Introduction
Idiopathic hypersomnia and narcolepsy are rare central disorders of hypersomnolence characterized primarily by excessive daytime sleepiness (EDS); these sleep disorders are similar but distinct.1–4 In addition to EDS, symptoms of idiopathic hypersomnia may include sleep inertia, prolonged, nonrestorative nighttime sleep, and long, unrefreshing naps.1,5 Impairment in daily functioning, moderate to severe cognitive complaints, depressive symptoms, and overall work productivity impairment have also been reported by people with idiopathic hypersomnia.6 Symptoms of narcolepsy, along with EDS, may include disrupted nighttime sleep and rapid eye movement (REM)–associated symptoms (sleep paralysis and hypnagogic or hypnopompic hallucinations).4,7 People with narcolepsy type 1 experience cataplexy and/or have low cerebrospinal fluid hypocretin levels. In people with narcolepsy type 2, cataplexy is absent (by definition), and hypocretin levels are normal.4 As with idiopathic hypersomnia, narcolepsy can have a profound impact on functioning, employment, productivity, and quality of life.8
Previous evidence has shown that people with narcolepsy experience a substantial clinical burden, particularly in terms of cardiovascular conditions.2,9–11 As evidenced by the literature, individuals with narcolepsy experience an array of comorbid conditions, including hypertension, diabetes, and obesity.9,12,13 Two previous analyses, 1) a claims analysis of Truven Health Analytics MarketScan® Research Databases and 2) an analysis of 2011, 2012, and 2013 US National Health and Wellness Survey data, found that individuals with narcolepsy experience higher overall healthcare resource utilization (HCRU) and higher overall medical costs when compared with matched individuals without narcolepsy (ie, controls).8,14
The literature detailing the clinical and economic burden of idiopathic hypersomnia is limited.15–17 Therefore, a real-world evidence study was conducted to provide further insight into this condition. This study aimed to evaluate the overall clinical and economic burden of idiopathic hypersomnia alongside that of narcolepsy because these conditions, though distinct, share many clinical features.4,5,18 The study objective was to separately describe the overall prevalence of comorbid clinical conditions, HCRU, and medical costs of people with idiopathic hypersomnia and people with narcolepsy.
Materials and Methods
Study Population
This retrospective cohort study used Merative™ MarketScan® Research Databases (formerly IBM® MarketScan®) administrative claims data, including de-identified, patient-level medical and drug data, which are nationally representative of US individuals with employer-provided health insurance. Data in the Merative™ MarketScan® Research Databases are contributed by large employers, managed care organizations, hospitals, electronic medical records providers, Medicare, and Medicaid. These databases contain data for more than 273 million unique patients since 1995.19
The study population includes eligible individuals during the study period from December 31, 2013, to February 29, 2020. Cohort entry was restricted to December 31, 2014, to March 1, 2019, to allow for a 2-year assessment period of 365 days before and 365 days after cohort entry.
Each individual’s cohort entry date was the date of that person’s earliest medical claim with a diagnosis code for idiopathic hypersomnia or narcolepsy when all inclusion and exclusion criteria were met. A 2-year assessment period (+/– 365 days on either side of cohort entry) was selected to capture comorbidities and medical history occurring more often than annually.
Eligible individuals were ≥18 years of age on cohort entry and were continuously enrolled for 365 days before and 365 days after cohort entry (ie, 2-year assessment period), with or without enrollment gaps of less than 30 days. The primary idiopathic hypersomnia cohort was defined by an inpatient or outpatient medical claim with a diagnosis for idiopathic hypersomnia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], 327.11, 327.12; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM], G47.11, G47.12) in any position.20,21 Individuals were excluded from the idiopathic hypersomnia cohort if they had a diagnosis code for cataplexy (ICD-9-CM, 347.01, 347.11; ICD-10-CM, G47.411, G47.421) in any position at any time before cohort entry or during the 365 days following their potential cohort entry date.21,22 The narcolepsy cohort was defined by an inpatient or outpatient medical claim with a diagnosis code for narcolepsy (ICD-9-CM, 347.0, 347.00, 347.01, 347.10, 347.11; ICD-10-CM, G47.41, G47.411, G47.419, G47.42, G47.421, G47.429) in any position21,22 (Figure 1).
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Figure 1 Study design. Notes: aCohort entry date was defined as the first date that the case definition for idiopathic hypersomnia or narcolepsy was met.
