[Federal Register Volume 85, Number 135 (Tuesday, July 14, 2020)]
[Notices]
[Pages 42402-42404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-15172]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Continuous Positive 
Airway Pressure Treatment for Obstructive Sleep Apnea in Medicare 
Eligible Patients

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for supplemental evidence and data submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review on Continuous 
Positive Airway Pressure Treatment of Obstructive Sleep Apnea in 
Medicare Eligible Patients, which is currently being conducted by the 
AHRQ's Evidence-based Practice Centers (EPC) Program. Access to 
published and unpublished pertinent scientific information will improve 
the quality of this review.

DATES: Submission Deadline on or before 30 days after date of 
publication of this Notice.

ADDRESSES: 
    Email submissions: [email protected].
    Print submissions:
    Mailing Address: Center for Evidence and Practice Improvement, 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.
    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement, Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 
or Email: [email protected].

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence for Continuous Positive 
Airway Pressure Treatment of Obstructive Sleep Apnea in Medicare 
Eligible Patients. AHRQ is conducting this systematic review pursuant 
to Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a).
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Continuous Positive Airway Pressure Treatment of 
Obstructive Sleep Apnea in Medicare Eligible Patients, including those 
that describe adverse events. The entire research protocol is available 
online at: https://www.ahrq.gov/research/findings/ta/index.html#supplemental.
    This is to notify the public that the EPC Program would find the 
following information on Continuous Positive Airway Pressure Treatment 
of Obstructive Sleep Apnea in Medicare Eligible Patients helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicalTrials.gov along with the 
ClinicalTrials.gov trial number.
    [ssquf] For completed studies that do not have results on 
ClinicalTrials.gov, a summary, including the following elements: study 
number, study period, design, methodology, indication and diagnosis, 
proper use instructions, inclusion and exclusion criteria, primary and 
secondary outcomes, baseline characteristics, number of patients 
screened/eligible/enrolled/lost to follow-up/withdrawn/analyzed, 
effectiveness/efficacy, and safety results.
    [ssquf] A list of ongoing studies that your organization has 
sponsored for this indication. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including a study number, the study period, 
design, methodology, indication and diagnosis, proper use instructions, 
inclusion and exclusion criteria, and primary and secondary outcomes.
    [ssquf] Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your organization for 
this indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the Program. Materials 
submitted must be publicly available or able to be made public. 
Materials that are considered confidential; marketing materials; study 
types not included in the review; or information on indications not 
included in the review cannot be used by the EPC Program. This is a 
voluntary request for information, and all costs for complying with 
this request must be borne by the submitter.
    The draft of this review will be posted on AHRQ's EPC Program 
website and available for public comment for a period of 4 weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions.

Contextual and Key Questions (KQ)

Contextual Questions

    CQ 1: What measures related to apneas and hypopneas (e.g., apnea 
indices, hypopnea indices, and apnea-hypopnea indices with various 
measurements) or other measures (e.g., time spent with oxygen 
saturation below 90% or other cutoffs, electrophysiologic signal 
analysis metrics such as time and frequency domain analyses of heart 
beats) are used in contemporary research and clinical settings? How 
have standard definitions of these measures changed over time and what 
is the explanation for such changes?
    CQ 2: What are commonly used sleep questionnaires and how have they 
been validated?
    CQ 3: What treatment modalities for OSA are currently being 
marketed in the U.S.? What OSA treatments (experimental or approved) 
are currently being investigated in ongoing trials for patients as an 
alternative to CPAP?
    CQ 4: What are the variable features of marketed CPAP devices?
    CQ 5: What are the patient-centered health outcome goals and 
symptom relief goals of CPAP devices?

Key Questions

    KQ 1: What is the efficacy, effectiveness, comparative 
effectiveness, and harms of CPAP devices to improve clinically 
significant outcomes?
    KQ 1a: How are respiratory disturbance events (apnea, hypopnea,

