1369-6998
`doi:10.3111/13696998.2013.877470
`
`Journal of Medical Economics
`
`Vol. 17, No. 4, 2014, 288–295
`
`Article 0150.R1/877470
`All rights reserved: reproduction in whole or part not permitted
`
`Original article
`Budget impact of pasireotide for the treatment of
`Cushing’s disease, a rare endocrine disorder
`associated with considerable comorbidities
`
`Copyright © 2014 Informa UK Limited
`Not for Sale or Com mercial Distribution
`Unauthorized use prohibited. Authorised users can download,
`display, view and print a single copy for personal use
`
`H. L. Truong
`D. Nellesen
`Analysis Group, Menlo Park, MA, USA
`W. H. Ludlam
`M. P. Neary
`Novartis Pharmaceuticals Corporation, East Hanover,
`NJ, USA
`
`Address for correspondence:
`Hong L. Truong, MPH, Analysis Group, 1010 El
`Camino Real, Menlo Park, CA 94025, USA.
`Tel: +1 650 463 2716; Fax: +1 650 323 2796;
`htruong@analysisgroup.com
`
`Keywords:
`Budget-impact – Cushing’s disease – Orphan disease
`
`Accepted: 17 December 2013; published online: 11 March 2014
`Citation: J Med Econ 2014; 17:288–295
`
`Abstract
`
`Objectives:
`Cushing’s disease (CD) is a rare condition with a prevalence of roughly 39 cases per million in the general
`population. Healthcare costs are substantial for CD patients with either untreated or inadequately controlled
`disease. This study assesses the 3-year budget impact of pasireotide on a US managed care health plan
`following pasireotide (Signifor*) availability.
`
`Methods:
`Two scenarios were evaluated to understand the differences in costs associated with the introduction of
`pasireotide. The first scenario evaluates the budget impact of pasireotide from the perspective of an entire
`health plan (total budget impact) and the second from the perspective of the pharmacy budget (pharmacy
`budget impact). Both scenarios evaluate the annual incremental budget impact with and without pasireotide.
`Scenario 1 includes costs for medical procedures, drug therapies, monitoring, surgical complications,
`comorbidities for patients with controlled or uncontrolled CD, and adverse events. Procedures include
`transsphenoidal surgery, bilateral adrenalectomy,
`radiotherapy and radiosurgery. Drugs include
`pasireotide (indicated for CD), mifepristone (indicated to control hyperglycemia secondary
`to
`hypercortisolism in patients with Cushing’s syndrome) as well as several off-label
`treatments
`(ketoconazole, cabergoline, mitotane). Scenario 2 considers costs solely from the perspective of a health
`plan pharmacy. Costs are in $2013.
`
`Results:
`The estimated total budget impact is $0.0115 per-member per-month (PMPM) in the first year following
`FDA approval, $0.0184 in the second year, and $0.0194 in the third year. Introduction of pasireotide is
`expected to increase the pharmacy budget by $0.0257 PMPM in the first year, $0.0363 in the second year,
`and $0.0360 in the third year.
`
`Limitations:
`Model inputs rely on the small body of literature available for Cushing’s disease.
`
`Conclusions:
`Cushing’s disease is severe disease with debilitating comorbidities and substantial healthcare costs when
`untreated or inadequately controlled. The inclusion of pasireotide in a health plan formulary appears to have
`only a small impact on the total health plan or pharmacy budget.
`
`Introduction
`
`Cushing’s disease (CD) is a rare disease and a form of Cushing’s syndrome that is
`a result of long-term exposure to glucocorticoids caused by excessive secretion of
`adrenocorticotropin hormone (ACTH) by a pituitary corticotroph tumor
`
`*Signifor is a registered trademark of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
`
`288 Budget impact of pasireotide for the treatment of Cushing’s disease Truong et al.
