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Volume 11 No. 05
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Scientific Investigations

A Cost-Effectiveness Analysis of Surgery for Middle-Aged Men with Severe Obstructive Sleep Apnea Intolerant of CPAP

Kelvin B. Tan, PhD1,2; Song Tar Toh, MBBS, MMED(ORL), FAMS(ORL)3; Christian Guilleminault, MD, DBiol4; Jon-Erik C. Holty, MD, MS2,5
1Stanford University, Management Science and Engineering Department, Stanford, CA; 2Center for Primary Care and Outcomes Research, Stanford University, Stanford, CA; 3Singapore General Hospital, Singapore; 4Division of Sleep Medicine, Stanford University School of Medicine, Stanford, CA; 5Pulmonary, Critical Care and Sleep Section, VA Palo Alto Healthcare System, Palo Alto, CA

ABSTRACT

Study Objectives:

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Conventional OSA therapy necessitates indefinite continuous positive airway pressure (CPAP). Although CPAP is an effective treatment modality, up to 50% of OSA patients are intolerant of CPAP. We explore whether surgical modalities developed for those intolerant of CPAP are cost-effective.

Methods:

We construct a lifetime semi-Markov model of OSA that accounts for observed increased risks of stroke, cardiovascular disease, and motor vehicle collisions for a 50-year-old male with untreated severe OSA. Using this model, we compare the cost-effectiveness of (1) no treatment, (2) CPAP only, and (3) CPAP followed by surgery (either palatopharyngeal reconstructive surgery [PPRS] or multilevel surgery [MLS]) for those intolerant to CPAP.

Results:

Compared with the CPAP only strategy, CPAP followed by PPRS (CPAP-PPRS) adds 0.265 quality adjusted life years (QALYs) for an increase of $2,767 (discounted 2010 dollars) and is highly cost effective with an incremental cost-effectiveness ratio (ICER) of $10,421/QALY for a 50-year-old male with severe OSA. Compared to a CPAP-PPRS strategy, the CPAP-MLS strategy adds 0.07 QALYs at an increase of $6,213 for an ICER of $84,199/QALY. The CPAP-PPRS strategy appears cost-effective over a wide range of parameter estimates.

Conclusions:

Palatopharyngeal reconstructive surgery appears cost-effective in middle-aged men with severe OSA intolerant of CPAP. Further research is warranted to better define surgical candidacy as well as short-term and long-term surgical outcomes.

Commentary:

A commentary on this article appears in this issue on page 509.

Citation:

Tan KB, Toh ST, Guilleminault C, Holty JE. A cost-effectiveness analysis of surgery for middle-aged men with severe obstructive sleep apnea intolerant of CPAP. J Clin Sleep Med 2015;11(5):525–535.


Obstructive sleep apnea (OSA) is a prevalent condition characterized by repetitive pharyngeal collapse during sleep resulting in apneas, oxygen desaturations, sympathetic surges, and electroencephalographic (EEG) arousals.1 Approximately 10% to 25% of US adults have OSA (defined as an apnea-hypopnea index [AHI] ≥ 5/h), with up to 10% of all adults having moderate to severe disease (AHI ≥ 15/h).2,3 Untreated OSA is associated with increased cardiovascular and cerebrovascular morbidity, increased excessive daytime sleepiness, poorer neurocognitive function and work performance, increased motor vehicular accidents, increased health-care expenditures, and reduced quality of life.410 The 15-year mortality for adults with severe untreated disease is increased by 30% with adjusted mortality hazards ratios of 1.4, 1.7, and 3.8 for mild, moderate, and severe disease, respectively (p-trend = 0.004).11

BRIEF SUMMARY

Current Knowledge/Study Rationale: Indications for the surgical modification of the upper airway to treat OSA are controversial given modest and inconsistent post-surgical results. We evaluate the tradeoff between imperfect surgical success versus no therapy in patients intolerant of CPAP with severe OSA utilizing a cost-effectiveness model.

Study Impact: Palatopharyngeal reconstructive surgery appears cost-effective (compared to no therapy) in middle-aged men with severe OSA intolerant of CPAP (ICER $10,421/QALY), with our model utilizing a 16% PPRS cure rate, 52% success rate, 2.5% surgical complication rate, 0.2% surgical mortality rate, and an 11% annual decay rate for surgical success and/or cure.