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Outcomes
Baseline demographic characteristics, comorbid clinical conditions, HCRU, and medical costs were described for both cohorts. Comorbid clinical conditions were defined with single-level and multilevel Clinical Classifications Software (CCS) codes and ICD-9-CM and ICD-10-CM codes. Appendix Table 1 lists the codes used to define demographic characteristics and comorbid clinical conditions. All-cause HCRU outcomes included inpatient admissions (any services from any non–emergency department [non-ED] inpatient services claims), emergency claims (any services from any ED claims), outpatient claims (any services from any non-ED outpatient services claims), and claims stratified by provider type: pulmonologists, neurologists, and psychiatrists. These provider types were chosen because sleep medicine is a subspecialty of neurology and psychiatry, and because a previous analysis found that idiopathic hypersomnia was most often diagnosed by pulmonologists.16 All-cause cost outcomes included total medical costs (sum of inpatient and outpatient costs), outpatient costs (total costs associated with outpatient claims), ED costs (total costs associated with ED claims), and inpatient costs (total costs associated with inpatient claims). All costs were expressed in 2020 constant US dollars and adjusted using the Medical Care components of the Consumer Price Index.
Statistical Analysis
Baseline demographic characteristics were assessed on each individual’s cohort entry date; comorbid conditions, HCRU, and medical cost outcomes were described for the 2-year assessment period. Percentages of individuals with comorbid conditions were reported by 4 categories (Appendix Table 1): 1) multilevel CCS categories, 2) sleep-related, 3) cardiovascular and cardiometabolic, and 4) neuropsychiatric conditions. HCRU outcomes were summarized as percentages of individuals with 1 visit or more, mean and median number of visits, and mean number of visits among individuals with 1 visit or more. HCRU was reported by care setting (outpatient claim, ED claim, inpatient admission) and provider type (pulmonologist, neurologist, psychiatrist). Mean and median total all-cause medical costs and all-cause medical costs stratified by care setting were reported. Categorical variables were summarized as number and percentage, and count and continuous variables were summarized as mean (SD) and median (IQR), as applicable. HCRU and medical cost outcomes were reported per patient per year (PPPY). HCRU and medical costs PPPY were calculated by adding HCRU or medical costs 365 days before and after cohort entry and dividing by 2. All analyses for this study are descriptive in nature; no direct comparisons were made between the idiopathic hypersomnia and narcolepsy cohorts. All statistical analyses were performed and documented within the Aetion Evidence Platform or R version 4.0.3.
Sensitivity Analyses
Two sensitivity analyses were conducted for idiopathic hypersomnia cohort definitions. In the first sensitivity analysis, the case definition for idiopathic hypersomnia was modified to require individuals to have at least 2 claims with a diagnosis code for idiopathic hypersomnia at least 1 day apart. The date of the second claim was the cohort entry date. If individuals had a claim with an idiopathic hypersomnia diagnosis at any time before the sensitivity analysis inclusion criteria were met, they were excluded from this cohort. In the second sensitivity analysis, individuals with idiopathic hypersomnia were required to have 1 claim with a diagnosis code for idiopathic hypersomnia, as in the primary analysis, but were excluded if they had a claim with a diagnosis for idiopathic hypersomnia before their cohort entry date. Aside from the outlined differences in case definitions and exclusion criteria, all other aspects of these sensitivity analyses were the same as in the primary analysis. A third sensitivity analysis of HCRU with idiopathic hypersomnia or narcolepsy in the primary position of the claim, as opposed to all-cause HCRU, was also conducted.
Results
Baseline Demographics
The MarketScan dataset included 119,089,548 individuals; after eligibility criteria were applied, 11,426 individuals were included in the idiopathic hypersomnia cohort and 31,214 individuals in the narcolepsy cohort (Figure 2). Median ages were 45 years (idiopathic hypersomnia cohort) and 43 years (narcolepsy cohort). Approximately 65% of the individuals in each cohort were female (idiopathic hypersomnia, 65.0%; narcolepsy, 64.9%), and approximately three-fourths of individuals in the cohorts were commercially insured (idiopathic hypersomnia, 75.0%; narcolepsy, 70.7%) (Table 1).
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Figure 2 Cohort attrition.