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`(pituitary adenoma)1–5. Patients with CD experience a
`remarkably broad spectrum and high prevalence of comor-
`bidities associated with chronic hypercortisolism, and
`diagnosis of CD is challenging in part because of the
`many disparate manifestations of the disease2. A claims
`study conducted in the US found that 44% of patients
`had a CD-related condition or procedure prior to their
`first Cushing’s syndrome diagnosis code, which suggests a
`delayed diagnosis cohort may exist6. Mortality studies have
`been conducted among only a limited set of patients.
`However, one meta-analysis
`shows
`that
`the overall
`CD-related mortality among CD patients that are treated
`primarily with transsphenoidal surgery (TSS) is roughly
`twice that of the general population7.
`Epidemiological studies of CD are few and provide
`only very limited information regarding estimates of the
`incidence and prevalence of this rare disorder in the
`general population8–10. A chart review of records from
`the National Health Service in Vizcaya, Spain found a
`prevalence of 39.1 CD cases per million inhabitants at
`the end of 1992 and an average incidence of newly diag-
`nosed cases was 2.4 per million per year. Another
`epidemiological study using registry data from Denmark
`found an incidence rate of 1.2–1.7 cases per million
`per year. A cross-sectional study in the province of
`Lie`ge, Belgium conducted in 2005 showed a prevalence
`of 94 cases of pituitary adenomas per 100,000; 5.9%
`of these cases, or 55 cases per million, were associated
`with CD. In the US, a retrospective cohort study of CD
`patients using claims data from 2007–2010 reported an
`incidence of 7.6 per million per year, with rates varying
`by age and sex11.
`Chronic comorbidities associated with CD place a
`substantial burden on patients. The many comorbidities
`associated with CD include ischemic heart disease,
`obesity, hypertension, impairment of glucose tolerance,
`dyslipidemia, and thrombotic diathesis3,12–14, which
`together increase cardiovascular risk. Other comorbidities
`found among CD patients include infections (urinary tract
`infections and pneumonia), psychopathologies (anxiety,
`depression, and cognitive deficit), as well as skeletal prob-
`lems (fractures and osteoporosis)3,12–14. Patients most
`often complain of fatigue/weakness (85%), changes in
`physical appearance (63%), emotional instability (61%),
`cognitive impairment (49%), depression (32%), and sleep-
`ing difficulties (12%); 80% report
`interference with
`family life and relations with their partner and 56%
`with school/work performance15. Elevated mortality in
`CD patients may reflect increased frequency or severity
`of
`infections as well as elevated cardiovascular and
`cerebrovascular risk16.
`The psychiatric effects of CD take a particularly large
`toll on patients’ health-related quality-of-life (HRQoL)
`and long-term function. A number of studies have docu-
`mented long-lasting adverse effects on behavioral and
`
`Journal of Medical Economics
`
`Volume 17, Number 4 April 2014
`
`cognitive functions caused by functional and, over time,
`structural alterations in specific brain target areas due to
`prolonged, increased endogenous or exogenous exposure
`to glucocorticoids17–19. In HRQoL studies among CD
`patients, the effects of hypercortisolism on HRQoL are
`seen in the physical, mental, and emotional compo-
`nents20–22. This finding was similar among children23.
`Cushing’s disease is associated with substantial health-
`care costs8,13,24. A cross-sectional US study found that
`the economic burden of CD patients is substantial, with
`hospitalizations or emergency department (ED) visits
`observed in 434% of patients, an average of 19.8 office
`visits per patient, and up to $35,000 in annual total
`costs, of which $31,395 is for medical costs25. Diagnosis
`of CD is complicated and associated with frequent phys-
`ician visits and diagnostic tests and procedures24.
`Following diagnosis, patients can undergo multiple
`surgeries and require long-term monitoring due to a
`threat of disease recurrence. These factors, along with
`management
`of
`comorbidities,
`increase healthcare
`resource utilization and place a heavy economic burden
`on patients and payers.
`The primary treatment for CD is TSS, a procedure in
`which the corticotroph adenoma is selectively removed,
`preferably performed by a surgeon with substantial experi-
`ence with this procedure26. Locating the tumor may
`require careful sectioning through the pituitary gland,
`because, while some tumors have an identifiable pseudo-
`capsule, others do not display a distinct border between the
`tumor and normal pituitary tissue2. Surgical complications
`frequently occur and are inversely related to the experi-
`ence of the neurosurgeon26. The reported initial success
`rate for pituitary surgery for CD varies between 60–86%.