Conventional OSA treatment necessitates indefinite positive airway pressure (e.g., continuous positive airway pressure [CPAP] or bilevel therapy) that works by pneumatically stenting open the airway during sleep.12 CPAP is an effective treatment modality that lowers the AHI, improves symptoms, reduces observed cardiovascular mortality, and potentially lessens healthcare utilization for adherent patients,1317 with prior studies demonstrating its cost-effectiveness for the treatment of severe OSA.1820 Unfortunately, between 30% and 50% of patients with OSA are intolerant of and ultimately reject CPAP therapy.2126 Surgical procedures such as palatopharyngoplasty reconstructive surgery (PPRS), including uvulopalatopharyngoplasty (UPPP) and its various modifications, with emphasis on reconstruction of the palatal isthmus and uvula-sparing surgery rather than ablative surgeries, are currently available to treat OSA in those intolerant to CPAP.27,28 However, current PPRS indications for OSA remain controversial,29,30 given the relatively low reported postoperative surgical success (< 60%) and cure rates (< 25%),31,32 and the inability to consistently predict preoperatively poor or negative surgical results. Nevertheless, limited low quality evidence suggests PPRS treated OSA subjects may have reduced mortality compared with untreated historical controls, suggesting PPRS may have benefit in treating CPAP intolerant patients.33 Despite such results, the cost-effectiveness of PPRS is uncertain, because of its high costs, modest postoperative morbidity, and imperfect success rates (around 50%).30,32,34 To improve success rates, PPRS is often combined with other pharyngeal surgeries (e.g. genioglossal advancement, hyoid suspension, tongue base reduction, septoplasty, and/or turbinectomy) at other sites.3538 Such multilevel or multimodality surgery (MLS) modestly improves reported surgical success,31 albeit at higher upfront costs. Thus to account for relative costs and outcomes, we evaluate the cost effectiveness of the PPRS and MLS for the treatment of middle-aged men intolerant of CPAP with severe OSA.

METHODS

Overview

We developed a semi-Markov model to assess health outcomes and costs and calculate the cost-effectiveness of the various OSA treatment strategies over a patient's lifetime with a yearly transition cycle using Treeage Pro 2009 (TreeAge Software, Inc., Williamstown MA). Reflecting current clinical practice guidelines,29 all treatment strategies in our model involve CPAP as a first-line treatment, followed by surgery for those intolerant of CPAP. The assessed treatment strategies include (1) no therapy, (2) CPAP only, (3) CPAP followed by PPRS for those non-adherent to CPAP (CPAP-PPRS), and (D) CPAP followed by MLS for those non-adherent to CPAP (CPAP-MLS). The model structure is shown in Figure S1 (supplemental material), with model parameters shown in Table 1 and Table S1 (supplemental material). This cost-effectiveness study assessed only existing publicly available data; thus it is is not considered human subjects research and does not require IRB approval.

Treatment parameters.

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Table 1

Treatment parameters.

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We model the incidence of coronary heart disease (CHD), stroke, and motor vehicle collision (MVC), with baseline rates of CHD and stroke (fatal or nonfatal) taken from the Framingham Heart Study39 and MVC rates obtained from the National Highway Traffic Safety Administration.40 Mortality due to other causes was calculated by deducting CHD, Stroke and MVC mortality from all-cause mortality estimates taken from the 2006 US Life tables.41

Stroke events could be either moderate or severe. Subjects with moderate stroke who suffer a subsequent stroke progress to severe stroke; while those with severe stroke die from a subsequent stroke. Those with severe stroke are unable to operate a motor vehicle and are at no further risk of MVC. Following stroke and CHD, mortality risks are increased by factor of 3.2 and 2.3, respectively.42,43 MVCs result either in property damage only or 5 degrees of injury stratified by the maximum abbreviated injury scale (MAIS) levels.44

Patient Population

The analysis was for a male cohort 50 years of age with severe OSA (AHI ≥ 30/h) who are candidates for and accepting of OSA surgery. Severity of sleep apnea was defined as mild (AHI 5 to 14.9/h), moderate (AHI 15 to 29.9/h), and severe (AHI ≥ 30/h).11

Untreated OSA Morbidity and Mortality

Several large-scale population studies report increased cardiovascular and cerebrovascular events for those with untreated OSA (Table S2, supplemental material).11,4549 In the baseline analysis, we use the risk adjusted estimates from Young et al. for mild (RR = 1.3) or moderate OSA (RR = 1.5),11 and estimates from Marin et al. for severe OSA (RR = 2.9).47 This strategy provides a conservative estimate of cardiovascular and cerebrovascular risk for untreated OSA. We performed sensitivity analysis using the range of risk estimates reported from these studies. Risk ratios for MVC were obtained from Young et al.,50 and closely match those derived by Ayas et al.,51 in a meta-analysis of 8 studies.

