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MS NO: ICO201865 SPECIAL ARTICLE The Economic Burden of Dry Eye Disease in the United States: A Decision Tree Analysis Junhua Yu, PhD,* Carl V. Asche, PhD,* and Carol J. Fairchild, PhD† Purpose: The aim of this study was to estimate both the direct and indirect annual cost of managing dry eye disease (DED) in the United States from a societal and a payer’s perspective. Methods: A decision analytic model was developed to estimate the annual cost for managing a cohort of patients with dry eye with differing severity of symptoms and treatment. The direct costs included ocular lubricants, cyclosporine, punctal plugs, physician visits, and nutritional supplements. The indirect costs were measured as the productivity loss because of absenteeism and presenteeism. The model was populated with data that were obtained from surveys that were completed by dry eye sufferers who were recruited from online databases. Sensitivity analyses were employed to evaluate the impact of changes in parameters on the estimation of costs. All costs were converted to 2008 US dollars. Results: Survey data were collected from 2171 respondents with DED. Our analysis indicated that the average annual cost of managing a patient with dry eye at $783 (variation, $757–$809) from the payers’ perspective. When adjusted to the prevalence of DED nationwide, the overall burden of DED for the US healthcare system would be $3.84 billion. From a societal perspective, the average cost of managing DED was estimated to be $11,302 per patient and $55.4 billion to the US society overall. Conclusions: DED poses a substantial economic burden on the payer and on the society. These findings may provide valuable information for health plans or employers regarding budget estimation. Key Words: dry eye, burden of illness, decision tree analysis, presenteeism, absenteeism (Cornea 2010;00:000–000) D in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface.’’1 DED causes degradation of visual acuity that can interfere with many ordinary activities of daily living such as reading, viewing a computer screen, and driving a car.2 DED may impose an economic burden on patients and on society because of the utilization of healthcare resources such as physician visits, medications, and surgical procedures. Moreover, DED is associated with decreased productivity and days missed from work.3 The economic impact of DED is magnified by its prevalence. The 2007 Dry Eye WorkShop reported that the global prevalence of dry eye ranged between 3.5% and 33.7%,4 depending on the age of the population and the diagnostic criteria that were used. DED occurs more frequently in older age groups5 and in females.6 Among US adults aged 50 years and older, the prevalence of DED has been reported as 1.68 million men7 and 3.23 million women.6 With projections of longer life expectancy, an even larger economic burden of DED on society can be expected. Although the cost of DED management may be an important economic burden for the healthcare system, very few studies are available about the cost of this illness in the United States. A comprehensive estimate of the economic burden of DED is needed to provide insight into how much society is spending on the disease and the potential impact that an effective new treatment may offer.8 The objective of this study was to evaluate the annual costs of caring for DED in the United States, from both a societal perspective and a payer’s perspective. MATERIALS AND METHODS Prevalence Approach ry eye disease (DED) has been defined as ‘‘a multifactorial disease of the tears and ocular surface that results Received for publication May 12, 2010; accepted August 12, 2010. From the *University of Utah, College of Pharmacy, Pharmacotherapy Outcomes Research Center, University of Utah, Salt Lake City, UT; and †Alcon Research, Ltd, Fort Worth, TX. Supported by Alcon Laboratories, Inc, Fort Worth, TX. This work was conducted at the Pharmacotherapy Outcomes Research Center at the University of Utah. Reprints: Carl V. Asche, Pharmacotherapy Outcomes Research Center, University of Utah, 421 Wakara Way, Suite 208, Salt Lake City, UT 84108 (e-mail: [email protected]). Copyright Ó 2010 by Lippincott Williams & Wilkins Cornea Volume 00, Number 0, Month 2010 Either the prevalence-based approach or the incidencebased approach can be used to establish the cost of an