`However, up to 25% of these patients with successful treat-
`ment suffer from recurrence after apparent remission27. In
`such instances, second-line therapeutic options include
`medical procedures such as repeat pituitary surgery, radio-
`surgery (RS), radiotherapy (RT), or bilateral adrenalect-
`omy (BLA). Medical therapies in this setting include
`mifepristone, which is indicated to control hyperglycemia
`secondary to hypercortisolism in patients with Cushing’s
`syndrome, or off-label medical therapies such as ketocon-
`azole and cabergoline2,28. Although uncommon, these
`treatment options may also be used as
`first
`line
`treatment29.
`Pasireotide (Signifor*) is a pituitary-directed somato-
`statin analog
`approved by
`the Food and Drug
`Administration (FDA) on December 14, 2012 for the
`treatment of adult patients with CD for whom pituitary
`surgery is not an option or has not been curative30. The
`objective of this study was to assess the total and the phar-
`macy budget impact of adding pasireotide to a health plan
`
`*Signifor is a registered trademark of Novartis Pharmaceuticals Corporation,
`East Hanover, NJ, USA.
`
`! 2014 Informa UK Ltd www.informahealthcare.com/jme
`
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`Journal of Medical Economics
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`formulary of a US managed care health plan for the treat-
`ment of this chronic disease with a broad spectrum of
`comorbidities.
`
`Methods
`
`Model design
`
`This study assesses the budget impact of pasireotide avail-
`ability in two scenarios. The base case scenario, Scenario
`1, evaluates the total budget impact to a US managed care
`health plan, including medical procedures and drug thera-
`pies, treatment-related complications or adverse events
`(AE), costs associated with managing comorbidities, and
`costs of monitoring. Assumptions used in Scenario 1 are
`listed in Supplementary Table 1. A second scenario, from
`the perspective of the pharmacy budget, includes only drug
`therapy options and drug costs. All costs were inflated to
`$2013 using the Consumer Price Index for Medical Care
`Services31. Neither scenario includes discounting as the
`models were designed per recommendations from the
`ISPOR Task Force on Good Research Practices—Budget
`Impact Analysis, which suggests that, as the budget impact
`analysis presents financial streams over time, it is not
`necessary to discount these costs32. The models were
`built in Microsoft Excel 2010.
`
`Patient population
`
`Both scenarios assume a health-plan covered population
`size of 1 million members in which the plan pays all health
`costs for those covered, and assume all patients with CD
`will be treated with some form of treatment. First-line TSS
`is the standard of care for patients with CD, but pharma-
`cologic treatment may be appropriate for some patients
`who are poor surgical candidates, including those with
`undetectable
`tumors,
`tumors
`that
`are
`surgically
`unapproachable, or comorbidities or contraindications
`intervention26,33. We assumed
`that preclude surgical
`75% of patients with CD receive first-line TSS while the
`remaining 25% receive drug therapies. Based on Alwani
`et al.27, which reports that 28 of 79 patients exhibited ‘early
`relapse’ following TSS while 10 of 79 patients exhibited
`‘late relapse’, for a total of 38 out of 79 or 48.1%, we
`assumed 50% of patients who received first-line TSS
`initially fail first-line TSS or have recurrent disease after
`initial success and are now seeking additional treatment27.
`Additionally, we assumed in Scenario 2 that 75% of these
`patients ineligible for first-line TSS or with recurrent CD
`after first-line TSS receive drug therapies. Prevalence rates
`and inputs for calculation of the CD patient population in
`Scenario 1 are shown in Table 1. Figure 1 illustrates the
`patient flow used to estimate the number of patients
`eligible for treatment in Scenario 1. Eligible patient
`
`Table 1. Treatment-eligible patient population estimates (Scenario 1).
