Surgical Treatment of Snoring and Obstructive Sleep Apnea Syndrome - CAM 701101

Description:
Obstructive sleep apnea (OSA) syndrome is characterized by repetitive episodes of upper airway obstruction due to the collapse of the upper airway during sleep. For patients who have failed conservative therapy, established surgical approaches may be indicated. This evidence review addresses minimally invasive surgical procedures for the treatment of OSA. They include laser-assisted uvuloplasty, tongue base suspension, radiofrequency volumetric reduction of palatal tissues and base of tongue, palatal stiffening procedures, and hypoglossal nerve stimulation. This evidence review does not address conventional surgical procedures such as uvulopalatopharyngoplasty, hyoid suspension, surgical modification of the tongue, maxillofacial surgery, or adenotonsillectomy.

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 a 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 two 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 two 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 five years in the pivotal single-arm study. Clinical input supplements and informs the interpretation of the published evidence. Clinical input indicates that HNS leads to a meaningful improvement in health outcomes in appropriately selected 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. Clinical input also supports that HNS results in a meaningful improvement in health outcomes in appropriately selected adolescents with OSA and Down’s syndrome who have difficulty in using CPAP. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome for patients meeting the following selection criteria which 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/m²in adults; AND
Favorable pattern of palatal collapse

Background
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction due to the collapse and obstruction of the upper airway during sleep. The hallmark symptom of OSA is excessive daytime sleepiness, and the typical clinical sign of OSA is snoring, which can abruptly cease and be followed by gasping associated with a brief arousal from sleep. The snoring resumes when the patient falls back to sleep, and the cycle of snoring/apnea/arousal may be repeated as frequently as every minute throughout the night. Sleep fragmentation associated with the repeated arousal during sleep can impair daytime activity. For example, adults with OSA-associated daytime somnolence are thought to be at higher risk for accidents involving motorized vehicles (i.e., cars, trucks, heavy equipment). OSA in children may result in neurocognitive impairment and behavioral problems. In addition, OSA affects the cardiovascular and pulmonary systems. For example, apnea leads to periods of hypoxia, alveolar hypoventilation, hypercapnia, and acidosis. This, in turn, can cause systemic hypertension, cardiac arrhythmias, and cor pulmonale. Systemic hypertension is common in patients with OSA. Severe OSA is associated with decreased survival, presumably related to severe hypoxemia, hypertension, or an increase in automobile accidents related to overwhelming sleepiness.

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 the 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 3% or 4% decrease in arterial oxygen desaturation (depending on the scoring criteria) or arousal. Hypopneas in children are scored by a ≥ 50% drop in nasal pressure and either a ≥ 3% decrease in oxygen saturation or 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 increased respiratory effort, terminating in 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 (previous 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
Hypoglossal nerve stimulation	Apnex System^®	Apnex

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
20118 Diagnosis and Medical Management of Obstructive Sleep Apnea Syndrome

Policy:
Palatopharyngoplasty (e.g., uvulopalatopharyngoplasty, uvulopharyngoplasty, uvulopalatal flap, expansion sphincter pharyngoplasty, lateral pharyngoplasty, palatal advancement pharyngoplasty, relocation pharyngoplasty) may be considered MEDICALLY NECESSARY for the treatment of clinically significant obstructive sleep apnea (OSA) syndrome in appropriately select adults who have failed an adequate trial of continuous positive airway pressure (CPAP) or failed an adequate trial of an oral appliance. Clinically significant OSA is defined as those patients who have:

Apnea/Hypopnea Index (AHI) or Respiratory Disturbance Index (RDI) of 15 or more events per hour, or
AHI or RDI of 5 or more events and 14 or less events per hour with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease, or history of stroke.

Hyoid suspension, surgical modification of the tongue, and/or maxillofacial surgery, including mandibular-maxillary advancement (MMA), may be considered MEDICALLY NECESSARY in appropriately selected adults with clinically significant OSA and objective documentation of hypopharyngeal obstruction who have failed an adequate trial of CPAP or failed an adequate trial of an oral appliance. Clinically significant OSA is defined as those patients who have:

AHI or RDI of 15 or more events per hour, or
AHI or RDI of 5 or more events and 14 or less events per hour with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease, or history of stroke.

Adenotonsillectomy may be considered MEDICALLY NECESSARY in pediatric patients with clinically significant OSA and hypertrophic tonsils. Clinically significant OSA is defined as those pediatric patients who have:

AHI or RDI of at least 5 per hour, or
AHI or RDI of at least 1.5 per hour in a patient with excessive daytime sleepiness, behavioral problems, or hyperactivity.

Hypoglossal nerve stimulation may be considered medically necessary in adults with OSA under the following conditions:

Age ≥ 22 years; AND
AHI ≥ 15 with less than 25% central apneas; AND
CPAP failure (residual AHI ≥ 20 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).

Hypoglossal nerve stimulation may be considered medically necessary in 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).

Surgical treatment of OSA that does not meet the criteria above would be considered not medically necessary.

The following minimally invasive surgical procedures are investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY for the sole or adjunctive treatment of OSA or upper airway resistance syndrome:

Laser-assisted palatoplasty or radiofrequency volumetric tissue reduction of the palatal tissues
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
Tongue base suspension
All other minimally invasive surgical procedures not described above.

Implantable hypoglossal nerve stimulators are investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY for all indications other than listed above.

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

Policy Guidelines
Clinically significant obstructive sleep apnea (OSA) is defined as those adult patients who have:

Apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) greater than or equal to 15 events per hour, or
AHI or RDI greater than or equal to 5 events and less than or equal to 14 events per hour with documented symptoms of excessive daytime sleepiness, impaired cognition, mood disorders or insomnia, or documented hypertension, ischemic heart disease, or history of stroke.

The AHI is the total number events (apnea or hypopnea) per hour of recorded sleep. The RDI is the total number events (apnea or hypopnea) per hour of 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 as compared to baseline, and with at least a 4% oxygen desaturation.

The presentation of OSA in pediatric patients may differ from that of adults. OSA in pediatric patients is defined as those who have:

AHI or RDI of at least 5 per hour, or
AHI or RDI of at least 1.5 per hour in a patient with excessive daytime sleepiness, behavioral problems, or hyperactivity.

Clinically significant upper airway resistance syndrome (UARS) is defined as greater than 10 EEG arousals per hour. The presence of abnormally negative intrathoracic pressures (i.e., more negative than 10 cm) in conjunction with the EEG arousals supports the diagnosis. The measurement of intrathoracic pressures requires the use of an esophageal manometer as an adjunct to a polysomnogram. Objective evidence of hypopharyngeal obstruction is documented by either fiberoptic endoscopy or cephalometric radiographs.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may only be assessed on the basis of their medical necessity. This consideration would apply to radiofrequency volumetric tissue reduction.

