Rationale: Management of idiopathic pulmonary fibrosis (IPF) is resource-intensive. Because an increasing prevalence of IPF was found among the elderly in the United States, it is important to understand the economic burden associated with the disease in this population.
Objectives: To compare health care resource utilization and costs between patients with IPF and matched control subjects without IPF in Medicare, the largest U.S. payer covering the elderly.
Methods: Administrative claims from a 5% random sample of Medicare beneficiaries (aged 65+) from years 2000 to 2011 were analyzed. Incident patients with IPF were identified on the basis of International Classification of Diseases, ninth revision, Clinical Modification diagnosis codes, with at least 1 year of enrollment before (preindex) and after (postindex) the first diagnosis (index date). Up to five beneficiaries without IPF were matched to each patient with IPF, based on age, sex, race, and region. Annual health care resource utilization and medical costs (excluding outpatient drug costs) during the preindex and postindex periods were compared between patients with IPF and matched control subjects.
Measurements and Main Results: A total of 7,855 patients with IPF were matched to 38,856 control subjects. Compared with matched control subjects during the preindex period, patients with IPF had an 82% higher risk of hospitalization (28.8 vs. 15.8%), and 72% higher total medical costs ($10,124 vs. $5,888). Compared with matched control subjects during the postindex period, patients with IPF had a 134% higher risk of hospitalization (48.7 vs. 20.8%), similar increased risk of emergency room visits (39.6 vs. 17.5%), and 134% higher total medical costs ($20,887 vs. $8,932).
Conclusions: In the U.S. Medicare population, patients with IPF incurred substantial health care resource utilization. The annual IPF-attributable medical cost to the U.S. health care system, excluding medication costs, is estimated at close to $2 billion.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause predominantly affecting older adults (1–3). IPF has a poor prognosis and is associated with a high risk of comorbidities such as gastroesophageal reflux disease (4–7), obstructive sleep apnea (8), and vascular disease (9, 10). Managing patients with IPF is resource-intensive given the complexity of reaching a confirmed diagnosis and the need for managing complications and concomitant comorbidities (2). We examined the U.S. Medicare population (the U.S. government health care insurance for people aged 65 yr and older) and found an increasing prevalence of IPF among older Americans (11). Our data also suggested increasing survival in recent years among these patients (11, 12). With more patients living with IPF, it is important to understand the economic burden associated with the disease.
Published data assessing the health resource utilization (HRU) in IPF are scarce. In the United States, only one population-based study, which used employer-sponsored private insurance claims from 2001 to 2008, has been published (10). Unlike private insurance plans, Medicare covers essentially all patients with IPF over the age of 65 years in the United States, and using a representative sample from Medicare should provide a more generalizable assessment of HRU in this patient population. The purpose of this study was to examine the HRU and economic burden associated with IPF using a large, contemporary, and generalizable database of older patients.
Claims data were obtained from a 5% random sample of Medicare beneficiaries from 2000 to 2011 (3.7 million beneficiaries). This population is representative of all individuals covered by the Centers for Medicare and Medicaid Services (CMS), the largest payer for the medical care in the elderly in the United States. Data included information on year of birth, sex, race/ethnicity, date of death (if deceased), reasons for Medicare entitlement, and Medicare Advantage (health maintenance organization) enrollment. Medicare Part A and Part B files contain Medicare-reimbursed claims from the following settings for fee-for-service enrollees: inpatient, outpatient, emergency room (ER), physician office, skilled nursing facility, hospice, home health agency, and durable medical equipment. A wide range of information is available from Medicare claims including calendar quarter and year of service, up to 12 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes, Current Procedural Terminology-4 and Healthcare Common Procedure Coding System procedure codes, provider specialty, charges, and Medicare payment amounts. The Medicare claims data were created in accordance with the principles of the Health Insurance Portability and Accountability Act. The current analysis of deidentified Medicare claims data was exempted from an institutional review board review.
From among the beneficiaries who received Medicare coverage between January 1, 2000 and December 31, 2011 due to age (age, ≥65 yr) without disability or end-stage renal disease, candidate case subjects with IPF were identified who had at least one claim with ICD-9-CM diagnosis code of 516.3 (idiopathic fibrosing alveolitis, a code commonly used by providers to identify IPF).
