Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA)

We received a request to reconsider the 2005 National Coverage Determination (NCD) for CPAP Therapy for OSA (CAG-00093R) to allow coverage of CPAP based upon a diagnosis of OSA by home sleep testing (HST).

Medicare currently covers the use of CPAP in beneficiaries who have been diagnosed with moderate to severe OSA when ordered and prescribed by a licensed treating physician and confirmed by polysomnography (PSG) performed in a sleep laboratory in accordance with § 240.4 of the Medicare NCD Manual. There are currently a number of procedures used by physicians singly or in combination that contribute to a diagnosis of OSA:

• Clinical evaluation
• PSG performed in a sleep laboratory
• HST using Type II, III, & IV devices
• Other devices

In this decision, we are proposing changes to our national coverage determination for CPAP.

1. We are proposing that, due to the evidence demonstrating that no combination of diagnostic procedures adequately identifies all of those beneficiaries who will benefit from CPAP, the coverage of CPAP is initially limited to a twelve week period to identify beneficiaries diagnosed with OSA as subsequently described who benefit from CPAP. CPAP is subsequently covered for those beneficiaries diagnosed with OSA who benefit from CPAP during this twelve week period.

2. We are proposing that the use of CPAP willbe covered when diagnosed using a clinical evaluation and PSG performed in a sleep laboratory. In addition, we are proposing to expand coverage of CPAP to include those beneficiaries with a diagnosis of CPAP made using a combination of a clinical evaluation and unattended home sleep monitoring using a Type II, III or IV device.

3. We are proposing to modify the criteria for a positive sleep study to remove the requirement for a minimum two hours of continuous recorded sleep and instead recognize shorter periods of continuous recorded sleep if the total number of recorded events during that shorter period is at least the number of events that would have been required in a two hour period.

4. We are proposing to delete the current distinct requirements that an individual have moderate to severe OSA and that surgery is a likely alternative because these terms are not sufficiently precise.

5. Due to a lack of sufficient evidence that clinical diagnosis alone or clinical diagnosis in combination with devices other than Type I, II, III, or IV adequately identify beneficiaries with OSA that will benefit from CPAP, we are proposing to expand Medicare coverage for CPAP in these instances only when provided in the context of a clinical study when that study meets the following standards:

   A clinical study seeking Medicare payment for CPAP provided to the beneficiary pursuant to Coverage with Evidence Development (CED) must address one or more of the following questions:

   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of a clinical trial of CPAP compare with PSG and Type II, III & IV HST in identifying subjects with OSA who will respond to CPAP?
   • In Medicare aged subjects with clinically identified risk factors for OSA who have not undergone confirmatory testing with PSG or Type II, III & IV HST, does CPAP cause clinically meaningful harm?
   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of tests other than PSG or Type II, III & IV HST, such as oximetry, peripheral arterial tone and actigraphy, alone or in combination, compare with PSG and Type II, III & IV HST in confirming a diagnosis of CPAP-responsive OSA?

   We are proposing that the study meet the following additional standards:

   • The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
   • The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
   • The research study does not unjustifiably duplicate existing studies.
   • The research study design is appropriate to answer the research question being asked in the study.
   • The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
   • The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is FDA-regulated, it also must be in compliance with 21 CFR Parts 50 and 56.
   • All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
   • The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
   • The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals.  Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR § 312.81(a) and the patient has no other viable treatment options.
   • The clinical research study is registered on the ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
   • The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three (3) years after the end of data collection.
   • The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial.  If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
   • The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

AHRQ believes that clinical studies answering the above questions and meeting the listed standards are consistent with section 1142 of the Social Security Act.

We are requesting public comments on this proposed determination pursuant to Section 1862 (1) of the Social Security Act (the Act). We are particularly interested in comments that include new evidence we have not reviewed here. After considering the public comments and any additional evidence we will make a final determination and issue a final decision memorandum.

To:		Administrative File: CAG #00093R2 Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA)    
    
From:	Steve Phurrough, MD, MPA    
		Director, Coverage and Analysis Group    
    
		Louis Jacques, MD    
		Director, Division of Items and Devices    
    
		Francina Spencer    
		Lead Analyst    
    
		Jean Stiller, MA    
		Analyst    
    
		Ross Brechner, MD, MS, MPH    
		Lead Medical Officer    
    
Subject:	Proposed Coverage Decision Memorandum for Continuous Positive Airway Pressure (CPAP)     
		Therapy for Obstructive Sleep Apnea (OSA) (CAG-00093R2)    
    
Date:		December 14, 2007

I. Proposed Decision

We received a request to reconsider the 2005 National Coverage Determination (NCD) for CPAP Therapy for OSA (CAG-00093R) to allow coverage of CPAP based upon a diagnosis of OSA by home sleep testing (HST).

Medicare currently covers the use of CPAP in beneficiaries who have been diagnosed with moderate to severe OSA when ordered and prescribed by a licensed treating physician and confirmed by polysomnography (PSG) performed in a sleep laboratory in accordance with § 240.4 of the Medicare NCD Manual. There are currently a number of procedures used by physicians singly or in combination that contribute to a diagnosis of OSA:

• Clinical evaluation
• PSG performed in a sleep laboratory
• HST using Type II, III, & IV devices
• Other devices

In this decision, we are proposing changes to our national coverage determination for CPAP.

1. We are proposing that, due to the evidence demonstrating that no combination of diagnostic procedures adequately identifies all of those beneficiaries who will benefit from CPAP, the coverage of CPAP is initially limited to a twelve week period to identify beneficiaries diagnosed with OSA as subsequently described who benefit from CPAP. CPAP is subsequently covered for those beneficiaries diagnosed with OSA who benefit from CPAP during this twelve week period.

2. We are proposing that the use of CPAP willbe covered when diagnosed using a clinical evaluation and PSG performed in a sleep laboratory. In addition, we are proposing to expand coverage of CPAP to include those beneficiaries with a diagnosis of CPAP made using a combination of a clinical evaluation and unattended home sleep monitoring using a Type II, III or IV device.

3. We are proposing to modify the criteria for a positive sleep study to remove the requirement for a minimum two hours of continuous recorded sleep and instead recognize shorter periods of continuous recorded sleep if the total number of recorded events during that shorter period is at least the number of events that would have been required in a two hour period.

4. We are proposing to delete the current distinct requirements that an individual have moderate to severe OSA and that surgery is a likely alternative because these terms are not sufficiently precise.

5. Due to a lack of sufficient evidence that clinical diagnosis alone or clinical diagnosis in combination with devices other than Type I, II, III, or IV adequately identify beneficiaries with OSA that will benefit from CPAP, we are proposing to expand Medicare coverage for CPAP in these instances only when provided in the context of a clinical study when that study meets the following standards:

   A clinical study seeking Medicare payment for CPAP provided to the beneficiary pursuant to Coverage with Evidence Development (CED) must address one or more of the following questions:

   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of a clinical trial of CPAP compare with PSG and Type II, III & IV HST in identifying subjects with OSA who will respond to CPAP?
   • In Medicare aged subjects with clinically identified risk factors for OSA who have not undergone confirmatory testing with PSG or Type II, III & IV HST, does CPAP cause clinically meaningful harm?
   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of tests other than PSG or Type II, III & IV HST, such as oximetry, peripheral arterial tone and actigraphy, alone or in combination, compare with PSG and Type II, III & IV HST in confirming a diagnosis of CPAP-responsive OSA?

   We are proposing that the study meet the following additional standards:

   • The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
   • The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
   • The research study does not unjustifiably duplicate existing studies.
   • The research study design is appropriate to answer the research question being asked in the study.
   • The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
   • The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is FDA-regulated, it also must be in compliance with 21 CFR Parts 50 and 56.
   • All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
   • The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
   • The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals.  Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR § 312.81(a) and the patient has no other viable treatment options.
   • The clinical research study is registered on the ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
   • The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three (3) years after the end of data collection.
   • The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial.  If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
   • The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

AHRQ believes that clinical studies answering the above questions and meeting the listed standards are consistent with section 1142 of the Social Security Act.

We are requesting public comments on this proposed determination pursuant to Section 1862 (1) of the Social Security Act (the Act). We are particularly interested in comments that include new evidence we have not reviewed here. After considering the public comments and any additional evidence we will make a final determination and issue a final decision memorandum.

II. Background

We use the abbreviation PSG to refer to attended polysomnography or an attended polysomnogram depending on the context of the sentence, unless we specifically describe an unattended use. We use the abbreviation HST to refer to unattended multichannel home sleep testing or multichannel home sleep monitoring.

OSA, sometimes referred to as Obstructive Sleep Apnea Hypopnea Syndrome-OSAHS, is associated with significant morbidity and mortality. It is a commonly underdiagnosed condition that occurs in 4% of men and 2% of women (Young et al. 1993). The prevalence increases with age (up to 10% in persons 65 and older), as well as with increased weight. Complications of OSA include excessive daytime sleepiness, concentration difficulty, coronary artery disease, and stroke (Kokturk et al. 2005). It is estimated that 10% of patients with congestive heart failure (CHF) have OSA, which is independently associated with systemic arterial hypertension (Caples et al. 2005). Also, untreated OSA is associated with a ten-fold increased risk of motor vehicle accidents (Teran-Santos et al. 1999). The most common clinical presentation of patients with OSA is obesity accompanied by excessive daytime drowsiness (20% of adults with BMI > 30 have OSA), although other clinical findings associated with OSA include nocturnal choking or gasping, witnessed apneas during sleep, large neck circumference and daytime fatigue.

Of the three different forms of sleep apnea (obstructive, central, or mixed), OSA is the most common. Patients suffering with sleep apnea may literally stop breathing (apnea) or have decreased breathing (hypopnea), repeatedly during sleep. The apnea episodes often last for a minute or longer, and can occur hundreds of times during a single night’s sleep. During the obstructive apnea episodes, either complete or partial obstruction of the airway occurs. The anatomic site of obstruction is thought to be the soft palate, extending to the base of the tongue. When patients with OSA fall asleep, muscles of this region relax to the point of permitting airway collapse and obstruction. When the airway closes, breathing stops and the sleeper awakens to open the airway. Arousals from sleep usually last only a few seconds, but these brief arousals disrupt continuous sleep and prevent persons from reaching deep stages of sleep (e.g., rapid eye movement sleep-REM), which is necessary in order for the body to rest and replenish strength. The patient repeats this cycle throughout the sleep period.

Diagnosis
OSA has been defined by an apnea/hypopnea index (AHI) of > 5 events per hour during sleep (when using this less restrictive definition, the prevalence may be as high as 25% of the population) or by a higher threshold e.g. AHI of ≥ 15 per hour (the prevalence is as reported above). Medicare has covered CPAP for the treatment of OSA if the beneficiary has an AHI greater than or equal to 5 and less than or equal to 14 events per hour with a co-morbidity related to OSA, or an AHI ≥ 15 per hour without a co-morbidity related to OSA. The key diagnostic finding in OSA is episodes of airflow cessation or reduction at the nose and mouth despite evidence of continuing respiratory effort.

Other common clinical findings used by physicians in the diagnosis of OSA include oxygen desaturation, abnormal oxygen desaturation index, and Respiratory Distress Index (RDI) which represents the total number of apneas and hypopneas in the total sleep period divided by the total number of hours in the sleep period. There is no universally accepted definition of either oxygen desaturation or an abnormal oxygen desaturation index in sleep-disordered breathing. Other measures such as arterial pulsatile volume changes, measurement of airflow, measurement of breathing patterns, Multiple Sleep Latency Testing (MSLT) and Maintenance of Wakefulness Testing, computerized EEG analysis, autonomic arousal detection, and body movement analysis are some of the measures currently being employed by physicians for diagnosis of OSA.

Diagnostic tests for OSA have historically been classified into four types. The most comprehensive is designated Type I: attended, or in-facility PSG, which is considered the reference standard for diagnosing OSA. Three categories of portable monitors (used both in attended and unattended settings) have been developed for the diagnosis of OSA. Type II monitors have a minimum of 7 channels (e.g., EEG, EOG, EMG, ECG-heart rate, airflow, respiratory effort, oxygen saturation-this type of device monitors sleep staging, so calculation of apnea/hypopnea index-AHI can be calculated). Type III monitors have a minimum of 4 monitored channels including ventilation or airflow (at least two channels of respiratory movement or respiratory movement and airflow), heart rate or ECG, and oxygen saturation. Type IV devices measure one or two parameters (e.g., oxygen saturation or airflow). There are other technologies that do not fall into the classification above, such as devices to assess peripheral arterial tension.

Overnight PSG is the conventional diagnostic test for OSA. The American Thoracic Society (ATS 1994) and the American Academy of Sleep Medicine (ASDA 1997) recommend supervised PSG in the sleep laboratory over 2 nights for the diagnosis of OSA and the initiation of CPAP.

According to Harrison’s Principles of Internal Medicine (2005):

Young et al. (1999) note limited capacity to provide PSG testing to all persons with symptoms of OSA due to the high prevalence of OSA. Some studies have noted false-negative rates of 14 to 25% (Le Bon et al. 2000; Littner 2000). And as noted by Klingshott et al. (2000) associates, the measures derived from PSG (e.g., AHI) correlate poorly with major consequences of OSA such as sleepiness and cognitive impairment. Loube et al. (1999) and others have also noted that these measures do not reliably predict the response to the standard therapy for OSA, nasal CPAP.