illness.9 Given the lack of existing longitudinal data about DED, a prevalence-based cost-of-illness analysis was selected for this study. Specifically, an internet-based survey was used to assess the prevalence of mild, moderate, and severe symptoms of DED and to assess the corresponding resource usage for each group of subjects. Prevalence and resource usage were assessed with respect to a 12-month treatment period, in accordance with durations examined in previous economic studies of DED.10,11 In the absence of longitudinal data about changes in severity over time, we assumed that treatment would not change significantly over a 1-year period. www.corneajrnl.com | 1 Yu et al Subjects The survey population was recruited via e-mail from the Sjogren’s Syndrome Foundation and from the Harris Interactive’s Harris Poll online participant panel. Eligible subjects had DED, were US residents aged 18 or older, and were employed at least part time. DED was established by a previous diagnosis of DED or Sjogren syndrome by an optometrist or ophthalmologist or by an ocular surface disease index score in the abnormal range (score .12 out of 100).12 Surveys The survey contained questions regarding demographics, health history (dry eye and other conditions), current dry eye treatments, physician visits, self-reported effectiveness of treatment, and effect of dry eye on quality of life. The impact of dry eye symptoms on work productivity was measured by the Work Productivity and Activity Impairment Questionnaire, a validated instrument for assessing productivity loss because of various health conditions.13 This questionnaire elicits information regarding the number of days and hours missed from work (absenteeism), the extent of limitation at work (presenteeism), and the impact of dry eye on usual daily activities. The domain scores represent the percentage of overall impairment in the past week. Calculation of Costs Five categories of healthcare resource use were assessed: ocular lubricant treatment, cyclosporine, punctal plugs, physician visits, and nutritional supplements. For topical treatments, compliance rate was calculated from questionnaire responses, to yield a ratio of actual use to prescribed use. Ocular Lubricants The average price per milliliter of ocular lubricant treatment was obtained from prices and volumes that were listed at pharmacy Web sites in 2008 for 32 products. Average cost was converted to price per drop by assuming that each drop had a volume of 0.05 mL.14 Subjects were assumed to use ocular lubricant treatment throughout the 1-year study period. The formula for calculating the yearly cost of ocular lubricant treatment for patients who sought professional treatment was as follows: mean price of each drop of ocular lubricant treatment 3 the recommended number of daily drops 3 compliance rate 3 365 days. The formula for calculating the yearly cost of ocular lubricants for subjects who did not seek professional treatment was as follows: mean price of each drop of ocular lubricant treatment 3 the average number of daily drops for a dry eye population (5.7 uses per day)15 3 365 days. Cyclosporine For subjects who reported cyclosporine usage, cyclosporine therapy was assumed to have been used throughout the study period. The yearly cost of cyclosporine was calculated as follows: recommended 2 vials per day15 3 the price of each vial of cyclosporine 3 compliance rate for cyclosporine 3 365 days. The price of each vial of cyclosporine was calculated by dividing the cost per product ($117.46 for a pack of Restasis, cyclosporine ophthalmic emulsion 0.05%; Allergan, Inc, Irvine, CA)16 by the total number of units of doses (36 unit- 2 | www.corneajrnl.com Cornea Volume 00, Number 0, Month 2010 dose vials per pack)16 to yield a price per vial of $3.26 in 2008 dollars, as shown in Table 1. Punctal Plugs Subjects who reported having punctal plugs at the time of the survey were assumed to have had 1 implantation procedure in the past year. According to a study based on a managed care database, the cost per procedure was estimated to be $256 in 2005 dollars.10 This number was adjusted from July 2005 dollars to July 2008 dollars via the consumer price index (CPI) for medical care services, published by the Bureau of Labor Statistics (http://data.bls.gov/cgi-bin/surveymost). The formula was as follows: (CPI in July 2008/CPI in July 2005) 3 (July 2005 dollars) = July 