Candidate case subjects were considered to have IPF (i.e., to be true case subjects) if they did not have any other diagnosis code for interstitial lung disease (see Table E1 in the online supplement) on or after the quarter of the last claim with ICD-9-CM diagnosis code 516.3, with the exception of ICD-9-CM diagnosis code 515 (postinflammatory pulmonary fibrosis, a second more general code also commonly used by providers to identify IPF) (11). The quarter of the first observed 516.3 diagnosis code was set as the index quarter. Incident case subjects with IPF were required to have at least 1 year of continuous coverage of Medicare Part A and Part B before the index quarter (preindex period) and after the index quarter (postindex period) to be included in the study.
For the control population, an index year was randomly assigned to beneficiaries without any diagnosis code 516.3. Control subjects were required to have continuous enrollment during 1-year pre- and postindex periods as for case subjects with IPF. For each incident case subject with IPF, we randomly selected as many control case subjects as possible (to a maximum of five) who were the same age in years; of the same sex and race/ethnicity (white, black, Hispanic, or other race); and from the same census region. Case subjects without any matched control subjects available were excluded from the analyses. Because control subjects were randomly selected, we did not expect or control for underlying correlations (paired observations).
Two subgroups of the case subjects with IPF were identified from within the main study cohort, following algorithms used in a previous U.S. epidemiological study (13). Subgroup A, which is consistent with the “broad case definition” in the previous study, excluded patients with ICD-9-CM diagnosis code 515 (postinflammatory pulmonary fibrosis) observed on or after the quarter when the last ICD-9-CM diagnosis code 516.3 was recorded in the database. Subgroup B, which is consistent with the “narrow case definition” in the previous study, included patients in subgroup A who also had at least one claim for a surgical lung biopsy, transbronchial lung biopsy, or computed tomography (CT) scan of the thorax on or before the quarter with the last ICD-9-CM diagnosis code 516.3 recorded in the database.
Claims for selected comorbidities (Table E2) in case and control subjects during the preindex period were examined to report prevalence. Annual HRU during pre- and postindex periods were summarized, including hospitalizations, ER visits, outpatient visits (including physician office visits and visits to specialists, hospital outpatient visits, and other outpatient visits), and use of procedures or tests that are commonly utilized in patients with IPF (Table E3). Medical costs were defined as the total dollar amount reimbursed as recorded in the medical claims, and were reported during pre- and postindex periods as a total amount and by setting. All costs were adjusted to 2012 value based on the Consumer Price Index Medical Component (14).
Summary statistics (mean and standard deviation for continuous and count variables and frequency distribution in percentage for categorical variables) were reported for case and control subjects. Because the health care costs were highly skewed by large amounts (i.e., outliers), the standard error and median of cost variables were reported.
Case and control subjects were compared by Student t test for continuous variables, by chi-square test for categorical variables, and by nonparametric Wilcoxon test for count and costs variables. The prevalence ratio (PR) of comorbidity and utilization ratio of HRU comparing case subjects with control subjects were calculated and the 95% confidence interval was estimated on the basis of Poisson distribution. Data were compiled and analyzed with SAS (version 9.2; SAS Institute Inc., Cary, NC).
A total of 7,855 patients met the case definition for incident IPF and were matched to 38,856 control subjects (Figure 1). The patients with IPF were on average 78 years old, 56.7% female, 91.5% white, 4.1% black, and 1.9% Hispanic (Table 1). The population was geographically diverse. The demographics were well balanced between patients with IPF and control subjects due to matching.

Figure 1. Sample selection. ESRD = end-stage renal disease; ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; IPF = idiopathic pulmonary fibrosis.