[[Page 42403]]

arousal) defined in each study? What are the diagnostic criteria for 
OSA (or criteria to treat with CPAP) in each study? How do the 
diagnostic criteria relate to time of AASM criteria? Do treatment 
effects of CPAP differ by the specific diagnostic criteria used within 
or across studies?
    KQ 1b: What is the within-study concordance in CPAP trials among 
apnea and hypopnea indices (e.g., AHI), sleep questionnaires (e.g., 
Epworth Sleepiness Scale), and clinically significant outcomes?*
    KQ 1c: Do the clinical effects or harms of specific CPAP devices 
differ by patient subgroups, duration of followup, or particular CPAP 
features?
    KQ 1d: Summarize the methodological issues in the existing studies.
    KQ 2: What is the evidence that apnea and hypopnea-based measures 
of sleep-disordered breathing (e.g., apneic indices, hypopnea indices, 
and apnea-hypopnea indices) used in current practice and research are 
valid surrogate or intermediate measures for clinically significant 
outcomes?
    KQ 2a: Summarize the methodological issues in the existing studies. 
What is the ideal study design for establishing the validity of a 
surrogate or intermediate measure?
    * Note that the association between changes in apnea and hypopnea 
indices and clinical outcomes across a broader set of studies is 
primarily addressed in KQ 2.

Systematic Review Study Eligibility Criteria

Eligibility Criteria Relevant to Both KQs

Population
 Adults (>18 years)
 Exclude studies with any pregnant women
 Exclude studies in which any participants are reported to 
have, at baseline, central sleep apnea (from any cause including prior 
stroke, severe heart failure, among others), obesity hypoventilation 
syndrome (Pickwickian syndrome), neuromuscular disease, Parkinson 
disease, Down syndrome, Prader-Willi syndrome, major congenital 
skeletal abnormalities, narcolepsy, narcotic addiction, Alzheimer 
disease, epilepsy and or with mild cognitive impairment
Intervention/Comparator
 Exclude studies of surgical interventions for OSA or bariatric 
surgery
Outcomes
 Hard clinical outcomes
    [cir] Major clinical outcomes
    [ssquf] Death
    [ssquf] Cardiovascular and cerebrovascular events or incident 
diagnosis
    [ssquf] Motor vehicle accidents
    [ssquf] Composite outcomes that include only major clinical 
outcomes (e.g., major adverse cardiovascular events defined as 
including all-cause mortality)
    [cir] Other patient-centered and/or clinically significant outcomes
    [ssquf] Other cardiovascular outcomes
     Objective measures of cardiovascular severity 
(categorized, not continuous measures such as intima media thickness)
     Incident hypertension (or regression to normotension)
     Arrhythmias
     Incident arrhythmias (or resolution of arrhythmias)
     Clinically significant ventricular arrhythmias
     Atrial fibrillation
    [ssquf] New-onset diabetes mellitus or prediabetes (or regression 
to normoglycemia)
    [ssquf] Mental health conditions, including depression, anxiety, 
and substance use disorder: Incident diagnosis or resolution
    [ssquf] Cognitive function: Clinical diagnosis (e.g., of dementia) 
or validated executive function measures
    [ssquf] Quality of life and functional outcomes (validated 
measures)
    [ssquf] Sexual function: Clinical diagnosis (e.g., diagnosis of 
erectile dysfunction or anorgasmia) or their resolution
    [ssquf] Sequelae of sleep deprivation (e.g., trauma, missed work or 
school)
    [ssquf] Other clinically significant outcomes reported in studies 
or as found for CQ 5
    [ssquf] Exclude
     Blood pressure
     Asymptomatic arrhythmias or laboratory measures (e.g., 
captured by electrophysiologic testing [heart rate variability, QTc 
interval, etc.])
     Glycemia measures (e.g., hemoglobin A1c, fasting blood 
glucose)
     Instruments to measure severity of OSA (including AHI and 
sleepiness)
 Minimum duration for associations with death, incident 
cardiovascular events, hypertension, or diabetes is 1 year
 Minimum duration for all other outcomes is 6 months
    Mediators of treatment effect (or association) (e.g., factors to be 
evaluated in subgroup analyses) Note that these are not eligibility 
criteria, but are factors that will evaluated to potentially explain 
different findings across studies; e.g., by subgroup analysis, 
regression, or other methods to evaluate heterogeneity of treatment 
effect)

 Body weight/obesity/neck circumference, etc.
 Weight change (loss or gain)
 Prior cardiovascular, cerebrovascular, or other major clinical 
disease/condition
 Sex/gender
 Race/ethnicity
 Severity of OSA (as defined by study)
 Other mediators as reported in primary studies
Setting
 Outpatient only (except for sleep laboratory setting for 
measurement of sleep and breathing measures)
 Exclude acute care hospital settings (including perioperative)

