Health Benefit Costs and Absenteeism Among Employed Patients With Acromegaly

Open AccessPublished:April 30, 2021DOI:https://doi.org/10.1016/j.eprac.2021.04.412

      Abstract

      Objective

      Acromegaly is associated with increased morbidity and mortality. Limited data are available on these patients’ utilization and costs of health care. This study assessed the impact of acromegaly on employees’ health benefit (direct and indirect) costs and absenteeism.

      Methods

      A retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.

      Results

      Forty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort’s total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups.

      Conclusion

      The presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.

      Key words

      Abbreviations:

      CPI (Consumer Price Index), GH (growth hormone), IGF-1 (insulin-like growth factor 1), LTD (long-term disability), RRDb (research reference database), SL (sick leave), STD (short-term disability), WC (workers’ compensation)

      Introduction

      Acromegaly is a rare disease characterized by chronic growth hormone (GH) hypersecretion that frequently results in GH excess and elevated insulin-like growth factor 1 (IGF-1) levels.
      • Melmed S.
      • Bronstein M.D.
      • Chanson P.
      • et al.
      A consensus statement on acromegaly therapeutic outcomes.
      ,
      • Melmed S.
      Acromegaly pathogenesis and treatment.
      The prevalence of acromegaly ranges between 2.8/100 000 and 13.7/100 000 people and the annual incidence rates range between 0.2/100 000 and 1.1/100 000 people.
      • Lavrentaki A.
      • Paluzzi A.
      • Wass J.A.H.
      • Karavitaki N.
      Epidemiology of acromegaly: review of population studies.
      Patients are most commonly diagnosed in their 40s, during their peak productive working years.
      • Lavrentaki A.
      • Paluzzi A.
      • Wass J.A.H.
      • Karavitaki N.
      Epidemiology of acromegaly: review of population studies.
      Effective multidisciplinary management to normalize GH and IGF-1 levels can help reduce the risk of the sequelae of acromegaly.
      • Giustina A.
      • Barkhoudarian G.
      • Beckers A.
      • et al.
      Multidisciplinary management of acromegaly: a consensus.
      Early diagnosis and optimal treatment to slow disease progression is crucial in reducing the risk of long-term morbidity (eg, cardiovascular disease, osteoarthritis, sleep apnea, and type 2 diabetes mellitus), abnormal tissue growth, and premature death.
      • Katznelson L.
      • Atkinson J.
      • Cook D.
      • et al.
      American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly—2011 update.
      Surgery is often considered first-line therapy for most patients with acromegaly, but many require additional therapy with somatostatin-receptor ligands (eg, octreotide and lanreotide), dopaminergic agonists (eg, bromocriptine or cabergoline), GH receptor antagonists (eg, pegvisomant), and/or radiotherapy.
      • Katznelson L.
      • Atkinson J.
      • Cook D.
      • et al.
      American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly—2011 update.
      Relatively little information is available on health services used by patients with acromegaly and their associated health expenditures. As acromegaly is most often diagnosed during a patient’s most productive years, considerable real-world information about how it is treated and how it affects patients’ ability to work might be obtained through the claims information of employer-sponsored health plans. Some studies of acromegaly that have been published use federal or commercial databases to analyze prevalence, treatment patterns, and adherence.
      • Gurel M.H.
      • Han Y.
      • Stevens A.L.
      • et al.
      Treatment adherence and persistence with long-acting somatostatin analog therapy for the treatment of acromegaly: a retrospective analysis.
      • Caputo M.
      • Ucciero A.
      • Mele C.
      • et al.
      Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont Region.
      • Chuang C.C.
      • Bhurke S.
      • Chen S.Y.
      • Dinet J.
      • Brulais S.
      • Gabriel S.
      Treatment patterns and economic burden in patients treated for acromegaly in the USA.
      • Burton T.
      • Le Nestour E.
      • Neary M.
      • Ludlam W.H.
      Incidence and prevalence of acromegaly in a large US health plan database.
      • Broder M.S.
      • Chang E.
      • Ludlam W.H.
      • Neary M.P.
      • Carmichael J.D.
      Patterns of pharmacologic treatment in US patients with acromegaly.
      However, data on the impact of acromegaly on employees’ health costs (direct and indirect) are limited. Furthermore, even less information is available on the burden of acromegaly from an employer’s perspective, including health benefit costs and worker productivity.
      Therefore, the objectives of this analysis are to contribute significantly to the information available on the clinical and economic burden associated with acromegaly. Specifically, we aim to describe the comorbidities of patients of working age with acromegaly and the utilization of medical interventions, assess the impact of acromegaly on health benefit costs in an employed population, and quantify lost time related to acromegaly in the work force.