2008 dollars. Therefore, the cost per plug procedure was (385.4/337.8) 3 $256 = $292 (Table 1). Oil-based Nutritional Supplements Survey results were used to calculate the usage of nutritional supplements among subjects who reported being instructed by an eye care professional to take oil-based dietary supplements, such as fish oil or flax seed oil. Results were stratified by dry eye severity, to yield percentage of patients in each severity group (mild, moderate, and severe) who reported consumption of nutritional supplements at the time of the survey. Prices for 3 oil-based nutritional supplements from various manufacturers were obtained through an online search; the average price was $0.52 per day in 2008 dollars. The annual cost of nutritional supplements for each dry eye severity group was calculated as follows: 365 days 3 mean daily price of nutritional supplement 3 percentage of patients reporting that they consumed nutritional supplements. TABLE 1. Parameters for Cost Estimations Variables Value Cyclosporine Price per vial Recommended no. vials per day Ocular lubricant Mean price per drop Average no. drops per day Cost of a plug surgery Visit to an eye care professional Price of the first visit Price of the ophthalmic follow-up visit Weighted average price† Average hourly wage Cost of nutritional supplement per day Source $3.26 2 Red Book Roberts et al $0.02 5.7 $292 Internet search Roberts et al Fiscella et al* $180 2008 Physicians Fee & Coding Guide* 2008 Physicians Fee & Coding Guide* Calculated Bureau of Labor Statistics Internet search $100 $149.50 $15.95 $0.52 *Adjusted to 2008 July price using CPI method as explained in the Methodology section. †The weighted average price per ophthalmologist or optometrist visit was calculated as 0.275 3 $180 (first visit) + $100 (follow-up visit), where 0.275 was the percentage of patients who reported that the DED lasted less than 1 year and thus was assumed to represent the percentage of first time visits. q 2010 Lippincott Williams & Wilkins Cornea Volume 00, Number 0, Month 2010 Cost of Visiting a Healthcare Professional The average annual numbers of visits per subject to optometrists, ophthalmologists, and other eye care professionals were derived from the survey. The calculations took into account the difference in cost between initial visits and follow-up visits because the first consultation has a higher charge than the follow-up visits.18 We assumed that the subjects who reported having suffered DED for less than 1 year were new patients. The cost per visit for an ophthalmologist or optometrist was estimated as a weighted average of the fee for the first visit and the follow-up visits, the formula for which was as follows: the percentage of new patients 3 fee for the first office consultation (Current Procedural Terminology code 99244)17,18 + fee for the ophthalmic follow-up examination with treatment (Current Procedural Terminology code 92014).17,18 Fees were adjusted from 2007 July price to 2008 July price using the CPI method as explained in the punctal plug section. The fees for office visits are shown in Table 1. The total cost of visits to eye care professionals was calculated as the total number of visits per subject reported in the previous year 3 the weighted average cost per visit. Indirect Cost Reductions in productivity because of absenteeism (the loss of working hours) and presenteeism (the hours of reduced effectiveness at work) were derived from the Work Productivity and Activity Impairment Questionnaire data. Lost work time was ascertained by the following question: ‘‘During the past 7 days, how many hours did you miss from work because of your dry eye problems?’’ Lost work equivalent, the hours of productivity lost because of reduced effectiveness because of dry eye symptoms, was calculated from responses to the following question: ‘‘During the past 7 days, how much did your dry eye problems affect your productivity while you were working?’’ Lost work equivalent was defined as the number of usual weekly work hours 3 degree of impairment to effectiveness (measured as a percentage). We assumed that the past-week productivity and loss patterns were representative for the year; therefore, the total annual indirect cost was calculated as (lost work equivalent + lost work time) 3 hourly wage 3 48 working weeks. The average hourly wage was assumed to be $15.95 per hour, according to data provided by the Web site of the Bureau of Labor Statistics (http://data.bls.gov/cgi-bin/ surveymost?le). Description of the Models Dry Eye Treatment Pattern Model Well-established treatment guidelines19–21 were used to develop a decision tree model. Although the guidelines vary slightly, they all recommend that therapy for DED should be initiated in a stepwise fashion, in accordance with disease severity. For patients with mild DED, the 3 guidelines recommend initial treatment with an ocular lubricant, such as artificial tears, lubricant eyedrops, and/or ointments. For some patients with moderate DED, the 3 guidelines recommend a topical antiinflammatory, such as cyclosporine. For some patients with severe DED, the 3 guidelines recommend punctal plugs. These consensus-based stepwise q 2010 Lippincott Williams & Wilkins Dry Eye Economic Burden treatments (ocular lubricants for mild DED, cyclosporine for moderate DED, and punctal plugs for severe DED) were included in the decision tree model. Burden of Illness Model Decision analytic models were employed to reflect preferred treatment patterns and to evaluate the healthcare utilization data in each treatment pattern under conditions of uncertainty because of variability in DED treatment patterns in the real world.22,23 Mutually exclusive categories of subjects were identified to differentiate between severity of dry eye symptoms and varying degrees of resource consumption. This approach reduced model complexity and allowed for the flexibility that real-world treatment patterns might deviate from the recommended guidelines. Subjects were sorted into 2 groups: those who sought professional eye care and those who did not. These groups were further classified as having mild, moderate, or severe DED, as determined by the selfreported severity of symptoms for the past week. In each severity group, subjects were further divided into 4 treatment groups: neither cyclosporine nor punctal plugs; only plugs; only cyclosporine; or both cyclosporine and plugs. This burden-ofillness model was used to calculate the direct medical costs to payers (payer cost model) and to calculate the cost of DED to society (societal cost model). The societal cost model included direct medical cost and indirect cost because of presenteeism and absenteeism. Validation Model To evaluate the validity of the payer cost model, a validation model was constructed based on a cost-oftreatment report that used information from a published retrospective healthcare claims database to calculate utilization and costs of topical cyclosporine and punctal plugs over a 1-year period.10 In that study, the population consisted of patients with DED that was treated with cyclosporine or punctal plugs; so, their results were compared only with results for our group of subjects similarly treated with cyclosporine or plugs. In the validation model, we assumed that all patients with dry eye who were treated with either cyclosporine or plugs were followed for 1 year after entry into the model. The cohort of cyclosporine-treated patients was divided into 2 groups depending on whether they received punctal plugs later in the 1-year period. Similarly, the plugs cohort was divided into 2 groups depending on whether they received cyclosporine in the 1-year follow-up period. The cost for cyclosporine was calculated from the reported mean number of prescriptions per year (3.93 per year)10 and from the mean days of supply per prescription (31.51 days).10 In accordance with the findings of their study, patients with plugs at entry into the validation model were assumed to have a mean of 2.85 procedures per year,10 and the patients receiving cyclosporine at entry into the validation model were assumed to have only 1 plug implantation procedure during the follow-up period. Using the same calculation method as was used in the payer cost model, we assigned path probabilities to each branch of patients in the validation model and used their treatment costs as payoffs to calculate the average costs per patient with dry www.corneajrnl.com | 3 Cornea Volume 00, Number 0, Month 2010 Yu et al that cyclosporine therapy was used throughout the study period. TABLE 2. Data Used for Validation Model* Variable Name Value Cyclosporine Mean number of prescriptions per year Days supply per prescription Compliance rate Proportion of patients initiated with cyclosporine Punctal