Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome
Conditions: Apnea, Sleep, Brain Injury, Traumatic
Sponsor: James A. Haley Veterans Administration Hospital

Protocol:  CSAS 
 
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Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and 
Outcome (C-SAS) 
 
NCT03033901 
 
Document Date: August 26, 2020 
 

Protocol:  CSAS 
 
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Title: Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation 
and Outcome (C-SAS) 
 
 
Primary Investigator: 
Risa Nakase-Richardson, Ph.D., FACRM, FNAN 
Mental Health and Behavioral Sciences, Defense and Veterans Brain Injury Center at James A. 
Haley Veterans’ Hospital, Morsani College of Medicine, Division of Pulmonary and Sleep 
Medicine, University of South Florida, Tampa, FL 
Phone: (813) 972-2000 
Fax: (813) 631-3243 
 
Sponsor: 
Patient Centered Outcomes Research Institute 
1828 L. Street, NW, Suite 900 
Washington, DC 20036 
Phone: (202) 827-7700 
Fax: (202) 355-9558 
 
 
 

Protocol:  CSAS 
 
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STUDY SUMMARY 
Title 
Comparison of Sleep Apnea Assessment 
Strategies to Maximize TBI Rehabilitation 
Participation and Outcome (C-SAS) 
Methodology 
Prospective, diagnostic clinical trial 
Study Duration 
Study recruitment was initiated on 05/2017 and 
completion of all participants in the protocol 
occurred on 02/2019. 
Study Centers 
Potential participants were consecutive patients 
enrolled in the TBI Model Systems (TBIMS) at six 
sites (Tampa, FL [James A. Haley Veterans 
Hospital]; Seattle, WA [University of 
Washington]; Dallas, TX [Baylor Scott & White 
Rehabilitation]; Columbus, OH [Ohio State 
University]; Denver, CO [Craig Hospital]; and 
Philadelphia, PA [Moss Rehabilitation Institute]). 
Objectives 
Aim 1: For individuals with TBI, determine 
comparative effectiveness of AASM endorsed 
patient-reported screening tools and objective 
actigraphy to identify those at high risk of sleep 
apnea as diagnosed through Level 1 Diagnostic 
Polysomnography. 
 
Aim 2: Determine the diagnostic accuracy (non-
inferiority of Level 3 portable diagnostic testing in 
determining presence of sleep apnea in patients 
with acute TBI patients in the rehabilitation 
setting. 
Number of Subjects 
Aim 1:   248   
Aim 2:   214 
Diagnosis and Main Inclusion Criteria 
Inclusion Criteria: 
*Damage to brain tissue caused by an external 
mechanical force 
*Alteration of consciousness > 24 hours, or loss 
of consciousness > 30 minutes, or Glasgow Coma 
Scale (GCS) score in the Emergency Department 
of 3-12, or intracranial abnormalities on imaging 
regardless of GCS 
*Admission to inpatient rehabilitation 
*Minimum age 16 years at civilian sites and 18 
years at the VA site 
*Consent to participate by person with brain 
injury (if able), family member or legally 
authorized representative into the TBI Model 
System lifetime study. This criterion was relaxed 
in Study Month 11.  
 

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Exclusion Criteria: 
*Habitual sleep duration > 2 hours/night for two 
(2) consecutive nights not being established prior 
to PSG 
*Presence of a physical deformity precluding 
sensitivity of PSG instrumentation (i.e. full body 
cast, PSG that could not be removed prior to PSG) 
*Medical instability as determined by the treating 
physician (i.e. agitation, acute illness) 
*Infeasibility of tracheostomy placement with 
decannulation or overnight capping during 
rehabilitation   
Study Product 
Aim1: Subjects will complete paper and pencil 
screening tests (STOPBang, Berlin, MAPI), 
actigraphy, and Level 1 Diagnostic 
Polysomnography. 
 
Aim 2: Subjects recruited will undergo 
simultaneous administration of Level 1 Diagnostic 
Polysomnography and Level 3 Portable Diagnostic 
tests. 
Statistical Methodology 
Aim 1: Area under the curve (AUC) of screening 
tools predicting sleep apnea status and severity. 
Aim2: Non-inferiority of Level 3 portable 
diagnostic tests to the criterion standard, Level 1 
Polysomnography.  
 

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Purpose: 
The primary objective is to identify the comparative effectiveness of existing screening and diagnostic 
tools for sleep apnea to promote earlier detection (thus treatment) during inpatient rehabilitation for 
moderate to severe traumatic brain injury (TBI).  
 