PSG alternatives have been sought. Predictive algorithms (predictive formulas) to determine optimal CPAP (Flemons et al. 1994; Maislin et al. 1995; Rowley et al. 2000), screening oximetry (Whitlaw et al. 2005; Chiner et al. 1999), attended/unattended home diagnostic apnea monitoring devices (Sériés et al 1993; Golpe et al. 2002; Whitelaw et al. 2005), and questionnaires (e.g., Epworth Sleepiness Scale; Sleep Apnea Clinical Scores) have been developed to help make a sensitive and specific diagnosis of OSA. Other strategies that have been suggested to reduce the delay, inconvenience and expense associated with sleep studies include split night studies (Yamashiro et al. 1995), partner titration, and home stepwise titration. These items have been proposed as a diagnostic aid for patients with a high suspicion of OSA (Ballester et al. 2000; Ficker et al. 2001; Ross et al. 1998; Verse Pirsig et al. 2000).

As noted in Harrison’s Principles of Internal Medicine:

Treatment of OSA
A number of treatment approaches have been recommended for patients with OSA, depending on severity of the disorder (e.g., the degree of clinical symptoms), as well as the objective level of nocturnal respiratory and sleep disturbance (e.g., daytime sleepiness or number of obstructive events per hour of sleep). For patients with severe OSA, nasal CPAP is the treatment of choice. Its regular use improves excessive sleepiness, cognitive performance, and quality of life (Jenkinson et al. 1999; Montserrat et al. 2001). In patients with severe OSA who can not tolerate nasal CPAP, surgical procedures (e.g., uvulopalatopharygnoplasty-UPPP, maxillofacial surgery) may be indicated. In patients with mild to moderate OSA, nasal CPAP may be indicated, though conservative measures such as weight reduction, avoidance of alcohol, avoidance of sleeping in a recumbent position, or intra-oral appliances may be better tolerated.

CPAP treatment uses air pressure to maintain airway patency. There are several types of CPAP devices used in the treatment of OSA. These include: (1) conventional CPAP devices which provide a constant, steady air pressure all night; (2) bi-level positive airway pressure devices, which, instead of providing a constant pressure throughout the night, sense inspiration and expiration and vary the level of pressure accordingly; and (3) responsive ("smart") airway pressure devices that incorporate flow and pressure sensors and automatic regulation systems to continuously adjust mask pressure to the actual needs of the patient.

Conventionally, technicians titrate CPAP pressures via a therapeutic mask pressure (i.e. the minimum pressure that eliminates abnormal breathing) as determined by manual titration over the course of a night in a sleep laboratory. But the long-held belief that fixed-pressure CPAP therapy is the standard is being challenged. The pressure required to maintain upper airway patency in patients with OSA varies throughout the night depending on body position (Jokic, Klimaszewski et al. 1999), sleep state and other factors. Also, CPAP requirements may change over time due to changes in upper airway properties as well as variation in body weight.

Alternatively, automatic computer-controlled CPAP titration (auto CPAP) can be performed over one or several nights, attended or unattended (a technician can be present or absent), in a sleep laboratory or a home setting. Auto CPAP devices can be used either for titration only, in order to choose a single therapeutic pressure that will be used on a long-term basis or permanently for adjusting to the patient’s changing needs. The use of auto-titrating CPAP based on algorithms has also been evaluated in the treatment of OSA (Berry et al. 2002; Stammnitz et al. 2004). Auto CPAP devices adjust pressure by feed-back control according to patterns of pressure, flow or other signals recorded during treatment. Information obtained on pressure readings during an unattended auto CPAP titration may determine therapeutic pressure for subsequent fixed pressure CPAP. A number of studies have been done which have shown that the use of autotitration CPAP machines, as opposed to fixed-flow CPAP machines, are effective in determining therapeutic CPAP, and as a method of treatment (Berry et al. 2002; Stammnitz et al. 2004; Massie et al. 2003).

III. History of Medicare Coverage

In 1986, the CMS (then known as the Health Care Financing Administration) asked the Office of Health Technology Assessment (OHTA) to conduct an assessment of the safety, clinical effectiveness and use of CPAP. OHTA reported that "the consensus of clinical opinion from the available information appears to be that CPAP can in the majority of cases prevent OSA and provide substantial clinical improvement with minimal associated morbidity." They went on further to recommend that "the use of CPAP be covered under Medicare when used in adult patients with moderate and severe OSA who have failed to obtain relief from other non-invasive therapies and for whom surgery would be the only other therapeutic alternative." The diagnosis of OSA required at least 30 episodes of apnea, each lasting a minimum of 10 seconds, during 6-7 hours of sleep. These specifications were based predominately on expert opinions at the time.

Based on the OHTA technology assessment, Medicare issued an NCD (see NCD Manual 240.4) which covered CPAP for adult patients with moderate or severe OSA for whom surgery is a likely alternative (effective date January 12, 1987) and adopted OHTA's recommendations on the diagnosis of OSA. Unattended HST has been reviewed by CMS since 1989. In 1995, the agency’s reviewing body for the development of national coverage determinationsconcluded that the safety and effectiveness of home studies used to diagnosis sleep disorders were unproven and thus should not be covered by the Medicare program. The TAC recommended that this issue be reconsidered for national policy following the completion of a large study of sleep disorders by the NIH. This was to include an evaluation of in-home testing. The study was expected to be completed within two to three years. Therefore, the coverage of unattended HST was left to carrier discretion.

In 2001, the national coverage policy on CPAP was expanded to include Medicare beneficiaries with an apnea/hypopnea index (AHI) of ≥ 15, or an AHI ≥ 5 and ≤ 14 with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease or history of stroke. However, the policy specified that only PSG done in a facility-based sleep study laboratory could be used to identify patients with obstructive sleep apnea.

In 2005, CMS determined that the evidence was not adequate to conclude that the use of unattended portable multi-channel sleep testing with a minimum of 7 monitored channels including EEG, EOG, EMG, ECG or heart rate, airflow, respiratory effort, and oxygen saturation (Type II Devices based on the 1994 ASDA classification) was reasonable and necessary in the diagnosis of OSA and these tests remain noncovered for the diagnosis of OSA.

Current Request

CMS is reviewing its NCD regarding the diagnosis of patients with OSA requiring CPAP therapy. Current national coverage policy specifies that only PSG done in a facility-based sleep study laboratory can be used to identify patients with OSA requiring CPAP (NCD 240.4).

CMS has received a complete formal written Request from the American Academy of Otolaryngology-Head and Neck Surgery to modify this decision to include the use of portable multi-channel HST devices as an alternative to facility-based PSG in the evaluation of OSA.

In addition, CMS has received an incomplete request from a Medicare beneficiary, numerous informal requests from stakeholders, and interest from Medicare contractors concerning the criteria for determining the Apnea-Hypopnea Index (AHI). The current NCD at section 240.4 states in part "…The AHI is equal to the average number of episodes of apnea and hypopnea per hour and must be based on a minimum of 2 hours of sleep recorded by polysomnography using actual recorded hours of sleep (i.e. the AHI may not be extrapolated or projected)." It has been suggested by some that this requirement be changed to "the AHI is equal to the average number of episodes of apnea and hypopnea per hour and must be based on a minimum of 2 hours of sleep or less, if the actual number of AHI episodes recorded is 30 or more in less than 2 hours, recorded by polysomnography using actual recorded hours of sleep (i.e., the AHI may not be extrapolated or projected).

We are also aware of recently published research suggesting a benefit for the use of CPAP without prior sleep testing in selected populations (trial of CPAP).

The scope of this reconsideration includes all aspects of this NCD.

Benefit Category

Medicare is a defined benefit program. All services furnished under the Medicare program must be medically reasonable and necessary, and appropriate for diagnosis and/ or treatment of an illness or injury. Furthermore, physicians and nonphysician practitioners must be authorized by the State in which the services are furnished to render the services. An item or service must fall within a benefit category as a prerequisite to Medicare coverage: § 1812 (Scope pf Part A); § 1832 (Scope of Part B); § 1861(s) (Definition of Medical and Other Health Services).

A CPAP device falls within the DME benefit category found at section 1861(s)(6) of the Social Security Act. Regulations found at 42 CFR 414.202 describe DME as equipment furnished by a supplier or a home health agency that: (1) can withstand repeated use; (2) is primarily and customarily used to serve a medical purpose; (3) generally is not useful to an individual in the absence of a illness or injury; (4) is appropriate for use in the home.

CMS considers diagnostic testing to be the appropriate coverage category for PSG and multichannel HST.

IV. Timeline of Recent Activities

V. Food and Drug Administration (FDA) Status

HST devices and other similar devices, such as multi-channel HST and other related devices have been considered and cleared for marketing by the FDA under a 510(k) process. The 510(k) is a notification of intent to market a specific device. The FDA has determined that certain home sleep study testing devices are "substantially equivalent to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act." A substantially equivalent determination assumes compliance with the Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the FDA will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. Typically, no clinical data is required as part of the 510 (k) application, but instead the clearance process focuses on technical performance. However, the FDA does request clinical data for snore validation as well as event detection (i.e. clinical validation that the apneas or hypopneas detected are also scored as apneas or hypopneas by a manual scorer). The FDA also compares sensitivity and positive predictive values to a predicate device.

The FDA has cleared numerous types of CPAP devices under the 510(k) process. These include but are not limited to many devices that allow a patient to wear a device that collects airflow and other patient measurements into a device that records data, while treating OSA with that device. The patient then takes the device to the physician and the physician downloads information that determines whether the patient has apnea sleep-related breathing disorder including obstructive sleep apnea or needs further sleep studies or assessment. There are currently many sleep assessment devices on the market cleared by the FDA through the 510(k) process for use in the home.

VI. General Methodological Principles

When making NCDs, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for Medicare beneficiaries. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary under § 1862(a)(1)(A) of the Act.

A detailed account of the methodological principles of study design that are used to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A. In general, features of clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, and the blinding of readers of the index test, and reference test results.

Public comment sometimes cites the published clinical evidence and gives CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination. CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum.

VII. Evidence

A. Introduction

We are providing a summary of the evidence that we considered during our review. We will, of course, consider additional evidence submitted through the public comment period. For this decision memorandum, CMS held a MedCAC meeting on September 12, 2007 and commissioned external technology assessments (TAs) from the Agency for Healthcare Research and Quality (AHRQ) to review published clinical evidence on the use of devices in the diagnosis of OSA and to do modeling of different scenarios of diagnosis. CMS reviewed information and recommendations provided as a result of the MedCAC meeting, the TAs provided by AHRQ, and conducted its own independent search and review of individual clinical studies addressing this issue. CMS also reviewed other information from professional societies and other groups/organizations, searched evidence based practice guidelines, consensus statements, and position papers.

We seek to determine if new evidence supports conclusions that differ from those in the decision we published in early 2005. For HST we focused on evidence published since the 2004 MCAC meeting and the 2005 reconsideration of this NCD. Because we had not previously reviewed the evidence pertinent to clinical diagnosis alone, our review of that literature includes evidence predating our 2005 decision.

B. Discussion of evidence reviewed

1. Questions & Outcomes

As diagnostic tests, PSG and HST would not be expected to directly change health outcomes. Rather, a diagnostic test affects health outcomes through changes in disease management brought about by physician actions taken in response to test results. Such actions may include decisions to treat or withhold treatment, to choose one treatment modality over another, or to choose a different dose or duration of the same treatment. To some extent the usefulness of a test result is constrained by the available treatment options. As noted in the Background section, the number of practical treatment options for OSA is limited. Most patients get CPAP; a few get oral appliances or surgery. A patient whose OSA is not readily controlled with CPAP may seek other treatment, continue CPAP with lesser benefit, or discontinue CPAP and not seek further medical treatment. In addressing the questions above, one of the factors we consider is whether there is sufficient evidence that the incremental information derived from PSG or HST leads to improved treatment of OSA by causing physicians to prescribe a different treatment than they would have prescribed without access to the test results.

The choice of specific treatment is influenced by many factors other than its predicted ability to reduce sleep apnea. Some patients may prefer to avoid a surgical intervention. Other patients may have comorbid conditions such as chronic cardiac or respiratory disease that will influence the use or avoidance of certain treatments.

Outcomes of interest for a diagnostic test are not limited to determining its accuracy but also include beneficial or adverse clinical effects, such as changes in management due to test findings or preferably, improved health outcomes for Medicare beneficiaries. Ideally, we would see evidence that the systematic incorporation of PSG or HST results into a treatment algorithm leads treating physicians to prescribe different and better treatment than they would otherwise have prescribed, and that patients whose treatment is changed by test results remain on the regimen and achieve better long term OSA control documented by repeated assessments over time.

There is no anatomic or physiologic "gold standard" for the diagnosis of obstructive sleep apnea, in contrast to conditions such as cancer where a tissue biopsy result is the definitive standard reference. In studies that compare HST to facility-based PSG, the investigators have used the PSG result as the standard reference, i.e. the PSG result is used to define the true disease state for the individual patient. This is less than ideal since the true sensitivity and specificity of PSG in diagnosing OSA is not well documented, and this deficiency poses a practical difficulty in diagnosing OSA. Given the absence of a true "gold standard" reference, the clinical application of terms such as sensitivity and specificity is not straightforward.

Such evidence permits only the comparison of HST to facility-based PSG. It is problematic to make the inferential leap from there to a judgment on the ability of HST or PSG to accurately identify those patients who will, if untreated with CPAP, suffer the morbidity and mortality of obstructive sleep apnea. If an individual patient has conflicting results with these two tests, e.g. a negative HST in the face of a positive PSG, there is no available higher reference to determine whether the conflict arises from a false negative HST or a false positive PSG.

2. External technology assessments

Systematic reviews are based on a comprehensive search of published studies to answer a clearly defined and specific set of clinical questions. A well-defined strategy or protocol (established before the results of the individual studies are known) guides this literature search. Thus, the process of identifying studies for potential inclusion and the sources for finding such articles is explicitly documented at the start of the review. Finally, systematic reviews provide a detailed assessment of the studies included. CMS commissioned two TAs from AHRQ:

• Home diagnosis of Obstructive Sleep Apnea-Hypopnea Syndrome, and
• Obstructive Sleep Apnea-Hypopnea Syndrome: modeling different diagnostic strategies.

