Terminology and diagnostic criteria for OSA are shown in Table 1

Table 1. Terminology and Definitions for Obstructive Sleep Apnea

Terms	Definitions
Respiratory Event
Apnea	The frequency of apneas and hypopneas is measured from channels assessing oxygen desaturation, respiratory airflow, and respiratory effort. In adults, apnea is defined as a drop in airflow by ≥90% of pre-event baseline for at least 10 seconds. Due to faster respiratory rates in children, pediatric scoring criteria define an apnea as ≥2 missed breaths, regardless of its duration in seconds.
Hypopnea	Hypopnea in adults is scored when the peak airflow drops by at least 30% of pre-event baseline for at least 10 seconds in association with either at least 4% arterial oxygen desaturation or an arousal.Hypopneas in children are scored by a ≥50% drop in nasal pressure and either a ≥3% decrease in oxygen saturation or an associated arousal.
RERA	Respiratory event-related arousal is defined as an event lasting at least 10 seconds associated with flattening of the nasal pressure waveform and/or evidence of increasing respiratory effort, terminating in an arousal but not otherwise meeting criteria for apnea or hypopnea
Respiratory event reporting
Apnea/Hypopnea Index (AHI)	The average number of apneas or hypopneas per hour of sleep
Respiratory Disturbance Index (RDI)	The respiratory disturbance index is the number of apneas, hypopneas, or respiratory event-related arousals per hour of sleep time. RDI is often used synonymously with the AHI.
Respiratory event index (REI)	The respiratory event index is the number of events per hour of monitoring time. Used as an alternative to AHI or RDI in home sleep studies when actual sleep time from EEG is not available.
Diagnosis
Obstructive sleep apnea (OSA)	Repetitive episodes of upper airway obstruction due to the collapse and obstruction of the upper airway during sleep
Mild OSA	In adults: AHI of 5 to <15. In children: AHI ≥1 to 5
Moderate OSA	AHI of 15 to < 30. Children: AHI of > 5 to 10
Severe OSA	Adults: AHI ≥30. Children: AHI of >10
Treatment
Positive airway pressure (PAP)	Positive airway pressure may be continuous (CPAP) or auto-adjusting (APAP) or Bi-level (Bi-PAP).
PAP Failure	Usually defined as an AHI greater than 20 events per hour while using PAP
PAP Intolerance	PAP use for less than 4 h per night for 5 nights or more per week, or refusal to use CPAP. CPAP intolerance may be observed in patients with mild, moderate, or severe OSA

OSA: obstructive sleep apnea; PSG : Polysomnographic

Regulatory Status

The regulatory status of minimally invasive surgical interventions is shown in Table 2.

Table 2. Minimally Invasive Surgical Interventions for Obstructive Sleep Apnea

Interventions	Devices (predicate or prior name)	Manufacturer (previously owner)	Indication	PMA/ 510(k)	Year	FDA Product Code
LAUP	Various
Radiofrequency ablation	Somnoplasty®		Simple snoring and for the base of the tongue for OSA	K982717	1998	GEI
Palatal Implant	Pillar® Palatal Implant	Pillar Palatal (Restore Medical/ Medtronic)	Stiffening the soft palate which may reduce the severity of snoring and incidence of airway obstructions in patients with mild-to-moderate OSA	K040417	2004	LRK
Tongue base suspension	AIRvance® (Repose)	Medtronic	OSA and/or snoring. The AlRvance TM Bone Screw System is also suitable for the performance of a hyoid suspension	K122391	1999	LRK
	Encore™ (PRELUDE III)	Siesta Medical	Treatment of mild or moderate OSA and/or snoring	K111179	2011	ORY
Hypoglossal nerve stimulation	Inspire II Upper Airway Stimulation	Inspire Medical Systems	Patients ≥ 18 years with AHI ≥15 and ≤65 who have failed (AHI >15 despite CPAP usage) or cannot tolerate (<4 h use per night for ≥5 nights per week) CPAP and do not have complete concentric collapse at the soft palate level. Patients between ages 18 and 21 should also be contraindicated for or not effectively treated by adenotonsillectomy.	P130008, S039	2014	MNQ
Hypoglossal nerve stimulation	aura6000®	ImThera Medical		IDE	2014
Hypoglossal nerve stimulation	Genio™	Nyxoa		European CE Mark	2019

AHI: Apnea/Hypopnea Index; CPAP: continuous positive airway pressure; IDE: investigational device exemption; LAUP: Laser-assisted uvulopalatoplasty; OSA: obstructive sleep apnea.

The expanded indication for hypoglossal nerve stimulation in patients age 18 to 21 was based on patients with Down Syndrome and is contingent on a post-approval study of the Inspire® UAS in this age group. The post-approval study will be a multicenter, single-arm, prospective registry with 60 pediatric patients age 18 to 21. Visits will be scheduled at pre-implant, post-implant, 6 months, and yearly thereafter through 5 years.

Related Policies

• Diagnosis and Medical Management of Obstructive Sleep Apnea Syndrome (Policy #002 in the Medicine Section)

• Apnea/Hypopnea Index (AHI) or Respiratory Disturbance Index (RDI) of 15 or more events per hour, or
• AHI or RDI of at least 5 events per hour with one or more signs or symptoms associated with OSA (e.g., excessive daytime sleepiness, hypertension [uncontrolled despite optimal medical therapy], cardiovascular heart disease, or stroke).

• AHI or RDI of 15 or more events per hour, or
• AHI or RDI of at least 5 events per hour with one or more signs or symptoms associated with OSA (e.g., excessive daytime sleepiness, hypertension [uncontrolled despite optimal medical therapy], cardiovascular heart disease, or stroke).

• AHI or RDI of at least 5 per hour, or
• AHI or RDI of at least 1.5 per hour in a member with excessive daytime sleepiness, behavioral problems, or hyperactivity.
  
  (NOTE: The American Academy of Pediatrics (AAP) published a 2002 guideline on the diagnosis and management of uncomplicated childhood OSA associated with adenotonsillar hypertrophy and/or obesity in an otherwise healthy child treated in the primary care setting; complex high-risk patients should be referred to a specialist. Adenotonsillectomy is the first line of treatment for most children, and CPAP is an option for those who are not candidates for surgery or do not respond to surgery; patients should be reevaluated postoperatively to determine whether additional treatment is required.)

A. Adults with OSA under the following conditions:
• Age > 22 years; AND
• AHI > 15 with less than 25% central apneas; AND
• CPAP failure (residual AHI > 15 or failure to use CPAP > 4 hr per night for > 5 nights per week) or inability to tolerate CPAP; AND
• Body mass index < 32 kg/m²; AND
• Non-concentric retropalatal obstruction on drug-induced sleep endoscopy (see Policy Guidelines).
B. Adolescents or young adults with Down syndrome and OSA under the following conditions:
• Age 10 to 21 years; AND
• AHI >10 and <50 with less than 25% central apneas after prior adenotonsillectomy; AND
• Have either tracheotomy or be ineffectively treated with CPAP due to noncompliance, discomfort, un-desirable side effects, persistent symptoms despite compliance use, or refusal to use the device; AND
• Body mass index < 95th percentile for age; AND
• Non-concentric retropalatal obstruction on drug-induced sleep endoscopy (See Policy Guidelines).

6. The following minimally-invasive surgical procedures are considered investigational for the sole or adjunctive treatment of obstructive sleep apnea (OSA) or upper airway resistance syndrome:

• Laser-assisted palatoplasty or radiofrequency volumetric tissue reduction of the palatal tissues
• Tongue base suspension
• Radiofrequency volumetric tissue reduction of the tongue (with or without radiofrequency reduction of the palatal tissues)
• Palatal stiffening procedures including, but not limited to, cautery-assisted palatal stiffening operation, injection of a sclerosing agent, and the implantation of palatal implants
• All other minimally-invasive surgical procedures not described above.