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Table 1 Baseline Demographic Characteristics of Idiopathic Hypersomnia and Narcolepsy Cohorts
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Comorbid Conditions
Over the 2-year assessment period, the mean (SD) number of comorbid conditions across all categories was 15.4 (5.4) for individuals with idiopathic hypersomnia and 14.6 (5.7) for individuals with narcolepsy. The most commonly observed multilevel CCS categories for individuals in both cohorts included symptoms, signs, and ill-defined conditions and factors influencing health status; diseases of the nervous system or sense organs; diseases of the respiratory system; endocrine, nutritional, and metabolic diseases, and immunity disorders; and diseases of the musculoskeletal system and connective tissue (Figure 3). Of note, the category of diseases of the nervous system or sense organs includes narcolepsy but does not include idiopathic hypersomnia.23 These multilevel CCS categories were also the most commonly observed in both cohorts utilizing sensitivity analysis cohort definitions for idiopathic hypersomnia (Appendix Table 2).
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Figure 3 Multilevel CCS comorbid condition categories in individuals with idiopathic hypersomnia or narcolepsy. Notes: aMultilevel CCS (Clinical Classifications Software) categories aggregate International Classification of Diseases, Ninth Revision, Clinical Modification/Procedure Coding System (ICD-9-CM/PCS) codes into clinically meaningful categories. bA range of conditions, including syncope; fever of unknown origin; lymphadenitis; gangrene; shock; nausea and vomiting; abdominal pain; malaise and fatigue; allergic reactions; rehabilitation care, fitting of prostheses, and adjustment of devices; administrative/social admission; medical examination/evaluation; other aftercare; and other screening for suspected conditions (not mental disorders or infectious disease).23 cNarcolepsy meets criteria for “diseases of the nervous system/sense organs”, hence 100% prevalence for this category.
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Sleep apnea was the most prevalent comorbid sleep-related condition for individuals with idiopathic hypersomnia (62.8%) and individuals with narcolepsy (52.1%) (Figure 4A). Hypertension defined as a hypertension diagnosis or use of hypertension medication (idiopathic hypersomnia, 45.7%; narcolepsy, 42.9%), cardiovascular disease (idiopathic hypersomnia, 24.4%; narcolepsy, 24.4%), and major adverse cardiovascular event (idiopathic hypersomnia, 5.7%; narcolepsy, 5.9%) were the most common comorbid cardiovascular conditions in both cohorts; hyperlipidemia (idiopathic hypersomnia, 42.2%; narcolepsy, 38.4%), obesity (idiopathic hypersomnia, 38.1%; narcolepsy, 34.6%), and diabetes (idiopathic hypersomnia, 27.6%; narcolepsy, 26.1%) were the most common comorbid cardiometabolic conditions in both cohorts (Figure 4B). Of the comorbid neuropsychiatric conditions reported, pain was most common for both cohorts (idiopathic hypersomnia, 66.4%; narcolepsy, 66.0%) (Figure 4C). Other common comorbid neuropsychiatric conditions observed for both cohorts were mood (idiopathic hypersomnia, 41.9%; narcolepsy, 43.3%), depressive (idiopathic hypersomnia, 41.7%; narcolepsy, 42.4%), and anxiety (idiopathic hypersomnia, 39.5%; narcolepsy, 40.1%) disorders (Figure 4C). Depressive disorders are a subgroup of the single-level CCS category for mood disorders; therefore, these categories may overlap.23
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Figure 4 Continued.
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Figure 4 Continued.
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Figure 4 Comorbid conditions in individuals with idiopathic hypersomnia or narcolepsy. (A) Comorbid Sleep-Related Conditions. (B) Comorbid Cardiovascular and Cardiometabolic Conditions. (C) Comorbid Neuropsychiatric Conditions. Notes: aHypertension is defined as hypertension diagnosis or antihypertensive use. bDepressive and anxiety disorders are a subgroup of mood disorders; therefore, there may be some overlap in reported odds ratios for depressive disorders.23.