      Methods

       Patient Selection

      To better understand the impact of acromegaly on health benefit costs in an employed population and on work absenteeism, the WorkPartners (formerly known as Human Capital Management Services) research reference database (RRDb) was analyzed. The Workpartners RRDb is a proprietary database of deidentified employee health claims (with information on 4.6 million lives, including 2.9 million U.S. employees), prescription drug, and medical claims (including site of care), in addition to human resource data on payments and absenteeism (including short-term disability [STD] and long-term disability [LTD], absenteeism, and workers’ compensation claims) from January 2001 to present. Employers in the RRDb represent the retail, service, manufacturing, transportation, energy, technology, financial, and utility industries. The database includes information on all individuals’ genders, ages, and health plan claims (medical and prescription) from multiple insurers across the United States, which is representative of general population and average patients with acromegaly.
      The database also includes information on 4 indirect absence benefits in terms of cost and lost time. Sick leave (SL) is typically provided for brief illnesses lasting less than 2 weeks. Although on SL, employees generally receive 100% of their salary, and the number of days of SL per year offered by employers varies by employer and often by employee level and tenure.
      National compensation survey
      Program perspectives on paid sick leave. US Bureau of Labor Statistics. 2(2).
      Short-term disability includes illnesses that last between 1 or 2 weeks and 6 months. Employees receive 60% to 100% of their salary while on STD leave. If the illness lasts longer than 6 months, the employee begins LTD and usually receives 50% to 80% of salary.
      • Hotfelder A.
      Understanding Your Long-Term Disability Policy.
      Employees injured on the job may file a workers’ compensation (WC) claim, which includes payments for medical services to treat the injury and salary-replacement payments (66% to 80% of salary, depending on location).
      • Hunt H.A.
      Is compensation for workplace injuries adequate?.
      Although this research focuses on 4 different types of absences, the categories are not substitutable, and attempts to redistribute LTD absence to STD, SL, or another benefit, for example, would be difficult due to the eligibility requirements for these conditions.
      From this database, we retrospectively identified patients with acromegaly based on claims with the International Classification of Disease ninth revision (ICD-9) code 235.0
      ICD-9-CM diagnosis Code 253.0: Acromegaly and gigantism. ICD9data.com.
      or tenth revisions (ICD-10) code E22.0, during the period between January 2010 and April 2019. The index date was defined as the date of the first acromegaly diagnosis identified in the database. All claims data were captured for the index date and the following 12 months (the study period).
      To be included in the study, patients had to be between 18 and 64 years of age on their index date to reflect the typical patients’ working years. Eligible patients had to be continuously employed and covered during the study period. In addition, patients had to have adjudicated claims meeting the following criteria:
      • At least 2 claims with diagnoses of acromegaly at least 30 days apart or
      • One diagnosis of acromegaly plus either a diagnosis of pituitary adenoma or 1 claim for pituitary surgery (hypophysectomy) or stereotactic radiosurgery
      Patients were excluded if there was evidence of any other nonacromegaly pituitary disorders in the claims information, such as prolactinoma, nonfunctioning pituitary adenoma, Cushing disease, or craniopharyngioma.
      The control group comprised randomly selected employees who did not have acromegaly as a diagnosis during the patient selection period and were continuously employed and covered by insurance during the study period. The claims for each eligible patient with acromegaly were matched with those of 20 randomly assigned control employees to provide increased statistical power for the between-group comparisons while studying patterns in a rare disease. Controls were matched according to demographics (age, sex, marital status, self-reported racial information), job-related variables (salary, full-time or part-time status, eligibility for overtime [ie, exempt or nonexempt status]), region of the country (based on the first digit of the employee’s ZIP code), and index date. Cost data were adjusted to constant 2019 dollars using the general Consumer Price Index (CPI), the medical CPI, and the prescription drug cost CPI from the U.S. Bureau of Labor Statistics.
      Consumer Price Index (November 2019)
      U.S. Bureau of Labor Statistics.

