Clinical Policy Title: Treatment for obstructive sleep apnea in adults

Clinical Policy Title: Treatment for obstructive sleep apnea in adults Clinical Policy Number: 07.01.01 Effective Date: March 1, 2014 Initial Review Date: October 16, 2013 Most Recent Review Date: October 19, 2016 Next Review Date: October 2017 Related policies: Policy contains: Positive airway pressure devices. Oral appliances. Surgery. Obstructive sleep apnea. CP# 08.03.02 CP# 07.01.05 CP# 10.03.05 Bariatric surgery for adults Diagnosing obstructive sleep apnea in adults Uvulopalatopharyngoplasty (UPPP) ABOUT THIS POLICY: AmeriHealth Caritas Pennsylvania has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas Pennsylvania s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas Pennsylvania when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas Pennsylvania s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas Pennsylvania s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas Pennsylvania will update its clinical policies as necessary. AmeriHealth Caritas Pennsylvania s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas Pennsylvania considers the use of treatments for obstructive sleep apnea (OSA) in adults (age 18 years) to be clinically proven and, therefore, medically necessary when the following diagnostic and treatment criteria are met: Diagnostic criteria: - Diagnosis of OSA is based on a positive attended full-channel nocturnal polysomnography (PSG) performed at a health care facility or on a positive home sleep test. - Severity of OSA is defined as follows: Severe OSA based on an apnea hypopnea index (AHI) or respiratory disturbance index (RDI) 30 events per hour. Moderate OSA based on an AHI or RDI 15 events per hour but < 30 events per hour. Mild OSA based on an AHI or RDI 5 events but < 15 events per hour. 1

Treatment criteria: - Continuous positive airway pressure (CPAP) or autopap should be offered as the initial therapy. Coverage is limited initially to a 12-week period to identify members diagnosed with OSA who benefit from CPAP or autopap. CPAP or autopap is subsequently covered only for those beneficiaries diagnosed with OSA who benefitted from CPAP during this 12-week period. - Mandibular advancement devices (MADs) or removable oral appliances may be offered as an initial treatment to either of the following members: For members with documented mild to moderate OSA. For patients with documented severe OSA who cannot tolerate or refuse PAP treatment. - The following surgical treatments may be offered after six-month failure of non-invasive therapies: Uvulopalatopharyngoplasty (UPPP) as a single surgery or in-phased surgery for members who meet the criteria for CPAP or autopap but who are intolerant to PAP treatment. Maxillomandibular advancement (MMA) with or without genioglossal advancement for persons diagnosed with severe OSA and who fail other treatment approaches. Tracheostomy for members with the most severe OSA not manageable by other interventions. Surgery to correct discrete anatomic abnormalities of the upper airway that significantly contribute to OSA (including, but not limited to, enlarged tonsils or an enlarged tongue) based on adequate documentation in the medical records. For Medicare members only: PAP (positive airway pressure): A. Single-level CPAP (E0601) covered when used in the treatment of OSA, if following criteria 1 3 are met: 1. The beneficiary has a face-to-face clinical evaluation by the treating physician prior to the sleep test to assess the beneficiary for OSA. 2. The beneficiary has a sleep test (as defined below) that meets either of the following criteria: a. AHI or RDI is 15 events per hour with a minimum of 30 events. b. AHI or RDI is 5 and 14 events per hour with a minimum of 10 events and documentation of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia; or hypertension, ischemic heart disease or history of stroke. 3. The beneficiary and/or their caregiver has received instruction from the supplier of the device in the proper use and care of the equipment. 2

B. Bi-level respiratory assist device without back-up rate (E0470) covered for those beneficiaries with OSA who meet criteria 1 3 above, in addition to criterion 4 below: 4. An E0601 has been tried and proven ineffective based on a therapeutic trial conducted in either a facility or a home setting. C. Adult beneficiaries who do not qualify for CPAP coverage based on criteria for OSA diagnosis do qualify under Coverage with Evidence Determination when enrolled in a registered clinical research study that addresses one of the two questions below: 1. 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 Types II, III and IV home sleep test (HST) in identifying subjects with OSA who will respond to CPAP? 2. In Medicare-aged subjects with clinically identified risk factors for OSA who have not undergone confirmatory testing with PSG or Types II, III and IV HST, does CPAP cause clinically meaningful harm? II. Oral appliances are considered medically necessary if criteria A D are met: A. The beneficiary has a face-to-face clinical evaluation by the treating physician prior to the sleep test to assess the beneficiary for OSA. B. Beneficiary has a Medicare-covered sleep test that meets one of the following criteria (1 3): 1. AHI or RDI is 15 events per hour with a minimum of 30 events. 2. The AHI or RDI is 5 and 14 events per hour with a minimum of 10 events and documentation of either: a. Excessive daytime sleepiness, impaired cognition, mood disorders or insomnia. b. Hypertension, ischemic heart disease or history of stroke. 3. If the AHI > 30 or the RDI > 30 and meets either of the following: a. The beneficiary is not able to tolerate a PAP device. b. The treating physician determines that the use of a PAP device is contraindicated. C. The device is ordered by the treating physician following review of the report of the sleep test. (The physician who provides the order for the oral appliance could be different from the one who performed the clinical evaluation in criterion A.) D. The device is provided and billed for by a licensed dentist (DDS or DMD). E. Oral maxillofacial prostheses used in the treatment of OSA will be covered when specifically fashioned to the needs and measurements of individual patients when used to treat essential sleep apnea (780.53) and OSA (780.57). III. Covered surgical treatments: A. UPPP for patients who meet all of the following criteria: 1. Diagnosed OSA (RDI 15). 2. Failure to respond to CPAP or intolerance for CPAP or other appropriate non-invasive treatment. 3. Documented counseling by a physician with recognized training in sleep disorders about the potential benefits and risks of the surgery. 3