We summarize them below. The full reports are available at the following CMS website: http://www.cms.hhs.gov/mcd/viewtechassess.asp?id=204.

Home diagnosis of Obstructive Sleep Apnea-Hypopnea Syndrome

Obstructive Sleep Apnea-Hypopnea Syndrome: modeling different diagnostic strategies

3. Internal technology assessments

Literature Search

CMS performed an extensive literature search utilizing PubMed for randomized controlled trials (RCTs), systematic reviews, and series studies evaluating the use PSG, HST, CPAP trial, and clinical diagnosis of OSA. The literature search was limited to humans. We focused on evidence published since the 2004-5 reconsideration of this NCD

There are currently several proposed mechanisms to diagnosis OSA and determine the need for and benefit of CPAP. These include clinical diagnosis alone, PSG, home testing with various devices and a diagnosis made by using a trial of CPAP. We will address the evidence for each individually.

Clinical Diagnosis

Crocker et al. (1990) studied whether the number of PSGs required for diagnosis of OSA could be reduced in the population. They enrolled 100 consecutive patients (average age 50) screened by family and sleep physicians. The patients were then tested by PSG. A clinical model was created for predicting a diagnosis of OSA as compared to PSG and was applied to the next 114 consecutive patients. The model correctly classified 33 of 36 persons with OSA by correctly predicting an AHI > 15 and it correctly classified 35 of 69 patients by correctly predicting an AHI ≤ 15. In the model, BMI, reported apnea, age, and hypertension were statistically significant factors. The model had a sensitivity of 92% for predicting OSA when compared to PSG and a specificity of 51%. The authors concluded that clinical observation might reduce the need for PSG in the diagnosis of OSA by one-third.

Deegan et al. (1996) compared the predictive value of certain clinical features to PSG for a diagnosis of OSA. Two hundred fifty consecutive patients (average age 45) were pre-screened by a physician and had a clinical assessment and administration of a sleep questionnaire, along with PSG. One hundred thirty six (54%) had an AHI ≥ 15 (considered positive for a diagnosis of OSA) and 114 (46%) had an AHI < 15 (not considered positive for OSA). Using clinical features and oximetry, 32.4% of patients could be confidently categorized, compared to PSG, as either having a true diagnosis of OSA or not having OSA. Significant factors in the model were BMI, alcohol intake, and age. The authors concluded that clinical observation may reduce the need for PSG in the diagnosis of OSA by approximately one-third.

Haponik et al. (1984) asked whether or not PSG is necessary to assess the presence and severity of sleep-disordered breathing. They enrolled 37 patients (average age 50) with clinically suspected OSA, administered a questionnaire and did PSG testing. Compared to PSG (AHI ≥ 15 as cutoff for positive diagnosis of OSA) the clinical testing information had a sensitivity of 64% for a correct diagnosis of OSA and a specificity of 100%. The authors concluded that a single, brief clinical observation alone is an ineffective screening procedure for detecting OSA.

Julià-Serdà et al. (1984) enrolled 225 consecutive referrals to a sleep clinic (average age 45 in the non-OSA group and 52 in the OSA group) with suspected OSA to determine whether or not cephalometry was useful in sparing PSG. All subjects had clinical assessment with an ESS questionnaire, physical exam and history. In addition they also had spirometry, cephalometry, and PSG testing. A statistical model was built to estimate a patient’s probability of a correct diagnosis of OSA as compared to PSG (using a cutoff value of AHI ≥ 10), based on clinical variables, physical examination, pulse oximetry, cephalometry, and soft palate and uvula measurements. The sensitivity of the model for a correct diagnosis of OSA as compared to PSG was 93% and the specificity was 83%. The authors concluded that cephalometry plus oximetry plus history and physical exam is capable of sparing the need for PSG in diagnosing OSA.

In 99 pre-operative Laparoscopic Adjustable Gastric Banding patients with average age in their four groups ranging from 35 to 44, Dixon et al. (1997) attempted to create a clinical model for predicting a correct diagnosis of OSA as compared to PSG. A thorough sleep history and physical examination were performed, checking for symptoms such as nocturnal choking, waking unrefreshed, morning headaches, excessive daytime sleepiness and poor sleep quality. An ESS was administered and all patients had a PSG test. The PSG was hand scored. For a PSG cutoff of AHI ≥ 15, independent predictors for a diagnosis of OSA were observed sleep apnea (the only positive symptom predictor of an AHI ≥ 15), male sex, higher BMI, age, fasting insulin and glycosylated hemoglobin A1c. From the model created, a scoring mechanism was established and a score of > 3 had a sensitivity of 89% for a correct diagnosis of OSA as compared to PSG and a specificity of 81% for moderate/severe OSA. The authors concluded that a simple method of predicting OSA in severely obese symptomatic subjects can assist in limiting the use of PSG to those with greater risk

In a rare RCT on the topic of clinical modeling of OSA, Mulgrew et al. (2007) investigated the utility of a diagnostic algorithm in conjunction with ambulatory CPAP titration in initial management of OSA. This open label RCT compared PSG with ambulatory CPAP titration in high-risk patients identified by a diagnostic algorithm in a tertiary referral sleep disorders program. Sixty-eight patients (average age 52 in the PSG group and 55 in the ambulatory group) with a high PSG pretest probability of moderate to severe OSA (AHI ≥ 15) were identified by ESS score, Sleep Apnea Clinical Score and oximetry. Patients were randomly assigned to PSG or ambulatory titration using a combination of auto CPAP and overnight oximetry. They were observed for 3 months. The main outcome measure was AHI on CPAP as compared to before CPAP, with secondary outcome measures being ESS score, quality of life and CPAP adherence. After 3 months, there was no difference in the primary outcome—AHI on CPAP (median, 3.2 vs. 2.5; difference, 0.8/h)—between the PSG and ambulatory CPAP groups. After 3 months, there were no differences between groups in the secondary outcomes of ESS score, Sleep Apnea Quality of Life Index, and CPAP. Of particular note was that adherence to CPAP therapy was better in the ambulatory group than in the PSG group. The authors concluded that PSG confers no advantage over the ambulatory approach in terms of diagnosis and CPAP titration in initial management of patients with a high probability of OSA. The authors also concluded that the ambulatory approach may improve adherence to treatment and that, when access to PSG is inadequate, the ambulatory approach can expedite treatment. The authors noted that their study was confined to a specific population and that more studies were needed to generalize the conclusions to other populations.

Lim et al. (2006) performed a study to determine if a clinical model could be developed to predict OSA diagnosis from clinical diagnosis only. Seventy-one consecutive snorers (average age 44) referred for an evaluation for OSA were enrolled. OSA status was determined by clinical assessment based on symptoms suggestive of OSA as well as an ESS and BMI measurement. A PSG was administered and a clinical assessment model was created and used in identifying the ‘non-apneic snorers’ among patients referred with snoring. The model made use of the ESS score (using a cutoff of ≥ 15), the BMI (using a cutoff of ≥ 28), and the presence of symptoms such as nocturnal choking, witnessed apnea, daytime hypersomnolence or morning headaches. Compared to PSG using a cutoff of AHI > 10, the model had a sensitivity of 93.4% and a specificity of 60% for correctly diagnosing OSA. The authors concluded that identifying ‘non-apneic snorers’ in whom PSG could be avoided can be correctly accomplished via a clinical assessment if two out of three of the following are absent: 1) ESS score ≥15; 2) a BMI ≥28; and 3) the presence of specified symptoms such as nocturnal choking, witnessed apnea, daytime hypersomnolence or morning headaches.

Hoffstein et al. (2006) utilized data from 594 patients with an average age 47 who were referred to sleep clinic for suspicion of sleep apnea and were all seen by the same physician to determine if it was possible to develop a clinical model to predict a correct diagnosis of OSA from a clinical exam. A PSG with a cutoff of AHI>10 was used for the diagnosis of OSA. The independent predictors of a correct diagnosis of OSA as compared to PSG were age, sex, BMI, partner observation of apnea and pharyngeal exam findings (normal vs abnormal). Compared to PSG, the subjective (clinical) impression alone showed a sensitivity of 63% for a correct diagnosis of OSA and a specificity of 60%. The authors concluded that subjective impression alone is not enough to reliably identify patients with or without a correct diagnosis of OSA as compared to PSG.

Garcia et al. (2003) studied whether or not they could predict a correct diagnosis of OSA with a clinical model. They enrolled 227 consecutive patients (average age 58) measuring clinical signs and symptoms and performing a PSG. They then took the next 102 patients and tested their model for clinical diagnosis of OSA (total 329). They utilized an AHI ≥ 30 as a cutoff for a correct diagnosis of OSA. In the model created, they utilized a cut point of 11 for the ESS and of 30 for BMI and included other significant and independent factors of age, sex, BMI, neck circumference history and the referring physician’s subjective feeling (dichotomized into ‘yes’ or ‘no’) as to each patient’s probability of having an AHI ≥ 30. Compared to PSG, the model had a sensitivity of 80% for a correct diagnosis of OSA and a specificity of 93%. The authors concluded that prior to diagnostic tests for OSA; clinical data can be useful for identifying patients suspected of having AHI ≥ 30.

Kushida et al. (1997) attempted to predict OSA with a morphometric predictor model. Thirty patients (age range 15-75) were used to create the model and the model was then prospectively tested on the first consecutive 300 of a total of 423 patients referred for a diagnosis of OSA. All patients were also tested with PSG using a cutoff of AHI ≥ 10. The regression model included oral cavity measurements of the palatal height by two separate calipers measuring the distance between the mesial surfaces of the crowns of the second molars to obtain either the maxillary intermolar distance or the mandibular intermolar distance. BMI and neck circumference measurements were also made. The morphometric model had a sensitivity of 97.6% for a correct diagnosis of OSA as compared to PSG and a specificity of 100%. The authors concluded that the model may be clinically useful as a screening tool for OSA rather than as a replacement for PSG.

To see which snorers referred to a sleep laboratory need PSG for the diagnosis of OSA, Rauscher et al. (1993) enrolled 98 habitual snorers and 89 patients (average age 58 overall) with a positive diagnosis of OSA by PSG. A regression model was created that included weight, height, sex, witnessed episodes of apnea and falling asleep reading. This model was applied to 116 consecutive patients referred for investigation of heavy snoring. All patients with negative oximetry and a probability value < 0.31 for having OSA had an AHI < 10 by PSG. The authors concluded that snorers with negative oximetry classified as not having OSA by this model do not need PSG.

Viner et al. (1994) examined whether or not history and physical examination can predict a correct diagnosis of OSA as compared to PSG. They enrolled 410 patients (average age 50) referred for clinically suspected OSA. They conducted a blinded comparison of history and physical examination versus results of nocturnal PSG utilizing a cutoff point of AHI ≥ 10. The regression model created included as significant independent factors age, BMI, sex, witnessed episodes of apnea and falling asleep reading. They noted that for p < 0.20 (a predicted probability of less than 20% of having OSA) the clinical model had 94% sensitivity and 28% specificity of correctly predicting a diagnosis of OSA as compared to PSG. Subjective impression alone had a sensitivity of 52% and a specificity of 70% for correctly predicting a diagnosis of OSA as compared to PSG. The authors concluded that in patients with a low predicted probability of having a correct diagnosis of OSA, approximately one-third do not need a PSG for diagnosis.

Tsai et al. (2002) performed a study to create a decision rule for diagnostic testing in OSA. They enrolled 75 patients (average age 47) referred to a sleep clinic for suspicion of sleep apnea. No mention of consecutive selection was made. Each patient had portable RDI testing (using a cutoff of RDI ≥ 10) and nocturnal oxygen saturation measurements. During the feasibility phase, patients underwent routine clinical assessment plus the upper airway physical examination protocol (UAPP), performed by two investigators. Unreliable or time consuming measurements were eliminated from the UAPP based on clinical judgments and history of snoring and body position based on the consensus of the two investigators. A decision rule was developed using three predictors: a cricomental space of 1.5 cm or less, a pharyngeal grade of more than II and the presence of overbite. For patients with all 3 predictors (17%), the decision rule had a PPV of 95% and an NPV of 49% for a true diagnosis of OSA by PSG. Comparable performance was obtained in a validation sample of 50 patients referred for diagnostic testing. The authors concluded that their decision rule provides a simple, reliable and accurate method of identifying a subset patients with and, perhaps more importantly, without a true diagnosis of OSA.

To compare clinical assessment with home oximetry in the diagnosis of OSA, Guylay et al. (2006) studied 98 non-consecutive patients referred to a sleep clinic for suspicion of sleep apnea. All patients answered a questionnaire, had a history and physical exam, and had PSG testing using a cutoff value of AHI ≥ 15 for diagnosis of OSA. Physicians also independently estimated the likelihood of their patient having a true diagnosis of OSA on PSG testing. Compared to PSG, the independent clinical (physician) assessment had a sensitivity of 79% and a specificity of 50% for correctly diagnosing OSA at the cutoff value of AHI ≥ 15. Compared to PSG, oximetry with a desaturation of 2% had a sensitivity of 65% and a specificity of 74% for diagnosing OSA at the cutoff value of AHI ≥ 15. For desaturations of 3%, the corresponding sensitivity and specificity were 51% and 90%, respectively. If the percentage of sleep time spent at SaO2 < 90 was ≥ 1%, the sensitivity for a true diagnosis of OSA as compared to PSG (AHI ≥ 15) was 93% and the specificity was 51%. The authors concluded that being at SaO2 < 90 for < 1% of the time on home oximetry practically excludes OSA.