plugs Cost per plug procedure Mean number of procedures, for those initiated with plugs Combination plugs and cyclosporine Proportion of patients using plugs after cyclosporine Proportion of patients using cyclosporine after plugs 3.93 31.51 33.9% 50.86% $270 2.9 21.1% 11.4% *Source: Fiscella et al. eye. Data for the validation model are given in Table 2. Average treatment costs (cyclosporine and plugs) from the validation model were compared with the corresponding average treatment costs from the payer cost model. RESULTS Demographics Among the 2171 respondents to the survey, 54% were women and more than 50% characterized their dry eye symptoms as mild. Table 3 shows the severity distribution of DED among the study participants. DED was reported to have lasted less than 1 year in 27.5% of patients, yielding a weighted average cost of price per visit to an eye care professional of $149.50 (Table 1). Resource usage among subjects who sought professional eye care is shown in Table 4. Resource usage among subjects who did not seek professional eye care is shown in Table 5. Confirmation of Assumptions The mean reported duration of ocular lubricant treatment was 47.1 months (95% confidence interval, 41.5– 52.7 months). Therefore, the assumption that subjects used ocular lubricant treatment throughout the 1-year study period was valid. The survey data indicated that the average treatment duration for cyclosporine was 22.7 months (95% confidence interval, 17.8–27.7 months), which validated our assumption TABLE 3. Distribution of Dry Eye Subjects by Severity of Symptoms Subjects Seeking Professional Eye Care Subjects Not Seeking Professional Eye Care Proportion of Subjects Mean LCI UCI Mean LCI UCI With Mild DED (%) With Moderate DED (%) With Severe DED (%) 53.9 34.0 12.0 49.5 29.9 9.2 58.3 38.1 14.8 59.9 31.4 8.7 53.2 25.1 4.8 66.6 37.8 12.5 LCI, lower confidence interval; UCI, upper confidence interval. 4 | www.corneajrnl.com Direct Costs The average annual direct cost for patients seeking medical care was calculated to be $783 per patient (Fig. 1). Taking into account the US DED prevalence among adults aged 50 years or older (1.68 million men7 and 3.23 million women6), the overall burden of DED for the health care system would be $3.84 billion. The average annual direct medical cost per patient was $678 for patients with mild dry eye, $771 for patients with moderate dry eye, and $1267 for patients with severe dry eye. A detailed breakdown of the total medical cost for each group of patients for plugs, cyclosporine, ocular lubricant treatment, office visits, and nutritional supplements TABLE 4. Utilization of Professional and Consumer Resources for DED Among Patients Who Sought Professional Eye Care Variables Mean Proportion of patients using plugs (%) Mild DED 24.2 Moderate DED 12.8 Severe DED 15.5 Proportion of patients using cyclosporine (%) Mild DED without plugs 4.1 Mild DED with plugs 16.1 Moderate DED without plugs 12.2 Moderate DED with plugs 16.3 Severe DED without plugs 30.3 Severe DED with plugs 35.2 Ratio of compliance with cyclosporine (%) Mild DED 93.3 Moderate DED 93.1 Severe DED 72.2 Proportion of patients using ocular lubricants (%) Mild DED 67.6 Moderate DED 81.3 Severe DED 86.9 Compliance with ocular lubricants (%) Mild DED 94.2 Moderate DED 72.9 Severe DED 58.6 Proportion of patients using nutritional supplements Mild DED 60.2 Moderate DED 63.3 Severe DED 71.5 Frequency of physician visits per year To ophthalmologist Mild DED 1.097 Moderate DED 1.137 Severe DED 1.847 To optometrist Mild DED 0.899 Moderate DED 0.878 Severe DED 1.682 LCI UCI 19.9 9.9 9.1 28.6 16.8 21.9 2.0 9.4 8.3 3.3 21.6 16.1 6.3 22.8 16.1 29.4 39.0 54.3 84.3 84.0 56.4 100.0 100.0 88.0 58.9 74.8 77.1 76.4 87.8 96.8 89.9 59.8 42.3 (%) 55.2 57.6 63.5 98.5 86.0 74.9 65.2 69.0 79.5 0.849 0.880 1.252 1.344 1.394 2.442 0.692 0.704 1.153 1.106 1.051 2.212 LCI, lower bound of confidence interval; UCI, upper bound of confidence interval. q 2010 Lippincott Williams & Wilkins Cornea Volume 00, Number 0, Month 2010 Dry Eye Economic Burden TABLE 5. Utilization of Consumer Resources for DED Among Subjects Who Did Not Seek Professional Eye Care Variables Mean (%) LCI (%) Proportion of subjects using ocular lubricants Mild DED 51.5 37.4 Moderate DED 55.7 32.8 Severe DED 78.1 41.2 Proportion of subjects using nutritional supplements Mild DED 49.4 40.5 Moderate DED 37.9 26.2 Severe