[More] [Minimize]Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | |
---|---|---|
Age (yr),* mean (SD) | 78.5 (6.9) | 78.4 (6.9) |
Age (yr),* % | ||
66–69 | 11.1 | 11.2 |
70–74 | 20.4 | 20.5 |
75–79 | 24.9 | 25.0 |
80+ | 43.6 | 43.4 |
Female, % | 56.7 | 56.9 |
Race, % | ||
White | 91.5 | 92.4 |
Black | 4.1 | 4.0 |
Hispanic | 1.9 | 1.5 |
Other† | 2.4 | 2.1 |
Census region, % | ||
New England | 5.3 | 5.4 |
Mid-Atlantic | 13.5 | 13.5 |
East North Central | 15.9 | 16.0 |
West North Central | 6.6 | 6.6 |
South Atlantic | 15.1 | 15.2 |
East South Central | 13.3 | 13.4 |
West South Central | 12.1 | 12.0 |
Mountain | 5.6 | 5.5 |
Pacific | 11.9 | 11.9 |
Unknown | 0.6 | 0.6 |
Index year, % | ||
2001 | 10.9 | 10.9 |
2002 | 10.8 | 10.8 |
2003 | 10.9 | 10.9 |
2004 | 10.0 | 10.0 |
2005 | 9.8 | 9.8 |
2006 | 9.5 | 9.6 |
2007 | 9.0 | 9.0 |
2008 | 9.1 | 9.1 |
2009 | 9.9 | 9.8 |
2010 | 10.0 | 10.0 |
Among case subjects, codes for other pulmonary conditions during the preindex period were common, including chronic obstructive pulmonary disease (41.0%) and respiratory infections (33.1%) (Table 2). Other common preindex comorbidities included nonmyocardial infarction coronary artery disease (40.3%), diabetes (40.0%), fatigue (30.3%), heart failure (25.3%), and gastroesophageal reflux disease (23.4%). All selected comorbidities were more common in case subjects than in control subjects (all P < 0.01), in particular, pulmonary hypertension (PR = 4.9), pneumonia (PR = 3.7), pulmonary embolism (PR = 3.1), chronic obstructive pulmonary disease (PR = 3.0), lung cancer/bronchogenic carcinoma (PR = 2.8), sleep apnea (PR = 2.7), and heart failure (PR = 2.2).
Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | Prevalence Ratio (95% CI) | |
---|---|---|---|
Pulmonary disease, % | 66.3 | 24.2 | 2.7 (2.6–2.8)* |
Chronic obstructive pulmonary disease | 41.0 | 13.5 | 3.0 (2.9–3.2)* |
Asthma | 15.1 | 5.6 | 2.7 (2.5–2.9)* |
Pulmonary infection, % | 33.1 | 13.3 | 2.5 (2.4–2.6)* |
Acute bronchitis and bronchiolitis | 18.8 | 8.9 | 2.1 (2.0–2.2)* |
Pneumonia | 19.9 | 5.3 | 3.7 (3.5–4.0)* |
Influenza | 1.6 | 0.7 | 2.1 (1.7–2.6)* |
Pulmonary hypertension, % | 2.6 | 0.5 | 4.9 (4.0–5.9)* |
Pulmonary embolism, % | 2.5 | 0.8 | 3.1 (2.6–3.8)* |
Lung cancer/bronchogenic carcinoma, % | 2.1 | 0.8 | 2.8 (2.3–3.4)* |
Sleep apnea, % | 4.5 | 1.7 | 2.7 (2.4–3.1)* |
Gastroesophageal reflux disease, % | 23.4 | 15.0 | 1.6 (1.5–1.6)* |
Heart failure, % | 25.3 | 11.5 | 2.2 (2.1–2.3)* |
Cerebrovascular disease, % | 19.0 | 14.8 | 1.3 (1.2–1.4)* |
Myocardial infarction, % | 7.8 | 4.9 | 1.6 (1.5–1.8)* |
Coronary artery disease (exclusive of myocardial infarction), % | 40.3 | 27.5 | 1.5 (1.4–1.5)* |
Acute coronary syndrome, % | 4.2 | 2.3 | 1.9 (1.7–2.1)* |
Atrial fibrillation, % | 19.1 | 11.9 | 1.6 (1.5–1.7)* |
Deep vein thrombosis, % | 1.0 | 0.6 | 1.6 (1.2–2.0)* |
Rib fractures, % | 1.2 | 0.8 | 1.6 (1.3–2.0)* |
Obesity, % | 4.2 | 2.8 | 1.5 (1.3–1.7)* |
Fatigue, % | 30.3 | 21.6 | 1.4 (1.4–1.5)* |
Depression, % | 10.5 | 8.0 | 1.3 (1.2–1.4)* |
Diabetes, % | 40.0 | 34.5 | 1.2 (1.1–1.2)* |
During the preindex period, case subjects had greater HRU in all types of health services than did control subjects (Table 3; all P < 0.01), especially the visits to pulmonologists and IPF-related procedures and tests. Procedures such as chest X-ray (67.2%), CT scan (28.7%), pulmonary function tests (26.5%), and oxygen therapy (16.3%) were common. Case subjects had a higher risk of hospitalization (28.8 vs. 15.8%) and ER visits (23.9 vs. 13.1%) than did matched control subjects (both P < 0.01).