8. All interventions, including laser-assisted palatoplasty, radiofrequency volumetric tissue reduction of the palate, or palatal stiffening procedures are not considered medically necessary for the treatment of snoring in the absence of documented OSA; snoring alone is not considered a medical condition.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Continuous positive airway pressure is the preferred first-line treatment for most patients. A smaller number of patients may use oral appliances as a first-line treatment (see separate policy on 'Diagnosis and Medical Management of Obstructive Sleep Apnea Syndrome' - Policy #002 in the Medicine Section). The Apnea/Hypopnea Index measures the total number of events (apnea or hypopnea) per hour during recorded sleep. The Respiratory Disturbance Index measures the total number of events (apnea or hypopnea) per hour during the recording time. An obstructive apnea is defined as at least a 10-second cessation of respiration associated with ongoing ventilatory effort. Hypopnea is defined as an abnormal respiratory event lasting at least 10 seconds with at least a 30% reduction in thoracoabdominal movement or airflow compared with baseline, and with at least a 4% oxygen desaturation.

The hypoglossal nerve (cranial nerve XII) innervates the genioglossus muscle. Stimulation of the nerve causes anterior movement and stiffening of the tongue and dilation of the pharynx. Hypoglossal nerve stimulation reduces airway collapsibility and alleviates obstruction at both the level of the soft palate and tongue base.

Drug-induced sleep endoscopy (DISE) replicates sleep with an infusion of propofol. DISE will suggest either a flat, anterior-posterior collapse or complete circumferential oropharyngeal collapse. Concentric collapse decreases the success of hypoglossal nerve stimulation and is an exclusion criteria from the Food and Drug Administration.


Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Surgical Treatment of Snoring and Obstructive Sleep Apnea Syndrome. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, determined that CPT codes 0466T, 0467T, 0468T are not reasonable and necessary, and are therefore not covered. Per LCD L35094, hypoglossal nerve stimulation is not reasonable and necessary and is therefore, not covered. For additional information, please refer to Novitas Solutions Inc, LCD L35094 Services That Are Not Reasonable and Necessary. Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35094&ver=124&name=331*1&UpdatePeriod=727&bc=AQAAEAAAAAAAAA%3d%3d&.. (effective until 3/15/20)

On 1/31/20, Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, released FUTURE Local Coverage Determination (LCD): Hypoglossal Nerve Stimulation for the Treatment of Obstructive Sleep Apnea (L38385) (to be effective 3/15/20) and FUTURE Local Coverage Article: Billing and Coding: Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea (A56938)(to be effective 3/15/20) providing coverage of FDA-approved hypoglossal nerve neurostimulation for the treatment of moderate to severe obstructive sleep apnea in individuals 22 years of age or older whose BMI is less than 35 when L38385 and Article A56938 criteria are met. For additional information and eligibility, refer to FUTURE Local Coverage Determination (LCD): Hypoglossal Nerve Stimulation for the Treatment of Obstructive Sleep Apnea (L38385) (to be effective 3/15/20) and FUTURE Local Coverage Article: Billing and Coding: Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea (A56938)(to be effective 3/15/20). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370. (Effective beginning 3/15/20)

HCPCS code S2080 is not a covered code per Medicare Billing Guidelines.

Mediciaid Coverage:
For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE-SNP Coverage:
For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[RATIONALE: This policy was created in 1997 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through May 11, 2020.

This review was informed by TEC Assessments on the surgical management and radiofrequency volumetric tissue reduction for obstructive sleep apnea (OSA).^1,2,

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Obstructive Sleep Apnea
Clinical Context and Therapy Purpose
Obstructive sleep apnea (OSA) is associated with a heterogeneous group of anatomic variants producing obstruction. The normal pharyngeal narrowing may be accentuated by anatomic factors, such as a short, fat “bull” neck, elongated palate and uvula, and large tonsillar pillars with redundant lateral pharyngeal wall mucosa. In addition, OSA is associated with obesity. OSA may also be associated with craniofacial abnormalities, including micrognathia, retrognathia, or maxillary hypoplasia. Obstruction anywhere along the upper airway can result in apnea. The severity and type of obstruction may be described with the Friedman staging system.^3, Nonsurgical treatment for OSA or upper airway resistance syndrome includes continuous positive airway pressure (CPAP) or mandibular repositioning devices (which are addressed in the separate policy on 'Diagnosis and Medical Management of Obstructive Sleep Apnea Syndrome' - Policy #002 in the Medicine Section). Patients who fail conservative therapy may be evaluated for surgical treatment of OSA.
Traditional surgeries for OSA or upper airway resistance syndrome include uvulopalatopharyngoplasty (UPPP) and a variety of maxillofacial surgeries such as mandibular-maxillary advancement. UPPP involves surgical resection of the mucosa and submucosa of the soft palate, tonsillar fossa, and the lateral aspect of the uvula. The amount of tissue removed is individualized for each patient, as determined by the potential space and width of the tonsillar pillar mucosa between the 2 palatal arches. UPPP enlarges the oropharynx but cannot correct obstructions in the hypopharynx. Patients who have minimal hypoglossal obstruction have greater success with UPPP. Patients who fail UPPP may be candidates for additional procedures, depending on the site of obstruction. Additional procedures include hyoid suspensions, maxillary and mandibular osteotomies, or modification of the tongue. Drug-induced sleep endoscopy and/or cephalometric measurements have been used as methods to identify hypopharyngeal obstruction in these patients. The first-line treatment in children is usually adenotonsillectomy. Minimally invasive surgical approaches are being evaluated for OSA in adults.
The question addressed in this policy is: Do the surgical interventions addressed in this policy improve the net health outcome in patients with OSA?
The following PICO was used to select literature to inform this policy.

Patients
The population of interest is patients with OSA who have failed or are intolerant of positive airway pressure. Indications for the various procedures are described in Table 3 and in the Regulatory Status section.

Interventions

The interventions addressed in this policy are laser-assisted uvulopalatoplasty (LAUP), radiofrequency (RF) volumetric reduction of palatal tissues and base of tongue, palatal stiffening procedures, tongue base suspension, and hypoglossal nerve stimulation (HNS) (see Table 3).

Table 3. Minimally Invasive Surgical Interventions for OSA

Interventions	Devices	Description	Key Features	Indications
LAUP	Various	Superficial palatal tissues are sequentially reshaped over 3 to 7 sessions using a carbon dioxide laser	• Part of the uvula and associated soft-palate tissues are reshaped• Does not alter tonsils or lateral pharyngeal wall tissues• Tissue ablation can be titrated	Snoring with or without OSA
RF volumetric reduction of palatal tissues and base of tongue	Somnoplasty	Radiofrequency is used to produce thermal lesions within the tissues	• Similar to LAUP• Can include soft palate and base of tongue	Simple snoring and base of tongue OSA
Palatal Implant	Pillar Palatal Implant	Braided polyester filaments that are implanted submucosally in the soft palate	Up to 5 implants may be used	Snoring
Tongue base suspension	AIRvance Encore	A suture is passed through the tongue and fixated with a screw to the inner side of the mandible, below the tooth roots	The aim of the suspension is to make it less likely for the base of the tongue to prolapse during sleep	Snoring and/or OSA
Hypoglossal nerve stimulation (HNS)	Inspire II Upper Airway Stimulation	Stimulation of the hypoglossal nerve which contracts the tongue and some palatal tissue	The device includes an implanted stimulator and a sensor implanted in the ribs to detect respiration.	A subset of patients with moderate-to-severe OSA who have failed or cannot tolerate CPAP (see Regulatory Status section)

CPAP: positive airway pressure; LAUP: laser-assisted uvulopalatoplasty; OSA: obstructive sleep apnea; RF: radiofrequency.

Comparators

The following therapies and practices are currently being used to treat OSA:

For patients with mild OSA who are intolerant of CPAP, the comparator would be oral appliances (see separate policy on 'Diagnosis and Medical Management of Obstructive Sleep Apnea Syndrome' - Policy #002 in the Medicine Section) or an established upper airway surgical procedure.