CPAP Treatment

CPAP adherence was defined as fully adherent (≥ 6 h use per night), partially adherent (4 to 6 h use per night), and non-adherent (< 4 h use per night). We conservatively modeled fully adherent CPAP users to have their CHD, stroke, and MVC risk ratios reduced to mild untreated OSA levels. Partially adherent users experience a pro-rated reduction based on average hours of use. There is no risk reduction for those non-adherent based on the Medicare policy of not reimbursing for CPAP (and presumed cessation of CPAP therapy) for those with < 4 h of use per night.52 Short-term (< 6 months) and long-term (> 2 years) adherence rates were obtained from a literature review of recent observational studies of CPAP treatment (Table 1 and Table S3, supplemental material).21,22,26,5363 Decay rates of CPAP adherence are derived by comparing long-term and short-term adherence rates reported in these studies.

Surgical Treatment

Surgical outcomes are classified as cure (AHI < 5/h), success without cure (5/h ≤ AHI < 20/h and ≥ 50% reduction in AHI), and failure (AHI ≥ 20/h or < 50% reduction). Similar to full CPAP adherence, surgical cure was modeled to reduce the risks down to mild untreated OSA levels, while surgical success was modeled to reduce the risks to moderate untreated OSA levels. Surgical cure and success rates were obtained from published meta-analyses of OSA surgery (Table 1).3032,34 OSA surgery studies included in these meta-analyses primarily enrolled subjects (mean age ∼45 years) with severe OSA (mean AHI ∼40/h) intolerant of CPAP.34 As no pooled surgical cure rates (only success rates) were reported for MLS in prior meta-analyses, we assume the same proportion of cure to success for MLS as reported for PPRS.

Because surgical cure or success is not permanent,6467 we estimate the decay rate from cure to partial success, and partial success to failure from studies reporting short-term and long-term surgical outcomes (Figure S2, supplemental material). For PPRS, this constant decay rate was obtained by minimizing weighted least square differences between the actual and predicted cure and success rates at the various long-term milestones.64,66 Due to a lack of studies reporting long-term outcomes for MLS, we use the same decay rates as for PPRS, but vary this assumption in sensitivity analysis.

Costs and Discounting

Our analysis is conducted from the perspective of a third-party payer in the U.S. Only direct costs are considered, and a discount rate of 3% is used. We model the cost of stroke and CHD events, with the initial costs covering hospitalization and inpatient rehabilitation and subsequent costs accounting for ongoing treatment of stroke and CHD survivors.68 MVC costs are provided from the year 2000 report of the National Traffic Safety Administration69 and are stratified by MVC levels. Baseline costs for CPAP and OSA surgery were derived from Medicare reimbursement rates based on national average relative value units for 2010 (Table 1).52,70 All costs (as applicable) were inflated to 2010 using the medical consumer price index.

Health Related Quality of Life Utility Measurements

We obtain health related quality of life (HRQoL) utility scores for patients with stroke and CHD from the literature (Table S1). The impact of MVCs on utility is taken from Blincoe et al.69 Because the derived post-MVC utilities appeared low (particularly if applied across the person's lifetime in relation the post-Stroke and post-CHD utilities for those without permanent disability), we conservatively apply these reduced utilities over a one-year period instead of a lifetime.

CPAP Therapy

The baseline HRQoL utility score for untreated OSA and CPAP therapy were derived from Weatherly and colleagues' meta-analysis of Epworth Sleepiness Scale scores pre- and post-CPAP treatment,20 and their reported conversion of HrQOL scores by regressing ESS scores against SF-36 scores from 3 separate studies (Table 1).

Surgical Therapy

Although improved patient satisfaction is noted post-surgery compared with CPAP treatment in those intolerant of CPAP,71 no study has utilized formal quality of life instruments in this assessment. The utility incremental of surgery over CPAP results from (A) improved symptoms and (B) dispensing with indefinite nightly CPAP use. Several studies have noted a post-surgical reduction in the Epworth Sleepiness Scale (ESS),7277 and the reported improvement in ESS following surgery is similar to ESS changes following CPAP therapy. Although up to 50% of patents after PPRS complain of mild persistent side effects (e.g. nasal regurgitation, voice changes, taste disturbance),78 health-related quality of life measures are better in patients with post-PPRS side effects compared with CPAP users (independent of compliance).71 In our analysis, we assume a similar utility improvement as with CPAP, but add an additional small utility increment of 0.02 to account for the avoided hassle of nightly CPAP use (Table 1).