Rationale
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
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.⁶ Nonsurgical treatment for OSA or upper airway resistance syndrome includes continuous positive airway pressure (CPAP) or mandibular repositioning devices, which are addressed in evidence review 8.01.67. 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.

Clinical Context and Therapy Purpose
The purpose of minimally invasive surgery in patients who have OSA is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Do the surgical interventions addressed in this evidence review improve the net health outcome in patients with OSA?

The following PICO was used to select literature to inform this review.

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

Interventions
The interventions addressed in this review 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 suspension aims to make it less likely for the base of the tongue to prolapse during sleep	Snoring and/or OSA
Hypoglossal nerve stimulation	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 Evidence Review 8.01.67 on diagnosis and medical management of OSA) 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 UPPP, depending on the location of the obstruction. It is uncertain whether UPPP variants without tongue volume reduction are the most appropriate comparator for HNS, since the procedures may 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 the 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 a 50% decrease in VAS^6, or final VAS of < 5 or < 3⁷
Epworth Sleepiness Score	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 television, 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.^8,
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 the 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; ESS: Epworth Sleepiness Score; MCID: minimum clinically import difference; OSA; obstructive sleep apnea; 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.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Laser-Assisted Uvulopalatoplasty
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.⁹ 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)⁹	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; OSA: obstructive sleep apnea.
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).

Table 6. Summary of Key Randomized Controlled Trial Results

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 the First Week	Difficulty Swallowing at Follow-up
Ferguson et al. (2003)⁹
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	< .001	NS	NS

AHI: Apnea/Hypopnea Index; ESS: Epworth Sleepiness Scale (maximum of 24); LAUP: laser-assisted uvulopalatoplasty; NS: not significant; NR: not reported; SAQLI: Sleep Apnea Quality of Life Index (maximum of 7); VAS: visual analog scale.
Study limitations 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	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Ferguson et al. (2003)⁹	1. Entry criteria include 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.

Table 8. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^d	Data Completeness^e	Power^d	Statistical^f
Ferguson et al. (2003)⁹		1. – 3. No blinding				4. Comparison of primary outcome not reported

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

Section Summary: Laser-Assisted Uvulopalatoplasty
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
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.4, All studies were nonrandomized.

Review of Evidence
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, visual analog scale (VAS) for snoring, ESS, or FOSQ between RF and sham (see Tables 9 through 11).10, 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.11,However, the improvement in the FOSQ score (1.2; standard deviation [SD], 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 Tables 10 and 12).

Table 9. Summary of Key Randomized Controlled Trial Characteristics

Study	Countries	Sites	Participants	Interventions
				Active	Comparator
Back et al. (2009)¹⁰	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)¹¹	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 a sham procedure to the 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 Score^a Median (Range)
Back et al. (2009)¹⁰
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	.628	.064	.941	.746	No significant differences after 6 d
	Change Score (SD)		Change Score (SD)	FOSQ Score (SD)
Woodson et al. (2003)¹¹
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; RF: radiofrequency; 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;
bp = .005 for baseline to posttreatment.

Tables 11 and 12 display notable limitations identified in each study.

Table 11. Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Back et al. (2009)¹⁰	4. Included patients with mild OSA and snoring	4. Single treatment with RFA
Woodson et al. (2003)¹¹

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.

Table 12. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^d	Data Completeness^e	Power^d	Statistical^f
Back et al. (2009)¹⁰		2. Surgeons also performed follow-up assessments				.
Woodson et al. (2003)¹¹						3. Comparative treatment effects not reported

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^aAllocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control
for selection bias.
^bBlinding 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.

Section Summary: Radiofrequency Volumetric Reduction of Palatal Tissues and Base of Tongue
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 the 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
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 operations are intended for snoring and are not discussed here. Palatal implants are cylindrically shaped devices that are implanted in the soft palate.

Review of Evidence
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.¹² In the study by Friedman et al. (2008), there was greater success in AHI (45% vs 0%, p < .001), improvement in snoring (-4.7 vs -0.7 on a 10-point VAS, p < .001), and improvement in ESS (-2.4 vs -0.5, p < .001) with palatal implants compared with sham controls.⁶ 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)¹²	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)⁶	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)¹²
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	.04	.052	NS	.05
Friedman et al. (2008)⁶		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	< .001	< .001	< .001
Summary: Range	26% to 44.8%

AHI: Apnea/Hypopnea Index; CI: confidence interval; ESS: Epworth Sleepiness Score; FOSQ: Functional Outcomes of Sleep Questionnaire; MD: mean difference; NS: not significant; 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).¹³ 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 case series and the RCTs described above.

Table 15. Summary of Key Case Series Characteristics

Study	Country	Participants	Follow-Up
Neruntarat et al. (2011)¹³	Thailand	92 patients with mild-to-moderate symptomatic OSA and palate > 2 cm	Minimum 24 mo

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	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Neruntarat et al. (2011)¹³			2. No comparator
Steward et al. (2008)¹²	4. Out of 968 patients assessed for eligibility, 100 were enrolled				1, 2. 3 mo
Friedman et al. (2008)⁶	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.
^aPopulation key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 
4. Study population not representative of intended use.
^bIntervention 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.

Table 18. Study Design and Conduct Limitations

udy	Allocation^a	Blinding^b	Selective Reporting^d	Data Completeness^e	Power^d	Statistical^f
Neruntarat et al. (2011)¹³	1.Retrospective	1.None (case series)
Steward et al. (2008)¹²
Friedman et al. (2008)⁶

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^aAllocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control 
for selection bias.
^bBlinding 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. 
 
Section Summary: Palatal Stiffening Procedures
Two sham-controlled trials and several case series have assessed palatal implants for the treatment of snoring and OSA. The 
sham-controlled 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
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 suspension aims 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)¹⁵	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)¹⁵
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.

Table 21. Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Thomas et al. (2003)¹⁵					1, 2. Follow-up was to 16 wk

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.

Table 22. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^d	Data Completeness^e	Power^d	Statistical^f
Thomas et al. (2003)¹⁵	3. Allocation concealment unclear	1. – 3. Not blinded			1. Feasibility study	4. Comparative treatment effects not calculated

Section Summary: Tongue Base Suspension
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
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.

Review of Evidence
Systematic Reviews
A summary of systematic reviews is included in Tables 23 and 24.