For patients with moderate-to-severe OSA who have failed CPAP or are intolerant of CPAP, the comparator would be conventional surgical procedures such as maxillofacial surgeries that may include UPPP, hyoid suspensions, maxillary and mandibular osteotomies, and modification of the tongue. UPPP may be modified or combined with a tongue base procedure such as uvulopalatopharyngoglossoplasty, depending on the location of the obstruction. It is uncertain whether UPPP variants are the most appropriate comparator for HNS, since the procedures address different sources of obstruction.

Outcomes
Established surgical procedures are associated with adverse events such as dysphagia. In addition, the surgical procedures are irreversible should an adverse event occur. Therefore, an improvement in effectiveness and/or a decrease in adverse events compared with standard surgical procedures would be the most important outcomes.
The outcomes measure used to evaluate treatment success are a decrease in Apnea/Hypopnea Index (AHI) and Oxygen Desaturation Index on polysomnography (PSG) and improvement in a measure of sleepiness such as the Epworth Sleepiness Scale (ESS) or Functional Outcomes of Sleep Questionnaire (FOSQ) (see Table 4).

Table 4. Health Outcome Measures Relevant to OSA

Outcome	Measure (Units)	Description	Clinically Meaningful Difference(If Known)
Change in AHI	AHI	Mean change in AHI from baseline to post-treatment	Change from severe to moderate or mild OSA
AHI Success	Percentage of patients achieving success.	Studies may use different definitions of success; the most common definition of AHI success is the Sher criteria	Sher criteria is a decrease in AHI ≥50% and an AHI <20. Alternative measures of success may be AHI <15, <10, or <5
Oxygen Desaturation Index	Oxygen levels in blood during sleep	The number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points	More than 5 events per hour
Snoring	10-point visual analog score	Filled out by the bed partner to assess snoring intensity or frequency	There is no standard for a good outcome. Studies have used 50% decrease in VAS3, or final VAS of <5 or <34,
Epworth Sleepiness Score (ESS)	Scale from 0 to 24	The ESS is a short self-administered questionnaire that asks patients how likely they are to fall asleep in 8 different situations such as watching TV, sitting quietly in a car, or sitting and talking to someone	An ESS of ≥10 is considered excessively sleepy. The MCID has been estimated at -2 to -3.5,
Functional Outcomes of Sleep Questionnaire	30 questions	Disease-specific quality of life questionnaire that evaluates functional status related to excessive sleepiness	A score of ≥18 is the threshold for normal sleep-related functioning, and a change of ≥2 points is considered to be a clinically meaningful improvement
OSA-18	18 item survey graded from 1 to 7	Validated survey to assess quality of life in children	Change score of 0.5 to 0.9 is a small change, 1.0 to 1.4 a moderate change, and 1.5 a large change

AHI: Apnea/Hypopnea Index; MCID: minimum clinically import difference; VAS: visual analog score.

The effect of surgical treatment of OSA should be observed on follow-up PSG that would be performed from weeks to months after the surgery. Longer term follow-up over 2 years is also needed to determine whether the effects of the procedure are durable or change over time.

Laser-Assisted Uvulopalatoplasty
Review of Evidence

LAUP is proposed as a treatment of snoring with or without associated OSA. LAUP cannot be considered an equivalent procedure to the standard UPPP, with the laser simply representing a surgical tool that the physician may opt to use. LAUP is considered a unique procedure, which raises its own issues of safety and, in particular, effectiveness.

One RCT (Ferguson et al [2003]) on LAUP has been identified.^6, This trial compared LAUP with no treatment, finding treatment success (AHI <10) to be similar between LAUP (24%) and no treatment controls (17%) (see Tables 5 and 6). The primary benefit of LAUP was on snoring as rated by the bed partner. Subjective improvements in ESS and quality of life were not greater in the LAUP group in this nonblinded study (see Tables 7 and 8). Adverse events of the treatment included moderate-to-severe pain and bleeding in the first week and difficulty swallowing at follow-up.

Table 5. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Participants	Interventions1
				Active	Comparator
Ferguson et al (2003)6,	Canada	1	46 patients with mild-to-moderate symptomatic OSA (AHI of 10 to 25) and loud snoring	21 patients treated with LAUP every 1-2 mo1	25 patients received no treatment

AHI: Apnea/Hypopnea Index; LAUP: laser-assisted uvulopalatoplasty.

¹The LAUP procedure was repeated at 1- to 2-month intervals until either the snoring was significantly reduced, no more tissue could safely be removed, or the patient refused further procedures. There was a mean of 2.4 procedures (range, 1-4).

Study	Treatment Success (AHI <10)	Change in Snoring (10- point VAS)	Change in ESS	Change in SAQLI Quality of Life	Moderate - to - Severe Pain in First Week	Bleeding in First  Week	Difficulty Swallowing at Follow-up
Ferguson et al (2003)6,
N	45	45	45`	45	45	45	45
LAUP	24%	-4.4	-1.4	+0.4	81%	19%	19%
No treatment	17%	-0.4	+0.8	+0.2
p	NR	<0.001	NS	NS

Study limitation are described in Tables 7 and 8. The major flaw is the uncertain clinical significance of the outcome measure.

Table 7. Study Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Ferguson et al (2003)6,	1. Entry criteria includes populations with mild OSA (AHI between 10 and 15) for whom an improvement to AHI <10 is not clinically significant		3. Controls had no treatment	6. The definition of success (AHI <10) combined with the eligibility criteria (AHI >10) can lead to clinically insignificant improvements being labeled success

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
AHI: Apnea/Hypopnea Index; OSA: obstructive sleep apnea.

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective  Reportingd	Data  Completenesse	Powerd	Statisticalf
Ferguson et al (2003)6,		1.-3. No blinding				4. Comparison of primary outcome not reported

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

A single RCT has been identified on LAUP for the treatment of mild-to-moderate OSA. LAUP improved snoring as reported by the bed partner, but did not improve treatment success in terms of AHI when compared with no treatment controls. Patients in this nonblinded study did not report an improvement in ESS or quality of life after LAUP.

Radiofrequency Volumetric Reduction of Palatal Tissues and Base of Tongue
Review of Evidence

RF is used to produce thermal lesions within the tissues rather than using a laser to ablate the tissue surface. In some situations, RF of the soft palate and base of tongue are performed together as a multilevel procedure.

The analysis of RF volumetric tissue reduction was informed by a TEC Assessment (2000) that evaluated 4 primary studies on palatal radiofrequency ablation (RFA) and 1 study on tongue base RFA.^2, All studies were nonrandomized.

Randomized Controlled Trials

Two RCTs have subsequently been identified on RF volumetric reduction of the palate and tongue. One of the trials (Back et al [2009]) gave a single RF treatment to palatal tissues and found no statistical difference in scores on the AHI, VAS for snoring, ESS, or FOSQ between RF and sham (see Tables 9-11).^7, The second trial (Woodson et al [2003]), provided a mean of 4.8 sessions of RF to the tongue and palate. This trial found a statistically significant improvement from baseline to posttreatment for ESS and FOSQ. However, the improvement in the FOSQ score (1.2; standard deviation, 1.6) was below the threshold of 2.0 for clinical significance and the final mean score in ESS was 9.8, just below the threshold for excessive sleepiness. AHI decreased by 4.5 events per hour, which was not statistically or clinically significant. The statistical significance of between-group differences was not reported (see Table 12).

Table 9. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Participants	Interventions
				Active	Comparator
Back et al (2009)7,	Finland	1	32 patients with symptomatic mild OSA and habitual snoring with only velopharyngeal obstruction	Single-stage RF to palatal tissues	Sham control with local anesthetic and multiple insertions of an applicator needle without the RF
Woodson et al (2003)8,	U.S.	2	90 patients with symptomatic mild-to-moderate OSA, randomized to RF, sham, or CPAP	30 subjects received up to 7 sessions (mean, 4.8) of RF to tongue base and palate	30 subjects received sham procedure to tongue for 3 sessions, including local anesthetic and multiple insertions of an applicator needle without the RF

CPAP: continuous positive airway pressure; OSA: obstructive sleep apnea; RF: radiofrequency.

