email, or other 
electronic means, such as FAX. 
 
Proactive, perseverant linkage efforts are a key element of the care management intervention. The 
investigators have previously developed aggregated lists of trauma center to community linkage resources. 
After a site has officially become part of the study, the research team may work with the care manager subjects 
to compile a list of community resources specific to their trauma center; this list may be entered into the 
computerized decision support tool. With the advent of health care reform, the team may also work to procure 
appropriate insurance coverage for trauma inpatients (e.g., through health benefit exchanges). 
 
A key aspect of the study will be to select appropriate PTSD intervention champion(s). The investigative 
team is aware that the champion could potentially be housed within a number of trauma center organizational 
work units.201,232,233 Procedures for identifying appropriate trauma center work units and individual PTSD 
intervention champions have been derived from the prior DO-SBIS investigation.130,136 This will allow the 
clinical research team first hand experiences with trauma surgery nursing, trauma center social work and 
psychiatric consultation liaison service care management options that could potentially support the activities of 
the PTSD intervention champion. The study team anticipates that the PTSD intervention champion will either 
be a nursing (RN), social work (MSW), or PhD-level routine trauma center practitioner.130,136 Dr. Zatzick will 
oversee the PTSD intervention care manager subject selection process.  
 
C. End of Participation 
While final patient subject follow-up interviews take place approximately 12 months post-consent, intervention 
activities with intervention patients are anticipated to conclude approximately 6 months after patient subjects 
consent into the trial. The objective of the final contact is to negotiate a specific plan for ongoing care. The care 
manager subjects will discuss strategies for maintaining treatment gains with each intervention patient. This 
means proper handoff of medication prescription management to a patient subject’s preferred primary care or 
other medical provider, linkage to community resources, and psychotherapy referrals. Resources to be 
recruited into treatment maintenance include ongoing relationships with the primary care or other providers, the 
patient subject’s family, and other community support services. 
 
Once the 12-month follow-up interview has been completed with control patient subjects, they will be 
informed of the end of their involvement with the research study. As these subjects will not receive any care 
other than what is usually provided at the hospital they were recruited at, there will be no transition of care 

19 
 
other than what they may already receive from their respective hospital. PTSD interventionist care manager 
may be invited at the end of their involvement to take part in a semi-structured exit interview with the UW study 
team (see below and Appendix 12). 
 
D. Fidelity Assessments 
The intervention fidelity assessments aim to simultaneously optimize the goals of fastidiously documenting 
intervention implementation process while also addressing the pragmatic trial requisite for minimal research 
specific resources dedicated to trial adjudication.184 The three fidelity domains assessed attempt to optimize 
these two at times competing implementation science and pragmatic trial aims.  
1. Workshop training. The PTSD interventionists and other on-site staff will attend a one-day intervention 
training workshop. The workshop training will be rated by study team members to ensure that key 
elements of the training are delivered (Appendix 7); aspects of each training workshop may be audio-
recorded and rated to assess fidelity to the intervention model. Trauma center staff attending the 
workshops may be asked to provide post-workshop evaluations (Appendix 12).  
2. Intervention fidelity. Level I trauma centers typically employ psychiatrists and psychologists as 
members of psychiatric consultation/liaison services, rehabilitation medicine services, and behavioral 
medicine and clinical pain teams. These highly trained mental health professionals are at the present 
time infrequently assigned supervisory roles in the delivery of services for injured patients suffering 
from PTSD and related disorders. The early intervention model restructures trauma center care by 
assigning two highly trained providers form the TSOS study team to supervise the delivery of evidence-
based treatments by the front-line care management providers. For the current study, Dr. Zatzick 
(Psychiatrist) and the supervising psychologist will provide weekly supervision individually with each of 
the PTSD interventionists and other site team members. The interventionist team will present new 
cases and treatment plans during the weekly team meeting. After this team discussion, the care 
managers will discuss treatment options with the patients and come to a shared decision about the 
initial treatment plan. Follow-up on active patients will also occur at team meetings, as will decision 
making around stepped-up care and psychopharmacology suggestions. Intervention team members will 
enter all assessments and treatment contacts into web-based forms contained within the study decision 
support tool.110-113,234 Because information is available in real time the system can be used by the 
MD/PhD intervention team supervisors to monitor and support the standardized implementation of the 
stepped care procedure. The automated decision support tool will also be used to assess adherence to 
specific care management, behavioral therapy, and pharmacotherapy elements of the clinical treatment 
protocol (Appendix 12).111,234,235 
3. Standardized patients. In the study team’s prior pragmatic trial focusing on alcohol screening and 
intervention, standardized patient fidelity assessments were used to assess fidelity to MI interventions 
delivered by front-line trauma center providers. In order to assess MI skills, intervention and control 
screening and brief intervention (SBI) providers participated in a total of seven, 20-minute standardized 
patient telephone interviews during which brief interventions were simulated.208,236 Prior to 
randomization, baseline standardized patient interviews took place with SBI providers at all 20 sites. 
Intervention site providers were scheduled for standardized patient interviews one week after workshop 
training and then again at 1-, 4-, 7-, 17-, and 27-months. Control site providers underwent a 
comparable sequencing of standardized patient assessments. Standardized patient scenarios were 
designed to reflect increasing clinical complexity over time. Initially, standardized patient actors role-
played injured patient scenarios that reflected optimal readiness to change at-risk drinking behaviors 
(e.g., the baseline, pre-randomization standardized patient was in “action”), while later standardized 
patients presented more difficult scenarios (e.g., the final 27-month standardized patient was “pre-
contemplative”).208,230 
 
Each standardized patient interview was scored using the Motivational Interviewing Treatment 
Integrity (MITI) coding system.237 Domains assessed by the MITI include the frequency of specific MI 
concordant behaviors such as counts of the delivery of open-ended questions. The MITI has 
established reliability and validity, and MITI coding procedures have been manualized.237 
 
The MITI will again be used to code patient standardized interviews in the UH3 study; in the 
UH3 protocol for the PTSD care manager interventionist subjects at each site, there are additional 
study procedures. Throughout the study, a member of the UW study team will conduct standardized 

20 
 
patient interviews (Appendix 12) with the care manager subjects. These standardized patient interviews 
will assess the PTSD interventionist subject's skill set in interviewing patient subjects and will be tape 
recorded and later coded by study team members. A standardized patient interview consists of the UW 
study team member trained in conducting these interviews calling the care manager subject, 
introducing a mock patient situation, and running through an approximately 15-20 minute role play in 
which the care manager subject addresses the mock patient’s presenting issues (e.g., symptoms of 
PTSD, depression, alcohol use, etc.). These sessions are recorded and later reviewed by the UW 
intervention supervision team to incorporate in regular intervention supervision calls. These four 
standardized patient interviews occur at baseline at the initiation of the stepped wedge randomization 
and again just before training in the intervention and after intervention workshop training has taken 
place, and at the end of recruitment. The care manager subject(s) will be paid $50 for their time for 
each session. This procedure was successfully piloted for four care managers (total of 16 standardized 
patient interviews) during the UH2 pilot. Standardized patient scenarios to be employed in the study are 
included in the appendices (Appendix 12).  
 
 

21 
 
5. Data Quality Assurance and Harmonization 
 
A. Overview 
The data quality assurance plan provides a framework for data quality assessment and ongoing data quality 
monitoring for the TSOS study. The TSOS study is a large scale 24 trauma center site pragmatic clinical trial 
that aims to directly inform national trauma care system policy for injured patients presenting with PTSD and 
related comorbidity. A series of prior single- and multi-site pragmatic trials have informed the design and 
implementation of the UH3 data quality and harmonization procedures; these procedures were piloted and 
refined during the UH2 start-up period.51,29,43,129,172,236  
The study will use electronic health record (EHR) data gathered at the sites during the course of routine 
clinical care to integrate patient eligibility screening into clinical workflow. A wide variety of EHR systems and 
variations in local capacity to leverage technology to deliver data for research projects is expected.108 This 
document describes strategies that will permit all sites to deliver highly reliable data, regardless of their 
technology leveraging capacity. These strategies include methods for creating local datasets of candidate 
patients, transforming data into a data model, techniques for detecting and reporting missing/erroneous data, 
and a process for harmonizing delivered data. 
After patients are enrolled in the study, front-line trauma center providers will collect and record new 
information used only for this research project, including patient reported outcomes (PROs). These data are 
gathered by front-line providers working across all 24 sites and are managed in a single electronic system 
maintained by the UW study data coordinating center. The TSOS data management plan describes strategies 
that will ensure all providers collect and record data uniformly across the 24 participating sites. These 
strategies include: (1) description of workflow, (2) standardization of injury cohort definition, (3) provider 
training, (4) validation of EHR PTSD risk domain screening, (5) training in standard operating procedures for 
patient interviewing and data collection, (6) periodic reviews of site providers to assess for process drift, and 
(7)  the data coordinating center will conduct an independent review of each patient’s EHR-derived trauma 
registry data; these results will be compared to site-submitted data to assess variance and data discrepancies. 
 
B. Conceptual Frameworks Informing the TSOS Data Quality Assurance Procedures: NIH Health Care 
Systems Research Collaboratory Assessing Data Quality – Version 1.0 
The methodological approach to developing data quality assessment and ongoing data quality monitoring 
procedures for the TSOS study has relied heavily upon conceptual frameworks developed by the NIH Health 
Care Systems Research Collaboratory Phenotypes Core (see Assessing Data Quality for Healthcare Systems 
Data Used in Clinical Research, Version 1.0).238 The following information derived from these guidelines 
informs the approach to data quality assurance in the TSOS study.  
1. Category of data collected. The NIH Health Care Systems Research Collaboratory Phenotypes Core 
explicitly defines two categories of data to be collected in pragmatic trials (Figure 7): 1) collection of 
data specifically for a pragmatic trial, where the investigative team is able to influence or control the 
data collection process,239 and 2) use of data generated in routine care, where the investigative team 
has little or no control over the data collection.238  (see Assessing Data Quality for Healthcare Systems 
Data Used in Clinical Research, Version 1.0; page 4).238 For both the first and second category of data, 
the Collaboratory Phenotype Data Standards and Data Quality core has articulated specific criterion for 
ascertaining data quality (see Assessing Data Quality for Healthcare Systems Data Used in Clinical 
Research, Version 1.0; page 13).238   
2. Data quality criterion. Specific Collaboratory guidelines have been developed for assessing the ability of 
pragmatic trials to produce data that sufficiently supports research conclusions (see Assessing Data 
Quality for Healthcare Systems Data Used in Clinical Research, Version 1.0; page 17).238 The 
Collaboratory recommends that demonstration projects address the following criterion pertaining to 
data collection, data quality assurance, harmonization and ongoing UH3 data quality control: 
 
Criterion 1: “Are data collection methods adequately validated?”  
Criterion 2: “Validated methods for the electronic health record information?”  
Criterion 3: “Demonstrated quality assurance and harmonization of data elements across healthcare   
 
         systems/sites?”  
Criterion 4: “Plans adequate for data quality control during the UH3 (trial conduct) phase?” 