DED 46.4 24.6 UCI (%) did not interact with health care systems, the model estimated that a cohort of 1000 subjects with varying severity of DED had a mean direct cost of $543 per person per year (Fig. 1). Indirect Costs 65.6 78.5 100.0 58.2 49.6 68.3 LCI, lower bound of confidence interval; UCI, upper bound of confidence interval. is presented in Table 6. For each severity group, patients treated with punctal plugs plus cyclosporine had the highest annual direct expenditure: $2964 for mild patients, $2959 for moderate patients, and $2698 for severe patients (Table 6; groups 4, 8, and 12). The total annual direct costs to the payer for a cohort of 1000 patients with varying severity of symptoms would be $782,673. The average annual direct cost for subjects who were self medicating with ocular lubricant treatment or nutritional supplements was calculated at $126 per subject (Fig. 1). Taking into account the proportions of patients who did and The average annual cost to society was calculated as $11,302 per subject with DED (Fig. 2). The overall burden to the US society was calculated at $55.4 billion. The loss because of diminished productivity considerably outweighed direct costs of DED treatment (Table 6). In a cohort of gainfully employed dry eye patients, the total productivity loss per person ranged from $12,569 to $18,168 per year. As shown in Figure 3, the loss because of presenteeism was substantially higher than the loss because of absenteeism. The calculated mean number of lost work days per year was 8.4 days for mild patients, 3.7 days for moderate patients, and 14.2 days for severe patients, whereas the equivalent lost work days because of affected performance was equivalent to 91 days for mild patients, 94.9 days for moderate patients, and 128.2 days for severe patients (Table 7). Subjects who had not visited a physician during the past year lost fewer days of productivity than subjects who had sought professional eye care in the past year. Sensitivity Analysis of Direct Medical Costs Multiple 1-way sensitivity analyses were performed for 7 key variables (listed in Tables 4 and 5) to test the robustness FIGURE 1. Decision tree used for estimating the direct cost per patient with dry eye. q 2010 Lippincott Williams & Wilkins www.corneajrnl.com | 5 Cornea Volume 00, Number 0, Month 2010 Yu et al TABLE 6. Estimate of the Annual Direct and Indirect DED Costs of Patients Seeking Professional Eye Care* Mild DED No Plugs Treatment group Patients (%) Costs Indirect, total Absenteeism Presenteeism Direct, total Plugs Cyclosporine Ocular lubricant Office visits Nutritional supplements Total (direct + indirect) Moderate DED With Plugs No Plugs Severe DED With Plugs No Plugs With Plugs No CS Yes CS No CS Yes CS No CS Yes CS No CS Yes CS No CS Yes CS No CS Yes CS 1 38.6 2 1.6 3 10.7 4 2.0 5 26.6 6 3.6 7 3.8 8 0.8 9 7.2 10 3.1 11 1.3 12 0.6 $12,686 $12,686 $12,686 $12,686 $12,569 $12,569 $12,569 $12,569 $18,168 $18,168 $18,168 $18,168 $452 — — $39 $298 $114 $13,138 $2672 — $2220 $39 $298 $114 $15,358 $744 $292 — $39 $298 $114 $13,430 $2964 $292 $2220 $39 $298 $114 $15,650 $452 — — $30 $301 $120 $13,021 $2667 — $2215 $30 $301 $120 $15,236 $744 $292 — $30 $301 $120 $13,313 $2959 $292 $2215 $30 $301 $120 $15,528 $688 — — $24 $528 $136 $18,856 $2406 — $1718 $24 $528 $136 $20,574 $980 $292 — $24 $528 $136 $19,148 $2698 $292 $1718 $24 $528 $136 $20,866 *Costs for patients with DED who self medicated are not included in this table. CS, cyclosporine. of the results. The upper and lower limits for each of the model variables are shown in Tables 3, 4, and 5. The 95% confidence intervals around the mean values were constructed by assuming a binomial distribution for binary variables and by assuming a Poisson distribution for count variables. The sensitivity analysis conducted on the list of variables is shown in Figure 4. The tornado diagram indicates that the distribution of severity of symptoms had a relatively large impact on the FIGURE 2. Decision tree used for estimating the total annual cost per patient with dry eye (societal prospective). 