Preindex | Postindex | |||||
---|---|---|---|---|---|---|
Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | Utilization Ratio (95% CI) | Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | Utilization Ratio (95% CI) | |
General Utilization Measures | ||||||
All-cause hospitalization, % | 28.8 | 15.8 | 1.8 (1.7–1.9)* | 48.7 | 20.8 | 2.3 (2.3–2.4)* |
Number of hospitalization, mean (SD) | 0.48 (0.99) | 0.24 (0.69) | 2.0 (1.9–2.0)* | 0.98 (1.44) | 0.36 (0.91) | 2.7 (2.7–2.8)* |
Emergency room visits, % | 23.9 | 13.1 | 1.8 (1.7–1.9)* | 39.6 | 17.5 | 2.3 (2.2–2.4)* |
Outpatient visits, % | ||||||
Physician office visits | 97.2 | 91.8 | 1.1 (1.0–1.1)* | 98.6 | 92.8 | 1.1 (1.0–1.1)* |
Visits to cardiologists | 52.9 | 34.3 | 1.5 (1.5–1.6)* | 67.4 | 40.4 | 1.7 (1.6–1.7)* |
Visits to pulmonologists | 35.4 | 6.9 | 5.1 (4.9–5.4)* | 65.4 | 9.2 | 7.1 (6.8–7.5)* |
Visits to surgeons | 8.1 | 4.5 | 1.8 (1.6–2.0)* | 11.3 | 6.0 | 1.9 (1.7–2.0)* |
Hospital outpatient visits | 71.5 | 52.7 | 1.4 (1.3–1.4)* | 84.0 | 57.5 | 1.5 (1.4–1.5)* |
Other outpatient visits | 68.5 | 61.4 | 1.1 (1.1–1.2)* | 75.2 | 66.5 | 1.1 (1.1–1.2)* |
IPF-Related Procedures/Tests | ||||||
Transbronchial lung biopsy, % | 1.6 | 0.1 | 15.3 (10.8–21.8)* | 4.7 | 0.2 | 26.1 (20.3–33.8)* |
Computed tomography of thorax, % | 28.7 | 5.5 | 5.3 (5.0–5.6)* | 53.5 | 7.4 | 7.3 (6.9–7.6)* |
Surgical lung biopsy, % | 0.4 | 0.1 | 8.3 (4.7–14.7)* | 1.9 | 0.04 | 43.1 (26.1–71.1)* |
Bronchoalveolar lavage, % | 2.2 | 0.2 | 10.8 (8.3–14.2)* | 5.2 | 0.3 | 17.9 (14.6–22.1)* |
Chest X-ray, % | 67.2 | 34.0 | 2.0 (1.9–2.0)* | 87.0 | 40.5 | 2.2 (2.1–2.2)* |
Diagnostic procedures on lung and bronchus, % | 2.6 | 0.3 | 10.3 (8.1–13.1)* | 6.6 | 0.4 | 15.5 (13.0–18.5)* |
Arterial blood gases, % | 1.0 | 0.1 | 7.0 (5.0–9.9)* | 2.3 | 0.2 | 11.3 (8.7–14.6)* |
6-Minute walk test, % | 2.4 | 0.2 | 10.6 (8.2–13.7)* | 6.5 | 0.3 | 19.0 (15.7–22.9)* |
Pulmonary function tests, % | 26.5 | 4.2 | 6.4 (6.0–6.8)* | 50.7 | 5.1 | 10.0 (9.5–10.6)* |
Pulmonary rehabilitation, % | 0.1 | 0.01 | 6.2 (1.7–23.0)* | 0.3 | 0.02 | 16.5 (6.6–41.1)* |
Oxygen therapy, % | 16.3 | 3.3 | 4.9 (4.5–5.3)* | 32.4 | 4.4 | 7.4 (6.9–7.8)* |
During the postindex period, case subjects also had greater HRU than control subjects (Table 3). All-cause hospitalization and ER visits occurred in 48.7 and 39.6% of the patients with IPF, respectively, both 2.3 times more likely than in the control subjects. More than half of case subjects had visits to specialists (67.4% to cardiologists, 65.4% to pulmonologists). The most commonly used procedures/tests among case subjects postindex were chest X-ray (87.0%), CT scan (53.5%), pulmonary function tests (50.7%), and oxygen therapy (32.4%).