Background: 
Given that sleep is critical for neural repair and disordered sleep may play a role in slowing functional 
recovery and prolonging rehabilitation, early detection of sleep apnea is critical (Stakeholder Input). The 
Agency for Healthcare Research and Quality’s (AHRQ) Comparative Effectiveness Review highlighted 
insufficient comparative effectiveness evidence for sleep apnea diagnostic and screening tools. This is a 
prospective, observational cohort study conducted on inpatient rehabilitation units at six Traumatic 
Brain Injury (TBI) TBI Model System sites. The diagnostic utility of existing sleep studies is needed to 
inform clinical management during acute recovery from TBI. 
 
Goals of the Study: 
(Aim 1: Screening) For individuals with TBI, determine comparative effectiveness of the American 
Academy of Sleep Medicine (AASM) endorsed screening tools and objective actigraphy (ACG) to identify 
those at high risk of sleep apnea as diagnosed through Level 1 polysomnography (PSG) which is the 
criterion standard. (Aim 2: Diagnosis). Determine the diagnostic accuracy (non-inferiority) of portable 
diagnostic testing (more accessible test) relative to Level 1 PSG (laboratory-quality study; criterion 
standard, less accessible test) in determining presence of sleep apnea in patients with acute TBI during 
inpatient rehabilitation hospitalization.  
 
Duration of the Study:  
The study completed enrollment and met recruitment goals within a 19-month period. Participants 
completed study activities upon completion of diagnostic testing. 
 
Product Description and Intended Use: 
Sleep Apnea Screening Tools (comparators) 
STOPBANG (OSA Screening Comparator). The STOPBANG is comprised of eight (8) items that refer to 
Snoring, Tiredness, Observed breathing pauses during sleep, treatment for high blood Pressure, 
elevated Body mass index, older Age, wide Neck circumference, and male Gender. An affirmative 
response to 2 items indicates low risk, 3-4 items intermediate risk, 5-8 items high risk.  
 
Berlin (OSA Screening Comparator). The Berlin Questionnaire is a 10-item measure that evaluates risk 
factors for sleep apnea into three (3) categories (snoring severity, excessive daytime sleepiness and 
history of high blood pressure or obesity). Positivity in two or more of these categories is associated 
with a high likelihood of clinically-relevant sleep apnea.  
 
Multivariate Apnea Prediction Index (MAPI; OSA Screening Comparator). The questionnaire consists of 
three breathing-related questions and utilizes information on demographics (sex, weight, height, age), 
from which a probability of having sleep apnea (0-100%) can be calculated.  
 
Actigraphy (ACG; Comparator). A wrist-worn accelerometer (Actiwatch Spectrum, Philips/Respironics, 
Bend, OR) was used to document sleep metrics during the trial. Activity data informing sleep statistics 
were recorded in 15-second intervals.  
 
Diagnostic Comparators 

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Level 1 Polysomnography (gold standard method) is the criterion standard for diagnosing sleep apnea 
with overnight monitoring conducted routinely in a sleep laboratory with a registered polysomnography 
technician in attendance to assure quality of the study through monitoring of data collection using 
computer interfaces. All sites utilized a uniform system which for this trial was the Philips Alice 6 LDx 
Diagnostic Sleep System with results scored in and generated by the Philips Sleepware G3 version 3.8.1 
software. The Alice has the capability for up to 55 channels of information collected during overnight 
monitoring to diagnose sleep disorders including 19 EEG (electroencephalography) inputs, 5 dedicated 
EMG (electromyography) channels, 3 Chin EMG inputs, EOG (ocular) channels and 7 ECG (heart) 
channels. Additional features include measurement of thermal flow, snoring, body position, actimeter 
inputs, light sensors, pulse oximetry, chest and abdominal effort with 8 AUC inputs, and video and audio 
integration.  Many devices are available on the market. Clinician stakeholders on the study (with no 
conflicts of interest) recommended the system chosen for study purposes.  
 
Portable Sleep Studies (comparator for non-inferiority) are also known as home sleep apnea tests 
(HSATs in the sleep medicine field). The portable sleep study device used in this trial was the Nox T-3 
Monitor [Nox Medical Inc., Reykjavik, Iceland] and Noxturnal version 4.4.2 software. This device used a 
total of four channels for assessment of sleep apnea including chest and abdominal effort (2), thermal 
flow (1), and pulse oximetry (1) along with audio recording of snoring. It does not utilize 
electroencephalography data to determine sleep states which is included in the scoring of sleep apnea 
using the criterion standard test, Level 1 PSG.  Technicians do not monitor the quality of the study 
information being collected overnight.  Many devices are available on the market. Clinician stakeholders 
on the study (with no conflicts of interest) recommended the system chosen for study purposes. 
 
Product Acquisition: 
The screening tests are in the public domain thus no cost to the participant or study institutions. The 
diagnostic tests, supplies, and software were purchased using grant funding for study purposes.  
 