Costantino et al. (2020) conducted a systematic review and meta-analysis of 6- to 60-month outcomes following HNS16, They identified 12 studies with a total of 350 patients with OSA who were treated with the Inspire, ImThera, or Apnex HNS systems. Only the Inspire device has obtained FDA approval as of May 2022, and contributed the largest number of patients to the meta-analysis. In addition to the trials described below by Steffen et al. (2015, 2018)17,18, and Strollo et al. (Stimulation Therapy for Apnea Reduction [STAR] Trial, 2014, 2018)^19,20 several other trials with the Inspire system were included in the meta-analysis. At 6 mo follow-up, the overall change in AHI was -17.74 with an improvement in ESS of -5.36. At 12 mo follow-up, the change in AHI was -17.50 with an improvement in ESS of -5.27. Sixty-month data were provided only by the STAR trial as reported by Woodson et al. (2018) and are described below.²¹

Table 23. Meta-analysis Characteristics

Study	Dates	Trials	Participants	N (Range)	Design	Duration
Constantino et al. (2020)¹⁶	Through 2018	12	Adult patients with moderate to severe OSA	350 (8 – 124)	Cohort	6, 12, and 60 mo

OSA: obstructive sleep apnea

Table 24. Meta-analysis Results

Study	AHI Change at 6 mo (95% CI)	AHI Change at 12 mo (95% CI)	ESS Change at 6 mo (95% CI)	ESS Change at 12 mo (95% CI)	AHI Success n(%) Sher Criteria^a
Constantino et al. (2020)¹⁶
Total N	210	255	210	255
Inspire	-17.74 (-24.73 to -10.74)	-17.50 (-20.01 to -14.98)	-5.36 (-6.64 to -4.08)	-5.27 (-6.18 to -4.35)	115 (70%)
ImThera	-9.50 (-19.14 to 0.14)	-24.20 (-37.39 to -11.01)	-3.70 (-5.65 to -1.75)	-2.90 (-6.97 to 1.17)	46 (35%)
Apnex	-24.20 (-30.94 to -17.45)	-20.10 (-29.62 to -10.58)	-3.87 (-5.53 to -2.21	-4.20 (-6.30 to -2.10)	115 (59.8%)
I² (p)	68% (.004)	0% (.77)	25% (.25)	27% (.24)
Range of N	8 to 56	13 to 124	21 to 56	13 to 124

AHI: Apnea/Hypopnea Index; CI: confidence interval; ESS: Epworth Sleepiness Score.
^aSurgical success according to Sher criteria is defined as a 50% recution in AHI and overall AHI < 20.

Randomized Controlled Trials
Only 1 RCT has been identified on the effect of HNS in patients with OSA. Heiser et al. (2021) conducted The Effect of Upper Airway Stimulation in Patients With Obstructive Sleep Apnea (EFFECT) trial, a multicenter, randomized, double-blind, crossover design study in adult patients with moderate-to-severe OSA (defined as AHI > 15) who were intolerant to CPAP.²² All individuals included in the study were white. All patients received implantation of HNS device (Inspire Medical Solutions) at least 6 months prior to enrollment. Baseline AHI before implantation was 32.2 events/h; after implantation, baseline AHI was approximately 8.3 events/h. All participants received therapeutic stimulation during the baseline visit. Patients were then randomized to 1 of 2 treatment groups: HNS-Sham (n = 45) or Sham-HNS (n = 44). After randomization, the HNS-Sham group received therapeutic stimulation and the Sham-HNS received sham stimulation for 1 week. During the second week, the HNS-Sham group received sham stimulation while the Sham-HNS group received therapeutic stimulation. Changes in AHI over time showed a statistically significant decrease in AHI with stimulation compared to sham stimulation during the baseline, week 1, and week 2 visits. This meant that during week 1 when the HNS-Sham group received stimulation, they had significantly lower AHI; during week 2, when the Sham-HNS group received stimulation, they had significantly lower AHI. Similarly, participants reported a lower ESS with stimulation compared to sham stimulation during all visits. The change of AHI and ESS from baseline to the 1-week and 2-week visits was analyzed between the groups and investigators found no evidence of a carryover effect for AHI or ESS. Study characteristics and a summary of results are described in Tables 25 and 26, respectively.

Table 25. Summary of Key RCT Characteristics

Study; Trial	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Heiser et al. (2021);²² EFFECT	Germany	3	2018 – 2019	Adults with moderate-to-severe OSA (AHI > 15), intolerant to CPAP; 100% of participants were white	HNS for week 1 followed by crossover to sham in week 2 (n = 45)	Sham stimulation for week 1 followed by crossover to HNS in week 2 (n = 44)

AHI: Apnea/Hypopnea Index; CPAP: continuous positive airway pressure; HNS: hypoglossal nerve stimulation; OSA: obstructive sleep apnea; RCT: randomized controlled trial.

Table 26. Summary of Key RCT Results

Study	AHI response after 1 week (AHI <15 events/h)	Change in ESS after 1 week	Overall change from baseline in FOSQ across treatment modalities
Heiser et al. (2021);²² EFFECT	N = 89	N = 89	N=86
HNS	73.3%	0.4 + 2.3	0.2 (-0.5 to 0.9)
Sham	29.5%	5.0 + 4.6	-1.9 (-2.6 to -1.2)
Difference (95% CI)	43.8% (25.1 to 62.5)	4.6 (3.1 to 6.1)	2.1 (1.4 to 2.8)
p-value	< .001	.001	< .001

AHI: Apnea/Hypopnea Index; CI: confidence interval; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep Questionnaire; HNS: hypoglossal nerve stimulation; HR: hazard ratio; NNT: number needed to treat; OR: odds ratio; RCT: randomized controlled trial; RR: relative risk.

Notable study limitations are described in Tables 27 and 28.

Table 27. Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Duration of Follow-up^e
Heiser et al. (2021);²² EFFECT	4. Study population was predominantly male and exclusively white				1., 2. Limited follow-up period precluded long-term evaluation of safety and efficacy

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. Study population is unclear; 3. Study population not representative of intended use; 4, Enrolled populations do not reflect relevant diversity; 5. Other.
b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest (e.g., proposed as an adjunct but not tested as such); 5: Other.
c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively; 5. Other.
d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. Incomplete reporting of harms; 4. Not establish and validated measurements; 5. Clinically significant difference not prespecified; 6. Clinically significant difference not supported; 7. Other.
e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms; 3. Other.

Table 28. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^c	Data Completeness^d	Power^e	Statistical^f
Heiser et al. (2021);²² EFFECT		4. Most participants randomized to sham stimulation became aware of the group allocation, possibly impacting subjective outcomes

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
STAR: Stimulation Therapy for Apnea Reduction.
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.; 5. Other.

Comparative Studies
Study characteristics and results are described in Tables 29 and 30. Limitations in relevance and design and conduct, including comparative
studies and 2 single-arm studies, are described in Tables 31 and 32.

Besides the RCT described above, comparative evidence consists of 3 studies that compared HNS with historical controls treated with UPPP or a
variant of UPPP (expansion sphincter pharyngoplasty) and a 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. Posttreatment ESS was below 10 in both groups.
It is not clear from some 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.