Given there is no published data on the temporary HRQoL utility decrement for PPRS or MLS during hospitalization and recovery, we use a temporary utility toll of −0.10 applied over 3 weeks post PPRS or MLS to capture the disutility during the hospitalization and recovery phase (Table 1). This −0.10 temporary utility toll estimate is derived from a quality of life study using the SF-36 to assess the acute effect of orthognathic surgery for malocclusion.79,80

Analyses

We calculate the expected costs, life expectancy, and QALYs of each treatment option, then derive the incremental cost-effectiveness ratio (ICER) to assess the cost-effectiveness of each treatment strategy. For example, the ICER between the “CPAP-only” compared with “CPAP followed by PPRS in those intolerant of CPAP” is the difference in costs between the two treatment strategies divided by the difference in QALYs. An ICER below $50,000 to $100,000 is generally considered cost-effective.8183 Univariate sensitivity analyses were performed varying key parameters by 50%, and uncertain ones such as surgical decay rates by larger ranges (ranges reported in Tables 1, 2, and S1). To compare CPAP-PPRS and CPAP-MLS strategies, we performed threshold and two-way sensitivity analyses on the cure, success, and decay rates of PPRS vis-à-vis MLS. To quantify the value of further research in resolving parameter uncertainties (± 50%), we calculate the expected value of perfect information (EVPI).84 We also performed a probabilistic sensitivity analysis (PSA) taking 1,000 random draws and varying input parameters over a triangular distribution between their lower and upper bounds. Risk ratios, however, are varied over a log-normal distribution based on their reported standard deviations.

Incremental cost-effectiveness ratios over different treatment strategies for severe OSA.

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Table 2

Incremental cost-effectiveness ratios over different treatment strategies for severe OSA.

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RESULTS

Mortality for Untreated OSA

Our model predicts a 12% mortality rate at 10 years and a 41% rate at 20 years for a 50-year-old male with untreated severe OSA (Figure S4, supplemental material). Compared with prior longitudinal population studies of untreated OSA, our model under-predicts untreated severe OSA associated mortality (Figure S4).

Analysis of Treatment Strategies

The effects of each OSA treatment strategy are presented in Table 2, Figure 2, and Table S4 (supplemental material). For a 50-year-old man with severe OSA, providing lifelong CPAP therapy compared with no-treatment (assuming a 67% ≥ 4 h/ night adherence rate) results in an incremental improvement in life-years by 0.69 years (0.98 QALYs) at an additional cost of $3,814. A CPAP-PPRS treatment strategy adds an incremental 0.25 life-years (0.27 QALYs) at an additional cost of $2,767 compared to the CPAP only treatment strategy. The CPAPMLS strategy adds a further 0.03 life-years (0.07 QALYs) at an additional cost of $6,213 compared to the CPAP-PPRS strategy. CPAP therapy is highly cost-effective with an ICER of $3,901/QALY compared with no therapy (Figure 1, Table 2). The CPAP-PPRS treatment strategy is also cost-effective at $10,421/QALY. A CPAP-MLS treatment strategy has a higher ICER of $84,199/QALY compared to the CPAP-PPRS strategy.

Incremental cost effectiveness ratios for each treatment strategy are shown for severe OSA in a 50-year-old man.

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Figure 1

Incremental cost effectiveness ratios for each treatment strategy are shown for severe OSA in a 50-year-old man.

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Sensitivity Analysis

One-Way Sensitivity Analyses

The cost-effectiveness of the CPAP-PPRS strategy is robust in one-way sensitivity analyses with all ICERs below the $50,000/ QALY threshold (Table 2, Figure 2, and Table S4). The CPAPMLS strategy is cost-effective at the $100,000/QALY threshold in 2 of 6 key one-way sensitivity analyses (Figure 2). The cost-effectiveness of the CPAP-MLS strategy appears most sensitive to estimate changes in the short-term surgical success/cure rates and their decay over time, as well as upfront surgical costs.

Tornado diagrams for CPAP-PPRS (A) and CPAP-MLS (B) treatment strategies.

These diagrams plot the incremental cost effectiveness ratios (ICER) of the respective treatment strategies versus the CPAP only strategy (or CPAP-PPRS strategy) varying the specified parameter by ± 50%. Each plot is ordered by the highest ICER based on the high estimate.

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Figure 2

Tornado diagrams for CPAP-PPRS (A) and CPAP-MLS (B) treatment strategies. These diagrams plot the incremental cost effectiveness ratios (ICER) of the respective treatment strategies versus the CPAP only strategy (or CPAP-PPRS strategy) varying the specified parameter by ± 50%. Each plot is ordered by the highest ICER based on the high...