       Study Variables

      Health care utilization and costs for the patient and control groups were compared for direct medical and prescription drug costs and indirect costs due to salary-replacement payments to the employee for absences due to SL, STD and LTD, and WC by benefit type. Patients with acromegaly were examined for evidence of acromegaly-related surgical procedures and radiotherapies. Additionally, patients and control subjects were evaluated for lost time, including SL, STD and LTD, and WC. The study plan included all absence claims initiated during the study period. Data collection on LTD claims continued beyond the follow-up period (owing to the potential lengthy duration of LTD).
      Analysis of each direct cost, indirect cost, or lost time (days absent) outcome included only those employees who were continuously eligible and/or enrolled in the appropriate medical leave plan for the entire study period. This ensures that employees with missing cost or lost time information, due to ineligibility for a benefit, did not skew the results for that benefit.

       Statistical Analysis

      Baseline demographic and job-related variables and comorbidities were compared between the cohorts using t tests for continuous variables and X2 tests for binary variables.
      Each outcome was analyzed using separate 2-stage regression models. The first stage used logistic regression to model the likelihood of an outcome greater than zero — for example, those with disability claims versus those without disability claims. The second stage used generalized linear models on the portion of the population with a greater-than-zero outcome. The results of the generalized linear models were then combined with the results of the logistic models to reach an expected value of cost or days for all employees. The following cost and absence outcomes were individually analyzed: direct medical costs, prescription costs for acromegaly and nonacromegaly drugs, SL cost, STD cost, LTD cost, WC cost, SL days, STD days, LTD days, and WC days. In each case, the regression models controlled for the impact of such confounding factors as age, sex, marital status, race, exempt/nonexempt status, full-time/part-time status, salary, region, and the Charlson comorbidity index score
      • Hunt H.A.
      Is compensation for workplace injuries adequate?.
      (a risk-adjusting score built from claims data indicators of serious comorbid conditions that are predictive of mortality).
      Comorbidity categories were defined using those of United States Agency for Health Research and Quality.
      • Elixhauser A.
      • Steiner C.
      • Harris D.R.
      • Coffey R.M.
      Comorbidity measures for use with administrative data.
      All models and statistics were generated via SAS Enterprise, version 7.15 (SAS Institute Inc). Continuous data are shown as means ± standard error of the mean, and a P value of < .05 was considered statistically significant.

      Results

       Demographic Analysis

      A total of 47 eligible patients with acromegaly were identified from the database (Table 1), and they were matched to 940 controls. An evaluation of baseline characteristics (Table 2) revealed similarities in the majority of demographic (age, gender, and self-reported race) and job-related variables (tenure, full-/part-time status, exempt status, and salary level). The only significant difference between the patient and control groups was a higher percentage of employees with acromegaly who reported an unmarried status compared with the matched control employees (21.3% vs 11.1%, respectively; P = .0326) (Table 2). However, the percentage of those reporting that they were married was not significantly different between the patient and matched control population; however, it should be noted that marital status (or racial information) was not available from the claims data for a portion of patient and control employees (Table 2).
      Table 1Identification of Eligible Patients With Acromegaly
      The criteria are not mutually exclusive.
      DescriptionNumber
      Employees in the database2 844 389
      Employees in the database from 2010 to 20191 201 197
      Employees with ≥2 acromegaly diagnoses ≥30 days apart52
      Employees with ≥1 acromegaly diagnosis plus 1 pituitary adenoma diagnosis within 1 year, plus 1 claim for pituitary surgery (hypophysectomy) or stereotactic radiosurgery8
      Exclude: Employees with other pituitary diseases (ie, Cushing disease)(1)
      Items in parentheses represent exclusion criteria.
      Exclude: Employees without continuous enrollment data(12)
      Items in parentheses represent exclusion criteria.
      Eligible employees with ≥1 year continuous post–index date records47
      a The criteria are not mutually exclusive.
      b Items in parentheses represent exclusion criteria.
      Table 2Baseline Characteristics Employees or Acromegaly
      VariableEmployees with acromegaly (N = 47)Employees without acromegaly (N = 940)Difference between cohortsP value
      MeanStandard errorMeanStandard error
      Age at index date (years)47.81.845.70.42.1.2243
      Tenure at index date (years)7.71.57.80.3-0.1.9110
      Sex (% female)40.4%7.2%46.7%1.6%-6.3%.3998
      % married14.9%5.2%13.5%1.1%1.4%.7871
      % Not married21.3%6.0%11.1%1.0%10.2%.0325
      Difference is statistically significant.
      % Married missing63.8%7.1%75.4%1.4%-11.6%.0737
      % White19.1%5.8%16.2%1.2%3.0%.5896
      % African American2.1%2.1%1.6%0.4%0.5%.7781
      % Hispanic6.4%3.6%4.0%0.6%2.3%.4326
      % Other race0.0%0.0%2.3%0.5%-2.3%.2888
      % Race missing72.3%6.6%75.9%1.4%-3.5%.5840
      % Exempt from overtime
      An indicator of the percentage of the employee population who are classified as management versus other employees.
      27.7%6.6%28.4%1.5%-0.7%.9120
      Annual salary
      For annual salary, data were based on 33 patients and 660 matched controls.
      $72 907$7724$72,904$1702$4.9996
      a Difference is statistically significant.
      b An indicator of the percentage of the employee population who are classified as management versus other employees.
      c For annual salary, data were based on 33 patients and 660 matched controls.