Several comparative studies have addressed these concerns by only including patients who meet the criteria for HNS in the control group.
Yu et al. (2019) compared outcomes for patients who met the criteria for both HNS (non-concentric collapse on drug-induced sleep endoscopy) and
transoral robotic surgery (retroglossal obstruction).²³ 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%. Huntley et al.
(2021) selected patients in the control group who met the criteria for HNS (non-concentric collapse on drug-induced sleep endoscopy and body
mass index [BMI] criteria) but had been treated at their institutions by single or multi-level palatal and lingual surgery.²⁴ There was no
explanation of why the different treatments were given during the overlap period of 2010 to 2019, but the HNS patients were older and heavier.
HNS resulted in a modestly greater decrease in AHI (HNS: -21.4 vs -15.9. p < .001), but not in ESS (HNS: -4.7 vs -5.8, p = .06). More patients
in the HNS group achieved success by the Sher criteria (70% vs 48 to 49%) suggesting that there might be a clinical benefit for some patients.

Another report from Adherence and Outcome of Upper Airway Stimulation for OSA International Registry (ADHERE) registry investigators
(Mehra et al., 2020) compared outcomes from HNS patients with patients who met the criteria but had been denied insurance coverage.²⁵ In a
post-hoc multivariate analysis, previous use of PAP and prior surgical procedures were predictors of insurance approval. In the group of
patients who received HNS, the average use downloaded from the device was 5.6 h/night and 92% of patients had usage greater than 20 h/week.
A majority of the comparator group (86%) were not using any therapy at follow-up. The remaining 14% were using PAP, an oral appliance, or
underwent OSA surgery. The AHI decreased to 15 events/h (moderate OSA) on the night of the sleep test in patients with HNS, with only a modest
improvement in patients who did not receive HNS. The hours of use on the night of the post-operative sleep study were not reported, and the
HNS patients may have been more likely to use their device on the test night. In addition, the use of a home sleep test for follow-up may
underestimate the AHI. The ESS improved in the HNS group but worsened in the controls. This suggests the possibility of bias in this
subjective measure in patients who were denied coverage.

Additional non-comparative reports from the ADHERE registry are described below.

Table 29. Summary of Prospective Single-Arm Study Characteristics

Study	Study Type	Country	Dates	Participants	HNS	Traditional Surgery	Follow-Up
Shah et al. (2018)²⁶	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 collapse^a	35% had previously had surgery for OSA	UPPP 50% of patients had additional surgical procedures	2 – 13 mo
Huntley et al. (2018)²⁷	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)²³	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 collapse^a	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
Huntley et al. (2020)²⁴	ADHERE registry compared to retrospective controls	U.S., EU	• HNS 2010 – 2019 • Modified UPPP 2003 – 2019	OSA patients who were intolerant to CPAP and met HNS criteria of AHI 15 to 65, BMI < 35, and favorable pattern of palatal collapse^a	465 registry patients treated with HNS who had 12 mo follow-up	233 patients who would have qualified for HNS and were treated by single level (68%) or multilevel (31%) surgery	173 days after surgery 383 days after HNS
Mehra et al. (2020)²⁵	ADHERE registry	U.S., EU	2017 – 2019	OSA patients who were intolerant to CPAP and met HNS criteria of AHI 15 to 65, BMI < 35, and favorable pattern of palatal collapse^a	250 registry patients treated with HNS	100 patients who qualified for HNS but were denied insurance coverage	6 to 24 months

AHI: Apnea/Hypopnea Index; 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.
^aA favorable pattern of palatal collapse is not concentric retropalatal obstruction on drug-induced sleep endoscopy.

Table 30. Summary of Prospective Single-Arm Study Results

Study	Baseline AHI (SD)	Posttreatment AHI (SD)	AHI Success n(%)Sher Criteria	Baseline ESS (SD)	Posttreatment ESS (SD)
Shah et al. (2018)²⁶
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)²⁷
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	.003	.003	.008	.565	NS
Yu et al. (2018) ²³		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		.002	< .001	.02
Huntley et al. (2020)²⁴
HNS	35.5 (15.0)	14.1 (14.4)	70	11.9 (5.5)	7.3 (4.7)
Single or multi-level UPPP	35.0 (13.1)	19.3 (16.3)	48 to 49	11.3 (5.1)	5.9 (4.0)
p-Value	.88	< .001	< .001	.22	.06
Mehra et al. (2020)²⁵
HNS	33.7 (13.4)	14.7 (13.8)		12.3 (5.5)	7.2 (4.8)
No HNS	34.9 (16.4)	26.8 (17.6)		10.9 (5.4)	12.8 (5.2)
p-Value	.95	< .001		.06	< .001

AHI: Apnea/Hypopnea Index; ESP: expansion sphincter pharyngoplasty; ESS: Epworth Sleepiness Score; HNS: hypoglossal nerve stimulation; NS: 
not significant; Sher criteria: 50% decrease in AHI and final AHI <20; SD; standard deviation; SaO_2: oxygen saturation; TORS: transoral 
robotic surgery; UPPP: uvulopalatopharyngoplasty.
^a Baseline vs posttreatment p < .05.
^b Baseline vs posttreatment p < .001.

Table 31. Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Shah et al. (2018)²⁶			2. UPPP may not be the preferred treatment for patients with primarily lingual obstruction
Huntley et al. (2018)²⁷	4. Study populations not comparable		1. Not clearly defined, few ESP patients had follow-up PSG
Yu et al. (2018) ²³					1, 2. Duration of follow-up unclear
Huntley et al. (2020)²⁴	4. Study populations not comparable				1. The timing of follow-up was different (173 days after surgery and 383 days after HNS)
Mehra et al. (2020)²⁵	4. Study populations not comparable		3. Hours of use on the test night was not reported. This may not represent the normal use of the device.		1. The timing of follow-up was different
Steffen et al. (2018)¹⁷			2.No comparator
STAR trial^19,^20,^28,^29,^30,³¹			2.No comparator

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
ESP: expansion sphincter pharyngoplasty; HNS: hypoglossal nerve stimulation; PSG: polysomnography; STAR: Stimulation Therapy for Apnea Reduction; UPPP: uvulopalatopharyngoplasty.
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.

Table 32. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^d	Data Completeness^e	Power^d	Statistical^f
Shah et al. (2018)²⁶	1. Not randomized (retrospective) 4. Inadequate control for selection bias	1. – 3. No blinding				4. Comparative treatment effects not calculated
Huntley et al. (2018)²⁷	1. Not randomized (retrospective)	1. – 3. No blinding
Yu et al. (2018) ²³	1. Not randomized (retrospective)
Huntley et al. (2020)²⁴	1. Not randomized (retrospective)	1. – 3. No blinding
Mehra et al. (2020)²⁵	1. Not randomized	1. – 3. No blinding			1. Power calculations not reported
Steffen et al. (2018)¹⁷	1. Not randomized	1. – 3. No blinding
STAR trial^19,^20,^28,^29,^30,³¹	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.