Potential Benefits and Risks to the Participants 
Protections Against Risk Implemented at Start of Trial:  To minimize the risk of uncomfortable questions 
on assessments, participants are instructed during the informed consent process that they can decline 
to answer any question or discontinue participation at any point in the study. Participants will be 
informed in the consent form that they do not have to discuss any topics and engage in any procedures 
that they do not wish to during the assessment periods. In addition, participants are informed during the 
consent process they are free to stop an assessment at any time. Participants are also informed before 
each assessment period that they may refuse to answer any questions or procedures that make them 
feel uncomfortable. Any discomfort from wearing the sleep monitoring equipment (ACG or PSG), either 
physical or emotional, should be readily resolved with adjustments and repositioning. Continuous 
monitoring by a registered sleep technician during the PSG study will provide the participant with 
physical assistance for adjusting the equipment and with reassurance for the duration of the study. Any 
skins problems related to wearing the equipment, should be readily treated with skin lotion and 
repositioning the device. If the sleep assessment procedures are determined to be too physically or 
emotionally uncomfortable for the participant by either clinical or research staff, he/she may be 
administratively withdrawn from the study. All changes in the participant’s medical status during an 
assessment will be communicated to clinical staff for follow up. Should the participant appear to 
become medically distressed during the course of an assessment, research staff will immediately contact 
the participant’s clinical staff and study investigators for follow up. If research personnel discover new 
medical or emotional concerns during study assessments, the research staff member will promptly 
report this information to clinical staff and to study investigators for follow up. If, during the course of 

Protocol:  CSAS 
 
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the study, the patient is discovered to have sleep apnea or another sleep disorder, this information will 
be communicated to the participant’s clinical staff for follow up. 
 
All unanticipated problems and adverse events will be tracked by research staff and promptly reported 
to the study investigators and IRBs for appropriate resolution. An unanticipated problem is defined as 
any incident, experience, or outcome that is unexpected (in terms of nature, severity, or frequency) 
given the research procedures that are described in the protocol‐related documents; possibly related to 
participation in the research; and suggests that the research places subjects or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) than was previously known or 
recognized. Unanticipated problems will be promptly reported immediately to the site investigator and 
to the local IRB, as well as to the study Principal Investigators. An Unanticipated Problem Report form 
will be completed and returned to all regulatory institutions as soon as possible. 
 
An adverse event (AE) is any unfavorable and unintended sign, symptom or disease temporally 
associated with a study procedure regardless of whether it is considered related to the procedure. A 
serious adverse event (SAE) is any untoward medical occurrence that 1) results in death, 2) is life‐
threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, or 4) results 
in persistent or significant disability/incapacity. AEs may be graded as mild (no limitation of usual 
activities), moderate (some limitation) or severe (inability to carry out usual activities) and attributed 
according to the relationship to the study procedures as not related, possibly related, or related. A 
clinical event form will be completed in the case of any and all reported adverse events associated with 
the treatment procedures. Copies of these forms will be sent to the Principal Investigators. The original 
will be placed in the participant’s study folder. The purpose of this procedure is to make certain all 
possible adverse events are examined to determine the proper action, if any, that needs to be taken. 
Mild and moderate AEs will be tracked and reported quarterly to the Principal Investigator. SAEs will be 
reported immediately to the site principal investigator and to the local IRB. An Adverse Event Report 
form will be completed and returned to all regulatory institutions as soon as possible. To protect 
confidentiality of data, all data will be maintained in a secure database on secure servers. Within the 
database and on all data collection forms, numbers will be used in place of names or other direct 
identifiers. Any hard copies of data collection forms and tools are kept in locked file cabinets. Only 
research staff members assigned to the project will have access to documents and computer databases. 
All investigators and research staff involved in the project will have completed online training in 
protection of human subjects. Research staff will not disclose the identity of a participant or any 
information regarding participation to anyone beyond legal parties who are privy to this information. 
 
Methods 
Study Design: Prospective diagnostic clinical trial of comparative effectiveness of screening and 
diagnostic tools for sleep apnea.  
 
Study population and selection criteria:  Potential participants were consecutive patients enrolled in the 
TBI Model Systems (TBIMS) at six sites (Tampa FL, Seattle WA, Dallas TX, Columbus OH, Denver CO, and 
Philadelphia, PA) described earlier and over 19 months. Study inclusion/exclusion criteria for the TBI 
Model Systems and this trial are described in Table 1.63 The requirement of TBIMS enrollment at time 
of consent for the clinical trial was relaxed at study-month 11 to allow for earlier enrollment during 
rehabilitation but the clinical criteria remained unchanged. 
 