4. Evidence of retropalatal or combination retropalatal/retrolingual obstruction as cause of OSA. B. Mandibular maxillary osteotomy and advancement and/or genioglossus advancement with or without hyoid suspension is covered for those patients who meet all of the following criteria: 1. Diagnosed OSA (RDI 15). 2. Failure to respond to CPAP or intolerance for CPAP or other appropriate non-invasive treatment. 3. Documented counseling by a physician with recognized training in sleep disorders about the potential benefits and risks of the surgery. 4. Evidence of retrolingual obstruction as the cause of OSA, or previous failure of UPPP to correct the OSA. Note regarding the mandibular maxillary osteotomy and advancement operation: a. Separate repositioning of teeth would not be necessary except under unusual circumstances, but if necessary the dental work would be covered. b. Application of an interdental fixation device is occasionally necessary and is a covered service. C. Tracheostomy is indicated either: 1. When patient is unresponsive to other means of treatment. 2. In cases where other means of treatment would be ineffective or not indicated. D. Surgery to correct discrete anatomic abnormalities of the upper airway that significantly contribute to OSA (such as, but not limited to, enlarged tonsils or an enlarged tongue) based on adequate documentation in the medical records. E. Submucous radiofrequency reduction of hypertrophied turbinates for treatment of nasal obstruction due to turbinate hypertrophy that significantly contributes to OSA or significantly compromises CPAP therapy. F. Submucosal radiofrequency tissue volume reduction of the tongue base only when performed with other medically necessary surgical procedures for the treatment of OSA that has not responded to appropriate medical management. Limitations: All other treatments for OSA in adults are not medically necessary. These include treatment for snoring alone without significant OSA or interventions intended to improve adherence to OSA treatment with PAP. Limitations to oral appliances: - Replacement of oral appliances at the end of their five-year reasonable useful lifetime (RUL) or prior to the end of the five-year RUL due to a change in the member s condition is covered. Replacement needed due to misuse or abuse is not covered. - Follow-up care, including fitting, adjustments, modifications, professional services (not allinclusive) required during the first 90 days after provision of the oral appliance are considered to be included in the payment for device. 4

- Dental rehabilitation services (dentures, bridgework, etc.) as treatment for OSA, even if medically necessary, are not available benefits. Members should review their dental benefits plan, if any. A minimum of two months of active treatment is required between each intervention. Note: The following CPT/HCPCS codes are not listed in the Pennsylvania Medicaid fee schedule: 21198 - OSTEOTOMY, MANDIBLE, SEGMENTAL 41512 - TONGUE BASE SUSPENSION, PERMANENT SUTURE TECHNIQUE 41530 - SUBMUCOSAL ABLATION OF THE TONGUE BASE, RADIOFREQUENCY, 1 OR MORE SITES, PER SESSION 41599 - UNLISTED PROCEDURE, TONGUE, FLOOR OF MOUTH 42299 - UNLISTED PROCEDURE, PALATE, UVULA E0485 - Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, prefabricated, includes fitting and adjustment [covered only for obstructive sleep apnea in persons that meet criteria for CPAP but who are intolerant to positive airway pressure devices] E0486 - Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, custom fabricated, includes fitting and adjustment Alternative covered services: Evaluation by participating physicians and weight management according to plan benefits if appropriate. Background Sleep apnea is a type of sleep disorder characterized by pauses in breathing (apnea) or instances of shallow or infrequent breathing during sleep. OSA is the most common type of sleep apnea, caused by an obstruction of the upper airway during sleep. Untreated OSA is associated with symptoms of sleep deprivation and excessive sleepiness, cognitive dysfunction, diminished quality of life and productivity, sexual dysfunction, mood changes, increased accident risk, hypertension, non-insulin-dependent diabetes and other metabolic abnormalities, cardiac disease, and stroke. OSA affects persons in all age groups, especially middle-aged and elderly persons. OSA rates are increasing, likely due to escalating obesity rates (AHRQ 2011). OSA is characterized by repetitive pauses in breathing during sleep, despite the effort to breathe, and is usually associated with a reduction in blood oxygen saturation. PSG performed at a sleep lab is the 5