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Threshold Analyses

For CPAP-MLS to be cost-effective vis-à-vis CPAP-PPRS at a $50,000/QALY willingness-to-pay threshold, the MLS decay rate would have to be ≤ 9.2% compared to the baseline rate of 11.3%, or the MLS cure rate would have to be > 34.3% compared to the baseline cure rate of 20%. If the ratio of cure to success rates is kept similar for both MLS and PPRS, surgical success rates would need to be ≥ 75.6% (instead of 66%) for MLS to be cost-effective at the $50,000/QALY threshold. Alternatively, MLS is cost-effective if costs are reduced by > 25% or if successful MLS provides an additional 0.025 QALY improvement over PPRS.

Two-Way Sensitivity Analyses

Figures 3A–3C present cost-effectiveness at different cure/ success and decay rates for PPRS and MLS. At a $50,000/ QALY threshold, PPRS dominates MLS over a wide range of short-term surgical success and cure rates (Figures 3A, 3C). However, the cost-effectiveness of MLS appears more sensitive to varying decay rates for surgical success and cure and dominates PPRS when the decay rate for MLS is ≤ 0.1 at a fixed PPRS decay rate of 0.11 (Figure 3B). Alternatively, MLS dominates PPRS if surgical costs are < $20,000 (at a fixed PPRS cost of $11,000; Figure 3D).

Two-way sensitivity analyses examining the optimal treatment strategy for a 50-year-old man with severe OSA.

Each shaded area represents the range of values that the treatment option is most cost effective at a $50,000/QALY willingness-to-pay threshold. (A) Two-way sensitivity analysis of the decay rate for PPRS cure and success rates vis-à-vis that for MLS. (B) Two-way sensitivity analysis of initial cure rate for PPRS vis-à-vis that for MLS. (C) Two-way sensitivity analysis of success rates for PPRS vis-à-vis that for MLS assuming baseline ratios of success to cure rates. (D) Two-way sensitivity analysis of costs for PPRS and MLS.

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Figure 3

Two-way sensitivity analyses examining the optimal treatment strategy for a 50-year-old man with severe OSA. Each shaded area represents the range of values that the treatment option is most cost effective at a $50,000/QALY willingness-to-pay threshold. (A) Two-way sensitivity analysis of the decay rate for PPRS cure and success rates vis-à-vis...

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Time-Horizon Analyses

At a $50,000/QALY threshold the CPAP-PPRS strategy is cost-effective at a 10-year (instead of life-time horizon; ICER $26,263) but not at a 5-year time horizon (ICER $71,808). At a $100,000/QALY threshold the CPAP-MLS strategy is not cost-effective at either a 10-year (ICER $144,085) nor 15-year (ICER $113,732) time horizon.

Expected Value of Perfect Information

The most sensitive surgical parameters in threshold (Table 2) and the two-way (Figures 3A–3C) sensitivity analyses are the MLS decay rates and MLS short-term surgical cure rates. The EVPI of resolving the uncertainty in the MLS short term cure/success and long-term decay rates is $449 and $297 per individual respectively (Table S5, supplemental material).

Probabilistic Sensitivity Analysis

The cost-effectiveness acceptability curve (Figure 4) shows that at a $50,000/QALY ICER level, CPAP-PPRS is the best strategy in 63% of simulations, while CPAP-MLS is best in 25% of simulations. At a $100,000/QALY ICER threshold, the CPAP-PPRS strategy is the best strategy in 49% of simulations, while the CPAP-MLS is best in 43% of simulations.

Cost-effectiveness acceptability curve of four alternative treatment strategies for a 50-year-old man with severe OSA.

The graph plots the probability that a particular treatment is the most cost-effective strategy at different willingness to pay thresholds. Willingness to pay is defined as the amount that a third-party accepts to pay in order to obtain one year of health.

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Figure 4

Cost-effectiveness acceptability curve of four alternative treatment strategies for a 50-year-old man with severe OSA. The graph plots the probability that a particular treatment is the most cost-effective strategy at different willingness to pay thresholds. Willingness to pay is defined as the amount that a third-party accepts to pay in order...