       Comorbidity Analysis

      Employees with acromegaly were found to have several significant differences with respect to comorbidities compared with the employees without acromegaly. At baseline, patients had a 0.30 greater Charlson comorbidity index score than their control counterparts (P = .029). Over the 12 months postindex, patients with acromegaly had significantly more claims for medical services associated with arthritis (difference between groups, 15.4%; P < .0001), chronic lung disease (14.5%; P = .012), diabetes (23.6%, P < .0001), hyperlipidemia (11.7%, P = .0350), hypertension (26.8%, P < .0001), and thyroid disease (23.0%, P < .0001) (Table 3).
      Table 3Comorbid Conditions in Employees With or Without Acromegaly
      Comorbidity categoriesEmployees with acromegaly (N = 47)Employees without acromegaly (N = 940)P value
      MeanStandard errorMeanStandard error
      Alcohol disorder0.0%0.0%0.6%0.3%.5827
      Anxiety8.5%4.1%7.6%0.9%.8090
      Arthritis19.1%5.8%3.7%0.6%<.0001
      Difference is statistically significant.
      Chronic lung disease31.9%6.9%17.4%1.2%.0120
      Difference is statistically significant.
      Depression12.8%4.9%6.7%0.8%.1116
      Diabetes31.9%6.9%8.3%0.9%<.0001
      Difference is statistically significant.
      Gastrointestinal disease21.3%6.0%15.1%1.2%.2528
      Hyperlipidemia27.7%6.6%16.0%1.2%.0350
      Difference is statistically significant.
      Hypertension40.4%7.2%13.6%1.1%<.0001
      Difference is statistically significant.
      Thyroid disease31.9%6.9%8.9%0.9%<.0001
      Difference is statistically significant.
      Charlson comorbidity index score0.600.150.300.03.0292
      Difference is statistically significant.
      a Difference is statistically significant.

       Health Care Utilization Analysis

      Patients with acromegaly had significantly greater utilization (or costs) associated with specific health care services compared with the matched control population. Employees with acromegaly were 12 times as likely to have undergone a magnetic resonance imaging scan as those without acromegaly (70.2% vs 6%, P < .0001).
      Out of the 47 identified patients with acromegaly, 27 (57.0%) had no claims for acromegaly-indicated medications during the 12-month follow-up period. Of the 20 patients who had claims for acromegaly-indicated medications, 90.0% used a single agent, 5.0% used 2 agents, and 5.0% used 3 agents. The most commonly used agents were somatostatin analogs, including lanreotide depot (10.6%), octreotide long-acting release (10.6%), and octreotide (2.1%); 11 were taking dopamine agonists (23.4%), including cabergoline (19.1%) and bromocriptine (4.2%); 3 were taking the GH receptor antagonist pegvisomant (6.4%); and no patients took pasireotide.
      During the study period, 10 out of 47 patients (21.3%) with acromegaly underwent pituitary tumor surgery, with 7 out of 10 (70%) surgeries performed using the transnasal or transeptal excision approach, whereas there were no claims for radiotherapy. There were no claims in the database for pituitary surgeries prior to patients’ first acromegaly claims in the database. The matched controls did not have claims for pituitary surgery or radiotherapy.

