The Associations between Insomnia Severity and Health Outcomes in the United States

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes.


Introduction
Insomnia, defined as difficulty initiating and/or maintaining sleep with associated daytime consequence, is the most common sleep disorder among adults. In the United States (US), 10-15% of the population experiences chronic insomnia disorder, defined as frequency of difficulty sleeping of three or more nights per week, and duration for three or more months, with associated daytime insomnia symptoms [1][2][3]. Chronic insomnia is associated with a broad range of adverse consequences, including increased rates of poorer mental health outcomes (e.g., depression, anxiety, chronic pain, substance abuse, suicide), poorer physical health outcomes (e.g., cardiovascular disease, diabetes, stroke) and worsened health-related quality of life (HRQoL) [4]. In addition to those consequences for patients and their families, insomnia is also associated with a substantial economic burden that is borne by payers, by employers, and by society. For example, untreated insomnia is associated with increased healthcare resource utilization (HCRU) and other related costs (borne by payers), as well as increased absenteeism and diminished workplace 2 of 13 productivity costs (i.e., presenteeism; borne by employers, but also impacting a country's economy) [5][6][7].
Daytime impairment is a core feature of insomnia disorder. Specific daytime insomnia symptoms can include fatigue, depressed mood, irritability, poor cognitive function, increased risk of accidents, and overall impaired social, vocational, educational, and behavioral functioning [4,[8][9][10]. Despite the potentially debilitating impact of these daytime insomnia symptoms, insomnia research to date has primarily focused on nighttime insomnia symptoms (i.e., difficulty initiating sleep and/or difficulty maintaining sleep) when considering adverse outcomes associated with insomnia.
In terms of the economic burden of insomnia, studies have examined insomnia, and assessed its severity, via diagnostic interview in prospective clinical studies, physicianassigned diagnoses in administrative claims studies, validated self-report instruments in survey research, and other approaches. [5,[11][12][13] To our knowledge, there are limited analyses with data from a large number of patients that could be correlated with longerterm health and lifestyle outcomes. Given that insomnia is widely recognized as a 24-h disorder that impacts sleep quantity and quality and affects daytime functioning, data relating the severity of insomnia to outcomes would provide clinicians and researchers evidence-based guidance regarding the importance of insomnia assessment and the need for effective insomnia care.
To address this important gap in knowledge, the purpose of the present study was to assess the association between insomnia severity and key health outcomes that matter to diverse stakeholders, including patients (HRQoL), payers (HCRU), and employers and government (workplace productivity). For each of these outcome domains, we hypothesized that increasing insomnia severity is associated with worse health outcomes.

Study Design and Data Source
This was a retrospective, cross-sectional, observational cohort study. Data were derived from the 2020 US National Health and Wellness Survey (NHWS, Cerner Enviza, New York, NY, USA) [14,15]. The NHWS is an annual, self-administered, nationwide, internet-based survey of adults (n =~75,000 US respondents aged ≥18 years) that collects demographic, general health, and disease-specific information and also includes measures of HRQoL, HCRU, and costs for more than 164 disease states. Respondents are recruited through a general-purpose, web-based consumer panel via channels such as opt-in e-mails, co-registration with panel partners, and e-newsletter campaigns. To ensure a representative sample of US adults, the NHWS employs a stratified random sampling procedure (including sex, race/ethnicity, and age). The data used included sociodemographic and general health characteristics, comorbidity burden, insomnia-related measures, current treatments, and EQ-5D-5L health states, among other data obtained from the survey respondents. Notably, while filling out the NHWS survey, if a person responded as having an insomnia diagnosis or as experiencing insomnia symptoms, then the questions of the Insomnia Severity Index (ISI) were posed within that survey. The NHWS protocol and survey were reviewed and determined exempt by the Pearl Institutional Review Board (Indianapolis, IN, USA; 19-KANT-204).

Participants
Participants were eligible for inclusion if they were ≥18 years old, residing in the US at the time of survey completion, and self-reported as having been diagnosed and/or experiencing insomnia during the past 12 months. Respondents were excluded from this analysis if they: (1) experienced symptoms, or had been diagnosed, with narcolepsy, sleep apnea, or other non-insomnia related sleep difficulties in the past 12 months; (2) experienced symptoms or self-reported a diagnosis of another serious medical condition (any type of cancer, chronic liver disease, cirrhosis, epilepsy, multiple sclerosis, muscular dystrophy, or Parkinson's disease); or (3) were pregnant at the time of survey completion.