22 
 
 
The Collaboratory further recommends that each question be considered distinctly for each of the two 
categories of data: data collected in routine care and research data (see Assessing Data Quality for 
Healthcare Systems Data Used in Clinical Research, Version 1.0; Table A1).238 Criterion 1, validation 
of data collection methods, applies only research data. Criterion 2, data quality assurance methods 
validation, applies only to data collected in routine care. Criterion 3 and 4 apply to both routine care and 
research data collection. The Collaboratory Phenotypes Data Standards and Data Quality core also 
recommends the creation and ongoing use of data flow and workflow diagrams for pragmatic trials (see 
Assessing Data Quality for Healthcare Systems Data Used in Clinical Research, Version 1.0 and 
Appendix 9).238 The Collaboratory recommends using generic workflow diagrams when assessing sites 
for incorporation into the study’s comprehensive data impact and harmonization strategy. Site-specific 
limitations and variances in clinical care processes can then dictate changes to the generic workflow to 
create a site-specific diagram that provides specific details regarding work flow and data flow that 
should inform data quality assurance processes for each site. 
EHR
 Injury 
Cohort
10 Domain 
PTSD 
Screen
PRO: 
PTSD 
Checklist
Other PRO:
e.g. PHQ-9, AUDIT, 
SF-36
TSOS 
Decision Support 
Tool
Trauma 
Registry
Data 
Patient Consent
Intervention Phase
Trauma Registry
Download
(Approx. 6 months 
post-admit)
Data 
Elements
Figure 7. TSOS Data Flow Chart
EHR DATA
RESEARCH DATA
C. Categories of Data Collected in the TSOS Study 
The investigation will include six key types of data (Table 6): 1) EHR data informing trauma cohort definition, 2) 
EHR data informing the 10 domain PTSD risk screen, 3) The PTSD Checklist 240 PRO measure used to define 
the PTSD phenotype, 4) Other patient reported outcomes for definition of secondary outcomes including the 
Patient Health Questionnaire (PHQ-9),241 the Alcohol Use Disorders Identification Test,242 and the Medical 
Outcomes Study SF-12/36 Physical Components Summary Score,243,244 5) Additional clinical data collected in 
the TSOS decision support tool and, 6) Trauma registry derived electronic health record data including 
traumatic brain injury and pre-injury chronic medical condition ICD codes. Each of the six data types are 
explicated in greater detail below. 
1. Traumatic injury cohort definition and exclusions. The trauma cohort definition describes the inclusion 
criteria a site will use to identify the pool of inpatients that are eligible to be screened for inclusion in the 
TSOS project. Potential patient subjects are identified by searching health records at each site for 
inpatients brought into the hospital for a traumatic injury. In order to review those records for this 
purpose, the study team will apply for and receive a waiver of consent and a waiver of HIPAA 
authorization. Further phenotypic review of these domains can be found in the Data 
Quality/Phenotyping Manual (Appendix 9.  
2. 10 domain PTSD risk screen. Once a list of eligible traumatically injured patients is derived, all patients 
on the list will be screened for the following 10-item risk factors. This evaluation utilizes 10 data 
elements that are readily available in a typical robust EHR to identify patients at high risk for the 
development of PTSD.49 The use of the 10 domain screen will increase screening efficiency in a clinical 
workflow integrated fashion for identifying patients at high risk for the development of high early PTSD 
symptom levels. However it is important to note that the PTSD cohort definition occurs after a patient is 
consented, and with the administration of the 17 item PTSD Checklist PRO measure. The 10 PTSD risk 

23 
 
domains include: 1) Female gender, 2) Non-white race/ethnicity, 3) Intentional injury, 4) Public or 
Veterans insurance status, 5) Intensive Care Unit (ICU) admission, 6) Previous hospitalizations 7) 
Substance use, 8) Tobacco use, 9) Evidence of PTSD diagnosis, 10) Other mental health diagnosis. 
Patients with ≥ 3 PTSD Risk Domains will screen into the study. The 10 domain screen can either be 
utilized as an automated or manual EHR abstraction procedure. Further discussion of the 10 domains 
can be found below and in Appendix 9. 
3. TSOS PTSD phenotype: PTSD Checklist 17 item patient reported outcome (see Measures and 
Assessments section and Appendix 10). 
4. Other patient reported outcomes for definition of secondary outcomes (see Measures and Assessments 
and Appendix 10). Other patient reported outcomes assessments that will be used to define the key 
secondary outcomes of depressive symptoms, alcohol use problems and impairments in physical 
function are described below. 
a. Depressive symptoms. The 9-item Patient Health Questionnaire (PHQ-9) brief depression 
severity measure will be used to assess depressive symptoms.241 The PHQ-9, item 9 will be 
used to assess for suicidal ideation, with an additional item to assess more recent suicidal 
intent. The PHQ-9 has established reliability and validity in acute and primary care medical 
patients.29,51,241,245,246  
b. Alcohol use problems. The AUDIT, a 10-item screening instrument for the early identification of 
problem drinkers,242 will be used to assess alcohol use problems before and after the injury 
hospitalization. The AUDIT’s reliability and validity are well established and the scale has been 
widely used in general medical settings.247 
c. Limitations in physical function MOS SF-12/36.243 The investigation will use the MOS SF-12 at 
baseline, and SF-36 at 3-, 6-, and 12-month follow-up to assess physical functional outcomes. 
The SF-12/36 has established reliability and validity and the measure has been used 
extensively with traumatically injured populations.244  
5. TSOS decision support tool data. Data collected in the TSOS decision support tool will be used to 
assess intervention activities and time (Appendix 7). 
6. Trauma registry derived electronic health record data. Key variables derived from the trauma registry 
include ICD codes required to assess the severity of covariates, such as the severity of traumatic brain 
injury and the presence or absence of chronic medical condition comorbidity and injury severity scores 
(ISS). Trauma registry data will also allow comparisons of the clinical, injury and demographic 
characteristics of patient subjects selected for the study with all other non-consented patient subjects 
admitted during the time period of the study at each of the 24 trauma centers but not included in the 
clinical trial. Electronic health record data collected in the trial will be compared to national trauma 
registry standards.63,248,249 
 
D. Summary of TSOS Data Characterization 
TSOS data for traumatic injury cohort definition, 10 PTSD risk domain assessment, and trauma registry data 
constitute data that is collected as part of routine trauma center care that will be utilized by the study to identify 
the traumatic injury cohort and to identify selected covariates such as the presence/absence of ICD injury 
codes, the presence/absence of pre-injury chronic medical conditions (see Table 6). 
 
Table 6. TSOS Data Types: Research versus Routine Care Categorization 
Data Type 
Category 1: 
Prospectively Collected 
Research Data 
Category 2: Routine 
Care Data 
Notes 
1) Injury Cohort 
Definition 
 
X 
 
2) 10 PTSD Risk 
Domains 
 
X 
 
3) PTSD Checklist PRO 
X 
 
 
4) Other PROs 
X 
 
 
5) TSOS Decision 
Support Tool  
X 
 
 
6) Trauma Registry 
 
X 
EHR Derived Registry Data 

24 
 
PTSD Checklist and other PRO and TSOS clinical tool data constitute data that will be collected specifically for 
the research study (see table below). For the study, PTSD and comorbidity cohort definition will occur with the 
use of the patient reported outcome, PTSD Checklist data. Patient reported outcome measures will also be 
used to define secondary outcomes including depression, alcohol use problems and physical functioning. 
Providers will assess organizational factors related to the implementation of PTSD screening and intervention 
services with provider reported outcome measures. The TSOS decision support tool data will document 
intervention patient activities. 
 
E. Data Quality Assessment and Harmonization for TSOS Data  
Data quality assessment and harmonization procedures for the TSOS study derive from application of the 
Collaboratory conceptual framework and TSOS study team previous investigation and piloting procedures (see 
Figures 8-10). 
 
 
 

25 
 
 
 
 
 
 

26 
 
F. Proposed TSOS UH3 Data Quality and Harmonization Procedures 
The UH3 data quality and assurance procedures will follow general phases of the UH2-UH3 protocol (Figures 
8-10 & Table 7). 
 
Table 7. TSOS UH3 Data Quality Assurance Procedures by Study Phase 
Study Phase 
TSOS Data Category 
Procedure 
Component of Collaboratory 
Conceptual Framework 
Addressed 
Pre-Randomization 
Injury cohort, 
10 domain PTSD risk 
screen 
 
Detailed survey 
Detailed workflow map 
Criterion 2: Methods for EHR 
data validation 
Pre-Randomization 
Injury cohort, 
10 domain PTSD risk 
screen  
5-patient sample 
evaluation 
Criterion 2: Methods for EHR 
data validation 
Pre-Randomization 
PTSD phenotype, 
Other PROs 
Baseline interviewer 
training 
Criterion 1: Methods for 
research data validation 
Randomization 
 
 
 
Control Initiation 
PTSD phenotype, 
Other PROs 
Initiate weekly intra- and 
inter-site data review 
Criterion 1: Methods for 
research data validation 
Criterion 3: Harmonization 
Control Initiation 
Injury cohort, 
10 domain PTSD risk 
screen 
5-patient sample 
evaluation 
Criterion 2: Methods for EHR 
data validation 
Control Initiation 
PTSD phenotype 
Drift assessment 
baseline of % PTSD 
positive on PTSD 
Checklist 
Criterion 2: Methods for EHR 
data validation 
Criterion 3: Harmonization 
Criterion 4: Quality control 
Control Initiation 
Injury cohort, 10 domain 
PTSD risk screen and 
TSOS decision support 
tool 
Weekly intra- and inter-
site data review/checks 
Criterion 4: Quality control 
 
Control Initiation 
Trauma registry  
Data comparisons 
across the 24 sites 
Criterion 3: Harmonization 
Follow-up 
PTSD phenotype, 
Other PROs 
 
Follow-up interviewer 
training 
Criterion 1: Methods for 
research data validation 
Criterion 4: Quality control  
Intervention Initiation 
TSOS decision support 
tool 
 
Baseline intervention 
team training 
 
Criterion 1: Methods for 
research data validation 
Criterion 3: Harmonization 
Intervention Initiation 
PTSD phenotype, 
Other PROs 
 
Continue weekly intra- 
and inter-site data 
review 
Criterion 1: Methods for 
research data, 
Criterion 4: Quality control 
Intervention Initiation 
Injury cohort, 
10 domain PTSD risk 
screen 
1-5-patient drift 
assessment 
Criterion 2: Methods for EHR 
data validation 
Criterion 3: Harmonization 
Criterion 4: Quality control 
Intervention Initiation 
PTSD phenotype 
Assessment baseline of 
% PTSD positive on 
PTSD Checklist 
Criterion 1: Methods for 
research data validation 
Criterion 3: Harmonization 
Criterion 4: Quality control 
Intervention Initiation 
Injury cohort, 10 domain 
PTSD risk screen and 
TSOS decision support 
Weekly intra- and inter-
site data review/checks 
Criterion 4: Quality control 
 
Intervention Initiation 
Trauma registry  
Data comparisons 
across the 24 sites 
Criterion 3: Harmonization 
Final Procedures 
Trauma registry  
Data comparisons 
across the 24 sites 
Criterion 3: Harmonization 

27 
 
Phase 1: Planning and start-up. In the planning phase, the UW study team has identified the 24 participating 
trauma center sites; potential wait list or “back-up” sites that could participate in the trial should initially 
contacted sites drop from the study have also been identified. During the planning phase, the UW team also 
piloted data collection and quality assessment procedures. These procedures included training providers in the 
10 domain PTSD risk factor screening procedure, training providers in the patient recruitment procedures, 
implementing and evaluating the one day provider workshop training, piloting the standardized patient 
procedures, testing and refining the provider coaching procedure that employs the computerized decision 
support tool, and establishing the feasibility of the investigation’s electronic data capture and transfer protocol 
from the pilot trauma center sites to the central University of Washington site. Data quality checks and 
harmonization procedures were also piloted and refined. 
 
Phase 2: Pre-randomization. Appropriate regulatory approvals (e.g., IRB and NIMH DSMB) will be obtained 
prior to initiation of this phase. All provider subjects will be consented and will complete a baseline 
organizational survey to assess their views and experiences of working in their respective trauma centers. The 
pre-randomization phase will include more detailed assessments of workflow at each site, capacity and specific 
assessments of injury cohort definition and 10 PTSD risk domain data quality procedures. Data quality 
assessments (e.g., validating process by which injury cohort definition and 10 domain PTSD risk factors are 
identified) will be initiated during this phase. A test transfer of de-identified data will occur during the pre-
randomization phase.  
 
a. Injury cohort definition, exclusions and 10 domain PTSD risk screening  
The overarching first step to identifying potential inpatient subjects requires utilizing the EHR systems at each 
site.  We recognize the diversity of EHR systems and procedures that can be used to produce a daily list of 
inpatients brought into the hospitals for traumatic injuries. In order to review those records for this purpose, the 
study team will apply for and receive a waiver of consent and a waiver of HIPAA authorization. The procedures 
used to define injury cohorts and characterize potential inpatient subjects for the recruitment process will vary 
between sites depending on a number of factors; the major factor is the capacity of the individual sites to 
automate the screening procedure within or external to the EHR (Figures 11 and 12). The automated form of 
the evaluation can be performed using EHR data queries or scheduled reports, while the manual form of the 
abstraction procedure involves reviewing individual health records. The fully automated form of the initial 
screening evaluation can be programmed into EHR systems resulting in a spreadsheet containing information 
about potential inpatients available for approach by the study team each morning. This report could have 
programmed study parameters or be a spreadsheet containing the injury ICD definitions, exclusion criteria, and 
the 10 risk domains. In contrast, the manual form of the abstraction procedure may involve using a manual list 
or printout of the daily inpatient census and manual screening of the individual’s EHR for injury definition, 
exclusion criteria or the 10 risk factors. Some sites will lie somewhere between the two examples and will be 
partially automated.  In this case, a hospital may have a daily list sent electronically with injured patients; these 
hospitals may employ manual screening and patient approach to fully capture the 10 risk factors and exclusion 
criteria. Therefore, the TSOS study team’s first task will be to work with each site to characterize the methods 
they will employ for defining their daily cohort of injured inpatients, assessing exclusion criteria, and 
determining the 10 risk factors. The study team will then create documents characterizing these procedures 
that will be reviewed by the sites.  Example workflow diagrams of the methods used to ascertain the daily list of 
potential patients according to the injury cohort definition with either automated or manual EHR review 
procedures are included (Appendix 9).  
1. Injury cohort definition. Appendix 9 has the study team definition of injury in terms of ICD codes and 
natural language indicators. These definitions will be applied by all sites. These definitions will be 
provided to each site during the pre-randomization phase. The study team will then have in-depth 
conversations with the IT champions and/or PTSD intervention champions at each site to identify the 
procedures used to generate the daily list of inpatients based on the definition. In these conversations, 
the study team will determine how the list of injured inpatients will be generated, what the list will 
contain, whether there needs to be manual editing of the list, and what criteria or risk factors will need 
to be gathered directly from the EHR. The study team also determines whether patients on the daily list 
include inpatients from a variety of services in order to increase generalizability. These services will 
include general surgery, orthopedics, neurosurgery, ENT/Maxillofacial, trauma ICU, and ER admissions 

28 
 
for ≥ 24 hours. Services available for the cohort will be noted for each site. This information will be 
incorporated into the workflow manual individualized for each site. These procedures have been piloted 
during the UH2 phase of the protocol and manuals and worksheet guides for these procedures have 
been refined and are included (Appendix 9). 
 