Recruitment Methods:  All participating sites received institutional review board approval for conduct of 
the study. Consecutive admissions were screened for eligibility. Participants who passed the first level of 

Protocol:  CSAS 
 
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screening (or their proxies) were consented and further screened for final eligibility including 1) ≥ 2 
hours sleep/night based on actigraphy placement or nursing logs/report, and 2) medical stability 
(including no emergent medical issues precluding overnight PSG and minimal to no post-traumatic 
agitation, as assessed by the Agitated Behavior Scale). Once determined eligible, an overnight PSG study 
was conducted by a registered polysomnographic technician (RPSGT) in the participant’s own bed. 
Within 72 hours of the PSG, questionnaire-based sleep apnea screening measures were completed with 
the participant and/or best source available using established TBIMS procedures by local staff blinded to 
PSG results. Sleep-related information during hospitalization was collected from the medical staff 
(snoring status, daytime sleepiness) or medical record (weight, height). The patient-reported outcome 
was the primary source of data. When data were missing due to the participant’s inability to respond or 
with unknown responses, it was imputed using best source data if available otherwise was considered 
missing data. 
 
Data collection and reporting:  Demographic and pre-injury medical histories, and medical record 
abstraction were conducted by trained research assistants following the TBIMS protocol.  Within 72 
hours of the PSG, questionnaire-based sleep apnea screening measures were completed with the 
participant and/or best source available using established TBIMS procedures by local staff blinded to 
PSG results. Sleep-related information during hospitalization was collected from the medical staff 
(snoring status, daytime sleepiness) or medical record (weight, height). The patient-reported outcome 
was the primary source of data. When data were missing due to the participant’s inability to respond or 
with unknown responses, it was imputed using best source data if available otherwise was considered 
missing data. Participants underwent simultaneous administration of Level 1 PSG (Philips Alice 6 LDx 
Diagnostic Sleep System with Philips Sleepware G3 version 3.8.1 software) and portable sleep study (i.e., 
HSAT using the Nox T-3 Monitor [Nox Medical Inc., Reykjavik, Iceland] and Noxturnal version 4.4.2 
software. Fully attended Level 1 PSG was conducted in accordance with the American Academy of Sleep 
Medicine recommended procedures.49 Staff were instructed to allow participants their normal sleep 
period.  
 
The lead center (James A. Haley Veterans’ Hospital, Tampa, FL) served as a centralized scoring center for 
all sleep studies. All Level 1 PSG studies were masked and scored within seven business days of PSG 
completion with results subsequently databased and entered by research assistants. The Level 3 
portable sleep studies were masked and scored in batches of 50+ studies approximately 3-6 months 
after completion and scoring of Level 1 PSG to assure blinding of portable study scoring from the Level 1 
PSG results. All portable sleep studies were edited by the RPSGT; the automated software results were 
not used in analyses. Editing entailed setting start/stop recording times based on assessment of 
embedded actigraphy (reduction in movement) in the portable device and elimination of data during 
periods of absent valid waveforms for oximetric plethysmographic data, nasal pressure transducer data, 
and effort signal data.   
 
Outcomes 
The psychometric properties of screenings tools for sleep apnea endorsed by the AASM are now 
available for persons with moderate to severe TBI undergoing inpatient rehabilitation.  
Nakase-Richardson R, Schwartz DJ, Drasher-Phillips L, Ketchum JM, Calero K, Dahdah MN, 
Monden KR, Bell K, Magalang U, Hoffman J, Whyte J, Bogner J, Zeitzer J. Comparative 
effectiveness of sleep apnea screening instruments during inpatient rehabilitation following 
moderate to severe TBI. Archives Phys Med Rehabil. 2020;101:283-96. doi: 
10.1016/j.apmr.2019.09.019. PMID:31705855 

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The comparative effectiveness (non-inferiority) of portable diagnostic testing relative to the criterion 
standard in persons with moderate to severe TBI undergoing inpatient rehabilitation is now available. 
See below: 
Nakase-Richardson R, Schwartz D, Ketchum J, Drasher-Phillips L, Dahdah M, Monden K, Bell K, 
Hoffman J, Whyte J, Bogner J, Calero K, Magalang U. Comparison of diagnostic sleep studies in 
moderate to severe traumatic brain injury neurorehabilitation admissions. Chest. 2020;pii: 
S0012-3692(20)30863-1. doi: 10.1016/j.chest.2020.03.083. [Epub ahead of print]. PMID:  
32387522 
 
Adverse Reactions 
None reported. 
 
Reasons for withdrawal or termination 
No subjects were terminated from the study. No participant completely withdrew from the study. 
However, some study procedures were refused as described in corresponding publications for each aim. 
 
Premature termination or suspension of the study 
Not applicable.  
 