Insomnia Cohort Identification
Participants were identified based on responses to two standard assessment items within the NHWS: 'Which of the following conditions have you experienced in the last 12 months?' and 'Which of your conditions have been diagnosed by a physician?'. Participants who reported experiencing insomnia in the previous 12 months, with or without receipt of a physician-assigned diagnosis of insomnia, completed the Insomnia Severity Index (ISI; see below). Insomnia severity was then determined based on responses to the validated ISI.

Health-Related Quality of Life
To provide insight into the burden of insomnia from the patient perspective, HRQoL was assessed using the Medical Outcomes Study 36-Item Version 2 Short Form Survey Instrument (SF-36v2) (RAND, Santa Monica, CA, USA) [20]. SF-36v2 is a measure of general HRQoL that comprises 36 items that map onto 8 health domains: physical functioning, physical role limitations, bodily pain, general health, vitality, social functioning, emotional role limitations, and mental health. These individual domains are summarized in two component summary scores, the physical component summary (PCS) and mental component summary (MCS). PCS and MCS scores range from 0 to 100, each based on a population norm with a midpoint of 50, with higher scores indicating better HRQoL. Differences greater than 3.0 on the norm-based scoring algorithm were considered to be minimal clinically important differences (MCID) for scores on both scales [21].

Health Utility Status
Health utilities were assessed using two established measures: the Short Form-6 Dimensions (SF-6D) and the EuroQoL-5 Dimensions (EQ-5D-5L). SF-6D health utility index scores were derived from responses on the SF-36v2 [22]. EuroQol-5D (EQ-5D) health utility index scores were derived from the EQ-5D-5L, a self-report measure of health for clinical and economic appraisal that is comprised of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression [20]. Both SF-6D and EQ-5D health utility index scores range from 0.00 (a health state equivalent to death) to 1.00 (a health state equivalent to perfect health), with higher scores indicating better health status. Consistent with previous studies, differences greater than 0.04 and 0.07 were considered to be MCID for SF-6D and EQ-5D, respectively [22,23].

Workplace Productivity
To provide insight into the burden of insomnia from the employer perspective, work productivity loss and non-work activity impairment were measured using the Work Productivity and Activity Impairment (WPAI) questionnaire, a validated 6-item instrument that includes four metrics: absenteeism (the percentage of work time missed because of one's health during the past 7 days), presenteeism (the percentage of impairment due to one's health experienced while at work during the past 7 days), overall work productivity loss (an overall impairment estimate that is a combination of absenteeism and presenteeism), and activity impairment (the percentage of impairment due to one's health in daily activities during the past 7 days) [24]. All respondents provided data for activity impairment, but only respondents who were employed (full-time, part-time, or self-employed) provided data for absenteeism, presenteeism, and overall work impairment. Higher scores on these measures indicated greater impairment. The values ranged from no impact (0%) to complete (100%) for absenteeism, presenteeism, and overall work impairment.

Healthcare Resource Utilization and Costs
To provide insight into the burden of insomnia from the payer perspective, HCRU was assessed based on the self-reported mean number of all-cause visits to a general practitioner and/or any healthcare provider, an emergency room (ER), or hospital during the past 6 months.

Analytic Plan
First, distributions and frequencies of all variables were assessed using descriptive statistics. Then, to test our hypothesis that insomnia severity is associated with worsened outcomes, we compared HRQoL, workplace productivity, and HCRU between the insomnia severity categories using ANOVA for continuous variables having normal distributions, the Wilcoxon Rank Sum test (Mann-Whitney U Test/Kruskal-Wallis) test for variables having non-Gaussian distributions, and the chi-squared test for categorical variables. Next, to control for potential confounders, we created a series of generalized linear models (GLMs) specifying a normal distribution and identity function for normally distributed outcomes (HRQoL and health status), and GLMs specifying a negative binomial distribution and log-link function for highly positively skewed variables (WPAI and HCRU). This approach to GLMs with normal and negative binomial distributions for these measures has been used previously [15,25,26]. All statistical analyses were performed using SPSS Version 23 (IBM, New York, NY, USA) or R version 3.6 or higher (RStudio, Boston, MA, USA). Statistical significance for all tests was set at p < 0.05.