standard diagnostic test for OSA, but it can be performed at home. Results from PSG are reported as the AHI and RDI. The AHI is a strong and independent predictor of all-cause mortality over several years of follow up, with the association being strongest among people with severe OSA (AHRQ 2011). According to the American Academy of Sleep Medicine (AASM), severity of OSA according to AHI is defined as mild (five to 14 events per hour), moderate (15 to 30 events per hour) and severe (> 30 events per hour) (Qaseem 2013). There is no current established threshold level for the AHI that would indicate the need for treatment, but generally, people with relatively few apnea or hypopnea events per hour (often < 5 or < 15, respectively) are not formally diagnosed with OSA (AHRQ 2011). The goal of OSA treatment is to alleviate airway obstruction during sleep, normalize sleep quality, and improve AHI and oxyhemoglobin saturation levels. It may improve comorbidities associated with untreated sleep apnea, primarily cardiovascular disease and non-insulin-dependent diabetes and associated mortality (AHRQ 2011, Randerath 2011).Treatment of OSA includes behavioral therapy (e.g., weight loss), drug therapy, CPAP, dental or mandibular advancement devices (MADs), palatal implants, and surgery (upper airway or bariatric). New minimally invasive surgical techniques are currently being developed to achieve better patient outcomes and reduce surgical morbidity. Surgical procedures include, but are not limited to, UPPP, MMA, multilevel surgery, and tracheostomy. Other interventions include devices to alter sleep position, physical therapy to improve oropharyngeal muscle tone, atrial overdrive pacing for patients with nocturnal bradycardia, complementary and alternative therapies and interventions to achieve weight loss (e.g., bariatric surgery). Searches AmeriHealth Caritas Pennsylvania searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on September 13, 2016. Search terms were: "Sleep Apnea, Obstructive/surgery" [MeSH] and "Sleep Apnea, Obstructive/therapy" [MeSH]. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. 6

Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings Assessment of effectiveness of OSA treatments is based primarily on improvement of daytime sleepiness. The effect on other clinical outcomes, including hypertension, cardiovascular events and death, is uncertain. Long-term outcomes for all interventions were rarely reported. Evidence of adverse effects related to various management strategies for OSA is sparse, especially from randomized controlled trials (RCTs). The most serious adverse effects were reported for surgical interventions, particularly for oronasopharyngeal or bariatric surgery. An estimated 5 to 15 percent of patients treated with CPAP reported substantial adverse effects that could be alleviated with termination or treatment modification. Tooth loosening, dental crown damage and temporomandibular joint pain were the most commonly reported adverse effects with MADs. No long-term adverse effects were reported for weight-loss interventions (AHRQ 2011). Among other findings: There is moderate-quality evidence supporting the effectiveness of CPAP for treating OSA. Data to determine the comparative efficacy of most CPAP modifications were insufficient; however, moderate-quality evidence showed that fixed and auto CPAP have overall similar efficacy and adherence despite small differences, and low-quality evidence showed that C-Flex and fixed CPAP were similarly efficacious. These modifications are used primarily as second-line measures for patients who are intolerant to CPAP. The American College of Physicians, the European Respiratory Society and the AASM recommend CPAP as the first-line therapy for severe OSA (Qaseem 2013, Randerath 2011, Aurora 2010). There is moderate-quality evidence supporting the effectiveness of MADs in patients with mild to moderate OSA to lower AHI scores and reduce sleepiness, but the evidence is insufficient to determine the comparative effectiveness of different MADs. There is moderate-quality evidence that CPAP is more effective than MADs. MADs are available typically for patients with mild-to-moderate disease who are unable to tolerate CPAP or who refuse CPAP (AHRQ 2011, Randerath 2011, Aurora 2010). There is insufficient evidence to determine which patients would benefit the most from either CPAP or MAD treatment. One recent discrete choice experiment of 121 newly diagnosed patients in France found that, when offered CPAP or MADs, patients preferred CPAP to MADs (60.2 percent vs. 36.2 percent, respectively); negative impact on daily life and effectiveness of treatment constituted the most important factors of choice ahead of side effects, but these choices could be influenced heavily by out-of-pocket expenses (Krucien 2013). There is insufficient evidence to evaluate the efficacy of interventions to improve OSA treatment adherence (primarily CPAP). 7