Pillar et al. (1994) compared a clinical diagnosis of OSA to PSG (cutoff AHI ≥ 10). Eighty-six patients (average age 47) referred to a sleep clinic for suspicion of sleep apnea were enrolled. The authors did not mention whether or not the subjects were consecutively enrolled. All patients answered a detailed sleep questionnaire, had a brief physical examination and had PSG testing. Compared to PSG (cutoff AHI ≥ 10), a clinical diagnosis of OSA had a sensitivity of 79% and a specificity of 50%. With regards to the model, the independent factors for a true diagnosis of OSA were neck circumference, age, self reporting of apnea and falling asleep unintentionally. Compared to PSG, the sensitivity was 92% and the specificity was only 18%. The authors concluded that clinical evaluation cannot replace PSG.

Laboratory Diagnosis using Polysomnography (Type I)

CMS has previously reviewed the data for diagnosis of OSA using PSG. We are not readdressing that literature in this decision.

Home testing for OSA

Types II, III & IV

CMS reviewed the AHRQ TA assessment above and found no additional evidence on HST for Types II, III & IV devices.

Oximetry

Both PSG and HST have an oximetry component, which monitors oxygen desaturation. A number of authors have claimed that just using the oximetry component alone can help in making a diagnosis of OSA (Nuber et al. 2000; Sériés et al 2005; Sériés et al.1993; Guylay et al. 1993).

As noted above, a number of studies have shown that oximetry measurement helps the diagnostic accuracy of OSA. One of the earliest studies exploring this relationship was performed by Sériés et al. (1993). Using 240 consecutive patients with a confirmed (AHI > 10 on PSG) diagnosis of OSA (all were clinically suspected of having OSA because of loud snoring; nocturnal choking and awakenings or apneic events or all three reported by a bedmate; bad sleep quality; and daytime hypersomnolence), they found that oximetry had a 98% sensitivity for diagnosing OSA (AHI > 10), but a specificity of only 48%.

Another study that explored the relationship between oximetry and OSA was performed by Magalang et al. (2003). They noted that several quantitative indices derived from overnight pulse oximetry have been used to predict the presence of OSA: (1) number of episodes of oxyhemoglobin desaturations below a threshold-usually a 3% or 4% decline below baseline, (2) the cumulative time spent below an oxyhemoglobin saturation of 90%, and (3) the Δ [delta] index—a measure of the variability of the oxyhemoglobin saturation. The researchers wanted to compare these indices and determine if some combination of these indices predicted an individual’s AHI as measured by PSG. Using a derivation group which consisted of 224 consecutive patients, a prediction model was generated based on AHIs from the calculated quantitative indexes. The model was further validated using two groups of consecutive eligible patients (group 1 consisted of 101 patients and group 2 consisted of 191 patients). All patients underwent standard overnight PSG and measurement of arterial oxyhemoglobin (by pulse oximeter). The major findings of the study revealed that among the different oximetry indices, the Δ index was the best predictor of the presence of OSA, though the number of desaturation events provided similar levels of diagnostic accuracy (sensitivity of a Δ index of > 0.63 in the diagnosis of OSA was 91%, while the specificity was 59%). An aggregation of the model using combinations of all oximetry indices reduced the prediction error (r² = 0.70, p < 0.05) compared to using the Δ index alone (r² = 0.60), improving the precision of prediction of the AHI. The correlation between the predicted and actual AHI was 0.77 when using the Δ index alone, but improved to 0.83 when using a combination of all three oximetry indices. The authors note that one limitation of the study is that the prediction model was validated using overnight pulse oximetry obtained simultaneously with PSG data in the sleep laboratory. However, one advantage of this approach is it eliminated the potential confounder of night-to-night variability of AHI, as well ensuring that oximetry data were collected in exactly the same environment as the PSG data.

Vazquez et al. (2000) studied the diagnostic performance of an automated digital oximetry analysis based on falls and recovery of oxygen saturation and compared the results to PSG. After excluding subjects not eligible for the study, 241 participants with suspected OSA were enrolled in the study and randomly assigned to either PSG or automated off-line analysis of the digitally recorded oximetry signal. Study outcomes included PSG-derived AHI, and oximeter-derived respiratory disturbance index (RDI). The study revealed that the PSG-derived AHI and the oximetry-derived RDI were strongly correlated (R=0.97); the mean (±2SD) of the differences between AHI and RDI was 2.18 (±12.34)/h. Using a case definition of 15 episodes/hour for both AHI and RDI, the sensitivity and specificity were 98% and 88% respectively. The authors noted that one limitation of the applicability of this study was that the algorithm was evaluated by comparison with simultaneous PSGs. They also commented that a number of studies have shown a difference in RDI between home and hospital settings, despite using the same monitor and controlling for technical difficulty. But the authors were quick to note that by evaluating patients in the sleep laboratory, potential confounders (such as technical difficulties associated with remote monitoring, night-to-night variability, and the effects of the home environment on RDI) are eliminated.

Other

Watch-PAT100 is a HST apparatus which measures the peripheral arterial tone (PAT) and actigraphy (a measure of movement) which are recorded with an ambulatory wrist-worn device (Watch-PAT100). The PAT signal is a measure of the pulsatile volume changes at the finger tip reflecting sympathetic tone variations. The algorithm was developed using a training set of 30 patients recorded simultaneously with polysomnography and Watch-PAT100. The WATCH-PAT100 indirectly detects apnea/hypopnea events by identifying surges of sympathetic activation associated with the termination of these events. This information is further combined with heart rate and pulse oximetry data that are analyzed by the automatic algorithm of the system. This detects respiratory events and calculates the PAT RDI (PRDI).

We found 19 separate articles, papers, editorials, and fact sheets addressing this technology. Of these, CMS determined that 13 were not relevant due to qualities pertaining to sample size, type of evidence, having not been published in a peer reviewed journal or not relevant to this data needed for this NCD. The remaining 6 are reviewed below.

Pittman et al. (2004) aimed at assessing the accuracy of a wrist-worn device (Watch-PAT 100) to diagnose obstructive sleep apnea in the home. Participants were not consecutive patients but were a sample of patients who disclosed on a comprehensive questionnaire between June and December of 2002 that they were interested in being contacted about research studies conducted at the sleep laboratory. All thirty subjects completed 2 overnight diagnostic studies with the test device: 1 night in the laboratory with concurrent polysomnography and 1 night in the home with only the Watch-PAT100. The mean age of these subjects was 43.2 ± 10.8 years and mean body mass index was 33.9 ± 7.1 kg/m2. The mean Epworth Sleepiness Scale score was 9.2 ± 4.7 (range 2-18). The order of the laboratory and home study nights was random. The frequency of respiratory events on the PSG was quantified using indexes based on 2 definitions of hypopnea: the respiratory disturbance index (RDI) using American Academy of Sleep Medicine (AASM) Task Force criteria for clinical research, and the Medicare guidelines. The PRDI and oxygen desaturation index (PAT ODI) were then evaluated against the polysomnography AASM guidelines (RDI.C) and Medicare guidelines (RDI.M), respectively, for both Watch-PAT100 diagnostic nights, yielding in-lab and home comparisons. The setting for the PSGs was a sleep laboratory affiliated with a tertiary-care academic medical center. The PDG and PAT measures were compared using the mean [2 SD] of the differences and the intra-class correlation coefficient (ICC). The receiver-operator characteristic curve was used to assess optimum sensitivity and specificity and calculate likelihood ratios. For the in-lab comparison, there was high concordance between:

• RDI.C and PAT RDI: ICC = 0.88, mean difference 2.5 [18.9] events per hour
• RDI.M and PAT ODI: ICC = 0.95, mean difference 1.4 [12.9] events per hour
• sleep time: ICC = 0.70, mean difference 7.0 [93.1] minutes

For the home-laboratory comparison, there was good concordance between:

• RDI.C and PAT RDI: ICC = 0.72, mean difference 1.4 [30.1] events per hour
• RDI.M and PAT ODI: ICC = 0.80, mean difference 1.6 [26.4] events per hour

Home studies were performed with no technical failures. The authors concluded, in this study of a population of 30 patients suspected of having obstructive sleep apnea, that the Watch-PAT100 can quantify an ODI that compares very well with Medicare criteria for defining respiratory events and an RDI that compares favorably with AASM criteria for defining respiratory events. They further believe that the device can be used with a low failure rate for single use in the lab and home for self-administered testing.

Zou et al (2006) aimed at assessing the accuracy of a portable monitoring device based on PAT to diagnose obstructive sleep apnea (OSA) and to propose a new standard for limited-channel device validation using synchronized polysomnography (PSG) home recordings in a population-based cohort, i.e. in a population sample not preselected for OSA symptoms. The 98 subjects (55 men; age, 60 ± 7 year; body mass index, 28 ± 4 kg/m²) from a community of 18,000 in Sweden had single-night, unattended PSG and Watch-PAT100 in the home. They were consecutively recruited from the Swedish Skaraborg Hypertension and Diabetes Project. The accuracy of Watch-PAT100 in RDI, AHI, ODI, and sleep-wake detection was assessed by comparison with data from simultaneous PSG recordings. The mean PSG-AHI in this population was 25.5 ± 22.9 events per hour. The Watch-PAT100 RDI, AHI, and ODI correlated closely (0.88, 0.90, and 0.92; p < .0001, respectively) with the corresponding indexes obtained by PSG. The areas under the curve for the receiver-operator characteristic curves for Watch-PAT100 AHI and RDI were 0.93 and 0.90 for the PSG-AHI and RDI thresholds of 10 and 20 (p < .0001) respectively. The agreement of the sleep-wake assessment was 82 ± 7%. The authors concluded that the Watch-PAT100 was reasonably accurate for unattended home diagnosis of OSA in a population sample not preselected for OSA symptoms. The authors propose that simultaneous home PSG recordings in population-based cohorts is a reasonable validation standard for assessment of simplified recording tools for OSA diagnosis.

In Pillar et al (2002), the authors state that arousals from sleep are associated with increased sympathetic activation and are therefore associated with peripheral vasoconstriction. The authors hypothesized that digital vasoconstrictions as measured by peripheral arterial tonometry (PAT), combined with an increase in pulse rate, will accurately reflect arousals from sleep and can provide an autonomic arousal index (AAI). According to the authors, a previously studied group of 40 sleep apnea patients simultaneously recorded by both PSG and PAT systems generated an automated algorithm using the PAT signal (and pulse rate derived from it) was developed for detection of arousals from sleep. This was further validated in this separate group of 96 subjects which included 85 patients referred with suspected obstructive sleep apnea and 11 healthy volunteers. All subjects underwent a whole night PSG with simultaneous PAT recording. The PSG recordings were manually (blindly) analyzed for arousals based on American Academy of Sleep Medicine (AASM) criteria, while PAT was scored automatically. There was a significant correlation between PSG and PAT arousals (R=0.82, p<0.0001) with good agreement across a wide range of values, and with a ROC curve having an area under the curve (AUC) of 0.88. The authors conclude that automated analysis of the peripheral arterial tonometry signal can detect EEG arousals from sleep in a relatively quick and reproducible fashion

In Bar et al (2003), the authors aimed at evaluating the efficacy, reliability, and reproducibility of the Watch-PAT100 device for the diagnosis of OSAS as compared to in-laboratory, standard PSG-based manual scoring. One hundred two subjects (69 patients with OSAS and 33 normal non-consecutively selected volunteers) underwent in-laboratory full PSG simultaneously with Watch-PAT100 recording. Fourteen subjects also underwent two additional unattended home sleep studies with the Watch-PAT100 alone. The PSG recordings were blindly scored for apnea/hypopnea according to the American Academy of Sleep Medicine criteria (1999) and the RDI [PSG-RDI] was calculated. The Watch-PAT100 data were analyzed automatically for the PAT RDI (PRDI) by a proprietary algorithm that was the authors reported was previously developed on an independent group of subjects. Across a wide range of RDI levels, the PRDI was highly correlated with the PSG-RDI (r = 0.88, p < 0.0001), with an area under the receiver operating characteristic curve of 0.82 and 0.87 for thresholds of 10 events per hour and 20 events per hour, respectively. The PRDI scores were also highly reproducible, showing high correlation between home and in-laboratory sleep studies (r =0.89, p < 0.001). The authors concluded that the Watch-PAT100 may offer an accurate, robust, and reliable ambulatory method for the detection of OSAS with minimal patient discomfort.

Ayas et al. (2003) aimed at assessing the accuracy of a wrist-worn device (Watch-PAT100) to diagnose obstructive sleep apnea (OSA). Thirty adult subjects (mean age was 47.0 ± 14.8 years, mean body mass index 31.0 ± 7.6 kg/m2) were recruited through advertisements and from a patient base of those with suspected OSA to participate in this study. The study included patients suspected of having sleep apnea and subjects without suspected sleep apnea. The subjects had simultaneous in-laboratory PSG and wore the Watch-PAT100 during a full-night recording. PSG sleep and respiratory events were scored according to standard criteria. The mean PSG AHI was 23 ± 23.9 events per hour and the mean PAT AHI 23 ± 15.9 events per hour. There was a significant correlation between the two (r = 0:87, p <0:001). To assess sensitivity and specificity of Watch-PAT100, receiver operator characteristic curves were constructed using a variety of AHI threshold values (10, 15, 20, and 30 events per hour). Optimal combinations of sensitivity and specificity for the various thresholds were 82.6/71.4, 93.3/73.3, 90.9/84.2, and 83.3/91.7, respectively. The authors concluded that the Watch-PAT100 is a device that can detect OSA with reasonable accuracy and that it may be a useful method to diagnose OSA.