`
`Covered population (third party
`reimbursement perspective)
`Prevalence (patients per million
`in general population, n)
`Total number of CD patients
`Portion of patients eligible for
`1st line TSS
`Portion of patients with recurrent
`CD after surgery
`Number of patients with
`recurrent CD
`Portion of patients ineligible
`for 1st line TSS
`Number of CD patients ineligible
`for TSS
`Total number of CD patients
`eligible for pasireotide
`
`Reference
`
`Value
`
`1,000,000
`
`Etxabe and
`Vazquez8
`
`Assumption
`
`Alwani et al.27
`
`Assumption
`
`39
`
`39
`75%*
`
`50%
`
`15
`
`25%*
`
`10
`25y
`
`*Portion of patients eligible for 1st line TSS may vary across different popu-
`lations.
`yValue presented has been rounded for demonstration purposes. Unrounded
`value: 24.38.
`CD, Cushing’s disease; TSS, transsphenoidal surgery.
`
`population inputs and references for Scenario 2 are pre-
`sented in Supplementary Table 2.
`
`Treated shares
`
`Treated shares provide a distribution of treatment options
`in a market with and without pasireotide availability.
`A treated share is the share of the market for each respect-
`ive treatment option. Treated shares for mifepristone
`are assumed to grow over time while shares for all other
`treatment are assumed to normalize in both scenarios.
`With the introduction of pasireotide, all annual treated
`shares are normalized to match expected market uptake
`of pasireotide. Therefore, the portion of patients who
`undergo medical procedures relative to those who receive
`drug therapies is dynamic and fluctuates over time in
`Scenario 1. However, Scenario 2 assumes that the portion
`of patients who receive either medical procedures or drug
`therapies is constant over time, with 75% receiving drug
`therapies. Both scenarios use the same treated shares, but
`drug therapy shares are normalized to 100% in Scenario 2.
`Please see Supplementary Tables 3–6 for more detail.
`
`Treatment duration
`
`Both scenarios incorporate treatment efficacy/failure rates
`to obtain the duration of treatment for drug therapies.
`Patients who fail repeat surgical therapy are assigned all
`costs, which are reflected in costs for the first year. Patients
`who fail drug therapies were assumed to incur a full year of
`costs, unless the prescribing information suggests that clin-
`ical benefit be monitored and treatment discontinued for
`
`290 Budget impact of pasireotide for the treatment of Cushing’s disease Truong et al.
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`Journal of Medical Economics
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`Total CD patients
`
`39
`
`Eligible for TSS
`
`29 (75%)
`
`Ineligible for TSS
`
`10(25%)
`
`Cured
`
`14(50%)
`
`Recurrent CD
`
`15 (50%)
`
`Pasireotide Eligible Population
`
`25
`
`Figure 1. Patient flow for Cushing’s disease treatments (Scenario 1). TSS, transsphenoidal surgery.
`
`non-responders. Clinical benefit in this case is defined to
`include clinically meaningful reduction in 24-h UFC
`levels and/or improvement in signs or symptoms of the
`disease. Based on this definition of clinical benefit,
`66.3% of patients responded to pasireotide treatment and
`continued treatment after 2 months of
`treatment
`(see Supplementary Table 1).
`
`Treatment costs
`
`Methods for calculating procedure costs were obtained
`from a detailed micro-costing analysis conducted from a
`US payer perspective that estimated treatment costs for
`TSS, BLA, RS, and RT in 201134. This analysis was
`then updated with 2013 values for use in the total
`budget impact model. TSS and BLA costs are comprised
`of hospitalization costs and physician fees for the surgery
`(based on CPT [Current Procedural Terminology] codes).
`Hospitalization charges, including nursing and room and
`board, are obtained from the Healthcare Cost and
`Utilization Project (HCUP) National Inpatient Sample
`database and converted to mean Medicare reimbursement
`ratio35.
`values
`using
`a Medicare
`cost-to-charge
`Calculations for the cost of RT and RS were taken from
`a literature poster presentation34. Reimbursement values
`for each CPT code (50th percentile) for physician services
`or outpatient
`services/procedures/labs were obtained
`from the MAG Mutual Physicians’ Fee and Coding
`Guide 2012, and were summed separately to generate
`costs of surgery or radiation therapy.