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HCRU
About half of the individuals in both cohorts had ≥1 ED visit (idiopathic hypersomnia, 46.6%; narcolepsy, 51.4%) and just over 10% had ≥1 inpatient visit over the 2-year assessment period (Figure 5A). Individuals in the idiopathic hypersomnia cohort with ≥1 visit had a mean (SD) of 28.2 (40.1) outpatient visits PPPY, and individuals in the narcolepsy cohort with ≥1 visit had a mean (SD) of 27.4 (40.6) outpatient visits PPPY (Figure 5B). The median (IQR) number of outpatient visits was 18.5 (10.5, 31.5) visits PPPY for individuals with idiopathic hypersomnia and 17.0 (9.0, 31.0) visits PPPY for individuals with narcolepsy. The sensitivity analysis assessing claims in the primary position showed that over 50% of individuals with idiopathic hypersomnia or narcolepsy had ≥1 outpatient visits with their condition in the primary position (idiopathic hypersomnia: 58.9%, narcolepsy: 62.7%), and the mean (SD) number of outpatient visits PPPY was 1.0 (3.0) for individuals with idiopathic hypersomnia and 1.6 (5.0) for individuals with narcolepsy (Appendix Table 3).
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Figure 5 All-cause healthcare resource utilization for individuals with idiopathic hypersomnia or narcolepsy by care setting. (A) Percentage of Individuals With 1 Visit or More (B) Mean Number of HCRU Visits Among Individuals With 1 or More Visits PPPY. Abbreviations: ED, emergency department; HCRU, healthcare resource utilization; IP, inpatient; OP, outpatient; PPPY, per patient per year; SD, standard deviation. Notes: aAll-cause outcomes were analyzed using all available claims for eligible individuals. bAll individuals were required (per an inclusion criterion) to have 1 inpatient or outpatient claim or more.
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The most common provider type for individuals within the idiopathic hypersomnia cohort was pulmonologists, with 33.3% of individuals having ≥1 visit with a pulmonologist. For individuals with narcolepsy, the most common provider type was neurologists, with 31.8% of individuals having ≥1 visit with a neurologist (Figure 6A). Individuals in both cohorts with ≥1 visit had more claims for psychiatrists than any other provider type (5.0 visits PPPY for individuals with idiopathic hypersomnia and 4.7 visits PPPY for individuals with narcolepsy) (Figure 6B). For individuals with idiopathic hypersomnia and individuals with narcolepsy, 14.0% of individuals in each cohort had ≥1 visit with a pulmonologist where their condition was in the primary position (Appendix Table 4).
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Figure 6 All-cause healthcare resource utilization for individuals with idiopathic hypersomnia or narcolepsy by provider. (A) Percentage of Individuals With 1 Visit or More (B) Mean Number of HCRU Visits Among Individuals With 1 or More Visits PPPY. Abbreviations: HCRU, healthcare resource utilization; PPPY, per patient per year; SD, standard deviation. Notes: aAll-cause outcomes were analyzed using all available claims for eligible individuals.
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Medical Costs
Individuals with idiopathic hypersomnia incurred mean (SD) total all-cause costs of $11,134 ($22,674) PPPY, mean (SD) all-cause outpatient costs of $7900 ($15,436) PPPY, median (IQR) total all-cause costs of $4856 ($2043, $11,379) PPPY, and median (IQR) all-cause outpatient costs of $4005 ($1790, $8410) PPPY. Individuals with narcolepsy incurred mean (SD) total all-cause costs of $11,591 ($25,956) PPPY, mean all-cause outpatient costs of $7665 ($17,666) PPPY, median (IQR) total all-cause costs of $4518 ($1680, $11,403), and median all-cause outpatient costs of $3484 ($1364, $7978) (Table 2).
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Table 2 Mean and Median All-Cause Medical Costs for Individuals with Idiopathic Hypersomnia or Narcolepsy
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Discussion
Previous studies evaluated the clinical and economic burden experienced by people with narcolepsy;2,8,9 this study aimed to expand on that research to describe clinical and economic burden for people with idiopathic hypersomnia alongside people with narcolepsy. Idiopathic hypersomnia and narcolepsy are distinct sleep disorders; people with idiopathic hypersomnia may experience prolonged sleep, while those with narcolepsy often experience disrupted nighttime sleep.24 Though these 2 sleep disorders are distinct, the results from this study demonstrate that individuals with idiopathic hypersomnia and individuals with narcolepsy experience a broad range of comorbid conditions across organ systems and have high HCRU and medical cost burden. This study found that a large percentage of individuals with idiopathic hypersomnia and narcolepsy have several comorbid sleep-related conditions including sleep apnea (62.8%, 52.1%); comorbid cardiovascular or cardiometabolic conditions including hypertension (45.7%, 42.9%); and neuropsychiatric conditions including pain (66.4%, 66.0%). Further, individuals with idiopathic hypersomnia and individuals with narcolepsy utilized all-cause outpatient services on approximately 25 visits per year and accrued mean all-cause total costs of more than $11,000 PPPY.