In Pillar et al. (2003), the authors stated that they had recently shown that automated analysis of in-lab recorded peripheral arterial tone (PAT) signal and the pulse rate derived from it can accurately assess arousals from sleep as defined by the American Academy of Sleep Medicine (AASM). In the current study they aimed at extending these findings to the Watch-PAT100. They recruited 68 subjects who underwent a whole night PSG with simultaneous recording of PAT signal by the ambulatory Watch-PAT100 device. The PSG recordings were blindly scored via manual analyzing for arousals based on AASM criteria, while PAT was scored automatically based on the algorithm developed previously. The authors determined that was a significant correlation between AASM arousals derived from the PSG and PAT autonomic arousals derived from the Watch-PAT100 (R=0.87, P<0.001), with consistency across a wide range of values of AHI. The sensitivity and specificity of PAT in detecting patients with at least 20 arousals per hour of sleep were 0.80 and 0.79, respectively, with a receiver operating characteristic curve having an area under the curve of 0.87. They concluded that that automatic analysis of peripheral arterial tonometry signal derived from the ambulatory device Watch-PAT100 can accurately identify arousals from sleep in a simple and time saving fashion

Diagnosis of OSA using CPAP

Senn et al. (2006) were one of a number of groups that studied the feasibility of using CPAP to make a diagnosis of OSA in patients with a high-pretest probability of disease. Specifically, using a study of diagnostic accuracy in a university sleep disorder setting, they wanted to evaluate whether the diagnosis of OSA could be inferred from the response to treatment with CPAP (CPAP trial); i.e. whether a CPAP trial predict an AHI ≥ 10 on PSG and how successfully OSA patients were treated over a period of 4 or more months. The accuracy of the CPAP trial would be evaluated by comparing results to those of PSGs performed in all patients (for validation) and by comparison to the clinical outcomes of OSA patients after 4 months of treatment with CPAP following a positive trial result. A trial by CPAP was considered positive if, at the end of the followup period, a patient reported using CPAP for 2 or more hours per night and wanted to continue using CPAP. Baseline ESS studies, quality of life measures (SF-36), a questionnaire (Kump), as well as vigilance measures (OSLER test) (Bennett et al. 1997; Jenkinson et al. 1999) were assessed in 76 sleepy snorers consecutively referred for a clinical diagnosis of OSA. A diagnosis of OSA was defined as a mean AHI > 10. Of the original 195 consecutive patients referred for possible participation in the study, after excluding patients not meeting criteria, 76 patients (100% of those with AHI > 10 fitting criteria, average age 52) were enrolled in the study. Forty-four of 76 patients (58%) had sleep apnea as confirmed by an AHI > 10/h. The CPAP trial predicted sleep apnea with a sensitivity of 80%, a specificity of 97%, and positive and negative predictive values of 97% and 78%, respectively. In 35 of 76 sleep apnea patients (46%) with positive CPAP trial results, polysomnography could have been avoided. These patients were prescribed long-term CPAP therapy. After 4 months, 33 of 35 patients (94%) still used CPAP and their symptoms remained improved. These patients were identified by the CPAP trial with positive and negative predictive values of 92% and 100%, respectively. The authors concluded that CPAP is a "pragmatic" approach to identify OSA patients with "CPAP-responsive disease" who benefit from long-term CPAP therapy. They further concluded that in a selected population, a trial of CPAP may help to diagnose OSA, identify patients who benefit from CPAP and reduce the need for polysomnography. Furthermore, long-term CPAP therapy can be established without the need for PSG.

Limitations of the study according to the authors included patients designated as being "false positive" and exhibiting a placebo effect from CPAP. Results may not be generalizable to the Medicare population since by figures given in the paper approximately one-sixth of the subjects were 65 years or older.

Some proponents of CPAP have proposed that patients with high pretest probability of diagnosis of OSA not undergo PSG but proceed directly to CPAP titration either in the laboratory or unattended with an autotitration device (Flemons et al. 2003; Masa et al. 2004; Mulgrew et al. 2007 mentioned above).

Fitzpatrick et al. (2003) reported similar outcomes between standard laboratory-based CPAP titration and patient self-titration in CPAP-naïve subjects. Eighteen CPAP-naive patients (16 males, 50 ± 15 years old, apnea hypopnea index 40 ± 20 with a new diagnosis of OSA) were tested. Testing was performed before and after CPAP treatment in each of two 5-week study limbs. Compliance with CPAP treatment, the Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire score, ESS score, sleep architecture, sleep apnea and maintenance of wakefulness tests were measured. Both modes of CPAP treatment significantly improved objective subjective measures of OSA, but they did not differ in efficacy. The authors concluded that home self-titration of CPAP is as effective as in-laboratory manual titration in the management of patients with OSA.

Hukins (2005) also evaluated the use of low arbitrary pressure CPAP before formal CPAP titration to determine if arbitrary pressure CPAP is equivalent to formal CPAP in terms of compliance and improvements in subjective sleepiness and quality of life. Using an open-labeled, randomized, parallel design, 93 subjects were randomized to start CPAP either after a CPAP titration sleep study (study-determined pressure) or at an arbitrary pressure before the treatment sleep study (arbitrary-pressure CPAP). Primary outcome included ESS scores and secondary outcomes were objective compliance, quality of life and the visual analog (VAS) scale of subjective feelings towards CPAP therapy. The results of the study revealed that although there were no differences in CPAP compliance, side effects, SF-36 parameters or ESS scores, there was significantly higher sleep efficiency (proportion of sleep in the period potentially filled by sleep- i.e. the ratio of total sleep time to time in bed) in the arbitrary-pressure group compared to the study-determined CPAP pressure group. The author also noted that subjects who were unable to tolerate CPAP were identified by the use of arbitrary pressure. This led to a reduction in the proportion of "wasted" PSGs; i.e. studies performed in subjects not persisting with treatment. According to the author, a limitation of the study was the fact that the results are not well generalizable to the Medicare population since the average age in both groups was close to 50 years.

Other Diagnostic Strategies

Rice et al. (2006) piloted a study to evaluate unattended cardiopulmonary (CP) sleep studies as a diagnostic and treatment tool for patients with OSA. After all 106 subjects were initially evaluated by a pulmonary physician to identify those with a high risk of OSA, an ESS was administered. Those who were felt to have a high suspicion of OSA were offered either a PSG (which could take up to 6 months to schedule), or an unattended CP sleep study. Patients electing to use the unattended CP sleep study were lodged as outpatients overnight in the medical center. The diagnostic portable system used was the Embletta PDS, which included an oral thermometer, a nasal flow sensor, a snore microphone, a pulse oximeter, and strain gauges for thoracic and abdominal expansion. AHI was the outcome of interest. Patients with a positive CP test (an AHI of 5 events per hour or greater) were sent home with a REMstar auto CPAP system and a mask that was custom-fitted by a trained respiratory therapist.

After using auto CPAP nightly for a week (REMstar auto CPAP system adjusted to the patient’s pressure needs by analyzing the shape curve of his/her airflow signal and peak flow), patients were then issued a home CPAP machine with settings based on the pressure that was found to be effective for at least 90% of the trial patients. ESS scores were measured at baseline and after 6 months of home CPAP use. Patients who had been prescribed home CPAP were assessed for global sleepiness at 12 months. CP studies were performed on 106 patients, all participants were males (mean age 59.9±10.1), mean BMI of 33.5 and mean ESS score (reference) of 13.1 ± 5.2. Of the 106 original patients, auto CPAP was initiated on 92 subjects. Based on the results of the one week auto CPAP, home CPAP was initiated on 84 patients. According to the authors, "among our patients, improvement in OSA symptoms and long-term adherence to prescribed CPAP was similar to published reports of patients who had undergone conventional PSG testing." At 6 months follow-up, 98% of CPAP patients were available; ESS scores at baseline and follow up were 14±4.6 and 10±5.6 (p=0.001), and adherence to CPAP usage was 84%.

Limitations of the study included the lack of confirmatory PSG to determine rate of false positives (but the mean AHI from this study was similar to that reported in published series of patients who had PSGs; and the absolute magnitude of ESS score improvement in this study was similar to that reported for patients who were prescribed CPAP after a PSG). Other limitations are the inability to calculate the diagnostic accuracy of a negative CP study for OSA; the fact that all subjects were male; and that adherence to prescribed CPAP was not based on objective data but rather on self-reporting.

CPAP Harms

A thorough review of the literature yielded almost no data on any harm from CPAP. One German paper (Fietze et al. 1996) reported on 9 patients with an increase of central apneas. Because of this complication, a rapid optimization of the respiratory pressure or a change to nBiPAP (nasal bilevel pressure support ventilation) therapy was necessary in five of the patients. Two of the patients showed cardiac arrhythmias, some of which were severe. One patient produced a remarkable central hypoventilation during the initial phase of CPAP-therapy. The nBiPAP-titration combined with right-heart catheter monitoring could demonstrate in another patient a possible cardiac decompensation through an increased ventilatory pressure. The authors concluded that the risk of positive-pressure ventilation is higher in patients with accompanying cardiac, pulmonary, neuropsychiatric and/or otorhinolaryngologic disorders. They suggested an intensive "apparative" [sic] monitoring as well as staff supervision during the introduction to a respiratory treatment in those patients. They believe that if complications from CPAP appear, a rapid optimization of the ventilatory pressure or a change to another respiratory treatment is indicated.

4. MedCAC

CMS convened the MedCAC on September 12, 2007 to consider questions pertinent to this reconsideration. The questions are included as Appendix B. Additional information about the meeting can be found at: https://www4.cms.hhs.gov/mcd/viewmcac.asp?where=index&mid=40.

• The MedCAC expressed moderate to high confidence that there was sufficient evidence to determine if clinical evaluation combined with PSG can, in routine use, produce an accurate diagnosis of OSA for the prescription of CPAP. Moderate confidence was expressed on the evidence for clinical evaluation combined with home sleep testing. Less confidence was expressed on the evidence for clinical evaluation used alone.
• Considering the evidence on the ability of various diagnostic strategies to correctly identify patients with OSA and exclude patients who do not have OSA, the MedCAC expressed the following levels of confidence.
  • Clinical evaluation combined with PSG: strong moderate to high
  • Clinical evaluation combined with Type 2 home sleep testing: strong moderate
  • Clinical evaluation combined with Type 3 home sleep testing: moderate
  • Clinical evaluation combined with Type 4 home sleep testing: less than moderate
  • Clinical evaluation alone: less than moderate
  • The MedCAC did not provide a formal consideration of home sleep testing strategies that would employ clinical evaluation in combination with an unclassified device, i.e. not within Types 1-4.
• The MedCAC decided not to address which clinical factors should be included in the clinical evaluation.
• Considering the evidence on the ability of various diagnostic strategies to predict successful use of CPAP, the MedCAC expressed moderately high confidence in clinical evaluation combined with PSG; moderate confidence in clinical evaluation combined with home sleep testing; low to moderate confidence in clinical evaluation combined with a trial of CPAP; and low confidence in clinical evaluation alone.
• The MedCAC expressed low to moderate confidence that the strategy of a trial by CPAP would not produce clinically meaningful harm. The concerns about potential harm relate to the possibility of missing the diagnosis of non-OSA pathology rather than concerns about CPAP itself.
• The MedCAC expressed low to moderate confidence that its conclusions could be generalized to the Medicare population or to community based providers.

5. Evidenced based Guidelines

A November 14, 2007 search of https://www.guideline.gov/ produced several guidelines relevant to CPAP or OSA in adults. All had been published or updated since 2003. Portions speaking to the questions posed in this memorandum are excerpted are included below. A link to each guideline is included for the convenience of the reader.

Institute for Clinical Systems Improvement (ICSI)
Diagnosis and treatment of obstructive sleep apnea. Bloomington (MN): 2007 Mar. 55 p. [115 references]
http://www.guidelines.gov/summary/summary.aspx?doc_id=10809&nbr=005634&string=CPAP

Scottish Intercollegiate Guidelines Network (SIGN).
Management of obstructive sleep apnoea/hypopnoea syndrome in adults. A national clinical guideline. Edinburgh (Scotland): 2003 Jun. 35 p. (SIGN publication; no. 73). [158 references].
http://www.guidelines.gov/summary/summary.aspx?doc_id=3878&nbr=003087&string=CPAP

The SIGN guideline has the following recommendations including a letter grade for the grade of the recommendation:

1. At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
2. A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+
3. A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++
4. Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+

American College of Chest Physicians
Pulmonary artery hypertension and sleep-disordered breathing
ACCP evidence-based clinical practice guidelines. Atwood CW Jr, McCrory D, Garcia JG, Abman SH, Ahearn GS. Chest 2004 Jul;126(1 Suppl):72S-77S. [27 references]
http://www.guidelines.gov/summary/summary.aspx?doc_id=5462&nbr=003739&string=CPAP

1. In the evaluation of patients with pulmonary arterial hypertension (PAH), an assessment of sleep-disordered breathing (SDB) is recommended. Quality of evidence: low; net benefit: small/weak; strength of recommendation: C.
2. In the evaluation of a patient with PAH for SDB, polysomnography is recommended if obstructive sleep apnea (OSA) is suspected as the etiology, if a screening test result for OSA is positive, or if a high clinical suspicion for OSA is present. Quality of evidence: expert opinion; net benefit: intermediate; strength of recommendation: E/B.
3. In the management of patients with OSA, routine evaluation for the presence of PAH is not recommended. Quality of evidence: low; net benefit: none; strength of recommendation: I.
4. In patients with OSA and PAH, treatment of OSA with positive airway pressure therapy should be provided with the expectation that pulmonary pressures will decrease, although they may not normalize, particularly when PAH is more severe. Quality of evidence: low; net benefit: small/weak; strength of recommendation: C.