Table 10. Summary of Key Randomized Controlled Trial Results

Study	AHI	Snoring	ESS	Function	Adverse Events
	Median (Range)	Snoring Median (Range)	Median (Range)	Compound End Point Scorea Median (Range)
Back et al (2009)7,
N	32	30	32	32	32
RF	13.0 (2.0-26.0)	5.0 (2.0-8.0)	7.0 (0-20.0)	6 (3-9)
Sham	11.0 (1.0-29.0)	6.0 (3.0-8.0)	5.0 (2.0-15.0)	7 (4-10)
p	0.628	0.064	0.941	0.746	No significant differences after 6 d
	Change Score (SD)		Change Score (SD)	FOSQ Score (SD)
Woodson et al (2003)8,
N	52		54	54	54
RF	-4.5 (13.8)		-2.1 (3.9)b	1.2 (1.6)b
Sham	-1.8 (11.5)		-1.0 (3.1)	0.4 (2.0)
Effect size	0.34		0.50	0.66	No significant differences after 1 wk

AHI: Apnea/Hypopnea Index; ESS: Epworth Sleepiness Scale (maximum of 24); FOSQ: Functional Outcomes of Sleep Questionnaire; MCS: Mental Component Summary score; PCS: Physical Component Summary score; SD: standard deviation; SF-36: 36-Item Short-Form Health Survey.

^a The compound end point scored added points derived from AHI, ESS, SF-36 PCS, and SF-36 MCS;
^b p=0.005 for baseline to posttreatment.

Table 11. Study Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Black et al (2009)7,	4. Included patients with mild OSA and snoring	4. Single treatment with RFA
Woodson et al (2003)8,

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
OSA: obstructive sleep apnea; RFA: radiofrequency ablation.

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective  Reportingd	Data  Completenesse	Powerd	Statisticalf
Back et al (2009)7,		2. Surgeons also performed follow-up assessments				.
Woodson et al (2003)8,						3. Comparative treatment effects not reported

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

The evidence on RF volume reduction includes 2 randomized trials, both sham-controlled. Single-stage RF to palatal tissues did not improve outcomes compared with sham. Multiple sessions of RF to the palate and base of tongue did not significantly (statistically or clinically) improve AHI, while the improvement in functional outcomes did not achieve a level of clinical significance.

Palatal Stiffening Procedures
Review of Evidence

Palatal stiffening procedures include insertion of palatal implants, injection of a sclerosing agent (snoreplasty), or a cautery-assisted palatal stiffening operation. Snoreplasty and cautery-assisted palatal stiffening operation are intended for snoring, and are not discussed here. Palatal implants are cylindrically shaped devices that are implanted in the soft palate.

Randomized Controlled Trials

Two double-blind, sham-controlled randomized trials with over 50 patients have evaluated the efficacy of palatal implants to improve snoring and OSA (see Table 13). AHI success by the Sher criteria ranged from 26% to 45% at 3-month follow-up. AHI success was observed in 0% to 10% of the sham control patients (see Table 14). In 1 study (Steward et al [2008]), the statistical significance of AHI success was marginal and there was no statistical difference in snoring or change in ESS between the 2 groups.^9, In the study by Friedman et al (2008), there was greater success in AHI (45% vs 0%, p<0.001), improvement in snoring (-4.7 vs -0.7 on a 10-point VAS, p<0.001), and improvement in ESS (-2.4 vs -0.5, p<0.001) with palatal implants compared with sham controls.^3, Patient selection criteria were different in the 2 studies. In the trial by Friedman et al (2008), patients with a Friedman tongue position of IV and palate of 3.5 cm or longer were excluded, whereas, in the trial by Steward et al (2008), selection criteria included patients with primarily retropalatal pharyngeal obstruction.

Table 13. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Participants	Interventions
				Active	Comparator
Steward et al (2008)9,	U.S.	3	100 patients with mild-to-moderate OSA (AHI ≥5 and ≤40), and primarily retropalatal pharyngeal obstruction, BMI ≤32 kg/m2	50 received the office-based insertion of 3 palatal implants	50 received the sham procedure
Friedman et al (2008)3,	U.S.	1	62 patients with mild-to-moderate OSA (AHI ≥5 and ≤40), soft palate ≥2 cm and <3.5 cm, Friedman tongue position I, II, or III, BMI ≤32 kg/m2	31 received the office-based insertion of 3 palatal implants	31 received the sham procedure

AHI: Apnea/Hypopnea Index, BMI: body mass index; OSA: obstructive sleep apnea.

Table 14. Summary of Key Randomized Controlled Trial Results

Study	AHI Success (Sher criteria)	Snoring (10- point VAS)	Change in ESS (95% CI) or (SD)	Change in FOSQ Score (95% CI)	Foreign Body Sensation/Extrusion
Steward et al (2008)9,
N	97	43	96	98	100
Palatal implants	26%	6.7	-1.8 (-0.8 to -2.9)	1.43 (0.84 to 2.03)	18%/4 extruded
Sham control	10%	7.0	-1.5 (-.04 to -2.5)	0.6 (0.01 to 1.20)	2%
p	0.04	0.052	NS	0.05
Friedman et al (2008)3,		Change in VAS
N	55	62	62
Palatal implants (SD)	44.8%	-4.7 (2.1)	-2.4 (2.2)		2 extruded
Sham control (SD)	0%	-0.7 (0.9)	-0.5 (1.5)
MD (95% CI)		4.0 (3.2 to 4.9)	1.9 (1.0 to 2.9)
p	<0.001	< 0.001	<0.001
Summary: Range	26%-44.8%

CI: confidence interval; ESS: Epworth Sleepiness Score; MD: mean difference; NS: not significant; RCT: randomized controlled trial; RR: relative risk; SD: standard deviation; VAS: visual analog scale.

Case Series

Uncontrolled series have provided longer follow-up data on patients treated with palatal implants. Using criteria of 50% improvement in AHI and final AHI of less than 10 events hour, Neruntarat et al (2011) reported a success rate of 52% at a minimum of 24 months (see Tables 15 and 16). Compared with nonresponders, responders had lower body mass index, lower baseline AHI and a lower percentage of patients with a modified Mallampati classification of III or IV (obscured visualization of the soft palate by the tongue). Tables 17 and 18 summarize the limitations of the studies described above.

Table 15. Summary of Key Case Series Characteristics

Study	Country	Participants	Follow-Up
Neruntarat et al (2011)10,	Thailand	92 patients with mild-to-moderate symptomatic OSA and palate >2 cm	Minimum 24 mo

OSA: obstructive sleep apnea.

Table 16. Summary of Key Case Series Results

Study	N	AHI (SD)	Snoring (SD) (10-point VAS)	ESS (SD)	Implant Extrusion
Neruntarat et al (2011)10,	92
Baseline		21.7 (6.8)	8.2 (1.2)	12.3 (2.6)
29 months		10.8 (4.8)	3.8 (2.3)	7.9 (1.8)	7 (7.6%)
p		<0.001	<0.001	<0.001

AHI: Apnea/Hypopnea Index; ESS: Epworth Sleepiness Score; SD: standard deviation; VAS: visual analog scale.

Table 17. Study Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Neruntarat et al (2011)10,			2. No comparator
Steward et al (2008)9,	4. Out of 968 patients assessed for eligibility, 100 were enrolled				1, 2, 3 mo
Friedman et al (2008)3,	4. Number screened was not reported. Soft palate was at least 2 cm but less than 3.5 cm.				1, 2, 3 mo

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective  Reportingd	Data  Completenesse	Powerd	Statisticalf
Neruntarat et al (2011)10,	1.Retrospective	1.None (case series)
Steward et al (2008)9,
Friedman et al (2008)3,

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Two sham-controlled trials have assessed palatal implants for the treatment of snoring and OSA. The studies differed in the inclusion criteria, with the study that excluded patients with Friedman tongue position of IV and palate of 3.5 cm or longer reporting greater improvement in AHI (45% success) and snoring (change of -4.7 on a 10-point VAS) than the second trial.

Tongue Base Suspension
Review of Evidence

In this procedure, the base of the tongue is suspended with a suture that is passed through the tongue and fixated with a screw to the inner side of the mandible, below the tooth roots. The aim of the suspension is to make it less likely for the base of the tongue to prolapse during sleep.