Figure 11. Manual Data Flow Diagram
Consent Process
During Rounds: 
Clinical Approach
Before Rounds: 
EHR Review
Exclusions
Data Quality
Site Recruiter
Manually transcribe 
new patients to 
worklist
Approach  for 
consent
Set status to 
“excluded” for 
patients who do not 
consent
Enter consented 
patients to TSOS 
Decision Support 
Tool
Administer PTSD 
checklist
Patient-by-patient, 
review EHR data & 
add to worklist
Enter data 
unavailable from 
EHR
Run ten-item screen 
stored procedure
Set status to 
“excluded” for 
patients with 
ineligibility criteria
Set status to 
“excluded” for 
patients with score 
of < 3
Query or manually 
examine EHR for 
new injury 
admissions
Patient already has 
≥ 3 points in ten-
item PTSD screen
Include patients 
with score ≥ 35 
points on PTSD 
checklist
TSOS tool status 
indicates exclusion if 
score < 35 on PTSD 
checklist
Compare detected 
injury cohort to 
Trauma Registry 
gold standard
Injury cohort and ten-item PTSD risk screening data validation by TSOS 
study team supervision of data collection and drift assessment
Weekly data quality 
check for TSOS 
decision support 
tool
Legend:
Compare de-identified eligible cohort statistics to site trauma registry and 
publish discrepancy rates.
Temporal trends within sites are analyzed periodically to detect sudden 
shifts in ten-item screen positive results.
Temporal trends within sites are analyzed periodically to detect sudden 
shifts in excluded patient volume.
Pre-randomization UAT: first five patients entered to TSOS Decision 
Support Tool are validated back to EHR data to confirm process validity.
Compare granular data on included patients to site trauma registry and 
publish discrepancy rates.
A
B
C
D
E
A
B
C
D
E
C
C
Ineligibility criteria:
Non-injury admission diagnosis
Non-English speaking
Acutely suicidal/self-inflicted injury
Cognitive impairment
Incarcerated or violent
Acutely psychotic
Deceased
 
 
2. Exclusion criteria. The study recruitment consort (Figure 6) and Appendix 9 define exclusion criteria. At 
each hospital, these criteria can be addressed in several ways, depending upon the capacity of the 
EHR and its programming potential. The fully automated sites will eliminate inpatients from the injury 
cohort daily list within the EHR query or using spreadsheet macros and those excluded individuals may 

29 
 
or may not be visible to the recruiter. In contrast, sites may use the manual abstraction procedure in 
which the first group of patients are chosen, and the exclusion criteria are examined in the EHR 
individually by the recruiter.  As soon as an exclusion is identified, the recruiter would go on and choose 
the next inpatient on the list for further examination. Some sites will use a combination of automated 
and manual exclusion procedures. These criteria can be determined from the EHR, by patient 
observation, or by patient interview. 
3. 10 domain PTSD risk screen. Appendix 9 describes in detail each of the 10 risk factors. These factors 
range from very easy to ascertain from the EHR, such as gender, to risk factors that involve the 
aggregation of past EHR elements such as previous inpatient hospitalizations or prior psychiatric ICD.  
Fully automated sites will be able to query the risk factors automatically from the EHR, and attach these 
10 indicators to the daily inpatient cohort report for the inspection of the recruiter. Hospitals not fully 
automated will have to determine these indicators from either the EHR, patient observation, or patient 
self-report. These procedures have also been piloted during the UH2 phase of the protocol and 
manuals and worksheet guides for these procedures have been refined and are included (Appendix 9).  
4. Training and validation of injury cohort definitions and PTSD risk screen. In an attempt to standardize 
injury cohort definition, both across sites in the initial pre-randomization training and also during the 
control and intervention phase drift assessments (Table 7), the study team will work with the site to 
understand the process by which the injury cohort is defined and patients are selected for PTSD 
screening at each site (Appendix 9). 
a. All sites will undergo a validation process whereby study team members, either in person or via 
secure web-based video conferencing, perform a validation check on injury cohort and risk 
domain identification (Appendix 9). This rating process will occur in the pre-randomization 
phase. Five patients will be evaluated with the expectation of 100% rating concordance; if the 
site recruiter and study coordinator do not reach rating concordance with the initial five patients, 
ratings will continue until 100% concordance is reached with five consecutive patients. General 
procedures for automated and manual screening sites are as follows: 1) At sites that have 
automation capacity (Figure 11), the phenotypes manual will be sent to the site complete with 
ICD and E-code identifiers (Appendix 9). Sites will proceed to write EHR queries; the study team 
will examine each site’s code. The study team will also validate with automated sites the 10 
domain risk screen results of five patients through web-based EHR review (see procedure 
below). 2) At manual EHR review sites (Figure 12), the study team will provide the appropriate 
manuals (Appendix 9); validation will also occur through web-based EHR review. Drift 
assessments that follow this procedure will occur once during the control phase recruitment and 
once during the intervention phase recruitment. The concordance between the cohort definition 
and 10 risk domain variables from the recruiters and our study coordinator will provide an 
indication of the drift in cohort definition. If significant drift is identified pre-randomization training 
procedures will be repeated. 
b. We recognize that within both the automatic and manually driven screening procedures, there 
will be variability in the capacity of the 24 hospitals to extract screening variables from the EHR, 
and that some hospitals will be able to automate varying numbers of the 10 risk factors and 
exclusion factors. In both cases, in the pre-randomization phase after appropriate regulatory 
approvals are in place, sites will implement at least one, pre-study de-identified (non-PHI) 
electronic data transfer to the UW data coordinating center.  
c. Trauma registry data checks. Trauma registry usually requires approximately 6 months to 
accrue after a patient subject is recruited. Using trauma registry data, the TSOS study team will 
compare the clinical and demographic characteristics of all patients included in the investigation 
with the characteristics of the population of injured patients potentially eligible for the study at 
approximately six-month intervals after recruitment initiation After these comparisons are 
performed, sites may receive feedback regarding any observed idiosyncrasies in injury cohort 
definition relative to other participating sites. Where possible (45 percent of items), the injury 
cohort data elements are directly normalized to the trauma registry (NTDB) data dictionary for 
this comparison.250 Where possible (70 percent of items), the 10 domain PTSD risk factor 
screening elements is also directly normalized to the trauma registry (NTDB) data dictionary for 
this comparison. 

30 
 
 
Phase 3: Randomization. Randomization of the 24 Trauma Centers occurs during this phase.  
 
Phase 4: Control phase initiation. Sites will be trained in the study protocol, recruitment procedures, consent 
process, and how to use the recruiter portion of the decision support tool; these trainings will either occur in-
person or over secure video conferencing. Before recruitment begins each site will be trained in the consent 
procedure and each site will be trained in the administration of the 17 item PTSD Checklist PRO measure. 
Sites will also be trained in the administration of the other PRO measures included in the baseline study 
interview. This training process will either occur in-person or via secure web-based video conferencing. Each 
site recruiter will undergo a pre-defined mock interview with a research associate trained as a standardized 

31 
 
patient. As the standardized patient interview occurs, the research study coordinator or other research staff will 
co-rate the interview that is performed by the site recruiter. Afterward, the site recruiter will receive feedback 
with a specific focus on discrepancies. As needed, repeat standardized patient interviews may occur. Trauma 
registry downloads also will begin during this phase.  
 
During the control phase intra- and inter-site assessments of baseline percentage of PTSD Checklist 
positive rates will occur. The investigative team expects by chance alone a 20% screen in rate for PTSD 
Checklist ≥ 35; utilizing the complete 10 domain risk screen rates of up to 67% on the PTSD Checklist ≥ 35 
have been achieved.49 Beginning with subject recruitment in the control phase, the study team will assess site 
rates of PTSD Checklist ≥ 35. Rate comparisons will also be made across sites. The study team hypothesizes 
that those sites that have a greater percentage of patients who have complete 10 domain PTSD risk screen 
data, will have greater rates of PTSD Checklist ≥ 35. As a result of this process, tailored feedback will be given 
to sites with lower PTSD Checklist screen in rates. Feedback will also be given to sites with high screen in 
rates. 
 
a. Weekly electronic data transfer (Figure 13) 
Recruitment data are aggregated in real-time as part of the site workflow. The de-identified data are submitted 
electronically from each of the 24 sites to the UW data coordinating center during this study phase. Weekly 
data include the following: 1) All de-identified data on non-consenting subjects required to construct the study 
consort diagrams; 2) All identified consenting patient baseline data. Once patients are consented and enrolled, 
their research data are directly entered in to the TSOS decision support tool and are available in real time to 
the data coordinating center. 
 
A. EHR Data
     1. Traumatic Injury Cohort
     2. 10 PTSD Risk Domains
B. Baseline Interview Data
C. TSOS Clinical Decision Support Tool Intervention Data
24 Sites
UW Data Coordinating Center
Weekly Data Quality 
Check
Monthly Site Tallies 
and Across Site 
Comparisons
Every 4-Month DSMB 
Reports
Figure 13. Weekly Data Transfer: 24 Sites
 
 
b. Weekly data integrity (Table 8) 
Weekly data checks will occur for incoming data from each site; data will be reviewed by the investigation’s 
data analyst, Dr. Wang, under the supervision of Dr. Russo. Incoming data from each site will be evaluated for 
missing data, contradictory, or out-of-bounds values. 
 
Table 8. Weekly Data Integrity Checks & Monthly and Tri-annual Progress Reports 
Data Category 
Weekly Data Check 
Monthly Progress Report 
Tri-annual DSMB Report 
Non-Consented Patient Data 
 
 
 
- Check for missing values 
X 
 
 
- Check for erroneous values 
X 
 
 
- Check for other data entry or 
transmission errors 
X 
 
 
Consented Patient Research Data 
 
 
 
- Check for missing values 
X 
 
 
- Check for erroneous values 
X 
 
 
- Check for other data entry or 
transmission errors 
X 
 
 
-PHQ-9 item 9 positive 
X 
 
X 
Summary Assessments 
 
 
 
PTSD Checklist screen in rate 
 
X 
 
PTSD Checklist positive /10 
domain screen in positive rates 
 
X 
 
Single and 24-site CONSORT 
 
X 
X 

32 
 
 
Dr. Wang will also perform additional assessments of data completion and consistency within and across sites. 
In cases where missing, contradictory or out-of-bounds values are identified, sites may be queried by the study 
coordinator; this querying process uses an escalation review process: 1) sites are asked to manually review 
questionable data against the EHR; 2) site workflow and data generation processes are reviewed in 
conference; 3) site workflow examples are observed in real time using secure remote desktop sharing 
software. The study data analyst will also begin single site assessments and across site comparisons of the 
percentages of patients consented and assessed versus the number of PTSD Checklist ≥ 35 followed 
longitudinally in the pragmatic trial during the control phase. 
 
c. Trauma registry downloads (Figure 14) 
Trauma registry data will be obtained for each site beginning at six months after control phase recruitment 
begins, and continuing at six-month intervals until study termination. Trauma registries will be used to compare 
the clinical and demographic characteristics of patients recruited into the study at each site to the final, cleaned 
and submitted NTDB data for the eligible population of patients at each site. These data will be used to 
conduct within-site consistency checking; between-site comparisons will also occur. 
 
Figure 14. Trauma Registry Data Transfer: 24 Sites
UW Data Coordinating Center
Data Quality Checks
Every 6 Month Site 
Tallies and Across- 
Site Comparisons
Every 6-Month
Trauma Registry Transfer
24 Sites
 
 
Phase 5: Follow-up outcome assessments (Figure 15). Blinded follow-up interviews will begin and continue 
ongoing throughout this phase. Blinded follow-up interviewers will be trained using manualized procedures 
prior to this phase (Appendix 6). 
 
Figure 15. Patient Reported Outcome Interview Data
UW Data Coordinating Center
Weekly Data Quality 
Check
Monthly Site Tallies 
and Across Site 
Comparisons
Every 4-Month DSMB 
Reports
3, 6 & 12 Month Follow-up Interviews
UW Outcome Assessment Interview Team
 
 
Phase 6: Intervention phase initiation. Recruitment of control patient subjects will end at each site based 
upon the wave they are assigned to in the stepped wedge design, and the UW study team will conduct a one-
day intervention training workshop at each site at this time. Following this training, each site begins recruitment 
of intervention patient subjects and their care manager subjects begin charting notes in the decision support 
tool and have regular supervision with the UW study team. Data quality assessment procedures including 
weekly data checks will also continue at each site in this phase. All provider subjects will be asked to complete 
another organizational survey, after this phase is completed. 
 