American Academy of Sleep Medicine
Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D, Boehlecke B, Brown TM, Coleman J Jr, Friedman L, Kapen S, Kapur VK, Kramer M, Lee-Chiong T, Owens J, Pancer JP, Swick TJ, Wise MS,. Sleep 2006 Mar 1;29(3):375-80. [94 references].
http://www.guidelines.gov/summary/summary.aspx?doc_id=9076&nbr=004899&string=CPAP

The AASM makes the following recommendations on the use of CPAP with the level of recommendation in parenthesis:

• Treatment with continuous positive airway pressure (CPAP) must be based on a prior diagnosis of obstructive sleep apnea (OSA) established using an acceptable method (Standard).
• CPAP is indicated for the treatment of moderate to severe OSA (Standard).
• CPAP is recommended for the treatment of mild OSA (Option).
• CPAP is indicated for improving self-reported sleepiness in patients with OSA (Standard).
• CPAP is recommended for improving quality of life in patients with OSA (Option).
• CPAP is recommended as an adjunctive therapy to lower blood pressure in hypertensive patients with OSA (Option).
• Full-night, attended polysomnography performed in the laboratory is the preferred approach for titration to determine optimal positive airway pressure; however, split-night, diagnostic-titration studies are usually adequate (Guideline).
• CPAP Usage should be objectively monitored to help assure utilization (Standard).
• Close follow-up for positive airway pressure (PAP) usage and problems in patients with OSA by appropriately trained health care providers is indicated to establish effective utilization patterns and remediate problems, if needed. This is especially important during the first few weeks of PAP use (Standard).
• The addition of heated humidification is indicated to improve CPAP utilization (Standard).
• The addition of a systematic educational program is indicated to improve PAP utilization (Standard).
• After initial CPAP setup, long-term follow-up for CPAP-treated patients with OSA by appropriately trained health care providers is indicated yearly and as needed to troubleshoot PAP mask, machine, or usage problems (Option).
• CPAP and bi-level positive airway pressure (BPAP) therapy are safe; side effects and adverse events are mainly minor and reversible (Standard).
• While the literature mainly supports CPAP therapy, BPAP is an optional therapy in some cases where high pressure is needed and the patient experiences difficulty exhaling against a fixed pressure or coexisting central hypoventilation is present (Guideline).
• BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with daytime hypercapnia (Option).

American Academy of Sleep Medicine
Practice parameters for the indications for polysomnography and related procedures: an update for 2005.
Kushida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman J Jr, Friedman L, Hirshkowitz M, Kapen S, Kramer M, Lee-Chiong T, Loube DL, Owens J, Pancer JP, Wise M. Sleep 2005 Apr 1;28(4):499-521. [150 references]
http://www.guidelines.gov/summary/summary.aspx?doc_id=8156&nbr=004545&string=CPAP

The AASM makes the following recommendations on the diagnosis of OSA with the level of recommendation in parenthesis:

1. Full-night PSG is recommended for the diagnosis of SRBDs (Sleep Related Breathing Disorders)
2. For patients in the high-pretest-probability stratification group (see sections titled "Snoring, sleepiness, obesity, and witnessed apneas" and "Other factors, clinical prediction rules, and neural networks" and the recommendation below concerning follow-up PSG; sections 4.1.2.1, 4.1.2.2, and 4.1.3(4) of the original guideline document), an attended cardiorespiratory (Type 3) sleep study may be an acceptable alternative to full-night PSG, provided that repeat testing with full-night PSG is permitted for symptomatic patients who have a negative cardiorespiratory sleep study. In the unattended setting, or in patients without qualifications of a high pretest probability stratification, the data does not support the use of these devices. (By using a cardiorespiratory sleep study to test only those patients who are in the high pretest-probability group, the clinician will reduce the probability of false-negative studies so that the need for PSG is lessened as well).
3. In patients where there is strong suspicion of obstructive sleep apnea syndrome (OSA), if other causes for symptoms have been excluded, a second night of diagnostic PSG may be necessary to diagnose the disorder.

1. A full night of PSG with continuous positive airway pressure (CPAP) titration is recommended for patients with a documented diagnosis of a SRBD for whom PAP is warranted.
2. PSG with CPAP titration is appropriate for patients with any of the following results:
   1. A respiratory disturbance index (RDI) of at least 15 per hour, regardless of the patient's symptoms
   2. A respiratory disturbance index of at least 5 per hour in a patient with excessive daytime sleepiness
3. A cardiorespiratory (Type 3) sleep study without electroencephalogram (EEG) recording is not recommended for CPAP titration. CPAP titration should include the ability to perform sleep staging (including documenting rapid eye movement [REM] sleep) and to identify and treat arousals. Even when apnea is eradicated by CPAP, residual hypopneas and respiratory-effort related arousals (RERAs) may require additional titration to determine optimal therapeutic pressures. These additional adjustments require EEG recording.
4. For CPAP titration, a split-night study (initial diagnostic PSG followed by CPAP titration during PSG on the same night) is an alternative to one full night of diagnostic PSG followed by a second night of titration if the following four criteria are met:
   1. An apnea-hypopnea index (AHI) of at least 40 is documented during a minimum of 2 hours of diagnostic PSG. Split-night studies may sometimes be considered at an AHI of 20 to 40, based on clinical judgment (e.g., if there are also repetitive long obstructions and major desaturations). However, at AHI values below 40, determination of CPAP pressure requirements, based on split-night studies, may be less accurate than in full-night calibrations.
   2. CPAP titration is carried out for more than 3 hours (because respiratory events can worsen as the night progresses).
   3. PSG documents that CPAP eliminates or nearly eliminates the respiratory events during REM and non-REM (NREM) sleep, including REM sleep with the patient in the supine position.
   4. A second full night of PSG for CPAP titration is performed if the diagnosis of a SRBD is confirmed but criteria b and c are not met.

A preoperative clinical evaluation that includes polysomnography or an attended cardiorespiratory (Type 3) sleep study is routinely indicated to evaluate for the presence of obstructive sleep apnea in patients before they undergo upper airway surgery for snoring or obstructive sleep apnea. (Standard)

Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is routinely indicated for the assessment of treatment results in the following circumstances: (Standard)

1. After good clinical response to oral appliance treatment in patients with moderate to severe OSA, to ensure therapeutic benefit. (American Sleep Disorders Association, 1995)
2. After surgical treatment of patients with moderate to severe OSA, to ensure satisfactory response. (American Sleep Disorders Association, 1996)
3. After surgical or dental treatment of patients with SRBDs whose symptoms return despite a good initial response to treatment. (American Sleep Disorders Association, 1996)

Follow-up polysomnography is routinely indicated for the assessment of treatment results in the following circumstances: (Standard)

1. After substantial weight loss (e.g., 10% of body weight) has occurred in patients on CPAP for treatment of SRBDs to ascertain whether CPAP is still needed at the previously titrated pressure
2. After substantial weight gain (e.g., 10% of body weight) has occurred in patients previously treated with CPAP successfully, who are again symptomatic despite the continued use of CPAP, to ascertain whether pressure adjustments are needed
3. When clinical response is insufficient or when symptoms return despite a good initial response to treatment with CPAP. In these circumstances, testing should be devised with consideration that a concurrent sleep disorder may be present (e.g., OSA and narcolepsy).

American Society of Anesthesiologists
Practice guidelines for the perioperative management of patients with obstructive sleep apnea: a report by the Task Force on Perioperative Management of Patients with Obstructive Sleep Apnea. Anesthesiology 2006 May ;104(5):1081-93. [3 references].
http://www.guidelines.gov/summary/summary.aspx?doc_id=9308&nbr=004978&string=CPAP

University of Texas, School of Nursing, Family Nurse Practitioner Program.
Screening for obstructive sleep apnea in the primary care setting.
2006 May. 13 p. [24 references]
http://www.guidelines.gov/summary/summary.aspx?doc_id=9436&nbr=005057&string=

6. Professional Society Position Statements

American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)
The AAO-HNS is the requestor of record for this reconsideration and supports extension of Medicare coverage of OSA diagnosis to portable home sleep testing devices.

The American Association for Respiratory Care (AARC)
The AARC recommends that CMS revise its coverage policy to require sleep testing to be performed in accredited facilities with accreditation to be determined by CMS. In addition, AARC recommends that any new device introduced into the home for sleep testing should meet minimum testing criteria. For example, central apnea versus obstructive apnea requires more physiologic data than pulse oximetry and flow. AARC further recommended and suggested language that CMS specify the types of personnel that are qualified to provide home testing.

The American College of Chest Physicians (ACCP)
The ACCP concluded that additional research is needed addressing clinical outcome in a variety of age and ethnic populations that reflect society before this NCD can be revised.

The American Association of Sleep Technologists (AAST)
The AAST supports the comments submitted by the requestor and commends CMS for its thorough review of the NCD.

The American Academy of Sleep Medicine (AASM)
The AASM requested that CMS not change its NCD on CPAP therapy for OSA to allow diagnosis based on portable monitoring. The AASM supports a modification of the two hour rule based on expert opinion and not evidence.

7. Expert Opinion

CMS did not seek outside expert opinion beyond the TAs and the MedCAC. However, many experts provided their opinions as comments or position statements which are considered in the relevant sections of this memorandum.

8. Public Comments

Initial public comments

Initial Comment Period 3/14/2007 – 4/13/07
As noted above CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum. CMS responses to initial comments are, as customary, incorporated into our analysis.

CMS received a total of 717 comments during the public comment period. Thirty-seven (5%) of the 717 comments were duplicates, resulting in 680 actual comments. Commenters included organizations, manufacturers and suppliers, physicians and other clinicians, and patients. One hundred-seventy comments were generated by an industry-sponsored write in campaign. Many stakeholders came in for face-to-face meetings with CMS staff members and also submitted formal comments. Fifty-seven percent (388/680) of the commenters (including all 170 write-in comments) agreed with the requestor and supported expansion of Medicare coverage to include the use of HST for the identification of beneficiaries eligible for CPAP. Forty-three percent (292/680) disagreed with the requestor.

Only 32 commenters expressed an interest in the trial use of CPAP without a sleep study test. One commenter recommended that the patient be allowed to have a trial period on CPAP therapy for 2 to 3 days before allowing Medicare coverage for CPAP therapy. Ten comments supported revision the requirement for 2 hours of recorded sleep.

Many commenters questioned the motives of parties whose opinions differed from their own. Specifically, some commenters alleged that economic self-interest had led to selective consideration of evidence in support of particular opinions or guidelines.

VIII. CMS Analysis

NCDs are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally under title XVIII of the the Act § 1869(f)(1)(B). In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, must not be otherwise excluded from coverage, and, generally, must be reasonable and necessary as defined in § 1862(a)(1)(A).

In addition to section 1862(a)(1)(A), a second statutory provision may permit Medicare payment for items and services in some circumstances. That statute, section 1862(a)(1)(E), provides, in pertinent part, that:

(a) Notwithstanding any other provision of this title, no payment may be made under part A or part B for any expenses incurred for items or services—

. . .

(E) in the case of research conducted pursuant to section 1142, which is not reasonable and necessary to carry out the purposes of that section[.]

. . .

Section 1142 describes the authority of the AHRQ.¹

Under the authority of section 1862(a)(1)(E), CMS pay for items and services furnished in connection with certain medical research. Coverage is conditioned on care being delivered in a setting with a pre-specified data collection process and additional protections in place such as are present in some research studies. Under section 1142, research may be conducted on the outcomes, effectiveness, and appropriateness of health care services and procedures to identify the manner in which diseases, disorders, and other health conditions can be prevented, diagnosed, treated, and managed clinically. In addition, evaluations of the comparative effects, health and functional capacity; alternative services and procedures utilized in preventing, diagnosing, treating, and clinically managing diseases, disorders, and other health conditions may be conducted.

In rare instances, for some items or services, CMS may determine that the evidence is very preliminary and not reasonable and necessary for Medicare coverage under section 1862(a)(1)(A), but, if the following criteria are met, CSP might be appropriate:

1. The evidence includes assurance of basic safety;
2. The item or service has a high potential to provide significant benefit to Medicare beneficiaries; and
3. There are significant barriers to conducting clinical trials.

These research studies will be rigorously designed and include additional protections and safety measures for beneficiaries.

To qualify for reimbursement, such a study must be designed to produce evidence that could be used in a future national coverage decision that would focus on whether the item or service should be covered by Medicare under 1862(a)(1)(A). Payment for the items and services provided in the study will be restricted to the Medicare qualified patients involved as human subjects in the study.

We have consulted with AHRQ who has agreed that the study questions and requirements outlined above are consistent with Section 1142 of the Act.

Study sponsors/principal investigators should submit their protocols to CMS to determine if they meet these standards.

A number of issues have emerged during our review of the evidence. Some physicians express concern about the lack of timely access to PSGs while others argue that access is not problematic; stakeholders debate the comparable accuracy of home apnea monitoring and PSGs; and recent research suggests that neither PSG nor HST may be needed for the diagnosis of CPAP-responsive OSA in selected patient populations. Paradoxically, some patients’ OSA symptoms may be so severe that they cannot sleep for a sufficient continuous duration to complete a PSG. Adding to the complexity of our review, the stakeholder community itself is clearly polarized into opposing camps.

The relevance of OSA diagnosis is founded on the long term morbidity and mortality that have been observed in patients who display a particular constellation of symptoms, signs and test results. Absent that morbidity and mortality, a self-limited apneic episode in and of itself appears of little consequence. Hence the challenge is to select for long term CPAP treatment only those patients who will benefit from OSA therapy, against a background of persons who may for various reasons have a normal or abnormal test on a given night.