There is low-quality evidence to support the effectiveness of dietary weight loss programs in reducing the severity of OSA, but not in relieving all respiratory events. There is insufficient evidence supporting the efficacy or comparative effectiveness of other non- CPAP or non-surgical OSA treatments. There is insufficient evidence to support the effectiveness of surgical interventions for OSA treatment, except for the following: - Low-quality evidence supports the effectiveness of MMA for treating severe OSA when used to correct hypopharyngeal and/or velo-orohypopharyngeal narrowing with or without skeletal hypoplasia. - Low-quality evidence supports the effectiveness of UPPP as a single procedure for treating moderate to severe OSA. - Low-quality evidence supports the effectiveness of multilevel surgery (simultaneous or phased) for treating severe OSA when MMA is used as the phase 2 procedure. - Sufficient evidence supports the effectiveness of tracheostomy for treating OSA, but it should be used as a salvage procedure. Policy updates: For the 2014 policy update, one new systematic review (Camacho 2014) and no new guidelines were identified. The new information is consistent with the current policy. Therefore, no changes to the policy are warranted. For the 2015 policy update, two meta-analyses (Knudsen 2015, Okuno 2014) and one systematic review (Ward 2014) were identified. These new studies would not change the previous conclusions. Therefore, no changes to the policy are warranted. In 2016, we added seven systematic reviews and meta-analyses, one evidence-based guideline and no economic analyses. Three analyses addressed the effect of surgical treatment of OSA: MMA (Zaghi 2016); temperature-controlled radiofrequency ablation (TCRFA) (Baba 2015); and glossectomy (Murphey 2015). Each procedure was studied in persons in whom other treatment options for OSA had failed. Low quality evidence suggests that TCRFA directed at the base of the tongue and glossectomy procedures are effective treatments for OSA in the short-term when performed as part of a multilevel procedure, but not as stand-alone procedures (Baba 2015, Murphey 2015). MMA is an effective treatment for patients with high residual AHI and RDI after other unsuccessful surgical procedures for OSA, and a preoperative AHI of< 60 events per hour was most strongly associated with the highest incidence of surgical cure (Zaghi 2016). Two meta-analyses compared the effectiveness of CPAP and MADs on blood pressure and sleepiness in persons with OSA (Bratton 2015a and 2015b). Both CPAP and MADs are effective at improving blood pressure and sleepiness outcomes, although CPAP has a significantly greater effect on sleepiness. For persons who cannot tolerate or refuse CPAP, MADs can be offered as an effective non-surgical option. 8

Two other systematic reviews provide inconclusive evidence demonstrating that treatment of OSA with CPAP reduces the risk of stroke or improves cognition (Kim 2016, Pan 2015). The use and published research of oral appliances/mads for treating OSA have increased considerably in recent years. Consequently, the AASM and American Academy of Dental Sleep Medicine (AADSM) updated their practice guideline from 2006 on oral appliances for treatment of OSA and snoring (Ramar 2015). The guideline encourages increased use of custom, titratable oral appliances, periodic follow-up by qualified dentists to assess dental side effects, and sleep testing to assess treatment efficacy. The new information does not change previous findings, and no policy changes are warranted. Summary of clinical evidence: Citation Kim (2016) Effect of CPAP on stroke Zaghi (2016) MMA Baba (2015) Temperature controlled radiofrequency tissue ablation (TCRFTA) Bratton (2015a) Effects of CPAP versus MADs on sleepiness Bratton (2015b) Content, Methods, Recommendations Systematic review and meta-analysis of one RCT, two cohort studies, and two studies using administrative health data (60,186 total subjects). Overall quality: moderate. Low risk of bias in the RCT, moderate or unclear risk of bias in other studies. CPAP may reduce the risk of stroke, but results are conflicting. Pooled analysis of individual patient data from 45 studies with 518 unique patients/interventions; 197 patients had undergone prior surgery for OSA. Significant improvements seen in the AHI and RDI, oxygen saturation and sleepiness post operatively. Surgical cure rate: 175 of 455 patients (38.5%) based on AHI data and 13 of 68 patients (19.1%) based on RDI data. Preoperative AHI < 60 events/h was most strongly associated with the highest incidence of surgical cure. Patients with a preoperative AHI > 60 events/h experienced large and substantial net improvements despite modest surgical cure rates. Systematic review and meta-analysis of 20 studies. Overall quality: low. High risk of bias and significant heterogeneity. TCRFTA is clinically effective in reducing RDI levels and symptoms of sleepiness in the short-term in patients with OSA syndrome when directed at the base of tongue as part of a multilevel procedure. Effect on AHI was not consistently reported. Studies with longer-term outcomes are needed. Network meta-analysis of 67 studies (6,873 total patients). Possible publication bias in favor of CPAP. Compared with inactive controls, both CPAP and MADs reduce sleepiness: Reduction in Epworth sleepiness scale (ESS) score of 2.5 points (95% CI 2.0 to 2.9) versus 1.7 points (1.1 to 2.3), respectively. CPAP versus MADs: 0.8 point greater reduction in ESS score with CPAP than MADs (95% CI 0.1 to 1.4; p=0.015). Effect of CPAP versus MADs on blood Systematic review and meta-analysis of 51 RCTs (4,888 total patients). Overall quality: Moderate to high with a low risk of bias. 9