Methods and Study Schedule 
Baseline Screening Visit:  All participating sites received institutional review board approval for conduct 
of the study. Consecutive admissions were screened for eligibility. Participants who passed the first level 
of screening (or their proxies) were consented and further screened for final eligibility including 1) ≥ 2 
hours sleep/night based on actigraphy placement or nursing logs/report, and 2) medical stability 
(including no emergent medical issues precluding overnight PSG and minimal to no post-traumatic 
agitation, as assessed by the Agitated Behavior Scale). Once determined eligible, an overnight PSG study 
was conducted by a registered polysomnographic technician (RPSGT) in the participant’s own bed. 
Within 72 hours of the PSG, questionnaire-based sleep apnea screening measures were completed with 
the participant and/or best source available using established TBIMS procedures by local staff blinded to 
PSG results. Sleep-related information during hospitalization was collected from the medical staff 
(snoring status, daytime sleepiness) or medical record (weight, height). The patient-reported outcome 
was the primary source of data. When data were missing due to the participant’s inability to respond or 
with unknown responses, it was imputed using best source data if available otherwise was considered 
missing data. 
 
Final Study Visit:  Fully attended Level 1 PSG was conducted in accordance with the American Academy 
of Sleep Medicine recommended procedures1. The RPSGT also conducted a physical examination of the 
participants and rated agitation. Staff were instructed to allow participants to sleep their normal 
habitual sleep period with a minimum of two hours of sleep needed for adequate study. The lead center 
(James A. Haley Veterans’ Hospital, Tampa, FL) served as a centralized scoring center for all sleep 
studies. All de-identified studies were scored by one of two certified RPSGT (CD, LW) and interpreted by 
a board-certified sleep medicine physician (DS, KC). All staff that scored and interpreted studies were 
blinded to other sleep assessments. 
 
Sample Size Justification  
Power Analyses from Research Plan:   
(Aim 1) To test the hypothesis for Aim 1, a paired‐sample diagnostic analysis (estimated 
sensitivities/specificities) for each screening measure relative to the criterion standard, Level 1 PSG) was 

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performed using the same sample of patients. Prevalence of sleep apnea (as determined by Level 1 PSG) 
was conservatively estimated to be 30% using investigators’ published reports of 37‐39% prevalence in 
acute rehabilitation TBI samples.36-37 A two‐sided McNemar’s test, assuming a significance level of α = 
0.05, will have at least 80% power to detect a difference in sensitivities of 20% between screening 
measures for a sample size of 237. The power of the test will increase if the prevalence is higher than 
30% (e.g., a prevalence of 35% would yield 87% power with 237 subjects and only require 203 subjects 
for 80% power). Furthermore, a sample size of 237 will have at least 80% power to detect a difference of 
20% in sensitivities between screening measures in detecting sleep apnea. 
 (Aim 2) To test the non-inferiority hypothesis of the portable device for diagnosing sleep apnea, the 
non-inferiority of SE and SP (relative to SEH = 0.9 and SPH = 0.6, each within Δ = 0.1) were jointly tested 
at the significance level of α=0.05 by estimating the cross-product of two one-sided 1-α* confidence 
intervals;96 SEH and SPH were selected a priori and were considered sufficiently large to obviate the 
need Level 1 PSG. For the purposes of the clinical trial, the study was powered to demonstrate non-
inferiority of Level 3 sleep studies relative to fixed values of sensitivity (SE) and specificity (SP).97 
Minimum sample sizes of 83 and 153 patients achieved at least 80% power to detect non-inferiority of 
SE to 90% and SP to 60% with a non-inferiority limit of Δ = 0.1, using one-sided exact tests each at a 5% 
level of significance. In total, 214 subjects were available for analysis which yields 83.9% and 98.8% 
power, respectively, when testing the non-inferiority of SE and SP each at a 2.53% level of significance 
and maintaining a 5% level of significance when testing SE and SP jointly.2 
 
Loss to follow-up: 
See sample flow diagrams for each aim in corresponding publications. 
 
Statistical Analysis Plan 
Primary Endpoint: (Aim 1) Receiver Operating Characteristic Area Under the Curve  
To determine the predictive utility of the screening tools for diagnosing mild (AHI ≥ 5), moderate (AHI ≥ 
15), and severe (AHI ≥ 30) sleep apnea, receiver-operating characteristics (ROC) curve analyses were 
performed. A ROC curve plots the true positive rate (sensitivity) against the false positive rate (1 – 
specificity) for all possible cut-off scores of the screening tools. The area under the ROC curve (ROC AUC) 
and corresponding 95% confidence interval (CI) were estimated to provide a measure of overall 
discrimination for each screening tool. Standard diagnostic measures including sensitivity (SE), specificity 
(SP), positive predictive value (PPV) and negative predictive value (NPV), and false negative rate (FNR) 
were calculated across varying cut-off scores for each screening tool. The Youden index, commonly used 
to determine the optimal cut-off score where equal weight is given to sensitivity and specificity (defined 
as “sensitivity + specificity – 1” was also calculated).88-91 For MAPI probability, cut-off scores of 0.1 to 
0.9 in increments of 0.1 were summarized along with the optimal cut-off score. For the Berlin, 
participants were either low risk (0 or 1 category positive) or high risk (≥2 categories positive), so there is 
only one possible cut-off score. For Actigraphy, since less sleep is thought to be associated with worse 
sleep outcomes (such as sleep apnea), 12 hours minus the total sleep time was examined at 60- minute 
cut points from 3 to 10 hours. The ROC AUCs were compared among the four screening tools using a χ² 
test. Median with interquartile range (IQR) are provided. 
 