It is important to state at the outset that sleep testing, whether via PSG or HST, is used to confirm or refute a clinical suspicion of OSA. In other words, we have no evidence that physicians refer "normal" patients, i.e. patients who manifest no symptoms or signs of OSA, for sleep testing. Sleep testing does not occur in a vacuum, divorced from the overall clinical evaluation. We also note that while this NCD speaks to the diagnosis of OSA in the context of Medicare coverage of CPAP devices, we are not establishing coverage criteria for the diagnosis of OSA for other purposes, such as the coverage of other OSA treatments. Nor are we addressing the use of sleep testing to diagnose conditions other than OSA. Hence the accurate identification of Medicare beneficiaries who will respond clinically to CPAP is at the heart of this review and analysis.

PSG is utilized as a reference standard in many clinical trials; however, we do not believe it is a true gold standard. In a circular argument, the test result has been incorporated into the diagnosis of the disease itself. In the absence of a pathologic gold standard, this is an understandable though not ideal concession to practicality. The accuracy and precision of PSG may be compromised by many factors such as inter-reader variability, the use of different test instruments, night to night variability in a given patient, and patient ability to sleep in a non-home setting. Even if all these variables are controlled, the PSG test itself has not been proven to identify all true cases of OSA, i.e. those persons who will develop OSA-associated morbidity and mortality if untreated.

Therefore, when PSG is performed and read with a threshold of AHI ≥ 15 events per hour for OSA, the sensitivity for detecting a true case of OSA is not known. Neither is its specificity for detecting those who do not have OSA truly known. An AHI suggestive of OSAHS does not conclusively identify those patients who will benefit from treatment. Since the true sensitivity and specificity of PSG are uncertain and the reported agreement between HST and PSG is not complete, we are concerned that a significant number of true cases of OSA are not detected by either test. We are also faced with evidence that some patients who test positive for OSA do not appear to respond appropriately to CPAP therapy, in some cases due to poor compliance with CPAP use.

Question 1: Is the evidence adequate to determine that diagnostic strategies other that facility based PSG accurately identify patients with OSA who will benefit from CPAP treatment?

We note evidence from our internal assessment and from the AHRQ TAs that HST devices may, with high positive likelihood ratios (> 10) and low negative likelihood ratios (< 0.1), identify patients who have AHIs suggestive of OSAHS. Although there is published data comparing HST with PSG, in the absence of a true gold standard it is challenging to categorize the discrepancies as errors .

The body of evidence pertinent to the use of HST devices for the diagnosis of OSA is significantly more robust than when we last considered this NCD. This is supported by the more favorable September 2007 MedCAC scores for HST compared to the September 2004 MCAC scores. Thus, we propose that the evidence is sufficient to conclude that, in appropriately selected patients, Type II, III and IV home sleep testing monitors will identify a significant proportion of patients with OSA who will respond clinically to CPAP and will exclude a significant proportion of those who will not.

CMS also reviewed oximetry alone for the diagnosis of sleep apnea. There was limited evidence and many of the authors recognized limitations of the studies. We believe the evidence reviewed does not demonstrate its utility in the diagnosis of OSA, and we cannot be confident that this diagnostic modality accurately identifies those patients with OSA who will respond clinically to CPAP and excludes those who will not.

Finally, CMS reviewed evidence on the use of the Watch-PAT100 device. The conclusions that can be confidently drawn from the evidence are constrained by methodologic limitations centering on sample and subject selection, sample size, non-consecutivity of subjects, confounders not accounted for, and combining results of different types of patients in analysis. Thus, combined with the paucity of data compared to those available for type II, III and IV devices, we cannot be confident that this diagnostic modality accurately identifies those patients with OSA who will respond clinically to CPAP and excludes those who will not.

Even though the evidence we reviewed was not adequate to support either Watch-PAT100 or oximetry alone, some of the evidence does suggest a benefit. Thus, we propose to cover CPAP based on the results of diagnostic procedures other than PSG or Type II, III, or IV HST for the diagnosis of OSA in the context of a clinical study that meets the criteria outline in our Coverage with Evidence Development Guidance Document. Specifically, the study needs to meet the requirements of the Clinical Trial Policy.

However, even though we believe the evidence supports using PSG or HST for diagnosis of OSA, the evidence also demonstrates that many patients with a positive PSG or HST do not benefit from CPAP. Our current NCD does not address this problem. We do, however, have evidence from our local contractors and an RCT (Mulgrew 2007) that a trial period of up to twelve weeks of CPAP after the initial diagnosis is beneficial in identifying those beneficiaries who positively respond to CPAP. The evidence indicates that patients who do not have true OSA (false positives) will quickly reject CPAP treatment in practice and will not be harmed by a short exposure to CPAP. Further coverage of CPAP in these patients is conditioned upon the patient’s response to CPAP during the initial twelve week period. We propose to adopt into the national coverage determination the requirement that coverage beyond the initial twelve week period be predicated upon documentation of appropriate use.

Question 2: Is the evidence adequate to determine that the accurate diagnosis of OSA requires at least two hours continuous recorded sleep?

We could find no rigorous evidence associating diagnostic accuracy with continuous sleep time recording of at least two hours duration. We are also confronted with reasonable arguments that patients with the most severe OSA are in practice incapable of continuous sleep of two hours duration. Therefore, we propose that the answer to Question 2 is no. However, the current standards of requiring a rate of ≥ 15 events/hour over two hours for less symptomatic patients and 5 through 14 events/hour over two hours for more symptomatic patients do require a minimum number of events. For example, a patient who has at least 15 recorded events per hour over a two hour period would have had at least 30 recorded events. Thus, while we no longer believe two continuous hours of recorded sleep are always necessary, we will continue to require that the total number of events needed for a positive test to be that which would need to occur over two hours to arrive at the specified rates in the current NCD. That is, recording of at least 30 events for patients without comorbidities and at least 10 events for patients with comorbidities is required for the computation of events per hour.

Question 3: Is diagnosis of OSA by clinical criteria alone sufficient for the use of CPAP in the absence of either a positive PSG or a positive unattended multichannel home sleep test?

The published literature on both PSG and HST for OSA diagnosis reflects the results of clinical studies enrolling subjects referred by a medical provider for a test based on clinical suspicion of OSA. Those providers likely made the referral because the subject presented with one or more symptoms or signs such as snoring, daytime sleepiness, witnessed apneic episodes, a thick neck, a higher BMI, or a positive sleep questionnaire, to mention some possibilities. If a patient with clinically suspected OSA undergoes PSG or HST, the patient is referred for CPAP if the PSG is positive. The evidence indicates that both of these strategies result in an unknown number of false positive and false negative diagnoses.

There is evidence, albeit limited, to support the use of CPAP in lieu of PSG or HST in the diagnosis of OSA. This is based on the observation that patients with OSA are more tolerant of CPAP than patients who do not possess this condition, and that the use of CPAP does not result in untoward effects even in patients who do not have a diagnosis of OSA. The MedCAC expressed little confidence in the evidence currently available to support this use. We do not believe that this evidence is currently sufficient to definitely answer this question and we therefore propose that the answer to Question 3 is no.

However, though the evidence we reviewed was not adequate to support a clinical evaluation alone in the diagnosis of OSA, some of the evidence does suggest a benefit. Thus, we propose to cover a clinical evaluation alone for the diagnosis of OSA in the context of a clinical study that meets the criteria outline in our Coverage with Evidence Development Guidance Document. Specifically, the study needs to meet the requirements of the Clinical Trial Policy.

Harms of CPAP
We found little evidence of harm attributable to CPAP. However there is limited evidence on this topic and thus we cannot confidently conclude that significant possible harm has in fact been excluded. In other words, the absence of evidence of harm does not reliably exclude the likelihood of harm if a methodologically rigorous assessment for harm has not been completed. Our concerns are shared by the MedCAC, which expressed low to moderate confidence that the strategy of a trial by CPAP would not produce clinically meaningful harm. We recognize that the population that currently undergoes CPAP is somewhat narrower than all clinically suspected cases. Further, persons with co-morbidities associated with OSA may be at more risk than suspected. Potential concerns about potential harm include the possibility of missing the diagnosis of non-OSA pathology in addition to concerns about potential harms attributable to CPAP itself

Summary

The diagnosis of OSA is extremely complex, reflecting the need to consider a very large number of variables and options as one proceeds from the initial clinical suspicion of the disease to its successful treatment with CPAP or another modality. No single tool reliably identifies all beneficiaries who will benefit from a CPAP device while excluding those who will not. Thus, we believe that the perfect tool for diagnosing OSA in all Medicare beneficiaries is not PSG, HST, or trial by CPAP. We believe that different beneficiaries will benefit from different strategies. The preferred strategy in a given individual will likely vary with the severity of the patient’s symptoms, local access to a sleep laboratory, and the need to rule out other conditions that may cause symptoms similar to OSA, for example nocturnal seizures or narcolepsy. We are concerned that, absent a true gold standard, neither PSG nor HST can perfectly identify patients with OSA who will benefit from CPAP while excluding those who will not benefit.

We propose that the evidence is adequate to conclude that a positive PSG or a positive HST is reasonable and necessary for the diagnosis of OSA and subsequent treatment with CPAP. We are including only Type II, III and IV devices under HST. Since we have evidence that not all patients with a positive PSG or HST will benefit from CPAP, we are proposing that CPAP is only reasonable and necessary for a period of twelve weeks to determine benefit from and compliance with this therapy. Coverage beyond that period must be contingent on the beneficiary’s clinical response to CPAP.

As we have not found rigorous evidence to support continuing the requirement for a minimum of two hours of continuous recorded sleep time, we propose to modify that requirement.

We also propose to delete the language in the current NCD that requires documentation of "moderate to severe OSA" and "surgery is a likely alternative" as a condition of CPAP coverage. We believe that they are no longer needed as standalone requirements since we have outlined in very specific terms the requirements for a positive diagnosis.

We acknowledge the concerns that some of these patients who do not tolerate CPAP may have other conditions for which PSG or other testing may be indicated and we anticipate that a prudent physician would refer the patient for such testing if needed. In light of the evidence and comments on longer than desired waiting periods for access to PSG, we do not believe that an interim HST and twelve week trial of CPAP will interfere with the timely accomplishment of PSG testing if such testing is indicated.

The evidence indicates that some risk factors for OSA are modifiable over time; for example, a patient may gain or lose weight, or resume or discontinue tobacco smoking. This raises two specific concerns. One, patients who initially have a true negative test may progress to more severe disease and may subsequently truly test positive. Second, patients who initially require CPAP may improve to the point that further treatment is not beneficial. We believe that these determinations are best made at this time by local Medicare contractors who can consider the medical information of the individual patient.

Finally, while we have not found adequate evidence to determine that CPAP is reasonable and necessary in beneficiaries who have a clinical diagnosis of OSA but have not had a PSG or a Type II, III, or IV HST, there is some evidence that suggests that other diagnostic tests or a clinical diagnosis alone may improve outcomes. Thus, we propose to determine that CPAP is reasonable and necessary in beneficiaries who have a clinical diagnosis of OSA but have not had a PSG or a Type II, III, or IV HST only when provided in a clinical study that meets the following requirements:

A clinical study seeking Medicare payment for CPAP provided to the beneficiary pursuant to CED must address one or more of the following questions:

• In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of a clinical trial of CPAP compare with PSG and Type II, III & IV HST in identifying subjects with OSA who will respond to CPAP?
• In Medicare aged subjects with clinically identified risk factors for OSA who have not undergone confirmatory testing with PSG or Type II, III & IV HST, does CPAP cause clinically meaningful harm?
• In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of tests other than PSG or Type II, III & IV HST, such as oximetry, peripheral arterial tone and actigraphy, alone or in combination, compare with PSG and Type II, III & IV HST in confirming a diagnosis of CPAP-responsive OSA?

CMS is requiring that the study meet the following standards:

• The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
• The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
• The research study does not unjustifiably duplicate existing studies.
• The research study design is appropriate to answer the research question being asked in the study.
• The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
• The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is FDA-regulated, it also must be in compliance with 21 CFR Parts 50 and 56.
• All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
• The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
• The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals.  Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR § 312.81(a) and the patient has no other viable treatment options.
• The clinical research study is registered on the ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
• The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three (3) years after the end of data collection.
• The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial.  If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
• The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

AHRQ believes that clinical studies answering the above questions and meeting the listed standards are consistent with section 1142 of the Social Security Act.

X. Conclusion

We received a request to reconsider the 2005 NCD on CPAP Therapy for OSA (CAG-00093R) to allow coverage of CPAP based upon a diagnosis of OSA by HST

Medicare currently covers the use of CPAP in beneficiaries who have been diagnosed with moderate to severe OSA when ordered and prescribed by a licensed treating physician and confirmed by PSG performed in a sleep laboratory in accordance with § 240.4 of the Medicare NCD Manual. There are currently a number of procedures used by physicians singly or in combination that contribute to a diagnosis of OSA:

• Clinical evaluation
• PSG performed in a sleep lab
• HST using Type II, III, & IV devices
• Other devices

In this decision, we are proposing changes to the NCD for CPAP.

1. We are proposing that, due to the evidence demonstrating that no combination of diagnostic procedures adequately identifies all of those beneficiaries who will benefit from CPAP, the coverage of CPAP is initially limited to a twelve week period to identify beneficiaries diagnosed with OSA as subsequently described who benefit from CPAP. CPAP is subsequently covered for those beneficiaries diagnosed with OSA who benefit from CPAP during this twelve week period.

2. We are proposing that the use of CPAP willbe covered when diagnosed using a clinical evaluation and PSG performed in a sleep laboratory. In addition, we are proposing to expand coverage of CPAP to include those beneficiaries with a diagnosis of CPAP made using a combination of a clinical evaluation and unattended home sleep monitoring using a Type II, III or IV device.