       Health Cost Analysis

      The direct medical costs of patients with acromegaly (expressed as mean ± standard error of the mean) were on average 10 times that for matched controls ($34 454 ± $6742 vs $3497 ± $162, respectively; P < .0001) (Table 4). Prescription drugs accounted for 25.2% of the costs for those with acromegaly and 25.6% in controls (but were 88.9% greater in cost for patients with acromegaly). Acromegaly drug costs ($9925 ± $3037) were 20.5% of the total direct medical expenditures for employees with acromegaly.
      Table 4Health Benefit Costs in Employees With or Without Acromegaly
      Cost categoryEmployees with acromegalyEmployees without acromegalyP value
      NAdjusted mean costsStandard errorNAdjusted mean costsStandard error
      Direct components
       Medical47$34 454$6742940$3497$162<.0001
      Difference is statistically significant.
       All Rx cost47$13 887$3110940$1173$62<.0001
      Difference is statistically significant.
       Total direct costs47$48 341940$4670
      Indirect components
      For indirect components, N equals employees or controls eligible for the benefit (not number of claims).
       Sick leave9$450$376209$372$44.8364
       Short-term disability25$1837$713469$139$43.0175
      Difference is statistically significant.
       Long-term disability
      Long-term disability costs based on a small sample and are the actual (not modeled) value for each cohort.
      21$10 084$10 084439$609$576.3593
       Worker’s compensation31$7$7610$109$24<.0001
      Difference is statistically significant.
       Total indirect costs
      Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      $12 378$1229
       Total indirect costs
      Sum of the adjusted means for components with varying sample sizes long-term disability costs excluded; therefore no standard error and P values were calculated.
      $2294$620
       Total health benefit costs
      Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      $60 720$5899
       Total health benefit costs
      Sum of the adjusted means for components with varying sample sizes long-term disability costs excluded; therefore no standard error and P values were calculated.
      $50 635$5289
      a Difference is statistically significant.
      b For indirect components, N equals employees or controls eligible for the benefit (not number of claims).
      c Long-term disability costs based on a small sample and are the actual (not modeled) value for each cohort.
      d Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      e Sum of the adjusted means for components with varying sample sizes long-term disability costs excluded; therefore no standard error and P values were calculated.
      The cost of nonacromegaly prescription drugs in the acromegaly cohort ($2255 ± $506) was approximately double the cost for matched controls ($1194 ± $63, P = .038). Total mean direct health costs (medical and pharmaceutical) for employees with and without acromegaly were $48 341 and $4670, respectively, more than a 10-fold difference.
      Total indirect costs (including SL and disability) were higher for patients with acromegaly ($10 395 vs $1128, respectively). STD costs were higher ($1837 ± $713 vs $139 ± $43, P = .0175), whereas WC costs for the patients with acromegaly were lower compared with the matched controls ($7 ± $7 vs $109 ± $24, P < .0001).

       Total Lost Time

      As shown in Table 5, compared with the employees without acromegaly, employees with acromegaly use more STD time (adjusted mean 9 days; P = .0117), whereas the number of absence days under the SL benefit were similar in the 2 groups. The logistic regression adjusted percentages of employees using their SL benefit were similar in the 2 groups. STD was used by 24.0% ± 9.0% of the cohort with acromegaly compared with 2.3% ± 1.0% of controls (P = .0112).
      Table 5Lost Work Days in Employees With or Without Acromegaly
      Absence categoryEmployees with acromegalyEmployees without acromegalyP value
      NAdjusted mean daysStandard errorNAdjusted mean daysStandard error
      Sick leave91.61.42091.10.1.7039
      Short-term disability259.63.64690.60.2.0117
      Difference is statistically significant
      Long-term disability
      Long-term disability and workers’ compensation absences based on small samples and are the actual (not modeled) value for each cohort.
      2186.986.94391.31.3.3362
      Worker’s compensation
      Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      310.00.06100.10.1.1212
       Total absence days
      Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      98.23.1
       Total absence days
      Sum of the adjusted means for components with long-term disability absences excluded; therefore no standard error and P values were calculated.
      11.21.8
      Abbreviation: N = number eligible for the benefit.
      a Difference is statistically significant
      b Long-term disability and workers’ compensation absences based on small samples and are the actual (not modeled) value for each cohort.
      c Sum of the adjusted means for components with varying sample sizes; therefore no standard error and P values were calculated.
      d Sum of the adjusted means for components with long-term disability absences excluded; therefore no standard error and P values were calculated.

