Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome

Background and Significance:

Meta-analyses of TBI studies found prevalence of obstructive sleep apnea (OSA) was 12 times
higher than community-based studies. Yet, sleep apnea in those with TBI is largely
undiagnosed. 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). Minimal guidance exists informing TBI and sleep
medicine physicians regarding assessment of sleep disorders in the acute rehabilitation
setting. The Agency for Healthcare Research and Quality's (AHRQ) Comparative Effectiveness
Review highlighted insufficient comparative effectiveness evidence for diagnostic and
screening tools. This study proposes to leverage the existing TBI Model System research
consortium (TBIMS), funded by the Departments of Health and Human Services and Veterans
Affairs, to improve early detection of sleep apnea in patients with TBI undergoing inpatient
rehabilitation at six study sites. Study aims are focused around components of phased testing
for sleep apnea. Findings will inform clinician's decisions for screening and diagnostic
tests to facilitate earlier recognition of sleep apnea (outcome) and subsequently prescribe
appropriate treatments.

Study Aims:

Aim I: (Screening) For individuals with TBI, determine comparative effectiveness of 2
American Academy of Sleep Medicine (AASM) endorsed screening tools (STOPBang vs. Actigraphy)
to identify those at high risk of sleep apnea as diagnosed through Level 1 PSG. Long-term
Objectives: To inform clinician's choices for screening measures to determine presence of
sleep apnea.

Exploratory Aim:

Evaluate alternative screening tools (Berlin, MAPI) to Level 1 PSG in Aim 1.

Aim II: (Diagnosis) This study will determine the diagnostic accuracy (non-inferiority) of
Level 3 PSG in determining presence of sleep apnea in patients with acute TBI patients in the
rehabilitation setting. Level 1 PSG will be used as the criterion standard. Long-term
Objectives: To inform clinician's choices of diagnostic tests to determine presence of sleep
apnea and prescribe appropriate treatments. If Level 3 portable PSG is equivalent to the less
accessible Level 1 PSG, this will increase consumer accessibility.

Study Design:

This is a 3-year, multi-center prospective observational cohort study.

Intervention and Comparators:

In Aim I, the screening tools STOPBang and ACG will be compared against one another to
determine their sensitivity and specificity in identifying patients with TBI at risk for
sleep apnea. In Aim II, the non-inferiority of Level 3 PSG in determining presence and
severity of sleep apnea in patients with moderate to severe TBI will be compared to Level 1
PSG.

Study Population:

Consecutive participants to neurorehabilitation at an existing National Institute on
Disability, Independent Living, and Rehabilitation Research (NIDILRR) or VA funded TBIMS
Center will make up the study population. Patients will be age 16 and older (18 or older at
VA sites), with moderate to severe TBI, admitted for rehabilitation in a U.S. TBIMS inpatient
rehabilitation facility, and sleeping > 2 hours/night suggesting habitual sleep duration.
Based on historical data from the six study sites participating in this study, investigators
in this study conservatively estimated that 70% of patients admitted for inpatient TBI
rehabilitation would consent into this study (N=20/month), resulting in a 13-month enrollment
estimate of 259 patients. Power analyses of each study aim suggest that a sample size of 237
is the largest sample size needed for sufficient power. The sites participating in this study
aim to collectively enroll 259 patients to account for possible further attrition. Based on
TBIMS data acquired over the past 25-years, 44% of the sample is female, 64% are categorized
as Non-White, median age is 38 years, with predominantly moderate to severe TBI.

Primary outcomes consist of:

1) Positive predictive power of screening tools: STOPBang and ACG, 2) Equivalency in
detection of sleep apnea via Level 1 and Level 3 PSG, with diagnosis of sleep apnea based on
overall apnea-hypopnea index (AHI) > 5.

Analytic Methods:

Aim 1: Investigators expect that STOPBang values > 5 and abnormal ACG total sleep time (< 5
hours with desaturation) will produce sufficiently high SEs with reasonable tradeoff in SP
(noting that SE and SP are inversely related). Similarly, for Level 1 PSG, a diagnosis of
sleep apnea will be made if AHI ≥ 5. Cross-tabulations of STOPBang and ACG screening for high
risk of sleep apnea (positive/negative) versus Level 1 PSG diagnosis (positive/negative) will
be constructed and estimates of diagnostic accuracy (i.e., sensitivity, specificity, positive
and negative predictive values, and diagnostic accuracy) will be estimated along with 95%
confidence intervals. To address hypothesis 1.1, two-sided McNemar's tests will be used to
compare the paired SEs and paired SPs between STOPBang and ACG assuming a significance level
of α = 0.05.