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DISCUSSION

Our cost-effectiveness model contributes several key findings to the literature. First, despite high non-adherence rates, we corroborate previous studies that CPAP therapy is highly cost-effective for patients with severe OSA. CPAP is cost-effective due to a modest increase in quality adjusted life years (0.69 years, 0.98 QALYs), albeit with additional costs (∼$3,800 over a lifetime) and is consistent with reported long-term healthcare utilization rates and costs after the initiation of CPAP.17 Second, we show that surgery for CPAP-intolerant patients is highly cost-effective compared to a CPAP-only strategy. The ICER of $10,421/QALY for the CPAP-PPRS strategy suggests that it is comparable in cost-effectiveness to other commonly accepted medical interventions such as primary angioplasty (vs. medical management) for reperfusion after myocardial infarction (ICER $12,000/QALY).85 We obtained this result despite using a model that under-predicts the mortality rate for untreated severe OSA, as compared with the mortality rates observed from several longitudinal population studies (Figure S4).11,48,49 Furthermore, our model may under-predict the survival advantage of PPRS—for example, our predicted survival advantage of 0.25 years (equivalent to a mortality reduction of 1.5%) for the CPAP-PPRS over the CPAP-only strategy is smaller than the reported survival advantage of UPPP by Weaver et al.86

Indications for PPRS including UPPP for the treatment of OSA have divided sleep medicine specialists and sleep surgeons. Recently, the American Academy of Sleep Medicine changed their practice parameter guidelines for OSA surgery and recommended against, “the use of UPPP as a single surgical procedure to treat moderate to severe OSA” because of inconsistent reported results (overall AHI reduction 33%; 95% CI 23% to 42%) associated with modest postoperative morbidity (2% risk of life-threatening events) and mortality (0.2% risk of death), and because many patients had significant residual OSA post-surgery (mean AHI 29.8/h).29,34 However, despite these modest and inconsistent post-surgical results, PPRS appears cost effective (compared to no therapy) in patients with severe OSA intolerant of CPAP (ICER $10,421/QALY) utilizing a 16% PPRS cure rate, 52% success rate, 2.5% serious surgical complication rate, 0.2% surgical mortality rate, and an 11% annual decay rate of surgical success and/or cure.

Soon after the introduction of UPPP by Fujita et al.,27 Silvestri and colleagues in 1982 questioned the efficacy of UPPP and argued, “removal of anatomical factors may not eliminate central nervous system dysfunction. One problem at this time is the failure, despite thorough examination, to predict poor or negative results.”87 Given these concerns as well as suspicions that uvulectomy may contribute to morbidity (e.g., swallowing/ nasal regurgitation or voice changes) and scarring of the upper airway with subsequent upper palate retraction with worsening airway obstruction over time, surgical modifications of the upper airway have evolved and now generally involve a modified UPPP with uvula preservation.28,88 These uvula sparing procedures may decrease inconsistent results and improve overall surgical success. Recently, a randomized trial of 65 consecutive patients with moderate to severe OSA treated with uvula-sparing UPPP (preservation of the palatopharyngeal muscles) reported a 60% short-term (6-month) reduction in AHI compared to 11% in the control group (p < 0.001) with no reported serious complications nor mortality and an overall surgical success rate of 59%.89 This AHI reduction was independent of BMI, tonsil size, or Friedman stage. This same group in a longitudinal study of UPPP with uvula preservation reported a 65% surgical success rate that was stable over a 15-year follow-up.90 Thus the benefits of PPRS using uvula sparing pharyngoplasty as a single surgical procedure may be warranted with benefits that are likely greater than that predicted by our cost-effectiveness model.

Finally, although we report the CPAP-MLS strategy is less cost-effective than the CPAP-PPRS strategy, it is still cost effective at the $100,000/QALY ICER threshold. While current recommendations are to adopt treatments under the $50,000/ QALY threshold, some have suggested that this threshold be raised to $100,000/QALY.8183 Furthermore, individual patients may have relatively higher or lower success with PPRS vis-àvis MLS (compared with population averages) based on the anatomical structure(s) of obstruction causing OSA—for example, a large study comparing PPRS to MLS reported significantly higher MLS success based on Friedman classification (stage II or III vs stage I).91 MLS appears cost effective (at the $50,000/QALY threshold) if the cure rate is greater than 32% (compared with a 16% PPRS cure rate, Figure 3A) or if the success rate is greater than 76% (compared with a 52% PPRS success rate, Figure 3C). Two recent MLS studies combining UPPP with tongue surgery reported surgical success rates of 76% and 78%.92,93 Although other OSA surgeries such as maxillomandibular advancement (MMA) appear more efficacious than either PPRS or MLS, albeit with substantially higher costs, the cost-effectiveness of MMA was beyond the scope of the current analysis.