      Discussion

      A growing number of people with potentially complex chronic conditions are employed in the U.S. workforce,
      • Vogenberg F.R.
      • Holland J.P.
      • Liebeskind D.
      Employer benefit design considerations for the era of biotech drugs.
      despite many chronic disease states resulting in lower productivity and even disability. Acromegaly is a rare disease, and to our knowledge, this is the first investigation of acromegaly that compared the health costs, health benefit utilization, and work absences to those of a general working-age population.
      This study has demonstrated acromegaly is linked to substantially higher total health benefit costs compared to those without acromegaly. Specifically, patients with acromegaly had medical service utilization, total prescription costs, total direct health costs, and indirect health care costs that were at least 10-fold as high as the matched employees, with claims up to $44 126 involving testing of GH and IGF-1 levels and other tests relevant for monitoring of acromegaly control (97.3% of costs and 78.5% of services were in nonlaboratory settings). However, data on acromegaly control were not obtainable from Workpartners RRDb. Most claims databases, including those used by Burton et al
      • Burton T.
      • Le Nestour E.
      • Neary M.
      • Ludlam W.H.
      Incidence and prevalence of acromegaly in a large US health plan database.
      and Placzek et al,
      • Placzek H.
      • Xu Y.
      • Mu Y.
      • Begelman S.M.
      • Fisher M.
      Clinical and economic burden of commercially insured patients with acromegaly in the United States: a retrospective analysis.
      do not include measures of acromegaly control. In addition, there were no claims for radiotherapy, suggesting that this form of therapy may not have been used within the 12-month study period but does not discount that it may have been used beyond the 12-month study period. In keeping with the present data, after analyzing the same database that included the spouses of patients with acromegaly, we found that acromegaly was also associated with significantly higher utilization of care and more chargeable services at all locations of care.
      • Ribeiro-Oliveira Jr., A.
      • Brook R.A.
      • Munoz K.A.
      • et al.
      Burden of acromegaly in the United States: increased health services utilization, location of care, and costs of care.
      The low utilization of pharmacotherapy (42.6%) and surgeries (21.3%) in the present study is consistent with the data from previous studies. In a study with a similar 12-month period and no preperiod eligibility requirement, Broder et al
      • Broder M.S.
      • Neary M.P.
      • Chang E.
      • Cherepanov D.
      • Katznelson L.
      Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases.
      reported 30.8% of patients using pharmacologic treatment and 5.3% receiving surgery. These authors suggested the low surgical rates may have been due to patients receiving a diagnosis before the study index date, and surgery procedures may thus have occurred before the 12-month follow-up period. It is also possible that the prior surgery may have successfully induced disease remission in some patients, resulting in the reduced need for pharmacotherapy, whereas for some patients not on pharmacotherapy, they might have been on a waiting list for surgery in centers where a neurosurgeon was not readily available, or they were lost to follow-up after surgery.
      The present study also demonstrated that the majority of costs in employees with acromegaly were related to treatments (eg, medical visits and therapies), whereas indirect costs (associated with absences and leaves) represented a quarter of the total. The present study was consistent with Broder and colleagues,
      • Broder M.S.
      • Neary M.P.
      • Chang E.
      • Cherepanov D.
      • Katznelson L.
      Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases.
      where they reviewed claims from 2 databases filed between 2002 and 2009, and identified nearly 2200 patients with acromegaly and found mean health care costs of $24 900 per patient/year. Direct medical costs were mostly associated with the utilization of outpatient services, and costs rose with more comorbid conditions (eg, cardiovascular conditions added a mean $18 840 to the total health care costs). However, Broder’s study
      • Broder M.S.
      • Neary M.P.
      • Chang E.
      • Cherepanov D.
      • Katznelson L.
      Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases.
      did not quantify indirect health costs, and no control groups were used. The direct medical costs resulted not only in a considerable economic burden for employers but also for the employees with acromegaly.
      Chuang and colleagues
      • Chuang C.C.
      • Bhurke S.
      • Chen S.Y.
      • Dinet J.
      • Brulais S.
      • Gabriel S.
      Treatment patterns and economic burden in patients treated for acromegaly in the USA.
      published the results of claims database analysis from 2007 to 2010 of 397 patients with acromegaly and stratified them into groups receiving surgical resection with or without medical therapy or medical therapy only. Their study demonstrated that patients who had received surgery had 69% higher mean direct health care costs compared with those in the medical therapy only group. In another study evaluating a commercial database covering claims from 2008 to 2012, Placzek and colleagues
      • Placzek H.
      • Xu Y.
      • Mu Y.
      • Begelman S.M.
      • Fisher M.
      Clinical and economic burden of commercially insured patients with acromegaly in the United States: a retrospective analysis.
      reported that just over half of the patients were on medical therapy, and 18.8% underwent a hospital stay related to acromegaly. These researchers found that the direct economic burden of acromegaly was driven largely by the costs of medical therapy and inpatient services, with the total 12-month, direct medical costs averaging $32 807.