3. We are proposing to modify the criteria for a positive sleep study to remove the requirement for a minimum two hours of continuous recorded sleep and instead recognize shorter periods of continuous recorded sleep if the total number of recorded events during that shorter period is at least the number of events that would have been required in a two hour period.

4. We are proposing to delete the current distinct requirements that an individual have moderate to severe OSA and that surgery is a likely alternative because these terms are not sufficiently precise.

5. Due to a lack of sufficient evidence that clinical diagnosis alone or clinical diagnosis in combination with devices other than Type I, II, III, or IV adequately identify beneficiaries with OSA that will benefit from CPAP, we are proposing to expand Medicare coverage for CPAP in these instances only when provided in the context of a clinical study when that study meets the following standards:

   A clinical study seeking Medicare payment for CPAP provided to the beneficiary pursuant to Coverage with Evidence Development (CED) must address one or more of the following questions:

   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of a clinical trial of CPAP compare with PSG and Type II, III & IV HST in identifying subjects with OSA who will respond to CPAP?
   • In Medicare aged subjects with clinically identified risk factors for OSA who have not undergone confirmatory testing with PSG or Type II, III & IV HST, does CPAP cause clinically meaningful harm?
   • In Medicare aged subjects with clinically identified risk factors for OSA, how does the diagnostic accuracy of tests other than PSG or Type II, III & IV HST, such as oximetry, peripheral arterial tone and actigraphy, alone or in combination, compare with PSG and Type II, III & IV HST in confirming a diagnosis of CPAP-responsive OSA?

   We are proposing that the study meet the following additional standards:

   • The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
   • The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
   • The research study does not unjustifiably duplicate existing studies.
   • The research study design is appropriate to answer the research question being asked in the study.
   • The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
   • The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is FDA-regulated, it also must be in compliance with 21 CFR Parts 50 and 56.
   • All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
   • The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
   • The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals.  Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR § 312.81(a) and the patient has no other viable treatment options.
   • The clinical research study is registered on the ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
   • The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than three (3) years after the end of data collection.
   • The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial.  If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
   • The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

AHRQ believes that clinical studies answering the above questions and meeting the listed standards are consistent with section 1142 of the Social Security Act.

We are requesting public comments on this proposed determination pursuant to Section 1862 (1) of the Social Security Act (the Act). We are particularly interested in comments that include new evidence we have not reviewed here. After considering the public comments and any additional evidence we will make a final determination and issue a final decision memorandum.

Appendix A: General Methodological Principles of Study Design

When making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. The critical appraisal of the evidence enables us to determine whether: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary.

CMS normally divides the assessment of clinical evidence into three stages: 1) the quality of the individual studies; 2) the relevance of findings from individual studies to the Medicare population; and 3) overarching conclusions that can be drawn from the body of the evidence on the direction and magnitude of the intervention’s risks and benefits.

The issues presented here represent a broad discussion of the issues we consider when reviewing clinical evidence. However, it should be noted that each coverage determination has unique methodological aspects.

1. Assessing Individual Studies

Methodologists have developed criteria to determine weaknesses and strengths of clinical research. Strength of evidence generally refers to: 1) the scientific validity underlying study findings regarding causal relationships between health care interventions and health outcomes; and 2) the reduction of bias. In general, some of the methodological attributes associated with stronger evidence include those listed below:

• Use of randomization (allocation of patients to either intervention or control group) in order to minimize bias.
• Use of contemporaneous control groups (rather than historical controls) in order to ensure comparability between the intervention and control groups.
• Prospective (rather than retrospective) studies to ensure a more thorough and systematical assessment of factors related to outcomes.
• Larger sample sizes in studies to help ensure adequate numbers of patients are enrolled to demonstrate both statistically significant as well as clinically significant outcomes that can be extrapolated to the Medicare population. Sample size should be large enough to make chance an unlikely explanation for what was found.
• Masking (blinding) to ensure patients and investigators do not know to which group patients were assigned (intervention or control). This is important especially in subjective outcomes, such as pain or quality of life, where enthusiasm and psychological factors may lead to an improved perceived outcome by either the patient or assessor.

Regardless of whether the design of a study is a randomized controlled trial, a non-randomized controlled trial, a cohort study or a case-control study, the primary criterion for methodological strength or quality is the extent to which differences between intervention and control groups can be attributed to the intervention studied. This is known as internal validity. Various types of bias can undermine internal validity. These include:

• Different characteristics between patients participating and those theoretically eligible for study but not participating (selection bias)
• Co-interventions or provision of care apart from the intervention under evaluation (confounding)
• Differential assessment of outcome (detection bias)
• Occurrence and reporting of patients who do not complete the study (attrition bias)

In principle, rankings of research design have been based on the ability of each study design category to minimize these biases. A randomized controlled trial minimizes systematic bias (in theory) by selecting a sample of participants from a particular population and allocating them randomly to the intervention and control groups. Thus, randomized controlled studies have been typically assigned the greatest strength, followed by non-randomized clinical trials and controlled observational studies. The following is a representative list of study designs (some of which have alternative names) ranked from most to least methodologically rigorous in their potential ability to minimize systematic bias:

• Randomized controlled trials
• Non-randomized controlled trials
• Prospective cohort studies
• Retrospective case control studies
• Cross-sectional studies
• Surveillance studies (e.g., using registries or surveys)
• Consecutive case series
• Single case reports

When there are merely associations but not causal relationships between a study’s variables and outcomes, it is important not to draw causal inferences. Confounding refers to independent variables that systematically vary with the causal variable. This distorts measurement of the outcome of interest because its effect size is mixed with the effects of other extraneous factors. For observational, and in some cases randomized controlled trials, the method in which confounding factors are handled (either through stratification or appropriate statistical modeling) are of particular concern. For example, in order to interpret and generalize conclusions to our population of Medicare patients, it may be necessary for studies to match or stratify their intervention and control groups by patient age or co-morbidities.

Methodological strength is, therefore, a multidimensional concept that relates to the design, implementation and analysis of a clinical study. In addition, thorough documentation of the conduct of the research, particularly study’s selection criteria, rate of attrition and process for data collection, is essential for CMS to adequately assess the evidence.

2. Generalizability of Clinical Evidence to the Medicare Population

The applicability of the results of a study to other populations, settings, treatment regimens, and outcomes assessed is known as external validity. Even well-designed and well-conducted trials may not supply the evidence needed if the results of a study are not applicable to the Medicare population. Evidence that provides accurate information about a population or setting not well represented in the Medicare program would be considered but would suffer from limited generalizability.

The extent to which the results of a trial are applicable to other circumstances is often a matter of judgment that depends on specific study characteristics, primarily the patient population studied (age, sex, severity of disease, and presence of co-morbidities) and the care setting (primary to tertiary level of care, as well as the experience and specialization of the care provider). Additional relevant variables are treatment regimens (dosage, timing, and route of administration), co-interventions or concomitant therapies, and type of outcome and length of follow-up.

The level of care and the experience of the providers in the study are other crucial elements in assessing a study’s external validity. Trial participants in an academic medical center may receive more or different attention than is typically available in non-tertiary settings. For example, an investigator’s lengthy and detailed explanations of the potential benefits of the intervention and/or the use of new equipment provided to the academic center by the study sponsor may raise doubts about the applicability of study findings to community practice.

Given the evidence available in the research literature, some degree of generalization about an intervention’s potential benefits and harms is invariably required in making coverage decisions for the Medicare population. Conditions that assist us in making reasonable generalizations are biologic plausibility, similarities between the populations studied and Medicare patients (age, sex, ethnicity and clinical presentation), and similarities of the intervention studied to those that would be routinely available in community practice.

A study’s selected outcomes are an important consideration in generalizing available clinical evidence to Medicare coverage determinations because one of the goals of our determination process is to assess health outcomes. We are interested in the results of changed patient management not just altered management. These outcomes include resultant risks and benefits such as increased or decreased morbidity and mortality. In order to make this determination, it is often necessary to evaluate whether the strength of the evidence is adequate to draw conclusions about the direction and magnitude of each individual outcome relevant to the intervention under study. In addition, it is important that an intervention’s benefits are clinically significant and durable, rather than marginal or short-lived.

If key health outcomes have not been studied or the direction of clinical effect is inconclusive, we may also evaluate the strength and adequacy of indirect evidence linking intermediate or surrogate outcomes to our outcomes of interest.

3. Assessing the Relative Magnitude of Risks and Benefits

Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits. Improved health outcomes are one of several considerations in determining whether an item or service is reasonable and necessary. For most determinations, CMS evaluates whether reported benefits translate into improved health outcomes. CMS places greater emphasis on health outcomes actually experienced by patients, such as quality of life, functional status, duration of disability, morbidity and mortality, and less emphasis on outcomes that patients do not directly experience, such as intermediate outcomes, surrogate outcomes, and laboratory or radiographic responses. The direction, magnitude, and consistency of the risks and benefits across studies are also important considerations. Based on the analysis of the strength of the evidence, CMS assesses the relative magnitude of an intervention or technology’s benefits and risk of harm to Medicare beneficiaries.

APPENDIX B [PDF, 44KB]

APPENDIX C

A. General

CPAP is a non-invasive technique for providing single levels of air pressure from a flow generator, via a nose mask, through the nares. The purpose is to prevent the collapse of the oropharyngeal walls and the obstruction of airflow during sleep, which occurs in OSA.

B. Nationally Covered Indications

1. A trial period of CPAP of up to twelve weeks duration is covered when ordered and prescribed by the licensed treating physician to be used in beneficiaries who have a positive facility-based PSG as defined by:
   • AHI (apnea hypopnea index) greater than or equal to 15 events per hour with a minimum of 30 events; or
   • AHI greater than or equal to 5 and less than or equal to 14 events per hour with a minimum of 10 events in patients with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease, or history of stroke.

   CPAP beyond the trial period for beneficiaries who qualified on the basis of a positive PSG is covered only in those beneficiaries who have demonstrated appropriate therapeutic use and response to the trial use of CPAP. Medicare contractors may include consideration of the reports obtained via a compliance monitor as a factor in making this determination.

2. A trial period of CPAP of up to twelve weeks duration is covered when ordered and prescribed by the licensed treating physician to be used in beneficiaries who have a positive home sleep test, including only Type II, III, or IV machines, as defined by:
   • AHI or RDI (respiratory disturbance index) greater than or equal to 15 events per hour with a minimum of 30 events; or
   • AHI or RDI greater than or equal to 5 and less than or equal to 14 events per hour with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease, or history of stroke; with a minimum of 10 events.

   CPAP beyond the trial period for beneficiaries who qualified solely on the basis of a positive home sleep test is reasonable and necessary only in those beneficiaries who have demonstrated appropriate therapeutic use and response to the trial use of CPAP. Medicare contractors may include consideration of the reports obtained via a compliance monitor as a factor in making this determination.

3. CPAP is covered in the absence of a facility based PSG or a home sleep test, based on a clinical diagnosis only, when the provider is participating in, and beneficiaries are enrolled in, a clinical trial of CPAP after clinical diagnosis alone. This clinical trial must meet all of the following standards:
   1. The primary purpose of the trial is to test whether the use of CPAP without a prior sleep study improves the participants' health outcomes.
   2. The trial design and protocol must include all the following parameters:
      • Prospective, sham (placebo)-controlled, double-blinded study with 3 arms: (1) auto CPAP group, (2) fixed CPAP group, and (3) sham group.
      • Appropriate Medicare beneficiary representation in the sample for a p < 0.05 and power of 80% for the primary outcomes, generalizable to the Medicare beneficiary population.
      • Appropriate exclusion criteria: including but not limited to contraindications to CPAP usage (unstable CHF, lung disease, obesity hypoventilation syndrome), significant nasal obstruction, and previous CPAP treatment.
      • Comprised of persons who are highly suspicious of having OSA, and have no history of other causes of abnormal sleep disorders.
      • Baseline and subsequent measures include history and physical examination, sleep questionnaire such as ESS, and a quality of life instrument validated for this use.
      • Subjects are followed longitudinally over at least a 12 month period. At baseline, 1 month, 3 months, and 12 months primary end points and measures are assessed.
      • For subjects in all groups, if improvement is measured at 3 months, they will continue in the study as is.
      • For subjects in all groups, if no improvement occurs at 3 months, PSG will be done to evaluate the diagnosis of OSA with an AHI > 15 considered as positive for OSA without comorbidities, or an AHI of > 5 and <14, without comorbidities.
   3. The trial is in compliance with Federal regulations relating to the protection of human subjects.
   4. The trial is listed in the National Library of Medicine clinical trials database.
   5. The sample of study subjects in the trial should include women and minorities.

Sponsors and/or principal investigators may submit their proposed studies to CMS for approval. CMS will post the approved studies on its website.

C. Nationally Non-covered Indications

Effective (date of final NCD), other diagnostic tests for the diagnosis of OSA for prescribing CPAP are not covered.

D. Other

The AHI is equal to the average number of episodes of apnea and hypopnea per hour of sleep..

The RDI is equal to the episodes of apnea and hypopnea per hour of measurement.

Apnea is defined as a cessation of airflow for at least 10 seconds. Hypopnea is defined as an abnormal respiratory event lasting at least 10 seconds with at least a 30 percent reduction in thoracoabdominal movement or airflow as compared to baseline, and with at least a 4 percent oxygen desaturation.

The AHI and/or RDI may be measured by polysomnography in a facility-based sleep study laboratory or by a Type II, III or IV home sleep study monitor.

Initial claims must be supported by medical documentation (separate documentation where electronic billing is used), such as a prescription written by the patient's attending physician.

The claim must also certify that the documentation supporting a diagnosis of OSA (described above) is available.

¹ CMS has described this statute more fully in a Guidance Document available at https://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=8.

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