Phase 7: Final study procedures. Final data cleaning and analyses will be conducted in this phase. 
Manuscript preparation and the end of study policy summit will occur in this phase. 
 
 

33 
 
6. Measures and Assessments 
 
A. Patient Baseline, and 3-, 6-, and 12-month Independent Outcome Assessments (Appendix 10)  
The baseline, 3-, 6- and 12-month outcome assessments are briefly described below; a full listing of the 
outcome assessments complete with questionnaire items is detailed in Appendix 10.  The timing of 
assessment administration is detailed in Table 9. All scales will be available both in the computerized decision 
support tool and as paper and pencil administered measures, so that the study can proceed in the event of 
information technology complications. 
 
1. Primary study outcome and PTSD phenotype: The PTSD Checklist240,251 PTSD Symptoms. The PTSD 
Checklist is a 17 item self-report questionnaire that will be used to assess PTSD symptoms. The instrument 
yields both a continuous PTSD symptom score and a dichotomized diagnostic cut-point for symptoms 
consistent with a DSM diagnosis of PTSD.252  A series of investigations have demonstrated the reliability and 
validity of the PTSD Checklist across trauma-exposed populations.253-257 Blanchard et al. reported a correlation 
of 0.93 between the PTSD Checklist total score and the CAPS in a study of injured trauma survivors.258,259  
Cronbach’s alpha for the 17 item scale in a prior investigation with injured trauma survivors by the study team 
was 0.92.51,136 In previous investigations, PTSD symptoms assessed with the PCL in the surgical ward were 
the strongest single independent predictor of PTSD symptom level over the course of the year after injury; 
PTSD Checklist scores of ≥ 35 in the days and weeks after injury admission have been shown to be 
associated with the development of higher PTSD symptom levels over the course of the year after injury.49 
 
2. Secondary study outcomes: depressive symptoms, alcohol use problems and physical function 
Other patient reported outcomes assessments that will be used to define the key secondary outcomes of 
depressive symptoms, alcohol use problems and impairments in physical function are described below. 
a. Depressive symptoms. The 9 item Patient Health Questionnaire (PHQ-9) brief depression severity 
measure will be used to assess depressive symptoms.241 The instrument yields both a continuous 
depressive symptom score and a dichotomized diagnostic cut-point for symptoms consistent with a 
DSM diagnosis of depression. The PHQ-9 has established reliability and validity in acute and primary 
care medical patients.29,51,245 Cronbach’s alpha for the PHQ-9 in prior study team investigations was 
0.83.29 The PHQ-9, item 9 will be used to assess for suicidal ideation; the PHQ-9 item 9 question asks, 
“How often have you been bothered by any of the following problems…Thoughts that you would be 
better off dead or of hurting yourself in some way?” In the current investigation an additional item has 
also been added to assess more recent suicidal intent, for those individuals who have any positive 
response on PHQ-9 item 9. 
b. Alcohol use problems. The Alcohol Use Disorder Identification Test (AUDIT), a 10 item screening 
instrument for the early identification of problem drinkers will be used to assess alcohol use problems 
before and after the injury hospitalization.242 The AUDIT’s reliability and validity are well established and 
the scale has been widely used in acute and primary care medical settings.242,260,261,29,51 Cronbach’s 
alpha for the AUDIT in prior investigations by the study team was 0.80.208 
c. Physical limitations. The investigation will use the MOS SF-12 at baseline and SF-36 at 3-, 6-, and 12-
month follow-up to assess physical, role, and social functional outcomes. The SF-12/36 has established 
reliability and validity,243 and the measure has been used extensively with traumatically injured 
populations.35,52,262 Cronbach’s alpha for the MOS SF-36 PCS in prior investigations by the study team 
was 0.90.136,51 
 
3. Baseline patient trauma center/emergency department electronic health record assessment  
EHR data will be collected from each of the 24 sites during the recruitment of study patients; this data will be 
de-identified for non-consenting patients and identified for consenting patients. Similarly, trauma registry data 
will be obtained from each of the 24 sites that will contain EHR derived ICD and other patient data.  
EHR 10 item PTSD risk factor screen. A previously developed EHR screen will be used to assess admitted 
injured trauma survivors at risk for the development of PTSD.49 The screen utilized 10 data elements that are 
both associated with increased risk for PTSD and that are readily available in any robust EHR system. When 
the 10 data elements were used to predict scores on the PTSD Checklist of ≥ 35, the EHR screen 
demonstrated adequate sensitivity (0.71), specificity (0.66), and area under the ROC curve (0.72).49 The 

34 
 
evaluation utilizes 10 data elements that are readily available in a typical robust EHR to identify patients at high 
risk for the development of PTSD. The 10 domains used for screening are: 1) Female gender, 2) Non-white 
race/ethnicity, 3) Intentional injury, 4) Public or Veterans insurance status, 5) Intensive Care Unit (ICU) 
admission, 6) Previous hospitalizations 7) Substance use, 8) Tobacco use, 9) Evidence of PTSD diagnosis, 
10) Other mental health diagnosis. 
a. Traumatic brain injury. Traumatic brain injury will be identified and categorized from hospital chart-
abstracted ICD codes indicative of traumatic injury. Specific ICD-9-CM codes used to prospectively 
identify traumatic brain injuries include 800.0-801.9, 803.0-804.9, 850.0-854.1, and 959.01.263,264 TBI 
severity will be coded based on a previously validated algorithm for hospitalized inpatients.  
b. Injury severity. Injury severity will be abstracted from surgical records using a conversion software 
program that transforms recognized ICD-9CM codes into Abbreviated Injury Scale (AIS) and 
subsequent injury severity scores (ISS).265 
c. EHR derived chronic medical conditions. Comorbid chronic medical conditions will also be taken from 
EHR and trauma registry data and will be derived from ICD diagnostic codes.36,266 Chronic medical 
comorbidity will also be assessed through patient self-report during the follow-up interviews. 
 
 
4. Other Patient baseline and 
longitudinal assessments  
a. The Glasgow Coma Scale and 
Mini-Mental State exam will be 
used to assess level of 
consciousness in hospitalized 
surgical inpatients. 
b. Drug use: Single Items and the 
Drug Abuse Screening Test 
(DAST). Single items will be used 
to assess the use of specific 
substances. Illegal and prescription 
drug use after the injury will also be 
assessed with the 10-item DAST.267 
The DAST has established validity 
among substance abusing 
inpatients.65,268-271 Tobacco use will 
also be assessed using a single-
item screen.271,272  
c. Pain. A modified version of 
the Brief Pain Inventory will be used 
to assess pain longitudinally in the 
study. The Brief Pain Inventory has 
established reliability and validity.273,274 
d. Postconcussive symptoms.43,44,262 A self-reported cognitive symptom scale with established reliability 
and validity in injured patients will be used to assess impairments in cognitive function.262 These items 
will be supplemented with the Rivermead assessment developed for TBI patients.275 
e. Violence.172 A set of previously developed items will be used to assess violence risk behaviors such as 
weapon carrying.  
f. 
Recurrent traumatic and stressful life events.6,90,276 The trauma history screen developed for the 
National Comorbidity Survey will be used to assess pre-injury trauma and recurrent traumatic and 
stressful life events.  
g. Reactions to Research Participation Questionnaire (RRPQ).277,278 A single item from the RRPQ will be 
used to assess injured patient experiences with participation in the research protocol. 
h. Patient satisfaction with care. Items assessing satisfaction with general health care services and 
emotional health care services are included at each assessment point.29,51 
 
 
Table 9. Assessments & Timing of Administration (Appendix 10) 
Study Measure 
Ward 
3-Mo 
6-Mo 
12-Mo 
EHR 10 Item PTSD Evaluation 
X 
 
 
 
ICD injury severity 
X 
 
 
 
ICD TBI severity 
X 
 
 
 
ICD/Self-report Chronic Medical Conditions 
X 
X 
 
 
EHR & Self-reported demographics  
X 
 
 
 
Consciousness/Glasgow Coma Scale 
X 
 
 
 
PTSD (PTSD Checklist DSM-IV & DSM-5) 
X 
X 
X 
X 
Depression (PHQ-9) 
X 
X 
X 
X 
Alcohol (AUDIT) 
X 
X 
X 
X 
Illegal and Prescription Drug Use (DAST) 
X 
X 
X 
X 
Pain (Brief Pain Inventory) 
X 
X 
X 
X 
Postconcussive (NSCOT/Rivermead) 
X 
X 
X 
X 
Functioning (MOS SF12/36) 
X 
X 
X 
X 
Violence risk behaviors 
X 
X 
X 
X 
Pre-Injury Trauma (NCS) 
 
X 
 
 
Recurrent Traumatic Events (NCS) 
 
 
X 
X 
Reactions to Research Participation (RRPQ) 
X 
X 
X 
X 
Satisfaction with Care (NSCOT) 
X 
X 
X 
X 
Health Services, Work & Cost (NSCOT/TSOS) 
X 
X 
X 
X 
Medication Use (NSCOT/TSOS) 
X 
X 
X 
X 
EHR/Trauma Registry Utilization Data 
Ongoing - Automated Data 

35 
 
5. Health care utilization and other costing/economic assessments 
a. Health Service Utilization, Work and Cost Items (NSCOT).11,28 The investigation will collect detailed 
information on post-injury health service utilization including inpatient, skilled nursing facility, 
emergency room, and outpatient utilization visits. Health service utilization will be primarily assessed 
from patient self-report items that were developed and used in the NSCOT study; EHR derived trauma 
registry data will be used to augment patient self-report whenever possible. Assessment of 
psychotherapeutic services targeting PTSD and comorbidity will be specifically assessed using 
previously derived items.29 The investigation will assess pre-injury employment and return to work over 
the course of the months post-injury.55 Patient-centered injury cost assessments will also be collected. 
Technology use in communication with health care providers will also be briefly evaluated.29 
b. Medication use.11,28,29,51 Patient self-report will be used to assess medication use targeting chronic 
medical and psychiatric conditions longitudinally. For psychiatric medications the initiation of 
appropriate medications, and the maintenance on adequate doses over time will be assessed. Dosing 
and missed medication days will be assessed over a 3-month period.  
c. The Time Trade Off (TTO). 279-281 The modified version of the TTO approach for determining the 
desirability of a health state and estimating health state utilities will be included as part of the patient 
assessment. 
d. Other costing/economic assessments. Start-up and ongoing personnel costs associated with the 
delivery of the screening and intervention procedures will be ascertained through review of 
interventionist case management notes and study team member costing logs (Appendix 12). Study 
team members will use logging procedures developed during previous pragmatic trials to document the 
nature and duration of all intervention activities.208,236 
 
6. Intervention specific assessments 
In order to not replicate instruments delivered in the independent assessments, a number of intervention 
specific measures will be included for the assessment of PTSD, depressive and other symptoms in the trial. 
Interventionists will use the Impact of Events Scale (Revised-IESR) 282 and the 10-item Center for 
Epidemiologic Studies Depression Scale (CES-D) 283 to assess anxiety and depression in the current study. 
The Cog-Log284,285 will be used to assess cognitive impairment in the wake of traumatic brain or other injury. 
Other single item assessments will be used for the evaluation of alcohol and drug use problems.270 
 
7. Provider assessments  
a. Trauma center organizational assessments.286-291 The study will modify previously developed 
organizational culture and climate assessment scales to evaluate trauma center organizational 
characteristics related to PTSD and comorbidity service implementation. Organizational implementation 
scales will assess the extent trauma centers were able to adapt to the changes required by PTSD and 
comorbidity screening and intervention service development. Trauma center provider attrition from the 
study and turnover will also be examined. Following the procedure established in the DO-SBIS trial, 10 
providers will be identified through an organizational mapping procedure to be part of the organizational 
work unit impacted by screening and intervention service delivery. These 10 providers will complete the 
organizational assessment packet at baseline in UH3 year 2, and again in UH3 year 4 after all patient 
intervention is complete.  
b. Trauma center provider exposure to critical incidents and job stress. Previously developed items will be 
used to assess trauma center provider job related stress (e.g., call frequency, work volume). 292 The 
secondary traumatic stress scale will be used to assess trauma center provider work related stress 
exposures.293  
c. Provider lifetime traumatic stress exposure and PTSD symptoms. Provider lifetime traumatic stress 
exposures will be assessed with the trauma history screen developed for the National Comorbidity 
Survey.6,90,276 Provider PTSD symptom development in the wake of trauma exposures will be assessed 
with the PTSD Checklist.240,251 
 
  
8. Nationwide trauma center information technology survey108  
In study year 4, Drs. Van Eaton and Zatzick will develop a nationwide trauma center IT survey that derives 
from and builds upon the previous survey implemented during the DO-SBIS investigation. Survey domains will 

36 
 
again include EHR capacity for routine clinical documentation and pharmacy procedures. Additional survey 
items may include questions regarding the ability to expose de-identified standardized data for federated 
queries and questions regarding the potential for the implementation of open source platforms that would 
permit the real-time, workflow integrated, automated EHR screening, computerized decision support tool, and 
trauma registry documentation procedures for PTSD and comorbidity. The survey will also evaluate the 
potential for trauma center participation in nationwide data aggregation that would facilitate inclusion in 
distributed research networks. Survey results will be presented at the year 5 College policy summit. 
 