Aim 2: The sensitivity (SE) and specificity (SP) of Level 3 PSG (compared to Level 1 PSG, the
reference gold standard) will each be estimated and compared to fixed hypothesized rates of
SE and SP of 90% and 60%, respectively, considered sufficiently large enough. Level 1 PSG
(reference) diagnosis of sleep apnea will be made based on AHI ≥ 5. Level 3 PSG (test)
diagnosis will be made based AHI ≥ 5. A cross-tabulation of Level 3 PSG (positive/negative)
versus Level 1 PSG (positive/negative) will be constructed and standard measures of
diagnostic accuracy will be estimated along with 95% confidence intervals (i.e., sensitivity,
specificity, positive and negative predictive values, and diagnostic accuracy).To test for
non-inferiority of the SE to 90% and the SP to 60%, a non-inferiority threshold of 0.1 is
assumed. If the lower bound on the 95% confidence interval for SE is strictly above 80% and
the lower bound on the confidence interval for SP is strictly above 50% then non-inferiority
of Level 3 PSG (compared to Level 3 PSG) can be established.

Inclusion Criteria:

1. Meet case definition for TBI:

(A). VA (for James A. Haley Veterans' Hospital): i. Persons fitting the definition of
traumatic brain injury (TBI), defined as a traumatically induced structural brain
injury, brain trauma, or damage to brain tissue, and/or physiological disruption of
brain function as a result of an external mechanical force (also including
acceleration/deceleration movement without direct external trauma to the head, a
foreign body penetrating the brain, forces generated from events such as a blast or
explosion, or other force) as evidenced by self-reported or medically
documented(physical examination or mental status examination) new onset or worsening
of at least one of the following clinical signs immediately following the event: (a) a
period of loss of or a decreased level of consciousness; (b) alteration in mental
state at the time of the injury (confusion, disorientation, slowed thinking); (c) loss
of memory for events immediately before or after the injury; (d) posttraumatic amnesia
(PTA); (d)neurological deficits (weakness, imbalance, change in vision, praxis,
paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient; or (e)
intracranial lesion. ii. Age 18 or older at the time of index TBI. iii. Admitted to
one of the five designated VA Polytrauma Rehabilitation Centers (PRCs) for
comprehensive rehabilitation with the presenting diagnoses of TBI. Comprehensive
rehabilitation must occur in the PRC and meet the following criteria: (a) Medical and
rehabilitation care are supervised on a regular basis by a physician affiliated with
the PRC; (b) 24-hour nursing care is provided to the patient;(c) PT, Occupational
Therapy (OT), Speech, Rehabilitation Psychology, Neuropsychology, and/or family
support/education are provided in an integrated team approach with the expectation of
further gain; (d) Operates in a manner consistent with Commission on Accreditation of
Rehabilitation Facilities (CARF) standards for brain injury inpatient rehabilitation
and/or Medicare requirements for inpatient rehabilitation.

OR

(B). Civilian (for civilian sites): 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 of3-12, or
intracranial abnormalities on imaging regardless of GCS;

AND

2. admission to an inpatient brain injury rehabilitation program;

3. minimum age 16 years at civilian sites and 18 years at the VA site;

4. Understands and provides informed consent to participate (or, if unable, healthcare
proxy / legal guardian understands and provides informed consent for the patient);

5. sleep duration > 2 hours/night.

Although not specifically targeted, pregnant women and people with intellectual
developmental disorders or prior psychiatric histories meeting the above
inclusion/exclusion criteria can be enrolled in this study. Individuals with known history
of sleep apnea will be eligible for the study and apnea status will be reconfirmed with new
diagnostic study.

Exclusion Criteria:

1. persons less than 16 years old at civilian sites and less than 18 years old at VA site
will not be included;

2. pre-injury diagnosis of narcolepsy or persistent daytime somnolence as documented in
patient's medical record and/or family report; and/or

3. tracheostomy placed and decannulation or overnight capping of the tracheostomy not
feasible during rehabilitation hospitalization.