(Aim 2) Sensitivity and Specificity Jointly Tested:  To test the non-inferiority hypothesis of the portable 
device for diagnosing sleep apnea, the non-inferiority of SE and SP (relative to SEH = 0.9 and SPH = 0.6, 
each within Δ = 0.1) were jointly tested at the significance level of α=0.05 by estimating the cross-
product of two one-sided 1-α* confidence intervals;e3 SEH and SPH were selected a priori and were 
considered sufficiently large to obviate the need Level 1 PSG.  
 

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Using individual significance levels of αSE = αSP = α*=0.0253 ensures that the overall significance region 
of the joint test of both SE and SP simultaneously remains no greater than α=0.05. If the lower 
confidence limits (LCL) from both 1-α* = 94.9% confidence intervals are strictly above 0.8 for SE and 0.5 
for SP, then a claim of non-inferiority of the portable diagnostic test would be established. Analyses 
were conducted for each AHI cutoff score (Total AHI ≥ 5, ≥ 15, and ≥ 30) for the overall sample and by 
subgroups. The non-inferiority thresholds were chosen based on a prior systematic review showing 
estimates of SEs and SP for AHI ≥5 were 0.96 (95% CI = 0.90, 0.98) and 0.76 (95% CI = 0.63, 0.85), 
respectively, across varying OSA prevalence rates.2  Based on the lower bounds of these 95% confidence 
intervals (rounded to the nearest 10th), 90% SE and 60% SP with a delta of 0.1 were selected for 
declaration of non-inferiority. 
1. Shayeb EM, Topfer LA, Stafinski T, Pawluk L, Menon D. Diagnostic accuracy of level 3 portable 
sleep tests versus level 1 polysomnography for sleep-disorders breathing: a systematic review 
and meta-analysis. CMAJ. 2014;186(1):E25-51. doi:10.1503/cmaj.130952 
2. Shayeb EM, Topfer LA, Stafinski T, Pawluk L, Menon D. Diagnostic accuracy of level 3 portable 
sleep tests versus level 1 polysomnography for sleep-disorders breathing: a systematic review 
and meta-analysis. CMAJ. 2014;186(1):E25-51. doi:10.1503/cmaj.130952 
3. Pepe MS. The statistical evaluation of medical tests for classification and prediction. 2003; 
Oxford University Press, New York. 
 
Assessment of Safety  
Potential adverse events were monitored by local study teams under oversight by local institutional 
review boards. Potential risks associated with this type of observational sleep research are minimal. The 
sleep assessment procedures employed in this study are commonly used in clinical sleep evaluations. 
Risk of physical harm or injury is unlikely given non‐invasive nature of ACG and PSG. The Actiwatches® 
(ACG) wrist bands could be physically or emotionally distracting. The multiple monitoring devices 
required for (PSG) may be uncomfortable either physically or emotionally. The placement of breathing 
bands could result in contact dermatitis. Some of the questions asked during the assessment periods 
might be deemed personal or sensitive and make the participant feel uncomfortable. There was the risk 
that the study assessments will discover a medical condition previously unknown to the participant such 
as the diagnosis of sleep apnea or another sleep disorder. There was also a chance that a participant 
could experience medical distress or a medical emergency unrelated to the study during the course of 
an assessment. There was a remote chance that an outside party may discover a participant’s identity 
and participation in the study. No risk to study personnel was anticipated. 
 
Pregnancy 
If a female participant was pregnant during the trial, no alteration of study procedures was indicated.  
 
Data Safety Monitoring 
 A data safety monitoring board was not required. 
 
Data Monitoring 
The PI and Site PIs were responsible for study conduct and compliance with the overall protocol, good 
clinical practice (GCP), applicable regulatory requirements, and that the data recorded were valid. To 
achieve this objective, the study team continuously monitored the enrollment and completion of 
participants in the trial on a weekly basis using live-reports and bi-weekly, multi-center meetings.  
 