Case subjects had higher total medical costs than control subjects during both the pre- and postindex periods (Table 4; all P < 0.01). The average preindex total medical costs were $10,124 per year for the case subjects; 72% more than for the control subjects ($5,888). During the postindex period, average total medical costs doubled to $20,887 per year for the case subjects; 134% more than for the control subjects ($8,932). The higher costs of patients with IPF were driven mostly by inpatient costs (50%) but were consistently higher across all settings. Postindex, total medical costs increased from preindex more substantially in case subjects than control subjects (2.1 vs. 1.5 times; Figure 2).
One Year before Index Quarter | One Year after Index Quarter | |||
---|---|---|---|---|
Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | Case Subjects (n = 7,855) | Control Subjects (n = 38,856) | |
Total medical costs, mean (SE) [median] | 10,124* (200) | 5,888 (162) | 20,887* (323) | 8,932 (220) |
[3,619] | [1,355] | [9,914] | [2,067] | |
Inpatient | 5,033* (152) | 2,530 (103) | 10,405* (219) | 3,821 (136) |
[0] | [0] | [2,577] | [0] | |
Physician office | 1,996* (40) | 1,282 (33) | 2,938* (60) | 1,691 (43) |
[1,141] | [607] | [1,773] | [815] | |
Outpatient hospital | 1,387* (45) | 851 (34) | 2,451* (74) | 1,242 (47) |
[427] | [148] | [982] | [255] | |
Skilled nursing facility | 621* (40) | 490 (37) | 1,884* (75) | 925 (55) |
[0] | [0] | [0] | [0] | |
Hospice | 21 (9) | 68 (18) | 437* (46) | 245 (37) |
[0] | [0] | [0] | [0] | |
Home health | 581* (30) | 474 (62) | 1,581* (77) | 728 (68) |
[0] | [0] | [0] | [0] | |
Durable medical equipment | 486* (14) | 193 (9) | 1,190* (25) | 279 (12) |
[0] | [0] | [163] | [0] |

Figure 2. Total medical costs per patient and distribution by setting between patients with idiopathic pulmonary fibrosis and matched control cohort. IPF = idiopathic pulmonary fibrosis; USD = U.S. dollars.
[More] [Minimize]Subgroup A (“broad case definition”) contained 3,380 case subjects and subgroup B (“narrow case definition”) contained 2,029 case subjects. Compared with each respective subgroup’s matched control subjects, the case subjects had higher medical costs than control subjects, similar to what was seen in the primary cohort (Figure E1).
The results of this study suggest that patients with IPF have increased health care utilization compared with demographically matched control subjects, and incur substantial costs for medical services both before and after the time of diagnosis. It is estimated that there could have been as many as 158,000 patients with IPF covered by Medicare in 2011; thus, estimates from our study lead to a total medical cost of more than $3 billion per year (11) among all patients with IPF, with $1.8 billion attributable to IPF and associated comorbidities.
These results complement a previous study performed using private, employer-based claims data, where 79.2% of the patients with IPF were 65 years of age or older at diagnosis and 45.4% were female (10). Both the current study and the previous publication assessed the economic burden of IPF by direct comparison between patients with IPF and demographically matched control subjects. Our study reported quantitatively similar HRU and cost data as the previous study. Indeed, when excluding outpatient medication costs from the previous study, the estimated total medical costs for patients with IPF were $19,813 per person-year, almost identical to the current study’s estimate. The current findings validate the increased HRU and cost estimates for patients with IPF and strengthen policy implications, because Medicare data are more broadly representative of the general older adult population. Further analyses could be conducted to examine how the burden of IPF varies by age, sex, comorbidity, and mortality.