One preliminary RCT with 17 patients was identified that compared UPPP plus tongue suspension with UPPP plus tongue advancement (see Table 19).^11, Success rates using the Sher criteria ranged from 50% to 57% (see Table 20). Both treatments improved snoring and reduced ESS to below 10. The major limitations of the trial were the number of subjects (n=17) in this feasibility study and the lack of blinding (see Tables 21 and 22). In addition, there was no follow-up after 16 weeks.

Table 19. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Participants	Interventions
				Active	Comparator
Thomas et al (2003)12,	U.S.	1	17 patients with moderate-to-severe OSA who failed conservative treatment	• UPPP with tongue suspension• Mean AHI=46 (n=9)	• UPPP with tongue advancement• Mean AHI=37.4 (n=8)

AHI: Apnea/Hypopnea Index; OSA: obstructive sleep apnea; UPPP:uvulopalatopharyngoplasty.

Table 20. Summary of Key Randomized Controlled Trial Results

Study	AHI Success (Sher Criteria)	Snoring (SD)	ESS (SD)	Pain, Speech, Swallowing
Thomas et al (2003)12,
N	11	17	17	17
UPPP plus tongue suspension	57%	3.3 (2.1)a	4.1 (3.4)b
UPPP plus tongue advancement	50%	5.0 (0.6)c	5.4 (3.5)d	No significant differences between groups

AHI: Apnea/Hypopnea Index; ESS: Epworth Sleepiness Score; SD: standard deviation; UPPP: uvulopalatopharyngoplasty.

^a Baseline to posttreatment p=0.02.
^b Baseline to posttreatment p=0.007.
^c Baseline to posttreatment p=0.04.
^d Baseline to posttreatment p=0.004.

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Thomas et al (2003)12,					1, 2. Follow-up was to 16 wk

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective  Reportingd	Data  Completenesse	Powerd	Statisticalf
Thomas et al (2003)12,	3. Allocation concealment unclear	1.-3. Not blinded			1. Feasibility study	4. Comparative treatment effects not calculated

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

One feasibility study with 17 patients was identified on tongue suspension. This study compared tongue suspension plus UPPP with tongue advancement plus UPPP and reported 50% to 57% success rates for the 2 procedures. RCTs with a larger number of subjects are needed to determine whether tongue suspension alone or added to UPPP improves the net health outcome.

Hypoglossal Nerve Stimulation
Review of Evidence

Stimulation of the hypoglossal nerve causes tongue protrusion and stiffening of the anterior pharyngeal wall, potentially decreasing apneic events. For patients with moderate-to-severe sleep apnea who have failed or are intolerant of CPAP, the alternative would be an established surgical procedure, as described above.

Comparative Studies

No RCTs have been identified on HNS. Comparative evidence consists of 2 studies that compared HNS with historical controls treated with UPPP or a variant of UPPP (expansion sphincter pharyngoplasty, see Table 23) and a third study that compared HNS with transoral robotic surgery. AHI success by the Sher criteria ranged from 87% to 100% in the HNS group compared with 40% to 64% in the UPPP group (see Table 24). Posttreatment ESS was below 10 in both groups. It is not clear from these studies whether the patients in the historical control group were similar to the subset of patients in the HNS group, particularly in regards to the pattern of palatal collapse and from patients who did not return for postoperative PSG (see Tables 25 and 26). UPPP may not be the most appropriate comparator for HNS, because UPPP is less effective for patients with obstruction arising primarily from the tongue base (the primary target for HNS).

A third study by Yu et al (2019) addresses these concerns and compares outcomes for patients who met criteria for both HNS (non-concentric collapse on drug-induced sleep endoscopy) and transoral robotic surgery (retroglossal obstruction).^13, When patients with similar anatomic criteria were compared, HNS led to significantly better improvements in AHI, cure rate (defined as AHI < 5) and the percentage of time that oxygen saturation fell below 90% (see Table 24).

Table 23. Summary of Observational Comparative Study Characteristics

Study	Study Type	Country	Dates	Participants	HNS	Traditional Surgery	Follow-Up
Shah et al (2018)14,	Retrospective series with historical controls	U.S.	• HNS 2015- 2016• UPPP 2003-2012	40 OSA patients with AHI >20 and <65, BMI ≤32 kg mg/m2, failed CPAP, favorable pattern of palatal collapsea	35% had previously had surgery for OSA	UPPP 50% of patients had additional surgical procedures	2-13 mo
Huntley et al (2018)15,	Retrospective series with historical controls	U.S.	• HNS 2014- 2016• Modified UPPP 2011-2016	Retrospective review included treated patients who had a postoperative PSG	75 patients age 61.67 y with a favorable pattern of palatal collapse	33 patients age 43.48 y treated by ESP	To post-operative PSG
Yu et al (2019)13,	Retrospective series with historical controls	U.S.	• HNS 2014- 2016• TORS 2011-NR	OSA patients with AHI >20 and <65, BMI ≤32 kg mg/m2, failed CPAP, favorable pattern of palatal collapsea	27 patients age 62 with retroglossal collapse amenable to TORS	20 patients age 53 y who would have qualified for HNS and were treated by TORS	NR

BMI: body mass index; CPAP: continuous positive airway pressure; ESP: expansion sphincter pharyngoplasty; HNS: hypoglossal nerve stimulation; NR: not reported; OSA: obstructive sleep apnea; PSG: polysomnography; TORS: transoral robotic surgery; UPPP: uvulopalatopharyngoplasty.

^a A favorable pattern of palatal collapse is not concentric retropalatal obstruction on drug-induced sleep endoscopy.

Study	Baseline AHI (SD)	Posttreatment AHI (SD)	AHI Success (%)Sher Criteria	Baseline ESS (SD)	Posttreatment ESS (SD)
Shah et al (2018)14,
HNS	38.9 (12.5)	4.5 (4.8)b	20 (100%)	13 (4.7)	8 (5.0)b
UPPP	40.3 (12.4)	28.8 (25.4)a	8 (40%)	11 (4.9)	7 (3.4)b
Huntley et al (2018)15,
HNS	36.8 (20.7)	7.3 (11.2)	86.7	11.2 (4.2)	5.4 (3.4)
ESP	26.7 (20.3)	13.5 (19.0)	63.6	10.7 (4.5)	7.0 (6.0)
p-Value	0.003	0.003	0.008	0.565	NS
Yu et al (2018) 13,		Average AHI Reduction	% Cure Rate	Change in SaO2 <90%
HNS		33.3	70.4%	14.1
TORS		12.7	10.0%	1.3
p-Value		0.002	<0.001	0.02

^a Baseline vs posttreatment p<0.05.
^b Baseline vs posttreatment p<0.001.

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Shah et al (2018)14,			2. UPPP may not be preferred treatment for patients with primarily lingual obstruction
Huntley et al (2018)15,	4. Study populations not comparable		1. Not clearly defined, few ESP patients had follow-up PSG
Yu et al (2018) 13,					1, 2. Duration of follow-up unclear
Steffen et al (2018)16,			2.No comparator
STAR trial17,18,19,20,21,22,			2.No comparator

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective  Reportingd	Data  Completenesse	Powerd	Statisticalf
Shah et al (2018)14,	1. Not randomized (retrospective) 4. Inadequate control for selection bias	1.-3. No blinding				4. Comparative treatment effects not calculated
Huntley et al (2018)15,	1. Not randomized (retrospective)	1.-3. No blinding
Yu et al (2018) 13,	1. Not randomized (retrospective)
Steffen et al (2018)16,	1. Not randomized	1.-3. No blinding
STAR trial17,18,19,20,21,22,	1. Not randomized	1.-3. No blinding

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Results of prospective single-arm studies show AHI success rates in 66% to 68% of patients who had moderate-to-severe sleep apnea and a favorable pattern of palatal collapse (see Tables 27 and 28). Mean AHI was 31 to 32 at baseline, decreasing to 14 to 15 at 12 months. ESS scores decreased to 6.5 to 7.0. All improvements were maintained through 5 years of follow-up. Discomfort due to the electrical stimulation and tongue abrasion were initially common, but were decreased when stimulation levels were reduced (see Table 29). In the post-market study, a normal ESS score (< 10) was obtained in 73% of patients. A FOSQ score of at least 19 was observed in 59% of patients compared to 13% at baseline. At the 12 month follow-up, 8% of bed partners regularly left the room due to snoring, compared to 75% of bed partners at baseline. The average use was 5.6 + 2.1 h per night. Use was correlated with the subjective outcomes, but not with AHI response.