`Costs for drug therapies in both scenarios are calculated
`based on the mean recommended daily dosage for each
`treatment (obtained from published literature)2,28,36–38.
`Daily drug costs are estimated by multiplying mean daily
`
`dose (in mg) with the lowest drug cost per mg that was
`obtained using the wholesale acquisition cost (WAC)
`from the 2013 Drug Topics Redbook39. Pharmacy dispen-
`sing fees were not incorporated.
`
`Surgical complications and adverse events
`
`A literature review was conducted and eight studies iden-
`tified as the most appropriate clinical studies for inclusion
`in the total budget impact model37,38,40–45. Fourteen
`unique AEs were identified, of which hypopituitarism
`was associated with TSS, RS, and RT. TSS was associated
`with the greatest number of AEs or complications (6),
`followed by mifepristone (3) and BLA (2). One AE or
`complication was identified for each pasireotide, ketocon-
`azole, cabergoline, RS, and RT.
`This model also accounts for only the most common
`surgical complications and treatment-emergent AEs asso-
`ciated with substantial costs and resource utilization. Costs
`for stroke, endometrial thickening, meningitis, cerebro-
`spinal fluid (CSF) leak, Nelson’s syndrome46, thrombolytic
`events, and hepatotoxicity are assumed to be one-time
`costs and are based on sources from the literature. Costs
`of each complication/AE and their corresponding preva-
`lence rates can be found in Supplementary Table 7.
`
`Comorbidities
`
`Data on prevalence of comorbidities, cost, and clinical
`effectiveness of available treatments were obtained from
`published literature47,48. Costs were obtained for CD
`patients with controlled and uncontrolled disease or,
`when not available in CD, from the general population.
`A total of 32 comorbidities associated with CD were
`
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`identified, of which 17 had sufficient data for inclusion in
`the analysis. The cost of comorbid disease for a patient
`with controlled or uncontrolled CD is calculated as the
`product of the cost of the comorbidity and the prevalence
`rate for that patient population.
`
`Monitoring
`
`In Scenario 1, post-operative lab monitoring is required
`after BLA at regular intervals. Reimbursement for each
`lab test is obtained using specific CPT codes for each test
`in the MAG Mutual Physicians’ Fee and Coding Guide
`2012. Costs were inflated to $2013 using the Consumer
`Price Index for Medical Care Services. Supplementary
`Table 8 presents the frequency and unit cost of each pro-
`cedure used in monitoring treatment and disease.
`
`Results
`
`Total cost of treatment
`
`The total annual cost per patient on each treatment option
`in Scenario 1 is presented in Table 2. These costs account
`for the cost and duration of the treatments themselves, the
`cost and rate of treatment-associated adverse events or
`complications, the cost of treating comorbidities, and
`
`the cost of monitoring the disease and treatment.
`Cost components are presented in Supplementary Tables
`7 and 8. Mifepristone is the most expensive drug therapy
`with an annual per patient cost of $207,562, while BLA is
`the most costly medical procedure at $72,525. Scenario 2
`only includes drug costs, as presented in in Supplementary
`Table 9.
`The cost of pasireotide is based on a cost of $14,383.56
`for 60 ampules or 30 days, for an annual cost of $175,000
`per year (365 days) regardless of starting dose, and incorp-
`orates a response rate of 66.3% after 2 months of full treat-
`ment (see Supplementary Table 1).
`
`Budget impact
`
`The expected total difference in the budget in Scenario 1
`for the entire US managed care health plan is $137,505 in
`the first year, $219,892 in the second year, and $231,954 in
`the third year after pasireotide launch, based on a covered
`population of 1 million members (Table 3). On a per-
`member per-month (PMPM) basis, the estimated budget
`impact on a health plan with one million covered lives is
`$0.0115 (1.15 cents) in the first year, $0.0184 (1.84 cents)
`in the second year, and $0.0194 (1.94 cents) in the third
`year (Figure 2). The estimated budget impact of pasireo-
`tide in Scenario 2 is $0.0257 (2.57 cents) PMPM in the
`first year, $0.0363 (3.63 cents) in the second year, and
`
`Table 2. Total cost estimates associated with Cushing’s disease treatments (Scenario 1).