6 | www.corneajrnl.com q 2010 Lippincott Williams & Wilkins Cornea Volume 00, Number 0, Month 2010 Dry Eye Economic Burden comparable to the results from the payer cost model, in which the annual cost for dry eye was calculated as $1092 for subjects who reported being treated with plugs or cyclosporine at the time of the survey. DISCUSSION FIGURE 3. Indirect costs because of productivity losses. estimates. This was followed by a few treatment characteristics for patients with mild DED (the frequency of ophthalmologist visits, combined punctal plugs and cyclosporine treatment, and frequency of optometrist visits) and compliance with cyclosporine by severe patients. However, the change in the magnitude around the mean direct cost of $783 was minimal, ranging from $757 to $809 approximately. Validation Results In the validation model, the yearly medical cost of cyclosporine and plugs was calculated to be $1123 per person (Fig. 5). These results from the validation model were TABLE 7. Impact of DED on Work Productivity Subjects Who Visited Physicians Mean LCI UCI Subjects Who Did Not Visit Physicians Mean LCI UCI Lost work hours per week Mild DED 1.40 1.07 1.74 0.04 0.01 0.10 Moderate DED 0.61 0.28 0.94 0.29 0.17 0.45 Severe DED 2.36 1.02 3.71 1.40 0.93 2.02 Affected performance (%) Mild DED 37.9 32.1 43.7 1.6 7.8 14.3 Moderate DED 39.5 33.8 45.2 4.1 19.2 35.4 Severe DED 53.4 44.6 62.2 8.5 38.0 73.7 Lost work days per year, assuming 40 hours per week and 48 weeks Mild DED 8.4 6.4 10.4 0.2 0.1 0.6 Moderate DED 3.7 1.7 5.6 1.7 1.0 2.7 Severe DED 14.2 6.1 22.3 8.4 5.6 12.1 Equivalent lost work days per year because of affected performance Mild DED 91.0 77.1 104.9 4.0 18.6 34.3 Moderate DED 94.9 81.1 108.6 9.8 46.0 85.1 Severe DED 128.2 107.0 149.4 20.3 91.1 176.8 LCI, lower bound of confidence interval; UCI, upper bound of confidence interval. q 2010 Lippincott Williams & Wilkins To our knowledge, this is the first study about the cost of DED in the United States. Reddy et al3 concluded that previously available data were insufficient to estimate the US cost of DED and therefore offered a conceptual framework for future studies. We followed the practices that were established by Clegg et al,11 who used the distribution of disease severity to estimate the average annual cost for patients with dry eye in Europe and used a sensitivity analysis to test the robustness of their findings. However, we calculated the cost of managing DED by using a decision tree analytical model, which is a flexible tool to examine the impact of uncertainty of the relevant parameters on the estimated costs. One advantage of the decision tree analytical method is that the model parameters and results can readily be updated when new information becomes available from future studies. The self-reported data from our survey revealed the current utilization pattern of the mainstay therapies for DED, including ocular lubricant treatment, prescribed eyedrops, and the associated compliance rates. Therefore, the costs calculated from these survey data provided information that was more comprehensive than information that can be obtained from claims databases. Self-reported survey data do have limitations in delivering comprehensive and generalizable information about resource use, but our results were comparable to results from a model that used claims database inputs.10 For example, the calculated annual cost of 2 mainstay treatments (cyclosporine and punctal plugs) from the survey data was only $31 lower than the annual cost that was calculated from a claims database in the comparator study. The consistency between the results of the 2 studies suggested that the data obtained from the population-based survey generally reflected the cyclosporine and plugs treatment pattern of dry eye revealed in the large claims database. Hence, our results represent a fairly complete and realistic costing of the burden of DED in the United States in 2008. The unique advantages of the survey data allowed us to identify the resource utilization and productivity losses for those dry eye sufferers who did not seek professional eye care for DED in the previous year. This provided an opportunity to measure the DED economic burden from both the society’s and the payer’s perspective. We have not found any study that has attempted to identify the cost associated with selfmedicating DED sufferers who remain outside the health care system. An important finding of the study is that approximately 40% of the subjects with dry eye symptoms (of varying degrees) did not seek medical care. This group incurred less direct cost but had substantial societal cost because of presenteeism and absenteeism. All modeling studies have limitations