pressure (BP) CPAP and MADs are associated with reductions in BP, but no statistically significant difference in BP outcomes between CPAP and MADs. Knudsen (2015) MMA with counterclockwise (CCW) rotation Murphey (2015) Glossectomy Pan (2015) Effects of CPAP on cognitive deficits in the middle-aged Ramar (2015) for the AASM and AADSM Clinical practice guideline for the treatment of OSA and snoring with oral appliance therapy in adults Okuno (2014) MAD versus CPAP Ward (2014) Users perspective of CPAP Camacho (2014) Meta-analysis of four randomized controlled trials (RCTs). Postoperative AHI and lowest oxygen saturation (LSAT) showed vast improvement. Insufficient sample size to correlate pharyngeal volume changes and surgical method. CCW-MMA or MMA in patients with OSA results in a statistically meaningful decrease in postoperative AHI and a statistically meaningful increase in postoperative LSAT. Systematic review and meta-analysis of 18 single-arm studies (522 total patients treated with midline glossectomy, lingualplasty, and submucosal minimally invasive lingual excision). Baseline versus post-surgery as part of multilevel surgery: Significant improvement in AHI, ESS, snoring visual analog scale, and lowest O2 saturation. Surgical success rate 59.6% (95% CI, 53.0% to 65.9%), surgical cure rate 22.5% (95% CI, 11.26% to 36.26%), acute complication rate 16.4%. Currently, there is promising but insufficient evidence to support glossectomy as a stand-alone procedure for OSA. Meta-analysis of 13 RCTs (1,744 middle-aged obese participants with mild to severe OSAS). Overall quality: Moderate to high with low risk of bias. CPAP improved attention, vigilance, processing speed, working memory, memory, verbal fluency, and visuoconstructive skills domains, but only vigilance was statistically significant. Rigorous RCTs are needed to obtain clear results. Key recommendations: Prescribe oral appliances, rather than no therapy, for adults who request treatment of primary snoring (without OSA). Use a custom, titratable appliance over non-custom oral devices. Prescribe oral appliances, rather than no treatment, if intolerant of CPAP therapy or prefer alternate therapy. Provide dental oversight to survey for dental-related side effects or occlusal changes and reduce their incidence. Conduct follow-up sleep testing to improve or confirm treatment efficacy. Encourage periodic office visits, as opposed to no follow-up. Meta-analysis of five studies comparing MAD to no treatment or to CPAP. MAD significantly improved AHI and arousal index versus untreated disease. AHI, lowest oxygen saturation rate (SpO2) and SF-36 were significantly better with CPAP than with MAD. Systematic review of 22 articles. Personality and attitude impact expectations about CPAP prior to use, and spouse and family engagement also influence experiences. More information from users is required to determine how CPAP can be managed successfully. 10

Tracheostomy for OSA Anandam (2013) Dietary weight loss programs Baessler (2013) CPAP on inflammatory markers Choi (2013) Pillar implant Iftikhar 2013 CPAP on insulin resistance in nondiabetic patients Mason 2013 Cochrane review Drug therapy Canadian Agency for Drugs and Technologies in Health (2012) Adaptive servo ventilation (ASV), CPAP, bi-level PAP (BPAP) Hayes (2012) Provent nasal device (Ventus Medical Inc.) Tomfohr (2012) Effect of CPAP on cortisol levels AHRQ (2011) Systematic review of 18 primarily retrospective case series or historical cohorts. Overall quality: low. Tracheostomies significantly decrease apnea index, oxygen desaturation index, sleepiness and mortality in subjects with severe OSA. Meta-analysis of nine studies. Dietary weight-loss programs are effective in reducing the severity of OSA but not adequate in relieving all respiratory events. Weight loss programs are adjunctive, not curative. Meta-analysis of 23 case-control studies. Inconclusive evidence with high uncertainty. Systematic review of seven studies of patients with mild-to-moderate OSA. Inconclusive evidence. Systematic review of five RCTs. Evidence shows a favorable effect of CPAP on insulin resistance as measured by homeostasis model assessment of insulin resistance HOMA-IR. Modest but significant effect size of CPAP vs. thiazolidinedione in non-diabetic patients with metabolic syndrome. Systematic review of 30 trials of 25 drugs (516 total patients). The overall quality of the available evidence was low. Inconclusive evidence. Rapid review of one systematic review, one RCT, one non-randomized study and one guideline. ASV is effective in treating OSA and congestive heart failure (CHF) compared with CPAP or BPAP. No evidence for the cost-effectiveness of ASV vs. conventional CPAP or BPAP for sleep apnea or CHF. Mostly industry-sponsored studies, uncertainty regarding the optimal settings for use. Low-quality evidence results inconclusive. No clear evidence that OSA is associated with alterations in cortisol levels or that treatment with CPAP changes cortisol levels. Multiple interventions Systematic review of 132 RCTs, six prospective nonrandomized comparative studies, five retrospective nonrandomized. Overall quality: Low to moderate. Few trials evaluated objective clinical outcomes and limited by short follow-ups, high dropout rates, and poor analyses and reporting. 11