`
`Treatment
`
`Annual cost
`per patient*
`
`Medical procedures
`Repeat TSS
`BLA
`Radiotherapy
`Radiosurgery
`Drug therapies
`Pasireotide
`
`Mifepristone
`Ketoconazole
`Cabergoline
`Mitotane
`
`$60,310
`$72,525
`$59,258
`$45,156
`
`$144,280
`
`$207,562
`$25,475
`$32,179
`$40,893
`
`Source
`
`Calculated using micro-costing methods from Patel et al.34
`Calculated using micro-costing methods from Patel et al.34
`Calculated using micro-costing methods from Patel et al.34
`Calculated using micro-costing methods from Patel et al.34
`
`Based on a monthly cost of $14,383.56 for 60 ampules or 30 days, for an annual cost of $175,000 per
`year (365 days), regardless of starting dose from Medi-Span Price Rx, March 15, 201349, and
`incorporates a response rate of 66.3% after 2 months of full treatment.
`Fleseriu et al.38; WAC (300 mg tabs) from First Databank50
`Biller et al.2; WAC (200 mg tabs) from Redbook39
`Pivonello et al.37; WAC (0.5 mg tabs) from Redbook39
`Biller et al.2; 2013 WAC (500 mg tabs) from Drug Redbook39
`
`*Includes treatment, complication, adverse event, comorbidity, and monitoring costs. See Supplementary Tables 7–9 for detailed cost data.
`BLA, bilateral adrenalectomy; TSS, transsphenoidal surgery; WAC, weighted average cost.
`
`Table 3. Cushing’s disease budget impact summary (Scenario 1).
`
`Total budget impact ($USD)
`
`PMPM (cents)
`
`2013
`
`2014
`
`2015
`
`2013
`
`2014
`
`2015
`
`Without pasireotide on the market ($)
`With pasireotide on the market ($)
`Difference ($)
`
`1,988,980
`2,126,485
`137,505
`
`2,142,497
`2,362,389
`219,892
`
`2,296,015
`2,527,969
`231,954
`
`16.57
`17.72
`1.15
`
`17.85
`19.69
`1.84
`
`19.13
`21.07
`1.94
`
`PMPM, per member per month.
`
`292 Budget impact of pasireotide for the treatment of Cushing’s disease Truong et al.
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`Figure 2. Cushing’s disease budget impact results on a per-member per-month basis (Scenario 1).
`
`Figure 3. Cushing’s disease budget impact model sensitivity analysis (Scenario 1). Input ranges for each parameter are as follows: pasireotide response rate/
`clinical benefit (60–73%), pasireotide treated share (8–10% in 2013, 14–18% in 2014, 17–21% in 2015), percentage of patients who fail first line TSS (45–
`55%), patients eligible for first line TSS (68–83%), and pasireotide percentage of controlled disease (50–61%). PMPM, per member per month; TSS,
`transsphenoidal surgery.
`
`$0.0360 (3.60 cents) in the third year after launch
`(see Supplementary Table 10).
`
`Sensitivity analysis
`
`Five model parameters in the total budget impact model
`are closely examined in a one-way sensitivity analysis:
`(1) percentage of patients who fail first line TSS, (2) per-
`centage of patients ineligible for first line TSS, (3) pasir-
`eotide treated shares, (4) pasireotide response rate/clinical
`benefit, and (5) pasireotide percentage of controlled dis-
`ease. By varying parameters by 10%, which translates
`into a 10% increase or decrease proportional to the value
`rather than an absolute 10 percentage point increase or
`decrease in the probabilities, the most significant impact
`is caused by the pasireotide response/clinical benefit rate at
`2 months after the initiation of treatment and is expected
`to alter the budget impact of the third year by less than
`
`$0.01 (1 cent) PMPM. Varying the parameters up to 25%
`rather than 10% produces a similarly small effect, altering
`the budget impact by less than $0.015 (1.5 cents). The
`range of the budget impact due to a 10% change in key
`parameters is presented in a tornado diagram in Figure 3.