9. Trauma center provider semi-structured interviews 
In the final year of the project (UH3 year 5), after completion of patient recruitment and intervention activities, 
study team members will conduct semi-structured interviews with PTSD intervention care managers at each of 
the 24 level I trauma center sites. The study team has developed a year 5 interview guide derived in part from 
the DO-SBIS site champion key informant interviews (Appendix 12). The UH3 year 5 interviews with site 
champions will explore barriers and facilitators of implementation of screening, intervention, and quality 
documentation procedures for PTSD and comorbidity at trauma center sites. The interviews will also assess 
the potential sustainability/maintenance of study procedures. Semi-structured interviews may also be 
conducted with UH3 year 5 policy summit attendees. 
 
 
 

37 
 
7. Statistical and Data Analysis Plan 
 
A. Statistical Analysis Plan 
1. Study aims and hypotheses  
The primary aim of the UH3 period is to conduct a pragmatic randomized effectiveness trial of a collaborative 
care intervention targeting PTSD and comorbid conditions after acute care injury hospitalization. The 
investigation aims to determine if injured patients receiving the collaborative care intervention demonstrate 
significant reductions in PTSD symptoms when compared to control patients receiving care as usual. The 
study also aims to determine if the intervention patients when compared to control patients will demonstrate 
significant reductions in depressive symptoms and alcohol use problems, and improvements in physical 
function. An exploratory aim of the investigation is to assess the effectiveness of the intervention in injury 
survivors with and without pre-existing chronic medical conditions and with and without TBI. Exploratory 
analyses will also assess whether the intervention successfully reduced enduring symptom development for 
other co-morbid presentations (e.g., suicidal ideation, physical pain, drug use problems). 
The primary hypothesis is that the intervention group when compared to the control group will 
demonstrate significant reductions in PTSD symptoms over the course of the year after injury. Secondary 
hypotheses are that intervention patients when compared to control patients will demonstrate, significant 
reductions in depressive symptoms, significant reductions in alcohol use problems, and improved post-injury 
physical function. 
 
2. UH3 statistical analysis plan  
All primary statistical analyses will be conducted using intent-to-treat methods. The primary goal of the 
statistical analyses is to examine and compare trends over time in the symptoms of PTSD. The major test of 
the intervention effect will be the change in PTSD symptoms from baseline to the 12-month study endpoint. We 
will also examine changes in PTSD symptoms from baseline to the 3- and 6-month study time points, as well 
as the treatment group by time by interaction for PTSD symptoms over the course of the 12 months after 
injury. This analytic approach will be replicated for all secondary outcomes; secondary analyses will examine 
trends over time for depression and alcohol use, and physical function. The major outcome variables are the 
continuous and dichotomous assessments of PTSD (PTSD Checklist), alcohol use problems (AUDIT), 
depression (PHQ-9), and physical function (MOS SF-36 PCS).  
The study team will use ANCOVA/mixed effects regression models to test the hypotheses. The 
investigative group has extensive experience with these analytic approaches in the analyses of longitudinal 
data after injury. These analytic approaches allow for the modeling of longitudinal data on patients, nested 
within trauma center sites (see also sample size and power discussion below for a more in-depth discussion of 
clustering). An important potential advantage of using longitudinal mixed models is the ability to use partial 
data on those of subjects with missing data, and therefore potentially ameliorate selection bias due to drop-out.  
In addition, mixed models naturally structure patient and center heterogeneity specifically allowing for random 
effects such as individual intercepts and slopes on time. Longitudinal regression models also allow the use of 
baseline covariates that may be prognostic or reflective of the study design. 
Exploratory analyses will assess the impact of the intervention on primary and secondary outcomes for 
patients with and without pre-injury chronic medical conditions and with and without TBI. Exploratory analyses 
will also assess for significant reductions in suicidal ideation, pain and drug use problems in intervention 
patients when compared to control patients. The study team will again use ANCOVA/mixed effects regression 
for these exploratory analyses.294-297 In order to assess for potential selection bias across clusters, 
demographic characteristics (e.g., gender, ethnicity, insurance status) will also be tested as main effects and 
interactions with treatment status. 
 
3. Stepped wedge cluster randomized design 
Variability in multiple trauma center characteristics can impact rates of recruitment (e.g., admission volumes, 
EHR capacity), rates of PTSD (e.g., percentages of patients with violent injury admissions, intensive care unit 
admission rates), and the ability to follow patients longitudinally (e.g., patient demographic characteristics such 
as being homeless, clinical characteristics such as substance use problems). The study team initially 
considered using a stratified randomization procedure; however given the potential variability in multiple 
trauma center characteristics the study team will use a stepped wedge cluster randomized design for the UH3 

38 
 
protocol. The stepped wedge design randomizes level I trauma center sites to sequentially initiate the 
intervention, thus allowing within site pre-, post- intervention comparisons, as well as between site 
comparisons. An additional advantage of the stepped wedge design for the UH3 protocol is that it would be 
impractical to roll out the entire intervention at 24 sites simultaneously. Finally, from an implementation science 
perspective there is an advantage to having the intervention ongoing at the end of the study at every site, 
should the intervention demonstrate a significant impact on PTSD and comorbidity. Given that there is little 
threat of contamination at each site across intervention and control patients and that the UH3 can 
accommodate the increased potential length of active recruitment and follow-up, the stepped wedge design 
appears to be an optimal choice for the UH3 protocol. In the proposed UH3 protocol stepped wedge design, all 
24 participating level I trauma centers are randomly assigned to 1 of four waves. Each wave is assigned a 
specific proportion of control and intervention patient recruitment. Wave 1 recruits 8 control and 32 intervention 
patients, wave 2 recruits 16 control and 24 intervention, wave 3 recruits 24 control and 16 intervention and 
wave 4 recruits 32 control and 8 intervention patients. Interventions are initiated in the second six months of 
the UH3. The proposed stepped wedge design is outlined in the figure below. 
 
Figure 16. Stepped Wedge Cluster Randomized Design 
 
 
The stepped wedge regression model will adapt the functional form given below, and uses a time-
dependent variable to code treatment status for cluster k at calendar time t, denoted as conditionkt.  For the 
stepped wedge study design there are now two key time scales: Period, which denotes the study period 
measured relative to the calendar time when the overall study begins; and Follow-up time which is a patient-
specific time scale relative to when they enrolled in the study.  In this model mean outcomes may have a 
temporal trend in calendar time and this will be captured by modeling “Period”, while the primary outcome will 
still be the 12-month patient outcome denoted by Yijkt where i=4. 
 
A) The primary analysis regression model will adapt the functional form given below: 
 
Y4jkt = β0 + β1*Period4jk1 + β2*Period4jk2 + β3*Period4jk3 + β4*Period4jk4  +β5*Y1jkt + β6*conditionkt +       Mean  model                    
         bk,0 + e4jkt                                                                                                 Trauma center random effect and error 

39 
 
For this analysis the null hypothesis of no intervention effect is captured by H0: β6=0, and the primary statistical 
test will be a Wald test of this null hypothesis. 
 
B) A secondary analysis will explore the potential for treatment effect heterogeneity at the center level through 
inclusion of an additional random effect that permits cluster-specific variability in the intervention impact, 
captured by a random coefficient on the time-varying condition covariate: 
 
Y4jkt = β0 + β1*Period4jk1 + β2*Period4jk2 + β3*Period4jk3 + β4*Period4jk4  +β5*Y1jkt + β6*conditionkt +       Mean  model                    
         bk,0 + bk,1 *conditionkt + e4jkt                                                Trauma center random intercept, slope, and error 
The key difference for this model is that the intervention effect at trauma center k would be allowed to vary 
across centers and would involve the overall average intervention effect and a center-specific random 
intervention effect: β6+ bk,1. For this analysis the null hypothesis of a null average intervention effect is still 
captured by H0: β6=0, and the primary test will be a Wald test of this null hypothesis, but now using an 
additional random intervention effect together with a standard random trauma center effect (random intercept).  
 
C) A secondary analysis will evaluate the impact of intervention at all of the longitudinal follow-up times by 
including additional outcome measures and associated follow-up time variables, and interactions between 
follow-up time and intervention: 
 
Yijkt = β0 + β1*Periodijk1 + β2*Periodijk2 + β3*Periodijk3 + β4*Periodijk4  +β5*Followup2jkt + β6*Followup3jkt + 
β7*Followup4jkt + β8*conditionkt + β9*Followup2jkt*conditionkt + β10*Followup3jkt*conditionkt + 
β11*Followup4jkt*conditionkt  +                                                                                                                      Mean  model                    
         ajk,0 + ajk,1*Followupijkt    +                                  Patient random effects 
         bk,0 + bk,1 *conditionkt  + eijkt                                      Trauma center random effects and error 
Yijkt denotes patient outcome at follow up time i (i=1,2,3,4) (baseline, 3m, 6m, 12m) 
for patient j (j=1,2,…,nk) 
at trauma center k (k=1,2,…,24) 
 
enrolled in time period t (t=0,1,2,3,4) 
For secondary analysis using the repeated measurements from each subject there are two key hypotheses to 
test.  First, the 12-month intervention effect would now be captured by the intervention-by-time interaction 
specific to the 12-month assessment time:  H0: β11=0; and evaluation of the intervention effect under this model 
evaluates any impact of using the partially complete longitudinal data for all subjects to estimate the 12-month 
intervention effect.  This analysis provides a sensitivity analysis evaluating the impact of missing 12-month 
data for subjects who do have partial follow-up data (e.g. 3 month, 6 month data).  A second exploratory 
hypothesis would be the global null of no intervention effect at all follow-up times, and this would be captured 
by the multivariate null hypothesis:  H0: β8=β9=β10=β11=0; and evaluated using a multivariate Wald test.  Under 
this hypothesis the intervention and control means within a given period would be equivalent for all patient 
follow-up times. 
 
The primary analysis is a single hypothesis test based on Model (A) and will use alpha=0.05.  All other 
statistical tests are conducted to evaluate the sensitivity of the primary analysis to either heterogeneity or 
missing data, and therefore multiple comparison corrections are not used for these secondary analyses. 
 
Subject Attrition: Some attrition is expected in the study sample due to the research context and the 
population under study (i.e., low income, ethnoculturally diverse, injured trauma survivors). Prior studies by the 

40 
 
investigative group have consistently achieved follow-up completion rates ≥ 75-80% at 12 months post-injury 
with this population. Estimates derived from these rates are incorporated into the descriptions of subject flow 
and power analyses. 
 
4. Sample size and power 
A number of issues specific to the design and analyses of cluster randomized trials are addressed by the 
current power analyses.298-302 A key consideration for the trial is the nesting of patients within trauma center 
sites and the ascertainment of associated intraclass correlations (ICC). The study team has extensive 
experience with prior multisite trauma center observational and pragmatic clinical trial investigations. Sample 
size estimates were therefore adjusted for the clustering of patients within trauma center sites, using 
appropriate ICCs derived from the study team’s prior multisite investigations; original ICCs utilized included, 
PTSD Checklist ICC = 0.0083, PHQ-9 ICC = 0.0259, AUDIT ICC = 0.0059, SF-36 PCS ICC = 0.003.Original 
sample size estimates suggested recruiting 20 trauma center sites with a total study N = 800 patients (n = 40 
patients per site). 
 
Table 10. PTSD Checklist Effect Sizes 
PTSD Checklist 
Intraclass Correlation 
0.005 
0.010 
0.020 
0.030 
Minimum Detectable  
Effect Size 
 
0.216 
 
0.220 
 
0.227 
 
0.231 
 
In response to a series of discussions with the NIH Health Care Systems Biostatistics Core, sample size 
estimates were revised using more conservative ICCs. The power analyses model the baseline to 12-month 
treatment effect for the primary outcome and secondary outcomes. Table 10, provides effect sizes for the 
PTSD Checklist with a range of ICCs that includes empirically derived ICCs from the investigative team’s prior 
studies as well more conservative ICC estimates suggested by the NIH Health Care Systems Collaboratory 
Biostatistics Core. Table 11 delineates the parameters used to estimate power for the PTSD Checklist, PHQ-9, 
AUDIT, and SF-PCS. Sample size estimates were derived using the STATA statistical package.303 With each 
of the 24 trauma center sites recruiting 40 patients into the study, the study has 80% power to detect effect 
sizes ranging from 0.22 to 0.23. These effect sizes are smaller than our previously observed treatment effect 
for PTSD symptoms of 0.34. In prior investigations PTSD treatment effects of 0.34 have been associated with 
clinically significant and policy relevant functional outcome improvements. 
 