      For the indirect cost components (including productivity), the present study analyzed the impact of claims initiated during the study period. Absences in our study were higher for the employees with acromegaly compared to the nonacromegaly employees and were reported based on 4 benefit types. Not all employers provide all absence benefits to all employees, and some benefits are earned by employees over time and require benefit eligibility at the index date. In the United States, absences reported under the SL benefit generally do not require evidence of a sickness or a doctor’s call and may be used by some employees for paid time off.
      Only 1 employee with acromegaly and 2 employees in the control cohort used the LTD benefit and could be considered outliers. Compared with controls, patients with acromegaly had $9475 higher LTD costs (16.6 times the controls) and 85.7 more LTD absence days (68.6 times controls). At the time of the analysis, the actual LTD claim for the employee with acromegaly was still ongoing after 1826 days. The average reported duration was calculated by dividing these days by the 21 participants with acromegaly to yield the 86.9 days. Despite the larger magnitude, the cost and lost time differences between cohorts were not statistically significant. Furthermore, people receiving STD benefits are more likely to have relatively high concurrent medical spending, often for conditions not directly related to the cause of the STD.
      • Contreary K.
      • Ben-Shalom Y.
      • Gifford B.
      Using predictive analytics for early identification of short-term disability claimants who exhaust their benefits.
      Unfortunately, the STD claims do not always include a reason for the claim, and these patients may have used their STD benefits for conditions other than acromegaly.
      The present study has several strengths. The study was conducted in a diverse, commercial workplace-centric database that was representative of patients dispersed throughout the United States. The database includes information on indirect components, and links all employees based on their employee identification, allowing for tracking and monitoring as the employees change their health plans. The database also includes job-related information (salary, exempt status, and full-time status), self-reported racial information not contained in the other databases, and differentiated types of employee absences from work. Other researchers
      • Chuang C.C.
      • Bhurke S.
      • Chen S.Y.
      • Dinet J.
      • Brulais S.
      • Gabriel S.
      Treatment patterns and economic burden in patients treated for acromegaly in the USA.
      • Burton T.
      • Le Nestour E.
      • Neary M.
      • Ludlam W.H.
      Incidence and prevalence of acromegaly in a large US health plan database.
      • Broder M.S.
      • Chang E.
      • Ludlam W.H.
      • Neary M.P.
      • Carmichael J.D.
      Patterns of pharmacologic treatment in US patients with acromegaly.
      ,
      • Placzek H.
      • Xu Y.
      • Mu Y.
      • Begelman S.M.
      • Fisher M.
      Clinical and economic burden of commercially insured patients with acromegaly in the United States: a retrospective analysis.
      have used commercial claims data to assess health care costs associated with acromegaly, but their analyses were based on single payors
      • Burton T.
      • Le Nestour E.
      • Neary M.
      • Ludlam W.H.
      Incidence and prevalence of acromegaly in a large US health plan database.
      ,
      • Placzek H.
      • Xu Y.
      • Mu Y.
      • Begelman S.M.
      • Fisher M.
      Clinical and economic burden of commercially insured patients with acromegaly in the United States: a retrospective analysis.
      or multiple insurer databases
      • Chuang C.C.
      • Bhurke S.
      • Chen S.Y.
      • Dinet J.
      • Brulais S.
      • Gabriel S.
      Treatment patterns and economic burden in patients treated for acromegaly in the USA.
      ,
      • Broder M.S.
      • Chang E.
      • Ludlam W.H.
      • Neary M.P.
      • Carmichael J.D.
      Patterns of pharmacologic treatment in US patients with acromegaly.
      limited to 4 United States census regions lacking continuity when patients change health plans.
      Claims and demographic information from patients with acromegaly and matched controls were obtained and compared, without reliance on subjective measurements or recall bias. The 20:1 matching process reduces the standard errors of the outcome variables for the control group, strengthening the power of the between-group comparisons.
      The inclusion of a control group allowed calculation of the incremental impact of acromegaly on study outcomes and significance between cohorts, whereas patient data were filtered for other complicating medical conditions.
      This study has several limitations, such as the small sample size of the patient population, which is likely attributable to the low prevalence of acromegaly in the population.
      • Burton T.
      • Le Nestour E.
      • Neary M.
      • Ludlam W.H.
      Incidence and prevalence of acromegaly in a large US health plan database.
      The 10-year database review yielded only 47 employees with acromegaly, for a prevalence of approximately 1 patient for every 25 500 employees in the database (ie, 3.76 per 100 000), which falls within the range of acromegaly prevalence previously reported.
      • Lavrentaki A.
      • Paluzzi A.
      • Wass J.A.H.
      • Karavitaki N.
      Epidemiology of acromegaly: review of population studies.
      These administrative claims data are derived from employees with commercial health insurance over the study period, and may not be generalizable to patients who do not have employer-sponsored health insurance or who are unemployed.
      The study did not assess the ramifications of treatment types on patient quality of life, direct health care costs, or employee productivity, and could not ascertain disease control of the patients. Finally, because the study was conducted over a relatively short period, an estimate cannot be inferred as to how longer follow-up might have affected health care utilization or costs in these patients; it may not be unreasonable to expect patients who had undergone hypophysectomy or radiosurgery to demonstrate lower utilization and costs over longer periods.