The main limitations of our study stem from incomplete short-term and long-term clinical data on the effects of surgical treatment for OSA. Due to these limitations, our model makes three key assumptions. First, we assume untreated severe OSA is associated with increased risk for CHD, stroke, MVA, and overall death. This assumption seems reasonable given multiple longitudinal population studies have reported untreated severe OSA is an independent risk factor for CHD, stroke, MVA, and overall death.11,45,46,48,49

Second, we assume that CPAP adherence reduces this risk (e.g., CHD, stroke, MVA) to that observed for mild untreated OSA. To date, there is only one long-term randomized trial evaluating the effects of OSA therapy on subsequent cardiovascular or cerebrovascular events in the general population. This recent randomized controlled trial reported a non-statistically significant trend favoring CPAP (HR 0.81, p = 0.13).15 However, 36% of patients randomized to CPAP were non-adherent. In post hoc analysis, CPAP adherence (≥ 4 h per night) was associated with a significant reduction in incident hypertension or cardiovascular events (HR 0.69, p = 0.02). Our model conservatively assumes that subjects with severe OSA who are fully CPAP adherent have their risk for CHD, stroke, and MVC reduced to that observed for those with mild untreated OSA. This assumption seems reasonable given six of eight observational studies16,94100 report statistically significant reductions in overall mortality (pooled relative risk reduction of 0.460; 95% CI 0.368 to 0.575), and four of six studies47,94,9698,101 report statistically significant reductions in cardiovascular mortality (pooled relative risk reduction of 0.294; 95% CI 0.198 to 0.438) associated with CPAP therapy (or CPAP adherence) compared with no CPAP therapy (or CPAP non-adherence) in OSA patients. Furthermore, nine observational studies have performed multivariate analyses assessing the effects of CPAP on mortality in general OSA populations—seven of these report statistically significant reductions in mortality (overall or cardiovascular) associated with CPAP treatment (or adherence).16,47,94,97,98,101,102 Additionally, a meta-analysis of nasal CPAP treatment of OSA on driving stimulator performance and real road accidents reported a statistically significant protective effect of CPAP on road traffic accidents,103 and observational data suggest a reduced rate of MVA after the initiation of CPAP.104,105

Finally, our model assumes that subjects with severe OSA who gain surgical cure have their risk for CHD, stroke, and MVC reduced to that observed for those with mild untreated OSA and subjects with surgical success (without cure) have their risk reduced to that observed for those with moderate untreated OSA. These assumptions seem reasonable given three retrospective single-center studies comparing CPAP versus PPRS-treated OSA populations reported no statistically significant difference in unadjusted mortality (pooled mortality 4.6% for UPPP and 2.9% for CPAP, p = 0.327).98,100,106 Additionally, Browaldh and colleagues report that the 18-year standardized mortality rate following PPRS is not statistically different from the general population.90 We limited our analyses to 50-year-old men, given the majority of published surgical studies enrolled mostly middle-aged men with severe OSA and thus are conclusions may not be generalizable to women or younger populations.

Despite these assumptions, we have proceeded by (1) using what we know; (2) making reasonable assumptions where possible; and (3) incorporating uncertainty into model parameters where there is a lack of information. Sensitivity analyses confirm that despite these assumptions, our results evaluating the CPAP-PPRS strategy are robust. For example, probabilistic sensitivity analyses demonstrate that at a $50,000/QALY threshold, surgery for intolerant CPAP users (CPAP-PPRS or CPAP-MLS) is preferred over a CPAP only or no treatment strategy, in 89% of simulations incorporating parameter uncertainty.

Not only is our model useful in identifying optimal treatment strategies, but also in recommending areas of future clinical research that are most valuable. EVPI calculations indicate that resolving uncertainty for the risk ratios for untreated severe OSA, short-term MLS success/cure and decay rates (i.e., long-term cure and success rates) of MLS are most valuable (Table S5). For example, at a $50,000/QALY threshold and a conservative estimated prevalence of 256,000 U.S. men age 40 to 60 years with severe OSA intolerant of CPAP and who are candidates for surgery (32 million male adults aged 40 to 60 years * 5% with severe OSA * 32% intolerant of CPAP * 50% surgical candidates), the value of further research for resolving uncertainty in the short-term MLS surgical cure and success rates is $74 million ($291/individual * 256,000). Conducting a large-scale trial that eliminated the current uncertainty in this estimate by 50% would be cost-effective if the expense of performing this study was below $37 million, a reasonable goal. The value for resolving uncertainty for long-term MLS decay rates is even higher. Thus, we advocate the need for funding further clinical research of OSA surgery to address these uncertainties. Furthermore, improved methods of selecting patients for MLS vis-à-vis PPRS by providing more precise estimates of the expected relative long-term individual success and cure rates will also reduce uncertainty over these parameters and are thus highly valuable.29

CONCLUSION

In summary, despite high upfront costs and imperfect cure rates, PPRS appear cost-effective for patients with severe OSA intolerant of CPAP. Given uncertainty regarding several key estimates of OSA surgical outcomes, performing additional studies to reduce this uncertainty, particularly regarding the short-term and long-term surgical success and cure rates appears highly cost-effective

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.