Additional Eligibility Criteria Specific to KQ 1

Populations
 As listed above, for both KQs
Intervention (CPAP)
 CPAP for treatment (not diagnosis or staging) of OSA
    [cir] At least 1 month of prescribed (planned) treatment
 Exclude intervention designed only to improve CPAP compliance/
adherence (i.e., not an intervention of CPAP, per se)
 Exclude evaluations of accessories only (e.g., nasal cannulas, 
head straps, humidifiers)
     Exclude evaluation of CPAP titration methods, per se, 
including specific parameters or modes (e.g., starting pressures)
 Exclude evaluations of other features meant to improve comfort 
or adherence
 Exclude other non-CPAP interventions (e.g., different times of 
monitoring, scoring), including noninvasive ventilation
Comparators
 No CPAP
 Non-CPAP active interventions for OSA (e.g., mandibular 
advancement device)
    [cir] Exclude bariatric surgery (as a comparator treatment)
    [cir] Exclude surgical OSA procedure (as a comparator treatment)
 Other CPAP modality or protocol (e.g., autoCPAP vs. bilevel 
CPAP)

[[Page 42404]]

    Exclude comparisons with different accessories, titration methods, 
features to improve comfort or adherence, other non-CPAP interventions 
(e.g., different times of monitoring, scoring), including noninvasive
Outcomes
 As listed above, for both KQs
 Sleep and breathing measures (e.g., AHI) and validated sleep 
questionnaires (e.g., Epworth Sleepiness Scale) (only for the purpose 
of addressing KQ 1b, not as outcomes of interest)
 Adverse events related to CPAP use
    Mediators of treatment effect (e.g., subgroup analyses; see note 
above about mediators)
 As listed above, for both KQs
 New or prior OSA diagnosis
 Treatment na[iuml]ve versus failed prior treatment
 First versus second or more use of CPAP
 Treatment (CPAP) compliance
 Treatment (CPAP) discontinuation
Design
 Randomized controlled trials (RCT)
    [cir] Consider whether study met power calculation for the 
outcome(s) of interest (including adverse events)
 Nonrandomized comparative studies (NRCS)
    [cir] Restrict to studies that use modeling or other analytic 
methods to minimize confounding bias (due to inherent differences 
between people who receive one or the other intervention)
    [cir] Exclude case-control design
    [cir] Exclude ``pre-post'' design (comparison of before and after 
CPAP treatment in a single group of participants)
 Longitudinal
    [cir] Exclude cross-sectional

Additional Eligibility Criteria Specific to KQ 2

    For KQ 2, we will include studies that measure a change in the 
intermediate/surrogate measure (e.g., AHI) over a period of time and 
report on outcomes of interest. We will include studies that provide 
formal evaluation of validity of the intermediate/surrogate measure for 
the clinical outcome and other studies that report sufficient data to 
analyze a potential association between the change in the measure and 
the clinical outcome.
Population
 Adults
    [cir] Do not require a diagnosis of OSA (for evaluations of 
associations of measures)
    [cir] Exclude populations as described under ``Eligibility Criteria 
relevant to Both KQs''
    Intermediate/Surrogate measures (variables of interest evaluated 
regarding their association with clinical outcomes)

 Sleep and breathing measures
    [cir] Indices based on apneas or hypopneas (e.g., AHI, RDI) or 
other respiratory events such as RERAs, oxygen desaturations
 Exclude evaluations of isolated neurophysiologic parameters of 
sleep (e.g., respiratory effort, heart rate, air flow, pulse oximetry 
alone) and cardiac electrophysiology indices (e.g., heart rate 
variability)
Outcomes
 As listed above, for both KQs
 Each study must report both one or more intermediate/surrogate 
measures (i.e., sleep and breathing measures) and one or more outcomes 
of interest

    Additional mediators of association (e.g., analyzed by subgroup 
analyses)

 As listed above, for both KQs
 Definition of sleep and breathing measure
Study Design
 Longitudinal studies informing on person-level associations of 
sleep and breathing measure(s) with outcome(s)
    [cir] Patient-level association between change in measure and 
change or incident outcome (i.e., evaluation of association reported 
within study)
    [cir] Exclude cross-sectional studies
 Comparative or noncomparative (single group) studies
 N >= 30 analyzed for a given association between intermediate/
surrogate measure and outcome

    Dated: July 9, 2020.
Virginia Mackay-Smith,
Associate Director.
[FR Doc. 2020-15172 Filed 7-13-20; 8:45 am]
BILLING CODE 4160-90-P