Data Handling and Record Keeping 

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Procedures for the current study were carefully documented in a Manual of Procedures, and adherence 
to the procedures will be regularly monitored by the lead site. Standard procedures as recommended by 
the American Association of Sleep Technologists were followed for performing the PSGs, with the 
exception that the studies will be conducted on the rehabilitation units rather the in a sleep lab. 
Likewise, standard procedures for administering the screening measures and other instruments were 
also followed.  
 
Institutional Review Board 
All sites received Institutional Review Board approval to conduct the study.  
 
Consent Process 
Summary of Existing Currently Funded TBIMS Study Procedures. Eligibility is determined in consecutive 
admissions to inpatient brain injury rehabilitation by TBIMS staff already in place at each site. (Consent) 
TBIMS procedures in place commonly identify eligible candidates prior to admission with consent 
obtained during rehabilitation. TBIMS procedures in place at each site track subject eligibility and reason 
for exclusion into the TBIMS. These data are submitted quarterly to the TBIMS National Data Center for 
quality control purposes and subject tracking to meet data quality standards and input into Standards 
for Reports of Diagnostic Accuracy (STARD) diagrams. Consent and eligibility were tracked for this 
project using the same procedures already in place.  
 
Protocol Deviation 
Protocol deviations occur when noncompliance with the clinical trial or GCP requirements. No protocol 
deviations occurred during the trial.  
 
Laws and Regulation 
The clinical study was completed in compliance with all national laws and regulations of the United 
States. The trial was registered on www.clinicaltrials.gov.  
 
Publication and Data Sharing Policy 
In accordance with Standard Operating Procedures in place for each TBI Model System and 
implemented by the TBIMS National Data Center (Infrastructure leveraged for this project), C‐SAS 
unique data elements will be archived at the lead study site (Tampa VA) and made available for future 
analyses and dissemination following TBIMS established procedures. Both internal and external 
investigators will be able to request the data following completion of a Notification Form and Data Use 
Agreement that was developed by the TBIMS National Data Center. Syllabus and protocol materials will 
be made available online similar to other data elements collected in the TBI Model Systems 
(https://www.tbindsc.org/Syllabus.aspx). The Internal and External Notifications for Data Use and Data 
Use Agreement Policies will remain a method for ongoing continued access for both funded TBI Model 
System investigators (Internal Requests) and other scientists (External Requests). Finally, all manuscripts 
describing the study’s procedures and protocols will be submitted to PubMed Central to maximize data 
sharing. 
 
Study Personnel and Roles by Site 
Name 
Title  
Responsibilities 
James A. Haley Veterans Hospital 
Risa Nakase-Richardson, PhD 
Principal Investigator 
All study-related activities 
Leah Drasher-Phillips, MPH 
Multisite Project Manger 
Multi-site coordination, fiscal 
management, regulatory, 

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Name 
Title  
Responsibilities 
technology acquisition, 
communication, meeting 
planning, and execution.  
Danielle O’Connor, MPH, 
MA; Lauren McGlynn, BA; 
Deveney Ching, MA, CRC, 
CBIS; Emily Noyes, MA 
Research Assistants 
Enrollment; data collection, 
entry, and auditing; sleep 
study scheduling 
Daniel Schwartz, MD 
Co-Investigator and Sleep 
Medicine Physician 
Review scored Level 1 and 
HSATs and provided clinical 
reports 
Karel Calero, MD 
Sleep Medicine Physician 
Review scored Level 1 and 
HSATs and provided clinical 
reports 
Lancie Wharton, RPSGT 
Registered 
Polysomnographic 
Technician 
Attend and score Level 1 and 
HST sleep studies; scored 
Level 1 and HSATs 
Carlos Diaz-Sein, RPSGT 
Registered 
Polysomnographic 
Technician 
Score Level 1 and HSATs 
Mary Muscolino, RPSGT; 
Kenneth Parker, RPSGT; 
Laura Naughton, RPSGT, 
Marc Copeland RPSGT 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
North Texas TBI Model System 
Marie Dahdah, PhD 
Site Principal Investigator 
All study-related activities 
Kathleen Bell, MD 
Co-Investigator 
All study-related activities 
Amber Merfeld, MPH-PAPH 
and Lacy McDonald 
Research Assistants 
Enrollment, data collection 
and entry, sleep study 
scheduling, regulatory 
Jessica Behrs, RPSGT; 
Michael Elliot, RPSGT 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
Craig Hospital 
Don Gerber, PsyD and 
Kimberly Monden, PhD 
Site Principal Investigator 
All study-related activities 
Cynthia Harrison-Felix, PhD 
Data Coordinating Center PI 
All study-related activities 
Jessica Ketchum, PhD 
Biostatistician 
Consult on study design, 
methodology, 
implementation; conduct 
statistical analyses, 
collaborate on dissemination 
activities, provide final 
dataset and data dictionary 
Jody Newman, MA, CCC 
Site Coordinator 
Enrollment, regulatory 
Angie Philippus, BA 
Data Collector 
Data collection, entry, and 
quality checks 