Association between Insomnia Severity and Outcomes
In unadjusted analyses, increasing insomnia severity was associated with poorer outcomes; and this pattern was evident across all outcomes examined (Table 2). Unadjusted outcome comparisons between severe, moderate, mild, and no clinically significant insomnia found that higher levels of insomnia severity were associated with worse scores for SF-6D, PCS, MCS, EQ-5D, absenteeism, overall work productivity, and overall activity impairment.

Discussion
In this national study, insomnia severity was associated with key outcomes that matter to patients (worsened quality of life), to payers (increased HCRU), and to employers In Supplementary Materials, a costing of the above health outcomes has been performed (Tables S3-S6), as well as an analysis of the unadjusted and adjusted associations between insomnia diagnosis status and health outcomes (Tables S1 and S2).

Discussion
In this national study, insomnia severity was associated with key outcomes that matter to patients (worsened quality of life), to payers (increased HCRU), and to employers and government (decreased work productivity and greater activity impairment). These associations highlight the importance of comprehensive clinical insomnia evaluation.
It is well-established that insomnia is associated with increased health and economic burdens, with costs borne by patients, payers, employers, and society. Our findings are, thus, consistent with and build upon previous results by utilizing the ISI, a validated measure of insomnia severity, to examine the associations between insomnia severity and a number of key outcomes that matter to patients, payers, and employers [5]. In this study, insomnia severity was linearly associated with the vast majority of health outcomes. Moreover, it is important to recognize that even the non-severe categories of insomnia were all associated with increased disease burden, highlighting not only the importance of sensitive research measures regarding insomnia severity, but also the potential clinical relevance of even mild insomnia. It is further notable that only a minority of patients who reported clinical insomnia symptoms on the ISI reported receiving a diagnosis by their physician, with even fewer reporting having treatment for their insomnia.
In aggregate, the findings of this study highlight the importance of thorough assessment of insomnia symptom severity among adult patients in real-world settings. From a harm reduction perspective, present data suggest that all patients who experience insomnia symptoms, and not just the most severe patients, should be evaluated and when indicated, considered for treatment.
Insomnia is a 24-h disorder that impacts individuals during both the night and the day. These important data are relevant to both research and clinical perspectives. From a research perspective, future studies could examine the impact of both daytime and nighttime insomnia symptom severity on other key health outcomes from varied perspectives, including the impacts on costs from the payer perspective, as well as how these treatment-related changes impact downstream health and mental health outcomes.
This study possesses multiple strengths. First, our NHWS (and ISI) data source was large and designed to represent the US adult population [27]. In addition, whereas most large-scale studies of insomnia have utilized non-validated measures, our operational definition of insomnia, the ISI, has undergone extensive psychometric validation for assessment of insomnia severity [18]. Finally, given the breadth of measures included in the NHWS, we were able to adjust for a broad range of potential confounders.
Simultaneously, our results must be interpreted in light of several important limitations. First, although NHWS is designed to mirror the US population and does control for age, sex, and self-reported race, participants are not randomly selected. It is, thus, unclear how well results will generalize to other adults. Second, all data are based on self-report, and we were unable to objectively assess sleep, HCRU, or other specific variables of interest. Third, although the ISI includes general measures of daytime insomnia symptom severity, it was neither developed nor validated to specifically assess granular domains of daytime impairment, and we were unable to assess granular daytime insomnia symptoms such as cognition, mood, or sleepiness. Fourth, although we controlled for a broad range of potential confounders, the potential for residual confounding remains. Finally, our study design was cross-sectional, and we are unable to determine causality.

Conclusions
This national analysis suggests that overall insomnia severity is strongly linearly related to adverse health outcomes including diminished HRQoL, greater activity impairment, decreased workplace productivity, and higher healthcare resource utilization. These findings add to the insomnia science literature and warrant further exploration in future studies, including prospective clinical and economic studies with long-term follow-up utilizing validated instruments.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/jcm12062438/s1, Table S1: Unadjusted outcome differences between insomnia, diagnosed and insomnia, experiencing. Table S2: Adjusted outcome differences between insomnia diagnosed and insomnia experiencing. Cost-related Supplementary Materials-Methodology for cost calculation.   Informed Consent Statement: Not applicable. Subjects had to opt-in to participating in the survey.

Data Availability Statement:
The NHWS is a commercial dataset. Access to the dataset used in this present paper must be requested to Cerner Enviza via the following link: https://www.cernerenviza.com/ contact-us, accessed on 22 July 2020. Data access conditions will be detailed by the responsible team.