Single-Arm Studies
Characteristics and results of single-arm studies are described in Tables 33 to 35. Limitations are mentioned in Tables 31 and 32, above.

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. Mean AHI was 31 to 32 at baseline, decreasing to 14 to 15 at 12 months. ESS scores decreased from 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 35). 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 hours per night. Use was correlated with the subjective outcomes, but not with AHI response. Two- and 3-year follow-up of this study were reported by Steffen et al. (2020)¹⁸ but the percentage of patients at follow-up was only 68% at 2 years and 63% at 3 years, limiting conclusions about the longer-term efficacy of the procedure. A comparison of the populations who had 12-month versus 2- or 3-year results showed several differences between the patients who followed up and those who dropped out, including higher baseline AHI, higher baseline Oxygen Desaturation Index (ODI), and trends towards lower usage per night and a lower responder rate at 12 months.

Table 33. Summary of Prospective Single-Arm Study Characteristics

Study	Country	Participants	Treatment Delivery	Follow-Up
STAR trial^19,^20,^28,^29,^32,²¹	EU, U.S.	126 patients with AHI > 20 and < 50, BMI ≤ 32 kg/m², failed CPAP, favorable pattern of palatal collapse^a	Stimulation parameters titrated with full PSG	5 y
Postmarket studies: Heiser et al. (2017)³³, Steffen et al. (2018)¹⁷, Hasselbacher et al. (2018)³⁴, Steffen et al. (2020)¹⁸	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 collapse^a		12 mo, 2 yr, and 3 yr

AHI: apnea/hypopnea index; BMI: body mass index; CPAP: continuous positive airway pressure; PSG: polysomnography; STAR: Stimulation Therapy for Apnea Reduction.
a A favorable pattern of palatal collapse is non-concentric retropalatal obstruction on drug-induced sleep endoscopy.

Table 34. Summary of Prospective Single-Arm Study Results

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 trial^19,^20,^28,^29,^32,²¹
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	116^a	65%	14.2 (15.9)	9.1 (11.7)	17.4 (3.5)^b	7.0 (5.0)^b
5 years	97^c	63%	12.4 (16.3)	9.9 (14.5)	18.0 (2.2)	6.9 (4.7)
Postmarket studies: Heiser et al. (2017)³³, Steffen et al. (2018)¹⁷, Hasselbacher et al. (2018)³⁴, Steffen et al. (2020)¹⁸
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	56^f	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%

AHI: Apnea/Hypopnea Index; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep Questionnaire; ODI: Oxygen Desaturation Index; PSG: polysomnography; SD: standard deviation; STAR: Stimulation Therapy for Apnea Reduction.

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 non-responders and their PSG results at 12 or 18 months were carried forward. b The change from baseline was significant at p < .001.
c Seventy-one participants agreed to a PSG.

d p < .001.
e p < .05.
f Four patients lost to follow-up were analyzed as treatment failures.

Table 35. Device-Related Adverse Events From Prospective Single-Arm Studies

Study	N	Discomfort due to Electrical Stimulation^a	Tongue Abrasion	Dry Mouth	Mechanical Pain From Device	Internal Device Usability	External Device Usability
STAR trial²¹
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 an event, n of 126 (%)		76 (60.3)	34 (27.0)	19 (15.1)	14 (11.1)	21 (16.7)	33 (26.2)

STAR: Stimulation Therapy for Apnea Reduction.
^aStimulation levels were adjusted to reduce discomfort

Down Syndrome
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.³⁵ Included were non-obese (BMI < 95%) children and adolescents aged 10 to 21 years who were refractory to tonsillectomy and either unable to tolerate CPAP or dependent on a tracheostomy. Patients who were included had an AHI 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 achieved 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.

Yu et al. (2022) reported on the safety and effectiveness of HNS in 42 adolescents with Down Syndrome and severe OSA (AHI of 10 events/h or greater).³⁶ This was a single-group, multicenter, cohort study with a 1-year follow-up that included non-obese (BMI < 95%) children and adolescents aged 10 to 21 years who were refractory to adenotonsillectomy and unable to tolerate CPAP. Patients who were included had an AHI between 10 and 50 on baseline PSG; the mean baseline AHI was 23.5 (SD, 9.7). All patients included tolerated HNS without any intraoperative complications. The most common complication was tongue or oral discomfort or pain, which occurred in 5 (11.9%) patients and was temporary, lasting weeks or rarely, months. Four patients (9.5%) had device extrusion resulting in readmissions to replace the extruded device. At 12 months, there was a mean decrease in AHI of 12.9 (SD, 13.2) events per hour (95% CI, -17.0 to -8.7 events/h). At the 12-month PSG, 30 of 41 patients (73.2%) had an AHI of less than 10 events/h, 14/41 patients (34.1%) had an AHI of less than 5 events/h, and 3/41 patients (7.3%) had an AHI of less than 2 events/h. There was also a significant improvement in quality of life outcomes. The mean improvement in the OSA-18 total score was 34.8 (SD, 20.3; 95% CI, -42.1 to -27.5) and the ESS improved by 5.1 (SD, 6.9; 95% CI, -7.4 to -2.8).

Registry
Boon et al. (2018) reported results from 301 patients in the multicenter Adherence and Outcome of Upper Airway Stimulation for OSA International Registry (ADHERE).³⁷ 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.³⁸ 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. A report of data from the ADHERE registry by Thaler et al. (2020) included 640 patients with 6-month follow-up and 382 with 12-month follow-up.39, AHI was reduced from 35.8 at baseline to 14.2 at 12 months (p < .001), although the number of hours of use during the sleep test was not reported and home sleep studies may underestimate AHI. ESS was reduced from 11.4 at baseline to 7.2 at 12 months (p < .001), and patient satisfaction was high. In a multivariate model, only female sex (odds ratio: 3.634, p = .004) and lower BMI (odds ratio: 0.913, p = .011) were significant predictors of response according to the Sher criteria. In sensitivity analysis, higher baseline AHI was also found to be a negative predictor of success.

In a retrospective analysis by Huntley et al. (2018) of procedures at 2 academic institutions, patients with a BMI of greater than 32 did not have lower success rates than patients with a BMI less than 32.⁴⁰ However, only patients who had palpable cervical landmarks and carried most of their weight in the waist and hips were offered HNS. 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 a systematic review, 1 RCT, nonrandomized prospective studies, nonrandomized studies with historical controls, and prospective single-arm studies. An RCT of 89 adults with moderate-to-severe OSA who did not tolerate CPAP found significant short-term improvement in AHI, ESS, and quality of life measures with HNS compared to sham stimulation. The study was limited by short duration of follow-up and lack of diverse individuals included in the trial. In nonrandomized studies, about two-thirds of patients with moderate-to-severe OSA who had failed conservative therapy (CPAP) and had a favorable pattern of palatal collapse met the study definition of success. Results observed at the 12-month follow-up were maintained at 5 years in the pivotal study. A prospective study that compared outcomes in patients who had received HNS to patients who were denied insurance coverage reported significant differences in both objective and subjective measures of OSA. However, there is a high potential for performance bias in this non-blinded 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. A larger study of 42 individuals with Down Syndrome and OSA found a similar success rate of 73.2% with 4 device extrusions corrected with replacement surgery. 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 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 AHI or symptoms in patients with mild-to-moderate OSA. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

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 that the technology results in an improvement in the net health outcome.