Table 27. Summary of Prospective Single-Arm Study Characteristics

Study	Country	Participants	Treatment Delivery	Follow-Up
STAR trial17,18,19,20,23,24,	EU, U.S.	126 patients with AHI >20 and <50, BMI ≤32 kg/m2, failed CPAP, favorable pattern of palatal collapsea	Stimulation parameters titrated with full PSG	5 y
Postmarket studies: Heiser et al (2017)25, Steffen et al (2018)16, Hasselbacher et al (2018)26,	3 sites in Germany	60 patients with AHI ≥15 and ≤65 on home sleep study, BMI ≤35 kg/m2, failed CPAP; favorable pattern of palatal collapsea		12 mo

AHI: apnea/hypopnea index; BMI: body mass index; CPAP: continuous positive airway pressure; STAR: Stimulation Therapy for Apnea Reduction.

^a A favorable pattern of palatal collapse is non-concentric retropalatal obstruction on drug-induced sleep endoscopy.

Study	N	Percent of Patients With AHI Success (Sher criteria)	Mean AHI Score (SD)	Mean ODI Score (SD)	FOSQ Score (SD)	ESS Score (SD)
STAR trial17,18,19,20,23,24,
Baseline	126		32.0 (11.8)	28.9 (12.0)	14.3 (3.2)	11.6 (5.0)
12 months	124	66%	15.3 (16.1)d	13.9 (15.7)d	17.3 (2.9)d	7.0 (4.2)d
3 years	116a	65%	14.2 (15.9)	9.1 (11.7)	17.4 (3.5)b	7.0 (5.0)b
5 years	97c	63%	12.4 (16.3)	9.9 (14.5)	18.0 (2.2)	6.9 (4.7)
Postmarket studies: Heiser et al (2017)25, Steffen et al (2018)16, Hasselbacher et al (2018)26,
Baseline	60		31.2 (13.2)	27.6 (16.4)	13.7 (3.6)	12.8 (5.3)
6 months					17.5 (2.8)d	7.0 (4.5)d
12 months	56f	68%	13.8 (14.8)e	13.7 (14.9)e	17.5 (3)e	6.5 (4.5)e
Normalized at 12 months					59%	73%

^a Ninety-eight participants agreed to undergo PSG at 36 months, of the 17 participants who did not undergo PSG at 36 months, 54% were nonresponders and their PSG at p<0.001.
^b The change from baseline was significantpolysomnography; SD: standard deviation; STAR: Stimulation Therapy for Apnea Reduction.
^c Seventy-one participants agreed to a PSG.
^f Four patients lost to follow-up were analyzed as treatment failures.
^d p<0.001.
^e p< 0.05.

Study	N	Discomfort due to Electrical Stimulationa	Tongue Abrasion	Dry Mouth	Mechanical Pain From Device	Internal Device Usability	External Device Usability
STAR trial24,
0 to 12 months	126	81	28	10	7	12	11
12 to 24 months	124	23	12	5	2	8	11
24 to 36 months	116	26	4	2	3	1	8
36 to 48 months	97	7	3	0	1	3	9
> 48 months		5	3	3	1	1	6
Participants with event, n of 126 (%)		76 (60.3)	34 (27.0)	19 (15.1)	14 (11.1)	21 (16.7)	33 (26.2)

^a Stimulation levels were adjusted to reduce discomfort

Caloway et al (2020) reported a safety study of HNS in 20 children with Down Syndrome and severe OSA (AHI of 10 or greater) treated at 3 tertiary care centers.^27, Included were non-obese (BMI < 95%) children and adolescents aged 10-21 years who were refractory to tonsillectomy and either unable to tolerate CPAP or dependent on a tracheostomy. Patients were included whose AHI was between 10 and 50 on baseline PSG; the median baseline AHI was 24.15 (interquartile range [IQR] of 19.88 to 35.10 ). All of the patients tolerated the stimulation, and at 2 months after implantation the median AHI was 3.56 (IQR 2.61 to 4.40). Success, defined as an AHI of 5 or less (mild) with HNS, was achieve in 14 of 20 patients (70%). The median percent reduction in AHI was 85% with a median usage of 9.21 h (IQR: 8.29 to 9.50) per night. The OSA-18 score improved by 1.15 (IQR: 0.02 to 1.97), indicating a moderate but clinically significant change.There were 2 adverse events related to extrusion or connectivity of the stimulation or sensation leads, which were both corrected with wound exploration surgery. Study in a larger population of children with Down Syndrome is ongoing.

Other

Boon et al (2018) reported results from 301 patients in the multicenter Adherence and Outcome of Upper Airway Stimulation for OSA International Registry (ADHERE).^28, The ADHERE registry included both retrospective and prospectively collected data from the U.S. and Germany between October 2016 and September 2017. Data were collected from PSG prior to implantation and between 2 and 6 months after implantation, or from home sleep tests which were often performed at 6 and 12 months after implantation as part of routine care. Mean AHI decreased from 35.6 (SD: 15.3) to 10.2 (SD: 12.9) post-titration with 48% of patients achieving an AHI of 5 or less. ESS decreased from 11.9 (5.5) to 7.5 (4.7) (P<.001).

Kent et al (2019) pooled data from the ADHERE registry plus data from 3 other studies to evaluate factors predicting success.^29, Over 80% of the 584 patients were men, and most were overweight. Seventy seven percent of patients achieved treatment success, defined as a decrease in AHI by at least 50% and below 20 events/per hour. AHI decreased to below 5 in 41.8% of patients. Greater efficacy was observed in patients with a higher preoperative AHI, older patient age, and lower BMI. In a retrospective analysis by Huntley et al (2018) of procedures at 2 academic institutions, patients with a body mass index (BMI) of greater than 32 did not have lower success rates than patients with a BMI less than 32.^30, However, only patients who had palpable cervical landmarks and carried most of their weight in the waist and hips were offered HGNS. Therefore, findings from this study are limited to this select group of patients with BMI greater than 32.

Section Summary: Hypoglossal Nerve Stimulation

The evidence on HNS for the treatment of OSA includes nonrandomized studies with historical controls and prospective single-arm studies. There are questions about whether UPPP is best comparator for HNS, since the procedures address different patterns of palatal collapse. For patients with moderate-to-severe OSA who had failed conservative therapy (CPAP) and had a favorable pattern of palatal collapse, about two-thirds met the study definition of success. Results observed at the 12-month follow-up were maintained at 5 years in the pivotal study. For children and adolescents with OSA and Down Syndrome who are unable to tolerate CPAP, the evidence includes a safety study with 20 patients treated at tertiary care centers. The success rate was 70% with 2 adverse events of the leads, these were resolved with further surgery. Study in a larger number of patients with Down Syndrome is ongoing. Limitations of the published evidence preclude determining the effects of the technology on net health outcome.