Randerath (2011) European Respiratory Society Task Force Non-CPAP interventions Caples (2010) CPAP: Effective in minimizing AHI and improving sleepiness (moderate evidence); auto-titrating and fixed CPAP have similar effects (moderate evidence); comparisons to other CPAP devices (insufficient evidence). MADs: overall effective (moderate evidence); CPAP is superior to MADs (moderate). Drug therapy: insufficient evidence. All other interventions, including surgery: insufficient evidence to compare outcomes between surgical procedures or between surgery and either CPAP or MAD. AHI and Epworth Sleepiness Scale are independent predictors of CPAP compliance; low evidence that some treatments improve CPAP compliance. Evidence supports the use of MADs in mild to moderate OSA. There is a trend toward improvement after weight loss. Positional therapy is clearly inferior to CPAP and long-term compliance is poor. Drugs, nasal dilators and apnea-triggered muscle stimulation: insufficient evidence. MMA is as efficient as CPAP in patients who refuse conservative treatment with some morbidity. Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement: insufficient evidence. UPPP, pillar implants and hyoid suspension: inconsistent results, most evidence available for UPPP. Multilevel surgery: inconsistent results regarding morbidity. Surgery Glossary Systematic review of 79 papers (three RCTs of single procedures, one RCT of multilevel procedures, 44 case series of single procedures, 31 case series of multilevel procedures). Overall low quality; highly selected patients, varied preoperative and surgical approaches. MMA: Substantial and consistent reductions in AHI for severe OSA caused by hypopharyngeal and/or velo-orohypopharyngeal narrowing with or without skeletal hypoplasia; adverse events uncommonly reported. UPPP: Used for moderate to severe OSA as single procedure but inconsistent reduction in AHI with some morbidity reported; often modified or combined with other surgical modifications. Other isolated pharyngeal/soft palatal interventions: for severe OSA, inconsistent results often with significant residual OSA post-surgery, poorly reported. Radiofrequency ablation: low-quality evidence for mild to moderate OSA. Multilevel surgery (simultaneous or phased): low-quality evidence, likely that significant benefit of phased surgeries for patients failing phase one treatment were derived from MMA used as phase two treatment. Apnea-hypopnea index (AHI) The number of apneic episodes (obstructive, central and mixed) plus hypopneic episodes per hour of sleep. Continuous positive airway pressure (CPAP) Device that delivers a steady, gentle flow of air through a soft, pliable face or nasal mask. Used to splint open a person s airway during sleep. 12

Genioglossus advancement (tongue advancement) A procedure that pulls the tongue forward in a manner that decreases the amount of tongue blockage during sleep. Hypopnea A partial reduction in breathing of at least 30 percent that lasts at least 10 seconds during sleep. This is measured by a nasal pressure transducer. Mandibular advancement devices (MAD) A type of pre-fabricated device worn in the mouth that holds the lower jaw and tongue forward making more space to breathe and prevent snoring. Maxillomandibular advancement (MMA) A surgical procedure that moves the upper jaw (maxilla) and the lower jaw (mandible) forward to widen the airway. Multi-level or stepwise surgery (MLS) Includes a wide array of combined procedures to address narrowing of multiple sites in the upper airway. MLS frequently consists of phase I using UPPP and/or genioglossus advancement and hyoid myotomy. Phase II surgeries consist of maxillary and mandibular advancement osteotomy, offered to those failing phase I surgeries. Oral appliance A device that repositions oral and pharyngeal tissues to create and maintain a patent airway during sleep. May be custom fabricated or pre-fabricated. Obstructive sleep apnea (OSA) A life-threatening and life-altering condition that causes a cessation in breathing repeatedly during sleep due to upper airway obstruction (e.g., a semi-collapsed trachea, tongue relaxed to the back of the throat or a large amount of tissue in the uvula area). Polysomnography (PSG) or overnight sleep study Standard method of detecting sleep disorders and evaluating treatments in children and adults while sleeping. PSG measures information such as airflow, brain activity (EEG), respiratory effort, eye movements (EOG), leg movements (EMG), blood oxygen saturation and unusual behavior. Positive airway pressure (PAP) Provides a stream of air through a mask or nasal appliance during sleep. This airflow keeps the airway open, preventing pauses in breathing and restoring normal blood oxygen saturation. PAP can be continuous (CPAP), bilevel (BPAP) or autotitrating (APAP). Radiofrequency ablation (RFA) Placing a temperature-controlled radiofrequency probe typically in the tongue and/or soft palate in an effort at palatal stiffening. Respiratory disturbance index (RDI) The number of apneas (obstructive, central or mixed) plus hypopneas per hour of total sleep time as determined by all-night polysomnography. Tracheostomy An opening in the trachea for placement of a long-term indwelling tube or stoma for ventilation that bypasses upper airway obstruction causing OSA. 13

Uvulopalatopharyngoplasty (UPPP) A procedure that enlarges the upper airway by removing excess tissue in the back of the throat. References Professional society guidelines/other: Aurora RN, Casey KR, Kristo D, et al. Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults. Sleep. 2010 Oct; 33(10): 1408 1413. Qaseem A, Holty JE, Owens DK, et al. Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2013; 159(7): 471 483. Ramar K, Dort LC, Katz SG, et al. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. J Clin Sleep Med. 2015; 11(7): 773 827. Randerath WJ, Verbraecken J, Andreas S, et al. Non-CPAP therapies in obstructive sleep apnoea. Eur Respir J. 2011 May; 37(5): 1000 1028. Peer-reviewed references: Agency for Healthcare Research and Quality (AHRQ). Diagnosis and treatment of obstructive sleep apnea in adults. Comparative Effectiveness Review No. 32. (Prepared by Tufts Evidence-Based Practice Center under contract 290-2007-100551). Rockville, MD. AHRQ website: http://www.effectivehealthcare.ahrq.gov/ehc/products/117/683/cer32_sleepapnea_finalreview_201 108.pdf. Anandam A, Akinnusi M, Kufel T, Porhomayon J, El-Solh AA. Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis. Sleep Breath. 2013 Mar; 17(1): 227 234. Baba RY, Mohan A, Metta VV, Mador MJ. Temperature controlled radiofrequency ablation at different sites for treatment of obstructive sleep apnea syndrome: a systematic review and meta-analysis. Sleep Breath. 2015; 19(3): 891 910. Baessler A, Nadeem R, Harvey M, et al. Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013 Mar 22; 10(1): 13. Bratton DJ, Gaisl T, Schlatzer C, Kohler M. Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis. Lancet Respir Med. 2015; 3(11): 869 878. (a) 14