Table 11. Stepped Wedge Power for UH3 Outcomes 
Continuous outcomes 
PTSD Checklist 
PHQ9 
AUDIT 
   SF-36 PCS 
Cluster size at baseline 
40 
40 
40 
40 
Cluster size estimation at 12m (25% 
attrition) 
30 
30 
30 
30 
Total Number of clusters 
24 
24 
24 
24 
alpha 
0.05 
0.05 
0.05 
0.05 
Power 
0.8 
0.8 
0.8 
0.8 
ICC 
0.02 
0.0259 
0.02 
0.02 
Baseline mean(SD) 
50(15) 
14(6) 
10(5) 
50(10) 
Autocorrelation 
0.7 
0.7 
0.7 
0.7 
Follow-up time points (including baseline) 
4 
4 
4 
4 
Minimal detectable effect size 
Stepped wedge (STATA) 
0.23 
0.23 
0.23 
0.23 
Stepped wedge (Excel) 
0.22 
0.23 
0.22 
0.22 
 
 
 

41 
 
B. RE-AIM Analyses 
A second aim of the UH3 project is to understand the processes of pragmatic trial implementation. The study 
team will use the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model to 
comprehensively assess factors related to intervention reach, effectiveness, adoption, implementation, and 
maintenance. When combined with the PRECIS pragmatic trial conceptual framework, RE-AIM can provide a 
model for the integration of pragmatic trial results into routine trauma center practice (see also Significance 
section).192,193 The study RE-AIM assessments and analyses are described in Table 12 below. 
 
1. Reach304-306  
Reach is defined as the percent and representativeness of participants. Reach is an individual level measure 
that can be assessed by comparing records of program participation with records from a complete sample or 
“census” of potential program participants. In the pragmatic trial context, reach can be seen as assessing the 
capacity of a program to attract a large and representative percentage of a target population. Other key 
questions related to pragmatic trial reach include: can the program reach those most in need and most often 
left out (e.g., low income, ethnoculturally diverse patients)? 
In the UH3 investigation reach will be estimated for individual patients by comparing the characteristics 
of injured trauma survivors included in the investigation, with the characteristics of eligible trauma survivors 
admitted during the time period of the study as documented in the trauma registry. The study team has 
extensive theoretical and applied experience conducting trauma registry reach assessments; in published 
reports of randomized clinical trials the study team typically reports on investigation reach criteria.51,172,307-309 
 
2. Effectiveness51,172,304-309 
Effectiveness relates to the program’s impact on key symptomatic outcomes and quality of life; RE-AIM 
effectiveness criteria are addressed in the Statistical Analysis Plan discussion of primary PTSD and secondary 
depression and alcohol use symptoms and physical function outcomes. Of note, the study team has conducted 
theoretical and applied work on the population impact construct that combines effectiveness and reach RE-AIM 
criteria.307,309 
 
Table 3. UH3 Assessments and Corresponding RE-AIM Framework Domains 
Patient, Provider or Site 
Assessment 
N 
How 
Assessed 
Measures/ Assessment 
RE-AIM Domain, 
Level 
Site Recruitment 
24/225 
CONSORT 
Characteristics of 24 study sites 
versus all other US sites 
Adoption, Site 
Trauma Center Providers 
10* 24 
Web 
Organizational change, & climate and 
culture surveys 
Implementation, 
Provider  
PTSD Interventionist 
24 
Tool 
Weekly decision support tool 
recruitment log activity 
Implementation, 
Provider & Site 
PTSD Interventionist 
24 
Tool 
Clinical notes in decision support tool 
Implementation, 
Provider  
Patient Flow 
960 
CONSORT 
Patient flow through protocol 
Reach, Patient 
Patient Outcomes 
960 
Phone 
PTSD & comorbidity, gender & 
ethnicity groups 
Effectiveness, 
Patient 
Patient Outcomes 
960 
Multiple 
EHR, trauma registry self-report logs 
Implementation, 
Patient 
Patient 3,6, &12-Mo. F/U 
960 
Phone 
≥ 6 months follow-up after 
intervention 
Maintenance, 
Patient 
PTSD Interventionist 
24 
Phone 
Semi-structured key informant 
interviews 
Implementation & 
Maintenance, 
Provider 
Policy Summit Participant 
20 
Phone 
Semi-structured key informant 
interviews 
Implementation & 
Maintenance, Site 
All US Level I Centers 
225 
Web 
National Trauma Center 
Questionnaire 
Maintenance, Site 

42 
 
 
3. Adoption304-306  
Adoption can be defined as the percent and representativeness of settings that participate in or adopt a 
specific program. For the TSOS study, adoption criteria are discussed in the Site Eligibility and Recruitment 
section. Of particular note, the 24 sites selected for the trial do not significantly differ from the potential 
population of sites eligible for the trial on the majority of key trauma center organizational characteristics (Table 
3). 
 
4. Implementation304-306   
A number of potential constructs can be used to describe implementation, including the consistency and cost 
of delivering a program and adaptations made. At an individual patient level, measures of adherence are 
necessary for understanding study outcomes, and can be used as implementation criteria. Provider ability to 
deliver an intervention can also be an important assessment of implementation. For the current study a number 
of implementation fidelity criteria will be used (Also see Implementation Manual, Treatment Conditions, Fidelity 
and Appendix 12). 
 
5. Maintenance304-306  
Maintenance is the extent to which a program is maintained over time, as well as the long-term effects at 
individual and setting levels, and modifications made. In the TSOS study, maintenance at participating sites will 
be assessed through in-depth semi-structured end of study interviews. Nationally, the UH3 year 5 American 
College of Surgeons’ Policy Summit will address maintenance of study procedures through regulatory 
guidelines and policy mandates. National trauma center surveys will also address questions related to 
maintenance of study procedures related to PTSD and comorbidity screening and intervention procedures.   
 
6. Other RE-AIM analytic considerations 
The TSOS longitudinal cohort is defined by the patient reported outcome of a PTSD Checklist ≥ 35, which is a 
reliable and valid measure of DSM-IV Posttraumatic Stress Disorder. 232,243,252 The 10 domain PTSD risk factor 
EHR evaluation serves to efficiently identify patients with high PTSD symptom levels.49 The study team is 
aware that patients with < 3 risk domains are excluded and not approached at the 24 sites for consent and 
PTSD checklist screening.  
Therefore, an additional consideration for the investigation is the observation that approximately 8-9% 
of patients in the cohort, or 20-25% of patients who have PTSD Checklist scores ≥ 35 will not be identified by 
the PTSD risk factor chart evaluation procedure. In a random sample of 878 injured trauma survivors at the 
Harborview level I trauma center approximately 1/4 patients with high early PTSD symptom levels had 10 
domain PTSD screen scores of < 3.208 Similarly, in a second nationwide US trauma center study approximately 
1/4 patients with high early PTSD symptom levels had 10 domain PTSD screen scores of < 3.21 
 
In an effort to determine the potential impact of excluding patients with PTSD risk domain scores < 3 in 
the current nationwide pragmatic trial, the study team performed a series of retrospective analyses of data 
derived from a prior NIMH funded R01 PTSD intervention trial.51  The intervention tested a stepped 
collaborative care protocol similar to the intervention to be implemented in the UH3 protocol. Instead of EHR 
PTSD screening however, patients were screened with the PTSD Checklist twice; the 10 PTSD risk domains 
where retrospectively assessed for these 207 patients. In this way the trial included patients with high early 
PTSD symptoms as defined as a score of ≥ 35 on the PTSD checklist, with < 3 and ≥ 3  risk domain scores; of 
the 207 patients n = 163 had ≥ 3 risk domains positive, while n = 44 had < 3 risk domains positive. Mixed 
model regression that tested the treatment condition by time by risk domain score interaction found no 
significant differences in the intervention treatment effect for patients with < 3 versus ≥ 3 risk domains positive 
(F5,792 = 0.56, p = 0.73). These results suggest that the intervention may be equally effective for subgroups of 
patients with PTSD Checklist scores ≥ 35 and risk domain scores < 3 or ≥ 3, and that exclusion of patients with 
< 3 PTSD risk factors may not substantially impact the results of the pragmatic trial demonstration project.  
 
C. Qualitative Data Analyses 
Drs. Palinkas227,310-312 and Zatzick will oversee all qualitative analyses.313-315 Audio-recorded key informant 
interviews will be transcribed verbatim. Personal information will be replaced with a participant ID during the 
transcription process. Drs. Palinkas and Zatzick will review a subsample of transcripts for accuracy while 
listening to the recorded interview.316 The Atlas.ti computer software program will be used to assist with the 

43 
 
management and coding of all interview data. Using a grounded theory317,318 methodology of “Coding 
Consensus, Co-occurrence, and Comparison,”319 key informant interviews and field notes will be analyzed in 
the following manner: Drs. Palinkas and Zatzick will review all material to develop a broad understanding of 
content as it relates to the project’s specific aims and to identify topics of discussion and observation. 
Investigators will prepare short descriptive statements or “memos” to document initial impressions of topics and 
themes and their relationships to define the boundaries of specific codes (i.e., the inclusion and exclusion 
criteria for assigning a specific code).121 The material contained in the field notes and interview transcripts will 
then be independently coded by the project investigators to condense the data into analyzable units. Segments 
of text ranging from a phrase to several paragraphs will be assigned codes based on a priori (i.e., from the 
interview guide) or emergent themes (also known as open coding).320 Following the open-coding, codes will be 
assigned to describe connections between categories (also known as axial coding).320 Codes will also be 
assigned to material to reflect the social and demographic characteristics of study participants. Lists of codes 
developed by each investigator will be matched and integrated into a single codebook. Five transcripts will be 
independently coded by at least two investigators. Disagreements in assignment or description of codes will be 
resolved through discussion between investigators and enhanced definition of codes. The final list of codes or 
codebook, constructed through a consensus of team members, will consist of a numbered list of themes, 
issues, accounts of behaviors, and opinions that relate to coalition structure, function, development, and 
sustainment. Investigators will separately review a sample of transcripts to determine level of agreement in the 
codes applied. A level of agreement in the codes applied ranging from 66%-97% depending on level of coding 
(general, intermediate, specific), indicates good reliability in qualitative research.321 Upon completion of the 
coding of the remaining transcripts, Atlas.ti will be used to generate a series of categories arranged in a 
treelike structure connecting text segments grouped into separate categories of codes or “nodes.” These 
nodes and trees will be used to further the process of axial or pattern coding to examine the association 
between different a priori and emergent categories. They will also be used in selective coding of material to 
identify the existence of new, previously unrecognized categories. The number of times these categories occur 
together, either as duplicate codes assigned to the same text or as codes assigned to adjacent texts in the 
same conversation, will be recorded for descriptive purposes, and specific examples of co-occurrence 
illustrated with transcript texts. Through the process of constantly comparing these categories with each other, 
the different categories will be further condensed into broad themes. In the site PTSD intervention care 
managers’ thematic analyses, we will focus on identifying commonalities and differences in responses to 
individual questions (e.g., how each participant defines barriers and facilitators of screening and intervention 
activities). We will explore and describe commonalities and differences in themes across the key informants. 
We will also identify the clinical contexts that drive any group differences. 
 