      Conclusion

      The findings of this study indicate that acromegaly has substantial implications on direct and indirect employee health benefit costs and increases work absenteeism. Acromegaly was associated with substantial direct and indirect costs, including at least 10-fold increases in direct medical/surgical and total direct costs compared with matched employees without acromegaly. Therefore, employers should take into consideration the impact of acromegaly on an employee’s work productivity, so that they can tailor working conditions accordingly and prevent unrealistic work expectations from their employees with this condition.

      Acknowledgment

      We thank Nathan L. Kleinman, PhD, of the Workpartners, Cheyenne, WY, for comments on the draft and interpretation of the results and Stanton R. Mehr of SM Health Communications, Newtown, PA, for providing medical writing and editorial support for this research. This study was sponsored by Ipsen , Cambridge, MA. This study was presented virtually at the 2020 Endocrine Society Annual Meeting, San Francisco, and the abstract was published as: Yuen KCJ, Munoz KA, Brook RA, et al. Acromegaly significantly impacts employees’ health benefit costs and increases work absenteeism. JESOCI. 2020;4(Suppl):A189-A190.

      Disclosure

      The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: K.C.J.Y has received research grants to his institution for clinical research studies from Ionis, Crinetics, and Novartis. R.A.B., I.A.B., N.J.R., and K.C.J.Y. are consultants to Ipsen. K.C.J.Y. has served on advisory boards for Pfizer, Ipsen, Crinetics, and Chiasma. The following authors are employees of Ipsen and hold company stock: A.R.-O., K.A.M., and J.D.W. These are the only disclosures relevant to this manuscript.

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