The results of this study corroborate previous analyses describing the clinical burden of idiopathic hypersomnia.16,25 A previous analysis of individuals newly diagnosed with idiopathic hypersomnia found a high prevalence of sleep-related comorbid conditions, cardiovascular and cardiometabolic comorbid conditions, and neuropsychiatric conditions when compared with matched controls.16 The Cardiovascular Burden of Individuals Diagnosed with Idiopathic Hypersomnia: Real-World Idiopathic Hypersomnia Total Health Model (CV-RHYTHM) study used the same dataset as the present study and focused on cardiovascular outcomes in individuals with idiopathic hypersomnia and matched non-idiopathic hypersomnia controls. Findings related to burden of cardiovascular conditions were similar between studies.26
Further, the results from this study align with previous research describing the clinical burden experienced by individuals with narcolepsy.9,12,13 The Burden of Narcolepsy Disease (BOND) study assessed the clinical profiles of individuals with narcolepsy in the United States. The BOND study retrospectively analyzed 5 years of US claims from the Truven Health Analytics MarketScan® Research Databases to compare individuals with a narcolepsy diagnosis with controls matched on demographic characteristics, including age, sex, geographic region, and payer. Like the present analysis, BOND used ICD diagnosis codes and single-level and multilevel CCS categories to define comorbid conditions. The mean age of individuals in the present analysis was 44 years of age for the idiopathic hypersomnia cohort and 43 years of age for the narcolepsy cohort; the mean age of patients with narcolepsy in the BOND study was 46 years.9 In both studies, a similar percentage of individuals with narcolepsy experienced comorbid conditions across each multilevel CCS category.9 Hypertension, diabetes, and obesity have been consistently observed in individuals with narcolepsy across several studies, including BOND and the present study.9,12,13 The CV-BOND study expands upon the cardiovascular burden in people with narcolepsy, noting that patients with narcolepsy have an increased risk of developing new-onset cardiovascular conditions.2
While literature describing HCRU and medical costs for individuals with idiopathic hypersomnia is sparse, the results of the present study are consistent with previous research describing HCRU and medical costs for people with narcolepsy.8,14,27 The BOND study, which assessed HCRU and medical costs in individuals diagnosed with narcolepsy in the United States, found that HCRU was significantly higher among these individuals and that their inpatient and outpatient HCRU was double that of matched controls. BOND further demonstrated that individuals with narcolepsy incurred combined medical costs nearly double those of matched non-narcolepsy controls ($8346 vs $4147).8 The present study found that individuals with narcolepsy had even greater all-cause medical costs ($11,591 PPPY), corroborating the high economic burden of narcolepsy. Another study reported that individuals with narcolepsy visited specialists, such as neurologists and psychiatrists, more frequently than matched non-narcolepsy controls.14 The all-cause economic burden experience of the people with narcolepsy in these studies, including in the present study, contextualizes this considerable burden in people with idiopathic hypersomnia.
The economic burden associated with idiopathic hypersomnia and narcolepsy likely extends beyond the direct HCRU and medical costs assessed in this analysis. Previous research shows that people with idiopathic hypersomnia experience high levels of absenteeism, presenteeism, and impaired overall work productivity.6 One study notes that patients with narcolepsy have a higher frequency of missed work days, a greater number of short-term disability days and incidents, and higher costs per employee for short-term disability compared with matched controls;8 another study found that patients with narcolepsy had higher costs associated with absenteeism and presenteeism compared with matched controls. While the results of the present study describe the direct economic burden on individuals with idiopathic hypersomnia or narcolepsy, these results likely underrepresent the overall economic burden of these 2 conditions.