Summary of Evidence

For individuals who have OSA who receive laser-assisted uvulopalatoplasty, the evidence includes a single randomized controlled trial (RCT). Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The trial indicates reductions in snoring, but limited efficacy on the Apnea/Hypopnea Index (AHI) or symptoms in patients with mild-to-moderate OSA. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have OSA who receive radiofrequency volumetric reduction of palatal tissues and base of tongue, the evidence includes 2 sham-controlled randomized trials. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Single-stage radiofrequency to palatal tissues did not improve outcomes compared with sham. Multiple sessions of radiofrequency to the palate and base of tongue did not significantly (statistically or clinically) improve AHI, and the improvement in functional outcomes was not clinically significant. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have OSA who receive palatal stiffening procedures, the evidence includes 2 sham-controlled randomized trials. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The 2 RCTs differed in their inclusion criteria, with the study that excluded patients with Friedman tongue position of IV and palate of 3.5 cm or longer reporting greater improvement in AHI (45% success) and snoring (change of -4.7 on a 10-point visual analog scale) than the second trial. Additional study is needed to corroborate the results of the more successful trial and, if successful, define the appropriate selection criteria. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have OSA who receive tongue base suspension, the evidence includes a feasibility RCT with 17 patients. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The single RCT compared tongue suspension plus uvulopalatopharyngoplasty with tongue advancement plus uvulopalatopharyngoplasty and showed success rates of 50% to 57% for both procedures. RCTs with a larger number of subjects are needed to determine whether tongue suspension alone or added to uvulopalatopharyngoplasty improves the net health outcome. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have OSA who receive hypoglossal nerve stimulation, the evidence includes 2 nonrandomized studies with historical controls and prospective single-arm studies. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Hypoglossal nerve stimulation has shown success rates for about two-thirds of a subset of patients who met selection criteria that included AHI, body mass index, and favorable pattern of palatal collapse. These results were maintained out to 5 years in the pivotal single-arm study. Prospective comparative trials are needed. For children and adolescents with OSA and Down Syndrome who are unable to tolerate CPAP, the evidence includes a safety study with 20 patients who were treated at tertiary care centers. The success rate was 70% with 2 adverse events of the leads, which were resolved with further surgery. Study in a larger number of patients with Down Syndrome is ongoing. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION
Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2018 Input

Clinical input was sought to help determine whether the use of hypoglossal nerve stimulation for individuals with obstructive sleep apnea would provide a clinically meaningful improvement in net health outcome and whether the use is consistent with generally accepted medical practice. In response to requests, clinical input was received from 2 respondents, including 1 specialty society-level response and physicians with academic medical center affiliation.

For individuals who have OSA who receive HNS, clinical input supports that this use provides a clinically meaningful improvement in net health outcome and indicates this use is consistent with generally accepted medical practice in subgroups of appropriately selected patients. One subgroup includes adult patients with a favorable pattern of non-concentric palatal collapse. The alternative treatment for this anatomical endotype is maxillo-mandibular advancement (MMA), which is associated with greater morbidity and lower patient acceptance than HNS. The improvement in AHI with HNS, as shown in the STAR trial, is similar to the improvement in AHI following MMA. Another subgroup includes appropriately selected adolescents with OSA and Down's syndrome who have difficulty in using CPAP. The following patient selection criteria are based on information from clinical study populations and clinical expert opinion.

• Age ≥ 22 years in adults or adolescents with Down's syndrome age 10 to 21; AND
• Diagnosed moderate to severe OSA (with less than 25% central apneas); AND
• CPAP failure or inability to tolerate CPAP; AND
• Body mass index ≤ 32 kg/m² in adults; AND
• Favorable pattern of palatal collapse

Practice Guidelines and Position Statements
American Academy of Sleep Medicine

The American Academy of Sleep Medicine (2010) published practice parameters for surgical modifications of the upper airway for obstructive sleep apnea (OSA).^24, The AASM practice parameters were based on a systematic review of the evidence that found the published literature was comprised primarily of case series, with few controlled trials and varying approaches to preoperative evaluation and postoperative follow-up.^31, Using the change in Apnea/Hypopnea Index as the primary measure of efficacy, substantial and consistent reductions were observed following mandibular-maxillary advancement, and adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent, and adverse events were more commonly reported. The review found that outcomes of studies with newer pharyngeal techniques and multilevel procedures, performed in small numbers of patients, appear promising. The practice parameters noted the lack of rigorous data evaluating surgical modifications of the upper airway, resulting in a recommendation of "option" (uncertain clinical use) for mandibular-maxillary advancement, uvulopalatopharyngoplasty as a sole procedure, or multilevel or stepwise surgery if patients failed uvulopalatopharyngoplasty as a sole treatment. Use of radiofrequency ablation was recommended as an "option" for patients with mild-to-moderate OSA who cannot tolerate or are unwilling to adhere to continuous positive airway pressure (CPAP), or in whom oral appliances have been found ineffective or undesirable. Palatal implants were recommended as an "option" for patients with mild OSA who failed medical therapy. Laser-assisted uvulopalatoplasty was not recommended as a routine treatment for OSA (standard). The practice parameters recommended as "standard" the need to determine the presence and severity of OSA before initiating surgical therapy, discussion of success rates, complications, and alternative treatments with the patient, and a postoperative follow-up evaluation, which includes a clinical evaluation and an objective measure of the presence and severity of sleep-disordered breathing and oxygen saturation. However, little guidance was available in the medical literature to recommend any particular monitoring strategy. The optimal interval and duration of this follow-up were also not clear from the available literature.

American Academy of Pediatrics

The American Academy of Pediatrics (2012) published a clinical practice guideline on the diagnosis and management of childhood OSA.^32, The Academy indicated that if a child has OSA, a clinical examination consistent with adenotonsillar hypertrophy, and does not have a contraindication to surgery, the clinician should recommend adenotonsillectomy as first-line treatment. The Academy recommended that patients should be referred for CPAP management if symptoms/signs or objective evidence of OAS persist after adenotonsillectomy or if adenotonsillectomy is not performed. Weight loss was recommended in addition to other therapy if a child or adolescent with OSA is overweight or obese.

American Academy of Otolaryngology - Head and Neck Surgery

The American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS; 2014) has a position statement on surgical management of OSA^33,. Procedures AAO-HNS supported as effective and not considered investigational when part of a comprehensive approach in the medical and surgical management of adults with OSA include:

• tracheotomy,
• nasal and pharyngeal airway surgery,
• tonsillectomy and adenoidectomy,
• palatal advancement,
• uvulopalatopharyngoplasty,
• uvulopalatoplasty (including laser-assisted and other techniques),
• genioglossal advancement,
• hyoid myotomy,
• midline glossectomy,
• tongue suspension,
• maxillary and mandibular advancement.

American Society for Metabolic and Bariatric Surgery

The American Society for Metabolic and Bariatric Surgery (2012) published guidelines on the perioperative management of OSA.^35, The guideline indicated that OSA is strongly associated with obesity, with the incidence of OSA in the morbidly obese population reported as between 38% and 88%. The Society recommended bariatric surgery as the initial treatment of choice for OSA in this population, as opposed to surgical procedures directed at the mandible or tissues of the palate.

National Institute for Health and Care Excellence

2017 guidance from the U.K.'s National Institute for Health and Care Excellence (NICE) concluded that evidence on the safety and efficacy of hypoglossal nerve stimulation is limited in quantity and quality.^36,

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this policy are listed in Table 30.

Table 30. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT03760328	Effect of Upper Airway Stimulation: A Randomized Controlled Crossover Study	100	Jun 2020
NCT02344108a	A Pilot Study to Evaluate the Safety and Efficacy of the Hypoglossal Nerve Stimulator in Adolescents and Young Adults With Down Syndrome and Obstructive Sleep Apnea	50	Sep 2021
NCT03359096	Cardiovascular Endpoints for Obstructive Sleep Apnea With Twelfth Nerve Stimulation (CARDIOSA-12): A Randomized, Sham-Controlled, Double-Blinded, Crossover Trial	80	Dec 2021
NCT02413970a	Inspire® Upper Airway Stimulation System (UAS): Post-Approval Study Protocol Number 2014-001	127	Dec 2021
NCT03868618a	A Multicenter Study to Assess the Safety and Effectiveness of the Genio Dual-sided Hypoglossal Nerve Stimulation System for the Treatment of Obstructive Sleep Apnea in Adults Subjects	136	Jun 2022
NCT02263859a	ImThera Medical Targeted Hypoglossal Neurostimulation Study #3 (THN3)	138	Dec 2022
NCT04031040a	A Post-market Clinical Follow up of the Genio™ System for the Treatment of Obstructive Sleep Apnea in Adults.	110	Oct 2023
NCT02907398a	Adherence and Outcome of Upper Airway Stimulation (UAS) for OSA International Registry	5000	Sep 2025
Unpublished
ACTRN12614000338662	Multi-level airway surgery in patients with moderate-severe Obstructive Sleep Apnoea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness.	102	Aug 2018

NCT: national clinical trial. ACTRN: Australian New Zealand Clinical Trials Registry

^a Denotes industry-sponsored or cosponsored trial.

2. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Radiofrequency volumetric tissue reduction for sleep-related breathing disorders. TEC Assessments. 2000;Volume 15:Tab 15.

3. Friedman M, Schalch P, Lin HC, et al. Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome. Otolaryngol Head Neck Surg. Feb 2008; 138(2): 209-16. PMID 18241718

4. Lee LA, Yu JF, Lo YL, et al. Comparative effects of snoring sound between two minimally invasive surgeries in the treatment of snoring: a randomized controlled trial. PLoS ONE. 2014; 9(5): e97186. PMID 24816691

5. Patel S, Kon SSC, Nolan CM, et al. The Epworth Sleepiness Scale: Minimum Clinically Important Difference in Obstructive Sleep Apnea. Am J Respir Crit Care Med. Apr 01 2018; 197(7): 961-963. PMID 28961021

6. Ferguson KA, Heighway K, Ruby RR. A randomized trial of laser-assisted uvulopalatoplasty in the treatment of mild obstructive sleep apnea. Am J Respir Crit Care Med. Jan 01 2003; 167(1): 15-9. PMID 12502473

7. Back LJ, Liukko T, Rantanen I, et al. Radiofrequency surgery of the soft palate in the treatment of mild obstructive sleep apnea is not effective as a single-stage procedure: A randomized single-blinded placebo-controlled trial. Laryngoscope. Aug 2009; 119(8): 1621-7. PMID 19504550

8. Woodson BT, Steward DL, Weaver EM, et al. A randomized trial of temperature-controlled radiofrequency, continuous positive airway pressure, and placebo for obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg. Jun 2003; 128(6): 848-61. PMID 12825037

9. Steward DL, Huntley TC, Woodson BT, et al. Palate implants for obstructive sleep apnea: multi-institution, randomized, placebo-controlled study. Otolaryngol Head Neck Surg. Oct 2008; 139(4): 506-10. PMID 18922335

10. Neruntarat C. Long-term results of palatal implants for obstructive sleep apnea. Eur Arch Otorhinolaryngol. Jul 2011; 268(7): 1077-80. PMID 21298386

11. Maurer JT, Sommer JU, Hein G, et al. Palatal implants in the treatment of obstructive sleep apnea: a randomised, placebo-controlled single-centre trial. Eur Arch Otorhinolaryngol. Jul 2012; 269(7): 1851-6. PMID 22228439

12. Thomas AJ, Chavoya M, Terris DJ. Preliminary findings from a prospective, randomized trial of two tongue-base surgeries for sleep-disordered breathing. Otolaryngol Head Neck Surg. Nov 2003; 129(5): 539-46. PMID 14595277

13. Yu JL, Mahmoud A, Thaler ER. Transoral robotic surgery versus upper airway stimulation in select obstructive sleep apnea patients. Laryngoscope. Jan 2019; 129(1): 256-258. PMID 30208225

14. Shah J, Russell JO, Waters T, et al. Uvulopalatopharyngoplasty vs CN XII stimulation for treatment of obstructive sleep apnea: A single institution experience. Am J Otolaryngol. May 2018; 39(3): 266-270. PMID 29540289

15. Huntley C, Chou DW, Doghramji K, et al. Comparing Upper Airway Stimulation to Expansion Sphincter Pharyngoplasty: A Single University Experience. Ann Otol Rhinol Laryngol. Jun 2018; 127(6): 379-383. PMID 29707958

16. Steffen A, Sommer JU, Hofauer B, et al. Outcome after one year of upper airway stimulation for obstructive sleep apnea in a multicenter German post-market study. Laryngoscope. Feb 2018; 128(2): 509-515. PMID 28561345

17. Strollo PJ, Soose RJ, Maurer JT, et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. Jan 09 2014; 370(2): 139-49. PMID 24401051

18. Strollo PJ, Gillespie MB, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months. Sleep. Oct 01 2015; 38(10): 1593-8. PMID 26158895

19. Woodson BT, Soose RJ, Gillespie MB, et al. Three-Year Outcomes of Cranial Nerve Stimulation for Obstructive Sleep Apnea: The STAR Trial. Otolaryngol Head Neck Surg. Jan 2016; 154(1): 181-8. PMID 26577774

20. Soose RJ, Woodson BT, Gillespie MB, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 Months. J Clin Sleep Med. Jan 2016; 12(1): 43-8. PMID 26235158

21. Woodson BT, Gillespie MB, Soose RJ, et al. Randomized controlled withdrawal study of upper airway stimulation on OSA: short- and long-term effect. Otolaryngol Head Neck Surg. Nov 2014; 151(5): 880-7. PMID 25205641

22. Kezirian EJ, Goding GS, Malhotra A, et al. Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes. J Sleep Res. Feb 2014; 23(1): 77-83. PMID 24033656

23. Gillespie MB, Soose RJ, Woodson BT, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: Patient-Reported Outcomes after 48 Months of Follow-up. Otolaryngol Head Neck Surg. Apr 2017; 156(4): 765-771. PMID 28194999

24. Woodson BT, Strohl KP, Soose RJ, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes. Otolaryngol Head Neck Surg. Jul 2018; 159(1): 194-202. PMID 29582703

25. Heiser C, Maurer JT, Hofauer B, et al. Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study. Otolaryngol Head Neck Surg. Feb 2017; 156(2): 378-384. PMID 28025918

26. Hasselbacher K, Hofauer B, Maurer JT, et al. Patient-reported outcome: results of the multicenter German post-market study. Eur Arch Otorhinolaryngol. Jul 2018; 275(7): 1913-1919. PMID 29808422

27. Caloway CL, Diercks GR, Keamy D, et al. Update on hypoglossal nerve stimulation in children with down syndrome and obstructive sleep apnea. Laryngoscope. Apr 2020; 130(4): E263-E267. PMID 31219619

28. Boon M, Huntley C, Steffen A, et al. Upper Airway Stimulation for Obstructive Sleep Apnea: Results from the ADHERE Registry. Otolaryngol Head Neck Surg. Aug 2018; 159(2): 379-385. PMID 29557280

29. Kent DT, Carden KA, Wang L, et al. Evaluation of Hypoglossal Nerve Stimulation Treatment in Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. Sep 26 2019. PMID 31556927

30. Huntley C, Steffen A, Doghramji K, et al. Upper Airway Stimulation in Patients With Obstructive Sleep Apnea and an Elevated Body Mass Index: A Multi-institutional Review. Laryngoscope. Oct 2018; 128(10): 2425-2428. PMID 30098035

31. 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. Oct 2010; 33(10): 1396-407. PMID 21061863

32. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. Sep 2012; 130(3): e714-55. PMID 22926176

33. American Academy of Otolaryngology -- Head and Neck Surgery. Position Statement: Surgical Management of Obstructive Sleep Apnea. 2014; http://www.entnet.org/Practice/policySurgicalMgmtApnea.cfm. Accessed May 18, 2020.

34. American Academy of Otolaryngology-Head and Neck Surgery. 2019 Position Statement: Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea (OSA) http://www.entnet.org/content/position-statement- hypoglossal-nerve-stimulation-treatment-obstructive-sleep-apnea-osa. Accessed May 18, 2020.

35. Clinical Issues Committee, American Society for Metabolic & Bariatric Surgery. Peri-operative management of obstructive sleep apnea. 2012; https://asmbs.org/resources/peri-operative-management-of-obstructive-sleep- apnea. Accessed September 1, 2017.

36. National Institute for Health and Care Excellence. Hypoglossal nerve stimulation for moderate to severe obstructive sleep apnoea (IPG598). 2017. https://www.nice.org.uk/guidance/ipg598/chapter/1-Recommendations. Accessed May 18, 2020.

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