Bratton DJ, Gaisl T, Wons AM, Kohler M. CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Jama. 2015; 314(21): 2280 2293. (b) Camacho M, Certal V, Brietzke SE, et al. Tracheostomy as treatment for adult obstructive sleep apnea: a systematic review and meta-analysis. Laryngoscope. 2014 Mar; 124(3): 803 811. Canadian Agency for Drugs and Technologies in Health (CADTH). Adaptive servo ventilation versus continuous or bi-level positive airway pressure: a review of the clinical effectiveness, cost-effectiveness and guidelines. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2012. Caples SM, Rowley JA, Prinsell JR, et al. Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis. Sleep. 2010 Oct; 33(10): 1396 1407. Choi JH, Kim SN, Cho JH. Efficacy of the Pillar implant in the treatment of snoring and mild-to-moderate obstructive sleep apnea: a meta-analysis. Laryngoscope. 2013 Jan; 123(1): 269 276. Hayes, Inc. Medical Technology Report. Provent sleep apnea therapy (Ventus Medical Inc.). Lansdale, PA: Hayes Inc; 2012. Iftikhar IH, Khan MF, Das A, Magalang UJ. Meta-analysis: continuous positive airway pressure improves insulin resistance in patients with sleep apnea without diabetes. Ann Am Thorac Soc. 2013 Apr; 10(2): 115 120. Kim Y, Koo YS, Lee HY, Lee SY. Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis. PLoS One. 2016; 11(1): e0146317. Knudsen TB, Laulund AS, Ingerslev J, Homoe P, Pinholt EM. Improved apnea-hypopnea index and lowest oxygen saturation after maxillomandibular advancement with or without counterclockwise rotation in patients with obstructive sleep apnea: a meta-analysis. J Oral Maxillofac Surg. 2015; 73(4): 719 726. Krucien N, Gafni A, Fleury B, Pelletier-Fleury N. Patients with obstructive sleep apnoea syndrome (OSAS) preferences and demand for treatment: a discrete choice experiment. Thorax. 2013 May; 68(5): 487 488. Mason M, Welsh Emma J, Smith I. Drug therapy for obstructive sleep apnoea in adults. Cochrane Database of Systematic Reviews [serial on the Internet]. 2013; (5): CD003002. Murphey AW, Kandl JA, Nguyen SA, Weber AC, Gillespie MB. The effect of glossectomy for obstructive sleep apnea: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2015; 153(3): 334 342. 15

Okuno K, Sato K, Arisaka T, et al. The effect of oral appliances that advanced the mandible forward and limited mouth opening in patients with obstructive sleep apnea: a systematic review and meta-analysis of randomised controlled trials. J Oral Rehabil. 2014; 41(7): 542 554. Pan YY, Deng Y, Xu X, Liu YP, Liu HG. Effects of continuous positive airway pressure on cognitive deficits in middle-aged patients with obstructive sleep apnea syndrome: a meta-analysis of randomized controlled trials. Chin Med J (Engl). 2015; 128(17): 2365 2373. Tomfohr LM, Edwards KM, Dimsdale JE. Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence. Sleep Med Rev. 2012 Jun; 16(3): 243 249. Ward K, Hoare KJ, Gott M. What is known about the experiences of using CPAP for OSA from the users' perspective? A systematic integrative literature review. Sleep medicine reviews. 2014; 18(4): 357 366. Zaghi S, Holty JE, Certal V, et al. Maxillomandibular advancement for treatment of obstructive sleep apnea: a meta-analysis. JAMA Otolaryngol Head Neck Surg. 2016; 142(1): 58 66. Clinical trials: Searched clinicaltrials.gov on September 14, 2016 using terms: Open Studies Exclude Unknown Interventional Studies "obstructive sleep apnea" NOT drug Adult, Senior. 47 studies found, 23 relevant. CMS National Coverage Determinations (NCDs): 240.4 Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA). CMS website. http://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?ncdid=226&ver=3. 240.4.1 Sleep Testing for Obstructive Sleep Apnea (OSA). CMS website. http://www.cms.gov/medicarecoverage-database/details/ncd-details.aspx?ncdid=330&ver=1. A52375 Category III CPT Code Coverage. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/article-details.aspx?articleid=52375&ver=25. A52512 Oral Appliances for Obstructive Sleep Apnea - Policy Article - Effective October 2015. CMS website. http://www.cms.gov/medicare-coverage-database/details/articledetails.aspx?articleid=52512&ver=5. A53497 Oral Maxillofacial Prosthesis. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/article-details.aspx?articleid=53497&ver=5. 16