Inpatient services accounted for half of the medical costs in patients with IPF, and these costs doubled in the postindex period. This reflects the poor prognosis of IPF and the fact that many patients with IPF suffer from acute respiratory events (e.g., pneumonia, acute exacerbation) (15, 16). Postindex HRU and cost increased across all other categories as well, suggesting that IPF is a condition that requires substantial ongoing management. Although patients undergoing evaluation for possible IPF may have more comorbidities identified simply because of the additional surveillance (17), the increased preindex prevalence of comorbidities such as chronic obstructive pulmonary disease, coronary heart disease, and diabetes suggests that comorbidity may be an important contributor to the increased HRU and cost associated with an IPF diagnosis. A structured, comprehensive, multidisciplinary management approach is likely needed (18).
It is probable that the publication of two landmark clinical trial results will have an impact on IPF-related cost in the United States moving forward (19, 20). Two novel drug agents, pirfenidone and nintedanib, appear to slow the rate of disease progression in IPF (as measured by decline in lung function), and were approved by the U.S. Food and Drug Administration. The costs of these therapies are high, and if being used broadly, may greatly increase the cost estimates, solely for medical services, provided here. Of course, if these drug agents are successful in reducing hospitalizations and other HRU (about which neither clinical trial reports data), there may be some reduction in the net cost increase.
An important cost not captured by this study is lung transplantation. For a small but significant minority of patients with IPF, lung transplantation is a life-saving therapy. Indeed, IPF (and other fibrotic lung diseases like IPF) has become a leading indication for lung transplantation in the United States (21, 22). In general, lung transplantation is performed on patients younger than age 65 years, and therefore associated costs are not reflected in the current study. Although our median cost estimates would be unlikely to change (as outliers are minimally influential), future studies should look at the added cost of lung transplantation in calculating the total HRU and cost of IPF.
Retrospective Medicare claims data analysis has several limitations. First, it is challenging to accurately identify patients with IPF from insurance claims data without access to patient-level test results (e.g., CT scan findings). For example, among the patients with IPF identified by ICD-9-CM diagnosis codes and/or procedure codes in our study, only 65.4% had visits to pulmonologists on or after diagnosis, and few (1.9%) underwent surgical lung biopsy to confirm the diagnosis. Nevertheless, it is reassuring that the demographic and survival data in this study cohort match what is described for IPF (11), but future studies should validate the case definitions used here in a data set that can be audited. Second, Medicare excludes both patients who are younger than age 65 years and those who are older but are not covered by the fee-for-service Medicare plans. However, the HRU and cost estimates in the current study match those derived from a private, employer-based data set that included the younger patient population (10). This suggests that the higher burden associated with IPF is true across age groups. Third, the patients with IPF were required to have at least 1 year of survival after diagnosis. Because the analyses excluded patients with shorter survival, and who may have had particularly high utilization, the results provide a conservative estimation of the economic burden of IPF. Last, health care medical costs measured are the amount reimbursed from Medicare, exclusive of outpatient pharmacy costs, and the out-of-pocket costs or supplemental insurance payments were not captured. The pharmacy costs were previously estimated to be $3,532 higher per person per year among patients with IPF compared with demographically matched control subjects (10), which accounted for 29% of the total health care costs attributable to IPF. Thus, the current results provide a conservative estimation of the economic burden of IPF.
The economic burden (HRU and cost) associated with IPF in the Medicare population is substantial, and is significantly greater than in beneficiaries without IPF. These costs are going to increase as the population of older Americans grows and as novel treatments for IPF emerge. Payers and other stakeholders in the care of patients with IPF should commit resources to understanding the care patterns that drive these increased costs and to developing a standard of care practice that provides high-quality, cost-effective care. Future research should focus on comparing the economic burden of IPF with those of other chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and on developing large, representative cohorts of patients with IPF that can be used to analyze the health care delivery process and to test quality improvement strategies to improve the efficiency and effectiveness of care.
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Supported by Biogen.
Author Contributions: H.R.C., S.-Y.C., W.-S.Y., and G.R. conceptualized the study. H.R.C., Q.L., and S.-Y.C. contributed to the study design. Q.L., Y.-C.L., and A.W. acquired and analyzed the data. H.R.C., S.-Y.C., W.-S.Y., Q.L., and G.R. contributed substantially to the interpretation. H.R.C., Q.L., S.-Y.C., and A.W. drafted the manuscript, and W.-S.Y., G.R., and Y.-C.L. critically reviewed and edited the manuscript.
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