For individuals who have OSA who receive palatal stiffening procedures, the evidence includes 2 sham-controlled randomized trials and several case series. 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 that the technology results in an improvement in the net health outcome.

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 UPPP with tongue advancement plus UPPP 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 UPPP improves the net health outcome. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have OSA who receive hypoglossal nerve stimulation, the evidence includes a systematic review, 1 RCT, nonrandomized prospective studies, nonrandomized studies with historical controls, and prospective single-arm studies. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. A double-blind, multicenter RCT of 89 adults with moderate-to-severe OSA who did not tolerate CPAP found significant short-term improvement in AHI, ESS, and quality of life measures with HNS compared to sham stimulation. The study was limited by short duration of follow-up and lack of diverse individuals included in the trial. Hypoglossal nerve stimulation has shown success rates for about two-thirds of a subset of patients who met selection criteria that included AHI, BMI, and favorable pattern of palatal collapse across nonrandomized trials. These results were maintained out to 5 years in the pivotal single-arm study. The single prospective comparative study of patients who received HNS versus patients who were denied insurance coverage for the procedure has a high potential for performance bias. 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. A larger study of 42 individuals with Down Syndrome and OSA found a similar success rate of 73.2% with 4 device extrusions corrected with replacement surgery. Limitations of the current evidence base preclude determination of who is most likely to benefit from this invasive procedure. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

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 (HNS) for individuals with obstructive sleep apnea (OSA) 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 Apnea/Hypopnea Index (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 continuous positive airway pressure (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
Further details from clinical input are included in the Appendix.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Academy of Sleep Medicine
The American Academy of Sleep Medicine (AASM, 2021) published practice guidelines on when to refer patients for surgical modifications of the upper airway for OSA.⁴¹ These guidelines replaced the 2010 practice parameters for surgical modifications.⁴² The AASM guidelines note that positive airway pressure (PAP) is the most efficacious treatment for OSA, but effectiveness can be compromised when patients are unable to adhere to therapy or obtain an adequate benefit, which is when surgical management may be indicated. The AASM guideline recommendations are based on a systematic review and meta-analysis of 274 studies of surgical interventions, including procedures such as uvulopalatopharyngoplasty (UPPP), modified UPPP, MMA, tongue base suspension, and hypoglossal nerve stimulation.⁴³ The systematic review deemed most included data of low quality, consisting of mostly observational data. The AASM strongly recommends that clinicians discuss referral to a sleep surgeon with adults with OSA and body mass index (BMI) < 40 kg/m2 who are intolerant or unaccepting of PAP. Clinically meaningful and beneficial differences in nearly all critical outcomes, including a decrease in excessive sleepiness, improved quality of life (QOL), improved Apnea/Hypopnea Index (AHI) or respiratory disturbance index (RDI), and sleep quality, were demonstrated with surgical management in patients who are intolerant or unaccepting of PAP. The AASM makes a conditional recommendation that clinicians discuss referral to a sleep surgeon with adults with OSA, BMI < 40 kg/m2, and persistent inadequate PAP adherence due to pressure-related side effects, as available data (very low-quality), suggests that upper airway surgery has a moderate effect in reducing minimum therapeutic PAP level and increasing PAP adherence. In adults with OSA and obesity (class II/III, BMI > 35) who are intolerant or unaccepting of PAP, the AASM strongly recommends discussion of referral to a bariatric surgeon, along with other weight-loss strategies.

American Academy of Pediatrics
The American Academy of Pediatrics (2012) published a clinical practice guideline on the diagnosis and management of childhood OSA.⁴⁴ 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 OSA 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; 2021 ) has a position statement on surgical management of OSA.⁴⁵ 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:

tracheostomy,
nasal and pharyngeal airway surgery,
tonsillectomy and adenoidectomy,
palatal advancement,
UPPP,
genioglossal advancement,
hyoid myotomy,
midline glossectomy,
tongue suspension,
maxillary and mandibular advancement.

In a 2021 position statement, AAO-HNS supported hypoglossal nerve stimulation as an effective second-line treatment of moderate-to-severe OSA.⁴⁶

American Society for Metabolic and Bariatric Surgery
The American Society for Metabolic and Bariatric Surgery (2012) published guidelines on the perioperative management of OSA.⁴⁷ 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, besides CPAP, as opposed to surgical procedures directed at the mandible or tissues of the palate. The updated 2017 guidelines reaffirmed these recommendations.⁴⁸

National Institute for Health and Care Excellence
The National Institute for Health and Care Excellence (NICE) 2017 guidance concluded that evidence on the safety and efficacy of hypoglossal nerve stimulation is limited in quantity and quality, and the procedure should only be used in the context of a clinical trial.⁴⁹

U.S. Preventive Services Task Force Recommendations
Not applicable.

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 36.

Table 36. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT02413970^a	Inspire^® Upper Airway Stimulation System (UAS): Post-Approval Study Protocol Number 2014-001	127	Jun 2025
NCT03868618^a	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	134	Jun 2027
NCT02263859^a	ImThera Medical Targeted Hypoglossal Neurostimulation Study #3 (THN3)	138	Dec 2022
NCT03763682^a	A Multicentre, Prospective, Open-label, 2 Groups Study to Assess the Safety and Performance of the Genio™ Bilateral Hypoglossal Nerve Stimulation System for the Treatment of Obstructive Sleep Apnoea in Adult Patients With and Without Complete Concentric Collapse of the Soft Palate	42	Dec 2023
NCT04801771^a	Effects of Hypoglossal Nerve Stimulation on Cognition and Language in Down Syndrome and Obstructive Sleep Apnea	68	Mar 2025
NCT04031040^a	A Post-market Clinical Follow up of the Genio™ System for the Treatment of Obstructive Sleep Apnea in Adults (EliSA)	110	Oct 2025
NCT02907398^a	Adherence and Outcome of Upper Airway Stimulation (UAS) for OSA International Registry	5000	Sep 2025
NCT04950894^a	Treating Obstructive Sleep Apnea Using Targeted Hypoglossal Neurostimulation	150	Jul 2023
NCT04928404	Barbed Suspension of the Tongue Base for Treatment of Obstructive Sleep Apnea Patients	13	Dec 2022
Unpublished
NCT03760328	Effect of Upper Airway Stimulation: A Randomized Controlled Crossover Study	100	Sep 2020
NCT03359096	Cardiovascular Endpoints for Obstructive Sleep Apnea With Twelfth Nerve Stimulation (CARDIOSA-12): A Randomized, Sham-Controlled, Double-Blinded, Crossover Trial	63	Jan 2022

NCT: national clinical trial. 
^a Denotes industry-sponsored or cosponsored trial.