imposed by the structure of the model, by the inherent assumptions, and by the source data. Given that the costs presented in this study were based on treatment patterns and level of resource use derived www.corneajrnl.com | 7 Yu et al Cornea Volume 00, Number 0, Month 2010 FIGURE 4. Tornado diagram for average direct costs per patient seeking professional eye care. from recent population-based surveys, the level of accuracy of self-reported data must be determined to further verify the estimation results. However, dry eye epidemiological studies rely on patient-reported symptoms to detect cases of DED. Symptoms that are felt as inconvenient for some patients might be considered debilitating by other patients, thus giving rise to inconsistent reports of severity across individuals. Moreover, studies have shown that patients’ self assessments of dry eye symptoms are significantly more severe than the severity that is perceived by their doctors.24 Physicians incorporate their assessments of symptoms and clinical signs of ocular surface diseases in determining severity. Therefore, care should be taken when attempting to extrapolate the results of this study to other populations. Our results are comparable to those reported in the DED burden-of-illness study by Clegg et al.11 The authors collected resource use data from interviews with a randomly selected sample of consultant ophthalmologists in Europe and estimated that the total annual health care cost of 1000 dry eye sufferers ranged from $0.27 to $1.10 million US dollars in 2004.11 Our study found a comparable distribution of severity and cost of DED ($0.78 million US dollars for 1000 sufferers). The impact of dry eye on indirect costs is important. We have included the indirect costs attributed to presenteeism and absenteeism using the self-reported results from the work productivity and activity impairment questionnaire. However, because the survey data were based on the subjects who were employed at least part time, the forgone productivity might be an overestimate of the general dry eye population, some of whom might be engaged in non–wage-earning or homeworking activities. A surprising finding of the study was that loss because of diminished productivity considerably outweighed direct cost of care. These findings underscore the impact of DED in the workplace and may provide valuable information to health plans or employers regarding budget estimation. It is hoped that information from this study can be helpful in setting priorities for health care efficiency research. We have presented a simplistic treatment and cost structure in the model. Refinement of the model to allow more sophisticated and detailed analysis would require additional data that are not currently available in the United States. Despite these limitations, this study improved upon previous studies by incorporating the indirect costs and the FIGURE 5. Expected direct medical costs for patients with dry eye in managed care database: cyclosporine and plug only. 8 | www.corneajrnl.com q 2010 Lippincott Williams & Wilkins Cornea Volume 00, Number 0, Month 2010 nonprescription medications in the calculation of annual cost of DED, with the aid of a rigorous decision tree model. Therefore, we believe this study represents a significant contribution to the field, given the lack of more robust data in the peer-reviewed literature. In summary, DED imposes a substantial economic burden on the payer and on the society. The overall burden of DED for the US health care system was calculated as approximately $3.84 billion, with subgroup costs that varied by severity of disease and by prevalence of those severity subgroups. A surprising finding of the study was that loss because of diminished productivity considerably outweighed the direct cost of care. These findings underscore the impact of DED in the workplace and may provide valuable information to health plans or employers regarding budget estimation. The information from this study can be helpful in setting priorities for health care efficiency research. ACKNOWLEDGMENTS The authors are grateful for the editorial assistance from Dana Wise and research assistance from Tran Le, Tracy Louie, Anh Luong, and Brando Kyle Bellows. REFERENCES 1. The International Dry Eye WorkShop Study Group. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). 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