Protocol:  CSAS 
 
14 
 
Name 
Title  
Responsibilities 
David Mellick, PhD 
Data Coordinating Center 
Manager 
Developed, implemented and 
maintained study web-based 
data management system  
William Williams, MS 
Data Coordinating Center 
Database Developer 
Supported and provided web 
programming for study web-
based data management 
system 
Emily Almeida, MS 
Data Analyst 
Data analyses 
 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
Albert Einstein Healthcare Network/Moss Rehabilitation Hospital 
John Whyte, MD, PhD and 
Thomas Watanabe, MD 
Site Principal Investigators 
All study-related activities 
Kelly Bognar, Rachel Raucci 
and Julie Wilson 
Research Assistants 
Enrollment, data collection 
and entry, sleep study 
scheduling, regulatory 
 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
University of Washington 
Jeanne Hoffman, PhD 
Site Principal Investigator 
All study-related activities 
Jesse Fann, MD 
Co-Investigator 
Collaborated on decision 
making, participated on local 
and multi-site calls 
Leslie Kempthorne, BS 
Research Manager 
Regulatory  
Erica Wasmund 
Research Study Coordinator 
Enrollment, data collection 
and entry, sleep study 
scheduling 
 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
Ohio State University 
Jennifer Bogner, PhD 
Site Principal Investigator 
All study-related activities 
Ulysses Magalang, MD 
Co-Investigator 
All study-related activities 
Randa Mireb 
Data Manager 
Data entry and quality checks 
Dominic Sauer and Jacob 
Goodfleisch 
Project Managers 
Regulatory, Data collection, 
and sleep study scheduling 
Elizabeth Windisch 
Recruitment Specialist 
Enrollment 
 
Registered 
Polysomnographic 
Technicians 
Conducted Level 1 and HST 
sleep studies 
North Florida/South Georgia Veterans’ Hospital 
Mo Modarres, PhD 
Co-Investigator 
study development, 
implementation, analysis, 
and dissemination 

Protocol:  CSAS 
 
15 
 
Name 
Title  
Responsibilities 
Palo Alto VA Healthcare System & Stanford University 
Jamie Zeitzer, PhD 
Co-Investigator 
experimental design and the 
analysis of all actigraphy data 
and dissemination 
University of South Florida 
Ambuj Kumar, MD and 
Athanasios Tsalatsanis, PhD 
Statisticians 
Data analyses and 
dissemination 
Tea Reljic, MPH 
Statistical Data Analyst 
Data analyses and 
dissemination 
Stakeholders 
Jill Coulter 
 
Caregiver of TBI Survivor 
Co-Chair Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Jill Massengale, ARNP, DNP 
Associate Chief of Nursing 
Research, James A. Haley 
Veterans’ Hospital 
Co-Chair Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Mark Aloia, PhD 
Associate Professor of 
Medicine, National Jewish 
Health Center, Denver; 
Senior Director of Global 
Clinical Research, Philips 
Healthcare 
Facilitate translation of 
findings to industry 
Joseph “Pepper” Coulter 
Veteran and TBI Survivor 
Study development, 
implementation, and 
dissemination 
Col. Geoffrey Grammer, MD 
and Scott Livingtson, PhD, 
PT, ATC, SCS 
Defense and Veterans Brain 
Injury Center 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination  
Sidney Hinds, MD 
Former DVBIC National 
Director, Program 
Coordinator for Brain Health 
Research for the DoD Blast 
Injury Research Program 
Coordinating Office 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination  
Kathryn Keiffer, SLP 
Speech Language 
Pathologist, James A. Haley 
Veterans’ Hospital 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Kerri Martin, OTR/L 
Occupational Therapist, 
James A. Haley Veterans’ 
Hospital 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination  

Protocol:  CSAS 
 
16 
 
Name 
Title  
Responsibilities 
Christina Montemayor-
Wong, RN 
Nurse, Brain Injury, James A. 
Haley Veterans’ Hospital  
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Linda Picon, MCD, CCC-SLP 
VA Senior Consultant, TBI 
Liaison to the Defense 
Centers of Excellence for PH 
and TBI 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Amy Pieragowski, OTR/L, 
CBIS 
Occupational Therapist, 
James A. Haley Veterans’ 
Hospital 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Joel Scholten, MD 
National Director,  
Physical Medicine and 
Rehabilitation, Veterans 
Health Administration 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination 
Steven Scott, DO 
Chief, Physical Medicine and 
Rehabilitation, James A. 
Haley Veterans’ Hospital 
Participate in Stakeholder 
Advisory Board Meetings, 
provide feedback on study 
materials, and dissemination