References:

Dudley KA, Patel SR. Disparities and genetic risk factors in obstructive sleep apnea. Sleep Med. Feb 2016; 18: 96-102. PMID 26428843
Cohen SM, Howard JJM, Jin MC, et al. Racial Disparities in Surgical Treatment of Obstructive Sleep Apnea. OTO Open. Jan-Mar 2022; 6(1): 2473974X221088870. PMID 35321423
Lee YC, Chang KY, Mador MJ. Racial disparity in sleep apnea-related mortality in the United States. Sleep Med. Feb 2022; 90: 204-213. PMID 35202926
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.
Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Surgical management of sleep apnea. TEC Assessments. 1995;Volume 10:Tab 32.
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
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
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
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
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
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
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
Neruntarat C. Long-term results of palatal implants for obstructive sleep apnea. Eur Arch Otorhinolaryngol. Jul 2011; 268(7): 1077-80. PMID 21298386
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
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
Costantino A, Rinaldi V, Moffa A, et al. Hypoglossal nerve stimulation long-term clinical outcomes: a systematic review and meta-analysis. Sleep Breath. Jun 2020; 24(2): 399-411. PMID 31418162
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
Steffen A, Sommer UJ, Maurer JT, et al. Long-term follow-up of the German post-market study for upper airway stimulation for obstructive sleep apnea. Sleep Breath. Sep 2020; 24(3): 979-984. PMID 31485853
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
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
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
Heiser C, Steffen A, Hofauer B, et al. Effect of Upper Airway Stimulation in Patients with Obstructive Sleep Apnea (EFFECT): A Randomized Controlled Crossover Trial. J Clin Med. Jun 29 2021; 10(13). PMID 34209581
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
Huntley C, Boon M, Tschopp S, et al. Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea. Ann Otol Rhinol Laryngol. Apr 2021; 130(4): 370-376. PMID 32862654
Mehra R, Steffen A, Heiser C, et al. Upper Airway Stimulation versus Untreated Comparators in Positive Airway Pressure Treatment-Refractory Obstructive Sleep Apnea. Ann Am Thorac Soc. Dec 2020; 17(12): 1610-1619. PMID 32663043
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
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
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
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
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
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
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
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
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
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
Yu PK, Stenerson M, Ishman SL, et al. Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. Apr 21 2022. PMID 35446411
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
Kent DT, Carden KA, Wang L, et al. Evaluation of Hypoglossal Nerve Stimulation Treatment in Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. Nov 01 2019; 145(11): 1044-1052. PMID 31556927
Thaler E, Schwab R, Maurer J, et al. Results of the ADHERE upper airway stimulation registry and predictors of therapy efficacy. Laryngoscope. May 2020; 130(5): 1333-1338. PMID 31520484
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
Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. Dec 01 2021; 17(12): 2499-2505. PMID 34351848
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. Oct 2010; 33(10): 1408-13. PMID 21061864
Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. Dec 01 2021; 17(12): 2507-2531. PMID 34351849
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
American Academy of Otolaryngology -- Head and Neck Surgery. Position Statement: Surgical Management of Obstructive Sleep Apnea. 2021; https://www.entnet.org/resource/position-statement-surgical-management-of-obstructive-sleep-apnea/. Accessed May 8, 2022.
American Academy of Otolaryngology-Head and Neck Surgery. 2021 Position Statement: Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea (OSA) https://www.entnet.org/resource/position-statement-hypoglossal-nerve-stimulation-for-treatment-of-obstructive-sleep-apnea-osa/. Accessed May 9, 2022.
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 May 8, 2022.
de Raaff CAL, Gorter-Stam MAW, de Vries N, et al. Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline. Surg Obes Relat Dis. Jul 2017; 13(7): 1095-1109. PMID 28666588
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 8, 2022.
Centers for Medicare & Medicaid Services. Decision Memo for Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA) (CAG-00093N). 2001; https://www.cms.gov/medicare-coverage- database/details/nca-decision- memo.aspx?NCAId=19&ver=7&NcaName=Continuous+Positive+Airway+Pressure+(CPAP)+Therapy+for+Obstr uctive+Sleep+Apnea+(OSA)&TAId=50&bc=AAAAAAAAEAAA&. Accessed May 9, 2022.