D. Mixed Method Analysis  
Mixed methods will be used to integrate the findings from the key informant interviews with pragmatic trial 
results. The design taxonomy follows a sequential (QUAN → qual) structure in which qualitative data collected 
from key informants will be used to explain quantitative data results from the pragmatic trial.225 Qualitative data 
will therefore be used to expand upon the results of the pragmatic trial in order to understand the 
implementation and policy processes as experienced by key stakeholders. The investigative team will use a 
mixed method data analytic approach in two ways. First, findings from the quantitative data will be used to 
identify patterns in the qualitative data. Data derived from the pragmatic trial, such as intervention and control 
site recruitment periods, will be entered into Altas.ti as a “document family” or attribute of each site provider 
key informant interview. Analyses would subsequently categorize and compare themes across attribute 
defined subgroups such as intervention and control group status. Second, the sequential QUAN → qual mixed 
methods design will be used to provide an understanding of pragmatic trial results that require further 
explanation (e.g., control patients that demonstrate substantial improvement in outcomes, despite not receiving 
intervention). Results of the mixed method analyses will be presented through a number of modalities that may 
include key informant narratives, tabular representation of themes with illustrative quotes, and thematic 
counts.225,314,315,322 
 
 

44 
 
 
E. Exploratory Health Economic Evaluation 
1. Background: Health care utilization analyses in trauma care systems  
The cost assessments are intended to contribute to an understanding of the resource implications of the UH3 
intervention and to American College of Surgeons’ and other national policy dialogues of post-injury health 
service utilization and costs.96-105 We note that in our prior policy collaboration with the American College of 
Surgeons’, health care resource utilization and cost findings have contributed to, but have not dominated the 
discussions related to the establishment of mandates and best practice recommendations for PTSD and 
comorbidity.63 The health care resource utilization and cost analyses therefore constitute an important 
exploratory aim of the investigation. 
Multiple perspectives informed the approach to health service resource evaluation and cost analyses 
for the UH3 proposal. Recent commentary on the role of economic evaluation in dissemination and 
implementation research and the related costing of behavioral interventions contributed substantially.215,216 The 
approach to these analyses is influenced in a large part by recent work by the project’s health economic 
consultant, Dr. Basu, and psychometrician, Dr. Russo, on the costing of mental health care management 
interventions for comorbid medical and psychiatric conditions.135,224 Also, prior investigation by members of the 
investigative group on the costing of health care utilization in trauma care systems that emphasized the costs 
of recurrent trauma center and emergency department admissions has also been incorporated into the 
economic analysis framework.220 Finally, general recommendations regarding approaches to economic 
evaluations in health care have been integrated.217,218 
 
2. Approach to cost analyses 
The investigation will collect detailed information on the following: 1) the costs of intervention implementation 
and delivery, 2) post-injury health service utilization costs (inpatient, skilled nursing facility, emergency room, 
and outpatient utilization), and 3) the costs of patient medications post-injury. We will generally follow the 
principle of measuring the resource uses in each of these categories and then valuing them with unit costs that 
resemble the opportunity costs of these resources in the United States. The costs of the intervention would be 
comprised of the implementation costs, intervention time, and supervision time. These categories of costs are 
important in determining what resources would be needed to implement or replicate the intervention at other 
trauma center sites. Study development costs will not be included, since it would be a one-time fixed cost for 
developing the intervention, and would not be incurred in further implementation. Start-up and ongoing 
personnel costs associated with the delivery of the screening and intervention procedures will be ascertained 
through review of interventionist and study team member logs (see Appendix 12).  
Health services utilization and medication use following index hospitalization will be collected based on 
self-reports. For the purposes of the analyses, hospital and emergency department admissions will be 
categorized as: 1) hospitalization/emergency department visits related to the original index injury admission, 2) 
hospitalization and emergency department visits related to a new injury, and 3) a non-injury related 
hospitalization (e.g., hospitalization for a chronic medical condition such as congestive heart failure). 
Costs of intervention are likely to be dwarfed by the total costs of post-injury care, which would make it 
difficult to estimate the incremental costs of intervention precisely, given our sample size. This is mainly 
because our prior investigations suggest that up to 15-20% of injured trauma survivors in both intervention and 
control conditions experience recurrent injury emergency department and hospital admissions related to the 
index injury event, increasing the variance of the cost estimators. We will therefore provide detailed impact 
inventory for the intervention to identify specific components of total costs. Also of relevance, preliminary 
studies by the investigative group suggest that emergency department and hospital admissions for a new injury 
are policy relevant outcomes that are potentially malleable by care management interventions targeting PTSD 
and related comorbidity.11,55,220  
 
3. Costing procedures  
The following categories of costing information will be collected: 1) total charges for the index injury visit will be 
extracted either from the hospital trauma registry or the hospital EHR as available across the 24 level I trauma 
center sites, 2) all follow-up hospital, emergency department, and outpatient visits and re-hospitalizations over 
the course of the 12-months after the injury will also be collected from patient 3-, 6-, and 12-month self-report 
data or from the trauma registry, 3) structured patient interviews will be used to assess medication use. 

45 
 
All units of service will be assigned standard procedure codes (e.g., Current Procedural Terminology, 
Fourth Revision codes) for procedures, Diagnostic Related Groups (DRGs) for hospitalizations, and National 
Drug Codes for prescribed medication.323 These codes will be converted into costs by using the Medicare 
reimbursement fee schedule for 2014.  We will employ a validated and standardized program, EZ Fees 2014 
http://www.rbrvs.net/, in this procedure.324 The EZ Fees program has the 2014 Medicare fee schedule and is 
frequently updated as payment changes. For services not covered by Medicare, we will use the prevailing fees 
available from aggregate hospital data at http://hrsa.dshs.wa.gov/rbrvs./. These codes will be translated into 
unit prices using the Resource Based Relative Value Scales underlying Medicare payment rates for visits of 
different types, using EZ Fees http://www.rbrvs.net/. Medication costs will be ascertained using the Federal 
Supply Schedule for a given medication based on its NDC code.325 All costs will be converted to 2018 using 
the PHC and PCE indices http://meps.ahrq.gov/about_meps/Price_Index.shtml.  
Effectiveness/utility assessments. Exploratory analyses of cost-effectiveness will be conducted only 
if we find robust treatment effects for PTSD and comorbidity. Gold et al. have suggested the use of generic 
preference-based utility measures for cost-effectiveness analyses for comparability.217  However, because of 
the unique characteristics of psychiatric populations, mental health services researchers frequently employ 
disease specific effectiveness measures.221,224,326 The study team may explore a series of policy relevant 
effectiveness measures. The study team may use a method employed in a number of mental health 
effectiveness trials221,224,326 to derive a disease specific clinical outcome entitled “PTSD-free days.”  The 
investigative team will also use the Time Trade-Off procedure to estimate health-related quality of life weights 
longitudinally, which could be used to calculate Quality of Life Adjusted Years (QALYs). Finally, the 
investigation may also employ the MOS SF-12, to ascertain a generic preference-based utility estimate that 
has been previously used with injured patients in prior study team investigation.243,262,327-329 
Cost analyses. The investigation’s exploratory cost analysis will first compare total costs for patients in 
the intervention and control conditions; total costs will be the primary dependent variable for this analysis. Total 
costs include the costs of the intervention, medication and health service utilization (i.e., inpatient, skilled 
nursing facility, emergency room, and outpatient utilization). After the total cost comparison is completed, other 
exploratory analyses will compare intervention and control costs restricted to intervention costs and costs of 
emergency department and hospital admissions. Randomization should ensure balance between the two 
groups in pre-injury utilization. So, our primary analyses will be to study incremental costs, effectiveness and 
cost-effectiveness without any adjustments. As a sensitivity analysis the study team will examine patient self-
report data to assess balance between the two and to determine if adjustments are necessary. 
If adjustments become necessary, we will use non-parametric methods previously employed by Drs. Basu and 
Russo.135,224 The choice of non-parametric methods, such as propensity score weighting, is mainly because of 
the sample size of our analyses, where complicated regression models will be difficult to fit.  Standard errors 
and 95% confidence intervals for incremental costs, effectiveness and cost-effectiveness will be obtained using 
clustered bootstrapping.224,330,331 
 

46 
 
8. Study Administration 
 
A. Study Governance 
The study organizational structure and governance plan aims to simultaneously optimize diverse stakeholder 
input into the trial design and implementation while maintaining the proposed study timeline and UH3 milestone 
completion. The study organizational structure is outlined in Figure 17.  
 
 
 
The principal investigator in collaboration with NIH program staff and the NIH Health Care Systems 
Research Collaboratory, will be charged with the overall trial orchestration and steering. This steering group 
that includes NIH program staff Jane Pearson, PhD (NIMH) and Brett Hagman, PhD (NIAAA), have 
successfully worked with Douglas Zatzick, MD the study principal investigator over the course of the UH2 year 
to complete UH2-UH3 transition milestones. For the UH3 period, this group will again focus in on the 
completion of study milestones, reporting, and staff and budgetary management. As with the UH2 period, the 
principal investigator will have regular NIH and Collaboratory contact at monthly Collaboratory Steering 
Committee Conference calls, biannual in-person Collaboratory meetings, and on an as needed basis. The 

47 
 
roles and functions of other trial committees and subgroups outlined in the study organizational diagram are 
described below. 
 
American College of Surgeons’ Policy Steering Committee. The principal investigator in collaboration with the 
American College of Surgeons’ Policy Steering Group will be charged with ensuring sites both adhere to study 
recruitment and data collection requirements, and receive appropriate American College of Surgeons’ waivers 
and research participation credits for study participation. Gregory Jurkovich, MD American College of 
Surgeons policy lead and study 24 site liaison will oversee  interchanges between the College and the sites. 
The American College of Surgeons’ Policy Steering Group that is led by Dr. Jurkovich and included Dr. 
Hoyt, Maier and Nathens, will assume overall orchestration and responsibility for planning and implementing 
the UH3 year 5 policy summit. In the initial years 2-3 of the UH3 award, this group will have an annual 
discussion to review the trial and plan for the policy summit. Beginning in year 4 of the award, this group will 
begin more regular meetings (e.g., monthly) to initiate policy summit planning (see also UH3 Milestones 
section below). The policy summit will occur in the final UH3 year. 
 
TSOS Methods, Information Technology and Intervention Cores The principal investigator in collaboration with 
the study Methods, Information Technology and Interventions cores will be responsible for implementing the 
pragmatic trial, assuring data accuracy and harmonization and analyzing and preparing study results for 
presentations and manuscripts. Led by Dr. Heagerty, the biostatistics group will interface with the Collaboratory 
Biostatistics Core regarding issues related to stepped wedge cluster randomized trial design and 
implementation. Members of the data quality group, Drs. Russo, and Wang and will oversee data collection 
and data quality and will meet monthly with the principal investigator to review study progress. The study 
information technology core, led by Dr. Van Eaton will be responsible for information technology start-up and 
ongoing data transfer from the 24 level I US trauma center sites. The intervention core led by the principal 
investigator will be responsible for training and ongoing supervision in the stepped collaborative care 
procedures.   
 
Data Safety and Monitoring. The NIMH DSMB will perform tri-annual review of the investigations data safety 
and monitoring procedures and progress (Appendix 4). The principal investigator in collaboration with 
members of the data quality group will prepare the tri-annual reports for NIMH DSMB review.  
 
B. Plans and Annual Milestones for the UH3  
Milestones for the UH3 years 2-5 that coincide with the UH3 timeline and study specific aims are articulated in 
Table 13. The TSOS study team will continue to work closely with NIH program staff and the Collaboratory 
towards the achievement of specific milestones. 
 
With regard to aim 1, the conduct of the pragmatic trial demonstration project, in the beginning of the 
UH3 year 2, the study team will continue to work toward site readiness for protocol implementation across the 
24 sites. This preparation includes finalizing IRB approvals, ensuring site information technology readiness for 
protocol implementation, and completing all other requisite pre-randomization procedures (Appendices 1, 3, 8, 
9). Other year 2 milestones include protocol registration with clinicaltrials.gov, the initiation of tri-annual NIMH 
DSMB report submission, and submission of the clinical trial protocol manuscript for publication (Table 13). 
Milestones related to protocol control and intervention patient recruitment, and intervention training workshop 
completion will occur over the course of years 2-4 of the study as dictated by the stepped wedge intervention 
rollout (Figure 2, Figure 16, and Table 13). Data analyses and primary outcome manuscript submission will 
occur in UH3 year 5. 
With regard to aim 2, evaluation of the trial implementation process, and ongoing RE-AIM and health 
economic data collection will occur over the course of the UH3 study. RE-AIM and health economic data 
analyses will coincide with primary trial data analyses in year 5 of the study (Table 13). For Aim 3, protocol 
dissemination and annual American College of Surgeons’ stakeholder policy discussions will occur over the 
course of UH3 years 2-4. As with previous American College of Surgeons’ policy summits orchestrated by the 
study team, in the later part of UH3 year 4 more regular (e.g., monthly) policy summit planning meeting phone 
conferences will occur. These planning calls will be designed to incorporate input from NIH program staff, 
Collaboratory Steering Committee members, and other key stakeholders. This intensive planning in UH3 years 
4-5 will culminate in the UH3 year 5 American College of Surgeons’ Committee on Trauma Policy Summit. 

48 
 
Contingency of UH3 milestone attainment on timely NIMH DSMB, IRB and information 
technology progression. The milestones progression presented in Table 13 below are contingent upon timely 
progression of coordinated NIMH DSMB and IRB review of the protocol. Delays in these or other regulatory 
approvals could push back the scheduled milestone completions presented in Table 13. Similarly, delays in 
site information technology assessments and/or implementation could serve to set back the scheduled 
milestone completion timeline. 
   