A52467 Positive Airway Pressure (PAP) Devices for the Treatment of Obstructive Sleep Apnea - Policy Article - Effective October 2015. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/article-details.aspx?articleid=52467&ver=7. Local Coverage Determinations (LCDs): L33611 Oral Appliances for Obstructive Sleep Apnea. CMS website. http://www.cms.gov/medicarecoverage-database/details/lcd-details.aspx?lcdid=33611&ver=6. L35047 Oral Maxillofacial Prosthesis. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=35047&ver=6. DL33468 Oral Maxillofacial Prosthesis. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=36756&ver=3. L33468 Oral Maxillofacial Prosthesis. CMS website. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=33468&ver=8. L33718 Positive Airway Pressure (PAP) Devices for the Treatment of Obstructive Sleep Apnea. CMS website. http://www.cms.gov/medicare-coverage-database/details/lcddetails.aspx?lcdid=33718&ver=8. L34526 Surgical Treatment of Obstructive Sleep Apnea (OSA). CMS website. http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?lcdid=34526&ver=8. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comment 21085 Impression and custom preparation; oral surgical splint. 21193 21194 21195 21196 Reconstruction of mandibular rami, horizontal, vertical, c, or l osteotomy; without bone graft. Reconstruction of mandibular rami, horizontal, vertical, c, or l osteotomy; with bone graft (includes obtaining graft). Reconstruction of mandibular rami and/or body, sagittal split; without internal rigid fixation. Reconstruction of mandibular rami and/or body, sagittal split; with internal rigid fixation. 17

21198 Osteotomy, mandible, segmental. 21199 Osteotomy, mandible, segmental; with genioglossus advancement. 21206 Osteotomy, maxilla, segmental (e.g., wassmund or schuchard). 21208 Osteoplasty, facial bones; augmentation (autograft, allograft or prosthetic implant). 21209 Osteoplasty, facial bones; reduction. 21685 Hyoid myotomy and suspension. 31600 Tracheostomy, planned (separate procedure). 41512 Tongue base suspension, permanent suture technique. 41530 Submucosal ablation of the tongue base, radiofrequency, 1 or more sites, per session. 41599 Unlisted procedure, tongue, floor of mouth. 42140 Uvulectomy, excision of uvula. 42145 Palatopharyngoplasty (e.g., uvulopalatopharyngoplasty, uvulopharyngoplasty). 42299 Unlisted procedure, palate, uvula. 42821 Tonsillectomy and adenoidectomy; age 12 or over. 94660 Continuous positive airway pressure ventilation (CPAP), initiation and management. ICD-10 Code Description Comment G47.31 Obstructive sleep apnea (adult) (pediatric). HCPCS Level II A4604 A7027 A7028 A7029 A7030 A7031 A7032 A7033 Description Tubing with integrated heating element for use with positive airway pressure device [4 per 12 months]. Combination oral/nasal mask, used with continuous positive airway pressure device, each [4 per 12 months]. Oral cushion for combination oral/nasal mask, replacement only, each [24 per 12 months]. Nasal pillows for combination oral/nasal mask, replacement only, pair [24 per 12 months]. Full face mask used with positive airway pressure device, each [4 per 12 months][replacement device is not covered due to misuse or abuse]. Face mask interface, replacement for full face mask, each [12 per 12 months] [replacement device is not covered due to misuse or abuse]. Cushion for use on nasal mask interface, replacement only, each [24 per 12 months] [replacement device is not covered due to misuse or abuse]. Pillow for use on nasal cannula type interface, replacement only, pair [24 per 12 months] [replacement device is not covered due to misuse or abuse]. Comment 18

HCPCS Level II A7034 A7035 A7036 A7037 A7038 A7039 A7044 A7045 A7046 E0485 E0486 E0601 Description Nasal interface (mask or cannula type) used with positive airway pressure device, with or without head strap [4 per 12 months][replacement device is not covered due to misuse or abuse]. Headgear used with positive airway pressure device [2 per 12 months] [replacement device is not covered due to misuse or abuse]. Chinstrap used with positive airway pressure device [2 per 12 months] [replacement device is not covered due to misuse or abuse]. Tubing used with positive airway pressure device [4 per 12 months] [replacement device is not covered due to misuse or abuse]. Filter, disposable, used with positive airway pressure device [24 per 12 months] [replacement device is not covered due to misuse or abuse]. Filter, non-disposable, used with positive airway pressure device [2 per 12 months] [replacement device is not covered due to misuse or abuse]. Oral interface used with positive airway pressure device, each. Exhalation port with or without swivel used with accessories for positive airway devices, replacement only. Water chamber for humidifier, used with positive airway pressure device, replacement, each [2 per 12 months]. Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, prefabricated, includes fitting and adjustment [covered only for obstructive sleep apnea in persons that meet criteria for CPAP but who are intolerant to positive airway pressure devices]. Oral device/appliance used to reduce upper airway collapsibility, adjustable or non-adjustable, custom fabricated, includes fitting and adjustment. Continuous airway pressure (CPAP) device [for OSA with AHI 15 or > = to 15 events per hour with minimum of 30 or AHI > 5 and < 15 events per hour with minimum of 10 + one related diagnosis] [not covered for C-Flex]. Comment May be evaluated under medical or dental benefits for covered benefits. May be evaluated under medical or dental benefits for covered benefits. 19