Coding Section

Codes	Number	Description
CPT	21199	Osteotomy, mandible, segmental; with genioglossus advancement
	41512	Tongue base suspension, permanent suture technique
	41530	Submucosal ablation of the tongue base, radiofrequency, 1 or more sites, per session
	42145	Palatopharyngoplasty (e.g., uvulopalatopharyngoplasty, uvulopharyngoplasty)
	42299	Unlisted procedure, palate, uvula
	42820-42821	Tonsillectomy and adenoidectomy, code range
	42825-42826	Tonsillectomy, primary or secondary, code range
	42830-42831	Adenoidectomy, primary, code range
	42835-42836	Adenoidectomy, secondary, code range
	42975 (Effective 01/01/2022)	Drug induced sleep endoscopy, with dynamic evaluation of velum, pharynx, tongue base, and larynx for evaluation of sleep disordered breathing, flexible, diagnostic
	64568	Incision for implantation of cranial nerve (eg, vagus nerve) neurostimulator electrode array and pulse generator
	64582 (effective 01/01/2022)	Open implantation of hypoglossal nerve neurostimulator array, pulse generator, and distal respiratory sensor electrode or electrode array
	64583 (Effective 01/01/2022)	Revision or replacement of hypoglossal nerve neurostimulator array and distal respiratory sensor electrode or electrode array, including connection to existing pulse generator
	64584 (Effective 01/01/2022)	Removal of hypoglossal nerve neurostimulator array, pulse generator, and distal respiratory sensor electrode or electrode array
	0466T(CODE DELETED EFFECTIVE 01/01/2022)	Insertion of chest wall respiratory sensor electrode or electrode array, including connection to pulse generator (List separately in addition to code for primary procedure) (new code 1/1/17)
	0467T (CODE DELETED EFFECTIVE 01/01/2022)	Revision or replacement of chest wall respiratory sensor electrode or electrode array, including connection to existing pulse generator (new code 1/1/17)
	0468T (CODE DELETED EFFECTIVE 01/01/2022)	Removal of chest wall respiratory sensor electrode or electrode array (new code 1/1/17)
HCPCS	S2080	Laser-assisted uvulopalatoplasty (LAUP)
ICD-9 Procedure	27.64	Insertion of palatal implant
	27.69	Palatoplasty
	27.73	Repair of uvula
	29.4	Pharyngoplasty
ICD-9 Diagnosis	327.23	Obstructive sleep apnea (organic sleep apnea)
	780.51	Sleep apnea (with insomnia)
	780.53	Sleep apnea (with hypersomnia)
	780.57	Sleep apnea, unspecified type
ICD-10-CM (effective 10/01/15)	G47.30-G47.39	Sleep apnea code range
ICD-10-PCS (effective 10/01/15)		ICD-10-PCS codes are only used for inpatient services.
	0CQ20ZZ, 0CQ23ZZ, 0CQ2XZZ	Surgical, mouth & throat, repair, hard palate, code by approach (open, percutaneous, external)
	0CQ30ZZ, 0CQ33ZZ, 0CQ3XZZ	Surgical, mouth & throat, repair, soft palate, code by approach (open, percutaneous, external)
	0CQN0ZZ, 0CQN3ZZ, 0CQNXZZ	Surgical, mouth & throat, repair, uvula, code by approach (open, percutaneous, external)
	0CQM0ZZ, 0CQM3ZZ, CQM4ZZ, 0CQM7ZZ, 0CQM8ZZ	Surgical, mouth & throat, repair, pharynx, code by approach (open, percutaneous, percutaneous endoscopic, via natural or artificial opening, via natural or artificial opening)
	0CR207Z, 0CR20JZ, 0CR20KZ	Surgical, mouth & throat, replacement, hard palate, open, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CR237Z, 0CR23JZ, 0CR23KZ	Surgical, mouth & throat, replacement, hard palate, percutaneous, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CR2X7Z, 0CR2XJZ, 0CR2XKZ	Surgical, mouth & throat, replacement, hard palate, external, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CR307Z, 0CR30JZ, 0CR30KZ	Surgical, mouth & throat, replacement, soft palate, open, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CR337Z, 0CR33JZ, 0CR33KZ	Surgical, mouth & throat, replacement, soft palate, percutaneous, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CR3X7Z, 0CR3XJZ, 0CR3XKZ	Surgical, mouth & throat, replacement, soft palate, external, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CRM07Z, 0CRM0JZ, 0CRM0KZ	Surgical, mouth & throat, replacement, pharynx, open, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CRM7JZ, 0CRM8JZ	Surgical, mouth & throat, replacement, pharynx, synthetic substitute, code by approach (via natural or artificial opening or via natural or artificial opening endoscopic
	0CS20ZZ, 0CS2XZZ	Surgical, mouth & throat, reposition, hard palate, no device, code by approach (open, external)
	0CS30ZZ	Surgical, mouth & throat, reposition, soft palate, open, no device
	0CU207Z, 0CU20JZ, 0CU20KZ	Surgical, mouth & throat, supplement, hard palate, open, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CU237Z, 0CU23JZ, 0CU23KZ	Surgical, mouth & throat, supplement, hard palate, percutaneous, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CU2X7Z, 0CU2XJZ, 0CU2XKZ	Surgical, mouth & throat, supplement, hard palate, external, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CU307Z, 0CU30JZ, 0CU30KZ	Surgical, mouth & throat, supplement, soft palate, open, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CU337Z, 0CU33JZ, 0CU33KZ	Surgical, mouth & throat, supplement, soft palate, percutaneous, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CU3X7Z, 0CU3XJZ, 0CU3XKZ	Surgical, mouth & throat, supplement, soft palate, external, code by device (autologous tissue substitute, synthetic substitute, nonautologous tissue substitute)
	0CUM0JZ, 0CUM7JZ, 0CUM8JZ	Surgical, mouth & throat, supplement, pharynx, synthetic substitute, code by approach (open, via natural or artificial opening or via natural or artificial opening endoscopic
	09QN0ZZ	Medical & surgical ear, nose, sinus, repair nasopharynx open
	09QN3ZZ, 09QN4ZZ, 09QN7ZZ, 09QN8ZZ	Surgical, ear, nose & sinus, repair, nasopharynx, code by approach (percutaneous, percutaneous endoscopic, via natural or artificial opening, via natural or artificial opening endoscopic)
	09RN0JZ	Surgical, ear, nose & sinus, replacement nasopharynx, open, autologous tissue substitute
	09RN7JZ, 09RN8JZ	Surgical, ear, nose & sinus, replacement nasopharynx, synthetic substitute, code by approach (via natural or artificial opening, via natural or artificial opening endoscopic)
	09UN0JZ, 09UN7JZ, 09UN8JZ	Medical & surgical ear, nose, sinus, supplement nasopharynx, synthetic substitute, code by approach (open, via natural or artificial opening, via natural or artificial opening endoscopic)
Type of Service	Surgery
Place of Service	Inpatient

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

History From 2014 Forward

07/07/2022	Annual review, no change to policy. Updating rationale and references
11/23/2021	Updating policy with 2022 coding. Adding codes 42975, 64582, 64583 and 64584. Codes 0466T, 0467T and 0468Twill be DELETED on 01/01/2022. No other change made.
07/08/2021	Annual review, no change to policy intent. Updating bacground, regulatory status, rationale and references.
07/24/2020	Annual review, updating criteria for hypoglossal nerve stimulation in adults to an AHI> 15, policy otherwise unchanged. Updating rationale and references
07/01/2019	Annual review, no change to policy intent. All needed updating was performed during the interim review done in March 2019.
03/18/2019	Interim review, updating policy to allow some medical necessity criteria for hypoglossal nerve stimulation which was previously considered investigational for all indications. Also updating description, background, rationale, references and regulatory status.
07/17/2018	Annual review, no change to policy intent. Updating rationale and references..
07/13/2017	Annual review, no change to policy intent. Policy verbiage updated in the medically necessary statement to include the variants of palatopharyngoplasty. Also updating background, description, rationale, references and coding.
09/27/2016	Updated the word guideline to policy when applicable. No change to policy intent.
07/01/2016	Annual review, no change in policy intent.
07/27/2015	Annual review, no change to policy intent. Updated background, description, regulatory status, rationale and references. Added coding.
10/07/2014	Updated investigational verbiage related to hypoglossal stimulators. Intent unchanged. New verbiage: Hypoglossal nerve nerurostimulation (e.g, the Apnex Hypoglossal Nerve Stimulation (HGNS™) system, the auro6000™ Neutostimulation System, ImThera's Targeted Hypoglossal Neurostimulation Therapy, and Inspire® II System for Upper Airway Stimulation (UAS Therapy) investigational for the treatment of all indications, including but, not limited to the treatment of OSA.
07/21/2014	Annual review. Updated policy verbiage to include "Implantable hypoglossal nerve stimulators are considered investigational for all indications, including but not limited to the treatment of OSA.". Also updated regulatory status, rationale and references. Added related policies.
06/25/2014	Annual Review. No changes made.

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