Table 13. TSOS UH3 Milestones 
UH3 Specific Aim 
UH3 Milestone 
Yr2 
Yr3 
Yr4 
Yr5 
1. Conduct pragmatic trial and 
assess effect of intervention on 
PTSD and comorbidity 
Finalize 24 site readiness for protocol implementation 
X 
 
 
 
Clinicaltrials.gov protocol registration 
X 
 
 
 
Clinical trial protocol manuscript submitted  
X 
 
 
 
Tri-annual DSMB reports and monitoring 
X 
X 
X 
X 
Recruit control patients 
- 30% Complete Year 2 
- 70% Complete Year 3 
-100% Complete Year 4 
 
X 
 
 
X 
 
 
 
X 
 
Conduct one-day intervention trainings 
- 10% Year 2 
- 60% Year 3 
-100% Year 4  
 
X 
 
 
X 
 
 
 
X 
 
Recruit intervention patients 
-5% Year 2 
-40% Year 3 
-100% Year 4 
 
X 
 
 
X 
 
 
 
X 
 
Complete patient follow-up 
-15% Year 3 
-50% Year 4 
-100% Year 5 
 
 
X 
 
 
X 
 
 
 
X 
Obtain final 24 site trauma registry data 
 
 
 
X 
Prepare and submit main study outcome paper 
 
 
 
X 
2. Evaluate trial implementation 
process 
 
RE-AIM & health economic data collection 
RE-AIM & health economic data analyses 
X 
X 
X 
X 
X 
3. Disseminate study findings 
through American College of 
Surgeons’ policy summit  
American College of Surgeons’ policy core meetings & 
policy discussions  
X 
X 
X 
X 
Convene American College of Surgeons’ policy summit  
 
 
 
X 
 
C. Study Resource Sharing Plan  
An overarching goal of the UH3 investigation and work with the NIH Health Care Systems Research 
Collaboratory is to produce and disseminate information and resources that will facilitate the widespread 
implementation screening and intervention procedures for PTSD and related comorbidity throughout trauma 
care systems nationwide. The resource and data sharing plan is in concert with this overarching goal. Any 
informational or other resources developed during the UH2 development and UH3 implementation of the 
pragmatic trial including treatment manuals, reports/white papers, and clinical/policy guidelines, are intended to 
be widely disseminated throughout trauma centers and affiliated trauma care systems nationwide.  
Specifically with regard to data sharing, the interdisciplinary group encourages the use of data collected 
during the study to further the empiric basis for American College of Surgeons’ policy mandates and clinical 
practice guidelines targeting screening, intervention, and referral for PTSD and related comorbidity. Of 
particular note, the investigative group has a history of this type of collaborative data and resource sharing in 
its previous efforts to share data derived from large scale NIH funded pragmatic trials to form the foundation for 
empirically-based American College of Surgeons’ policy mandates and clinical best practice guidelines. The 
final data set will include patient, provider, and setting level demographic clinical, EHR, and trauma registry 
data from the 24 level I trauma centers and their affiliated trauma care systems that participated in the 
pragmatic trial. Along with the data set, we will create a code book documenting all variables (e.g., common 
names for trauma registry variables, names for single questionnaire items, scoring rules for derived variables). 

49 
 
After acceptance of the main manuscript for the study, which is anticipated to be 12-18 months after study 
completion, requests for access of data files will be considered. We will prioritize access to research groups 
that have a clearly articulated aim and rationale for how secondary data analyses will impact future policy 
and/or clinical practice for trauma care systems nationwide; the study team will also prioritize groups affiliated 
with the NIH Health Care Systems Research Collaboratory. Researchers requesting data will need to complete 
a request form outlining intended use of the data and agree to use the data for this intended purpose. Prior to 
data release, researchers requesting data will be required to sign a confidentiality agreement specifying that 
they will not identify any individual participant, that they will use secure technology to safeguard the data, and 
that they will destroy or return the data after their analyses are completed. The UH3 investigative team will also 
require documentation of IRB approval from the host institution prior to release of the data. 
We do not expect to make a public use data file available from the study given the nature of our sample 
and trauma care system context. Study participants may have substance abuse or other diagnoses that may 
be stigmatizing and may prefer that the conditions of the traumatic injury event remain entirely confidential. 
Although the data analytic files will not have direct identifiers (only study IDs), the possibility of deductive 
disclosure of subjects with unusual demographic, injury, or clinical characteristics remains. In order to 
safeguard against the unlikely event of deductive disclosure, we will make the data files and codebook 
available to other researchers only on a case-by-case basis.  
 
D. Study Software Sharing Plan  
The software sharing plan is in concert with the overall application goal that targets the production and 
dissemination of resources that will facilitate the widespread implementation of PTSD screening and 
intervention procedures throughout trauma care systems nationwide. An aim of the proposed work is to create 
open access software that will allow trauma centers and affiliated trauma care systems to screen for PTSD 
using automated EHR data sources. Thus, the intent of the UH2-UH3 investigative team is to develop a 
software sharing plan that is in concert with the stated goals of the NIH Collaboratory RFA RM-13-012 “NIH 
Health Care Systems Research Collaboratory – Demonstration Projects for Pragmatic Clinical Trials Focusing 
on Multiple Chronic Conditions (UH3),”332 including the following: 
1. The software should be freely available to biomedical researchers, health care delivery systems, 
research institutions, and government health care systems and researchers.  
2. The terms should also permit the dissemination and commercialization of enhanced or customized 
versions of the software, or incorporation of the software or components of it into other software 
packages.  
3. The terms of software availability should include the ability of individuals outside the applicant institution 
and its collaborating organizations to modify the source code and to share modifications with other 
colleagues.  
4. The investigative team will therefore choose a permissive open source software license that allows us 
to freely share any code/software developed for the UH3 project. 
 

50 
 
9. Dissemination Plan 
 
American College of Surgeons’ policy collaboration optimizes engagement of trauma care systems 
nationally as research partners and the potential public health impact of the pragmatic trial (Figure 18). 
Level I trauma centers care for the most severely injured patients and are mandated by the College to uphold 
the highest standards of trauma center care.63 Level I trauma centers are distinct from Level II-V trauma 
centers and other emergency department settings in that they treat the most severely injured patients with 
highly prevalent multiple chronic conditions.30,63  
 
The College oversees the development of national policy mandates and clinical best practice 
guidelines that inform the integrated operation of US trauma centers and affiliated trauma care 
systems.63 The College has successfully linked trauma center funding to verification site visits and other 
quality indicators.63,106,107 Gregory Jurkovich, MD, project consultant, has a longstanding history of collaboration 
with the College and helped to spearhead the 2005 alcohol policy mandate as Vice Chair of the College 
Committee on Trauma. Dr. Jurkovich has collaborated closely with David Hoyt, MD, FACS, current Executive 
Director of the College and UH2-UH3 project consultant, in these activities. Both Drs. Jurkovich and Hoyt have 
extensive applied and academic policy experience and expertise with PTSD and related comorbid 
conditions.75,156 Simultaneously, as the investigation is being conducted, the study team will be actively 
developing with Drs. Jurkovich and Hoyt, a College policy agenda targeting the use of pragmatic trial results to 
directly impact mandates and practice guidelines for PTSD and related comorbidity. 
Trauma centers are required by the College to maintain registry information systems that document 
adherence to policy mandates and other clinical guidelines. Study consultant, Avery Nathens, MD, PhD, 
directs national efforts by the College to harness trauma registry data for ongoing quality improvement 
initiatives.333,334 Currently, national trauma data efforts almost completely rely on post-hoc manual data 
extraction procedures that vary from site to site, and use vendor-specific data models.63,106,107 These systems 
neither support real-time, workflow integrated screening and intervention for PTSD and comorbidity, nor do 
they provide a way for trauma centers to participate in national initiatives to create population-level, de-
identified clinical data repositories for comparative effectiveness research.335 The overarching goal of 
participation in the Collaboratory could be seen as a national trauma health care system that enforces and 
supports trauma quality mandates, facilitates automation and real-time, workflow integrated data capture, and 
contributes to nationwide research goals targeting PTSD and comorbidity.  
This focus on trauma center policy directly addresses issues of engagement of trauma centers 
nationally as full research partners, as well as issues of intervention maintenance/sustainability. The 
scientific aims and results of the UH3 project have tremendous potential public health impact by directly 
informing nationwide policy mandates and clinical practice guidelines. The College policy support in the current 
investigation facilitates the endurance of new policy mandates and clinical guidelines, and ensures that 
sustained attention will be given to the underlying issue of wide-spread implementation of screening and 
intervention procedures for PTSD and related comorbidity, long after the completion of a single pragmatic 
trial.190,336-338 Thus, the research team is fully committed to developing and implementing, with the aid of the 
Collaboratory, a flexible care management intervention targeting PTSD and comorbidity that is sustainable 
both within their own trauma center and also throughout trauma care systems nationally. This strategy is 
entirely in concert with the Collaboratory RFA-RM-13-012/MCC approach 332 that strongly encourages 
implementation of any developed care intervention model within the “home” health care systems (Figure 3). 
The results of the trial will directly inform future American College of Surgeons’ policy regarding 
screening and intervention for PTSD and comorbidity (Figure 18). In January of 2005, the College made a 
landmark policy decision to mandate health services targeting screening and intervention for alcohol related 
disorders as a requisite for trauma center accreditation.63 Prior pragmatic randomized clinical trial 
investigations from the study team provided evidence supporting the College’s alcohol mandate.18,75,129 In May 
of 2011, the investigators presented results from effective NIH funded PTSD screening and intervention trials 
at a College policy summit.129,136,137,172 Following the proposed summit in UH3 year 5, for the first time, the 
College intends to include PTSD screening and intervention as a best practice level recommendation in 
national guidelines for trauma center care. These new College clinical guidelines set the stage for a novel 
demonstration project that tests high quality, feasibly implemented, screening and intervention procedures for 
PTSD and related comorbidity. Dr. David Hoyt, the Executive Director of the College, is committed to a follow-
up policy summit in 2019-2020 to integrate pragmatic trial results into the next edition of College guidelines for 

51 
 
the operation of trauma centers (Figure 18). Thus, simultaneously as the investigation is being conducted, the 
study team will be actively developing a College summit agenda targeting the broader aim of engaging trauma 
care systems nationwide in the research by using pragmatic trial results to directly impact policy mandates and 
clinical practice guidelines for PTSD and comorbidity. An overarching goal of the study team is to work with the 
Collaboratory to comprehensively refine procedures developed in prior investigation in order to develop real-
time, workflow integrated, automated data screening, intervention and quality documentation procedures for 
the chronic disease cluster of PTSD and comorbidities that can be deployed across trauma care systems 
nationally. The proposed UH2-UH3 pragmatic trial is novel in suggesting both the specific technologic 
innovations that trauma centers could implement, and a national policy mechanism aimed to ensure that this IT 
innovation occurs. 
 
Harborview 
Implementation of 
Single Site Alcohol 
RCT
ACS Policy 
Mandate 
for Alcohol
Harborview 
Implementation of 
Single Site PTSD 
Pragmatic Trials
Study Team 
Orchestrates 
Policy Summit
Study Team 
Orchestrates 
Policy Summit
ACS Policy 
Best Practice 
Guideline for 
PTSD
Proposed UH2-
UH3 Pragmatic 
Trial for PTSD & 
Comorbidity
Study Team 
Orchestrates 
Policy Summit
ACS Policy Revision 
Based on UH3 
Pragmatic Trial for 
PTSD & Comorbidity
2000
2006
2014
2020
Figure 18. Two Decades of Orchestration of American College of Surgeons’ (ACS) Policy & NIH Funded Clinical Trials
 
 
UH3 American College of Surgeons’ Policy Summit. In the UH3 year 5 of the proposal, the results of the 
pragmatic trial will be presented at a College policy summit. The preparation for the summit will follow similar 
guidelines as were developed for the May 2011 summit. Dr. Zatzick will convene a monthly meeting of the 
interdisciplinary team that will include Drs. Hoyt and Jurkovich; Collaboratory and NIH program staff will also 
be invited to participate. A key focus of the summit will be discussion of the implications of trial results for 
screening and intervention for PTSD and comorbidity, clinical practice guidelines, and policy mandates. In 
particular, the study team will discuss findings that facilitate the implementation of real-time, workflow 
integrated screening and intervention procedures for PTSD and comorbidity across trauma care systems 
nationally. Following the summit, the multi-stakeholder group will work together to develop a white paper that 
reviews the state of the science and recommendations for future directions for screening and intervention 
procedures for PTSD and related comorbidity at trauma centers nationwide. The summit will be timed to 
optimally impact the next version of trauma center guidelines (Figure 18).63 
Ongoing American College of Surgeons’ Stakeholder Commitment to UH3 Aims & 
Implementation (Appendix 2). The transition request includes letters from senior American College of 
Surgeons’ policy advisors: Dr. David Hoyt, MD Executive Director of the American College of Surgeons’, Dr. 
Ronald Maier, First Vice President of the American College of Surgeons’ and Surgeon-in-Chief at the 
Harborview level I trauma center at the University of Washington, and Dr. Gregory Jurkovich, MD study policy 
lead and Chief of Trauma Surgery at Denver Health and the University of Colorado. The letters substantiate 
College support for the trial. This support includes commitment to convening an American College of 
Surgeons’ policy summit to discuss implications for current practice guidelines and policy mandates targeting 
PTSD and comorbidity. This support also includes granting College research participation credit to the study 24 
level I trauma centers and granting waivers of alcohol screening and brief intervention verification site visit 
requirements to participating centers. 
 
 

52 
 
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