ABBREVIATIONS

AHI

apnea-hypopnea index

BMI

body mass index

CHD

coronary heart disease

CPAP

continuous positive airway pressure

ICER

incremental cost-effectiveness ratio

MLS

multilevel surgery

MMA

maxillomandibular advancement

MVC

motor vehicle collision

OSA

obstructive sleep apnea

PPRS

palatopharyngeal reconstructive surgery

QALYs

quality adjusted life years

UPPP

uvulopalatopharyngoplasty

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SUPPLEMENTAL MATERIAL

Baseline model parameters.

jcsm.11.5.525.t0S1.jpg

table icon
Table S1

Baseline model parameters.

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The cost-effectiveness decision model.

Schematic illustration of semi-Markov model used in analysis. Cloned trees are represented by square parentheses. A square node represents a decision to treat OSA with either no therapy, CPAP only, CPAP followed by PPRS in those intolerant (CPAP-PPRS) or CPAP followed by MLS in those intolerant (CPAPMLS). All patients are at risk for complications due to OSA or treatment. Probabilities for OSA complications (i.e. stroke, CHD, MVC) depend on the treatment strategy and how effective that strategy is at improving OSA. Patients undergoing surgery could develop fatal or non-fatal surgical complications. The end of each pathway in the decision tree represents the sum of both the health-effects and costs for all associated consequences in that particular pathway.

jcsm.11.5.525s1.jpg

jcsm.11.5.525s1.jpg
Figure S1

The cost-effectiveness decision model. Schematic illustration of semi-Markov model used in analysis. Cloned trees are represented by square parentheses. A square node represents a decision to treat OSA with either no therapy, CPAP only, CPAP followed by PPRS in those intolerant (CPAP-PPRS) or CPAP followed by MLS in those intolerant (CPAPMLS)....

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Untreated OSA risk ratios for stroke, CHD, MVC.

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Table S2

Untreated OSA risk ratios for stroke, CHD, MVC.

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Reported CPAP adherence rates.

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Table S3

Reported CPAP adherence rates.

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Costs, life expectancy and quality-adjusted life-years of treatment strategies for severe OSA.

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Table S4

Costs, life expectancy and quality-adjusted life-years of treatment strategies for severe OSA.

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Annual decay rate for surgical cure (A) and success (B) derived from three studies reporting both short-term (6-months) and long-term sleep study results (54 to 87 months) post PPRS.6467

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Figure S2

Annual decay rate for surgical cure (A) and success (B) derived from three studies reporting both short-term (6-months) and long-term sleep study results (54 to 87 months) post PPRS.64–67

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Expected value of perfect information (EVPI) in resolving uncertainty of key parameters.

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Table S5

Expected value of perfect information (EVPI) in resolving uncertainty of key parameters.

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Proportion of patients with surgical success over time for MLS and PPRS using baseline annual decay rate of 11.3% and an initial success rate of 51.5% for MLS and 66% for PPRS.

This model estimates that by 10-years post surgery, only 30% of those receiving MLS and 24% of those receiving PPRS will still be considered to have surgical success.

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Figure S3

Proportion of patients with surgical success over time for MLS and PPRS using baseline annual decay rate of 11.3% and an initial success rate of 51.5% for MLS and 66% for PPRS. This model estimates that by 10-years post surgery, only 30% of those receiving MLS and 24% of those receiving...

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Our model conservatively over-estimates the survival of male patients aged 50 years with untreated severe OSA (Predicted Severe OSA [Model]) compared with the survival reported by several longitudinal OSA population studies (1. Wisconsin Cohort Study – mean age 50 years, 78% male; Young et al., Sleep 2008; 2. Busselton Health Study Cohort – mean age 55 years, 72% male; Marshall et al., J Clin Sleep Med 2014; 3. Marin Cohort Study – mean age 50 years, 100% male; Marin et al., Lancet 2005; 4. Sleep Heart Health Study (SHHS) – mean age 65 years, 71% male; Punjabi et al., PLoS Medicine 2009).

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Figure S4

Our model conservatively over-estimates the survival of male patients aged 50 years with untreated severe OSA (Predicted Severe OSA [Model]) compared with the survival reported by several longitudinal OSA population studies (1. Wisconsin Cohort Study – mean age 50 years, 78% male; Young et al., Sleep 2008; 2. Busselton Health...

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