This study demonstrates that individuals with these conditions experience a myriad of comorbid conditions that warrant consideration, and that their HCRU and medical cost burden is substantial. People with either condition have significant sleep instability with inadequate treatment that negatively impacts EDS, disease severity, and quality of life.24,28 By acknowledging this clinical and economic burden, providers may individualize treatments to address either sleep disorder without exacerbating existing comorbid conditions.28
A strength of this study is the use of a nationally representative sample of people with idiopathic hypersomnia or narcolepsy. Further, this study included assessments of an array of comorbid clinical conditions across organ systems. The results of the primary analysis case are corroborated by the results of the sensitivity analyses, which utilized stricter inclusion and exclusion criteria for their respective idiopathic hypersomnia cohorts. To minimize potential confounding of decreased HCRU during the COVID-19 pandemic, the study period ended on February 29, 2020; as it has been noted that overall HCRU decreased by 23% in March 2020 and by 52% in April 2020 relative to existing time trends.29
This analysis has several limitations. The limitations associated with all administrative claims studies apply here, and include potential misclassification, cohort selection bias, and limited observability of people who change health insurance plans or lose insurance coverage.30 Idiopathic hypersomnia and narcolepsy, though distinct, are often difficult to distinguish, and both conditions require clinical sleep testing to accurately diagnose.4 Thus, under- and/or misdiagnoses may be present in the claims analyzed. While these results may be generalizable to insured individuals in the United States, they may not be generalizable to the broader US population, including uninsured individuals.19 Because uninsured individuals may have unmet health needs, which may worsen and result in greater medical costs, results of this present study may not reflect the magnitude of the clinical and economic burden of the uninsured population.31 Comorbid conditions may not be accurately accounted for in claims data; for example, upwards of 22% of people with diabetes may be undiagnosed and untreated, which would lead to an underrepresentation of this condition in the current dataset.32 However, this underrepresentation would apply to both cohorts. The objective of this analysis was to assess the overall burden experienced by individuals with either condition, and was not designed to parse out the burden directly attributable to idiopathic hypersomnia and narcolepsy. The sensitivity analysis with idiopathic hypersomnia or narcolepsy in the primary position suggests that some of the overall economic burden of these conditions is related to associated comorbid conditions experienced by these individuals. Despite this limitation, the presentation of all-cause HCRU and medical costs emphasizes the high degree of overall health burden experienced by individuals with idiopathic hypersomnia or narcolepsy.
Conclusion
Individuals with idiopathic hypersomnia or narcolepsy experience a large number of comorbid conditions and higher HCRU and medical costs, indicating a substantial overall clinical and economic burden, which may bear significant consequences for healthcare systems. These findings are consistent with the narcolepsy literature, but, importantly, they also add to the limited evidence surrounding idiopathic hypersomnia. The clinical and economic burden of idiopathic hypersomnia and narcolepsy should be considered when diagnosing, managing, and evaluating treatment options for patients with either condition.
Abbreviations
BOND, Burden of Narcolepsy Disease; CCS, Clinical Classifications Software; CV-BOND, Cardiovascular Burden of Narcolepsy Disease; CV-RHYTHM, Cardiovascular Burden of Individuals Diagnosed With Idiopathic Hypersomnia: Real-World Idiopathic Hypersomnia Total Health Model; ED, emergency department; EDS, excessive daytime sleepiness; HCRU, healthcare resource utilization; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; IQR, interquartile range; NT1, narcolepsy type 1; NT2, narcolepsy type 2; OSA, obstructive sleep apnea; PPPY, per patient per year; REM, rapid eye movement; SD, standard deviation.
Data Sharing Statement
The data that support the findings of this study are available from Merative™ MarketScan®. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the authors with the permission of Merative MarketScan.
Ethics Approval and Informed Consent
This was a secondary analysis of deidentified data without access to personal identifying information. The data are compliant with the US Health Insurance Portability and Accountability Act of 1996; ethical review and informed consent were not required for this study.
Acknowledgments
This study was supported by Jazz Pharmaceuticals. Under the direction of the authors, Peloton Advantage, LLC (an OPEN Health company) employees Joseph Mansonet, MPH, and Nicole Boyer, PhD, provided medical writing support and Christopher Jaworski provided editorial support, which were funded by Jazz Pharmaceuticals.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Funding
This study was sponsored by Jazz Pharmaceuticals. Authors from Jazz Pharmaceuticals were involved in the conception and design of the study; the acquisition, analysis, and interpretation of the data; and the development of this manuscript.
Disclosure
R Saad and P Lillaney are former full-time employees of Jazz Pharmaceuticals who, in the course of this employment, received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc. SC Markt, DA Profant, DS Fuller, EM Poole, M Whalen, and W Ni are full-time employees of Jazz Pharmaceuticals who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc. T Alvord is a former full-time employee of Aetion, Inc, who, in the course of this employment, held stock options or equity in Aetion. P Prince and S Desai are full-time employees of Aetion, Inc. and hold stock options or equity in Aetion. J Black is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals, plc. The authors report no other conflicts of interest in this work.
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