`
`Discussion
`
`Treatment options for CD are few, consisting of medical
`procedures like TSS and BLA that have substantial com-
`plications. Pasireotide is a new alternative drug therapy for
`patients with CD. This model was developed to make both
`a comprehensive estimate of the PMPM impact to a health
`plan’s total budget of including pasireotide on drug formul-
`aries and provide an estimate specific to pharmacies. Costs
`for the total budget impact include medical procedures,
`drug therapies, complications and AEs, comorbid disease,
`
`! 2014 Informa UK Ltd www.informahealthcare.com/jme
`
`Budget impact of pasireotide for the treatment of Cushing’s disease Truong et al. 293
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`Journal of Medical Economics
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`Volume 17, Number 4 April 2014
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`and monitoring. Only the cost of drug therapies was
`considered for the pharmacy budget impact. To our know-
`ledge, there are no other studies that estimate the budget
`impact of treatments for CD. This study is the first to
`analyze the budget impact of treatments for CD from the
`perspective of a US health plan.
`The budget impact of adding pasireotide to a drug phar-
`macy and to a health plan is small, which is common for
`rare diseases. The total budget impact on a PMPM basis is
`$0.0115 (1.15 cents) PMPM in the first year, $0.0184 (1.84
`cents) in the second year, and $0.0194 (1.94 cents) in the
`third year. The estimated pharmacy budget impact of
`pasireotide is similarly modest at $0.0257 (2.57 cents)
`PMPM in the first year, $0.0363 (3.63 cents) in the
`second year, and $0.0360 (3.60 cents) in the third year
`after launch.
`There are several limitations to the present analysis.
`Because CD is an orphan condition with limited published
`data, a number of assumptions were made that may influ-
`ence the interpretation of results. First, assumptions were
`made to estimate the expected duration of treatment based
`on anticipated monitoring for response. Second, AE and
`complication rates were often taken from single-armed
`studies with small patient populations. Third,
`in the
`analysis of the total cost of CD comorbidities, some
`comorbidity cost estimates were obtained from the general
`population due to limited data availability, and only
`selected comorbidities were included to avoid double
`counting, limiting the accuracy of the estimate. Fourth,
`no co-payment structures were incorporated into this
`budget analysis, therefore the findings of this model may
`not be generalizable to plans with cost-sharing arrange-
`ments. Fifth, since published estimates are not available,
`the estimate of shares for CD treatments may under- or
`over-estimate the actual utilization. Finally, these results
`are relevant for US managed care health plans and not
`necessarily generalizable to other countries or health
`systems.
`According to the sensitivity analysis, the most substan-
`tial cost driver is the pasireotide response rate/clinical
`benefit, for which a 10% variation in its price changes
`the PMPM budget impact in the third year by less than
`$0.005 (0.5 cents). The next largest cost drivers are the
`pasireotide treated shares and percentage of patients who
`fail first line TSS. Please see Figure 3 for more detail.
`
`Conclusion
`
`Cushing’s disease is severe disease with debilitating comor-
`bidities and substantial healthcare costs when untreated or
`inadequately controlled. The inclusion of pasireotide in a
`health plan formulary appears to have a small impact on
`the total health plan or pharmacy budget.
`
`Transparency
`Declaration of funding
`This
`research was
`sponsored by Novartis Pharmaceuticals
`Corporation.
`
`Declaration of financial/other relationships
`H.L.T. and D.N. are employees of Analysis Group and have dis-
`closed receiving consulting fees from Novartis Pharmaceuticals.
`M.P.N. and W.H.L. have disclosed that they are employees of
`Novartis and are stock option share-holders of Novartis
`Pharmaceuticals. The authors have disclosed that they have
`received no additional support or contributions from others in
`the preparation of this manuscript. The authors also declare that
`they have no competing interests. CMRO Peer Reviewers on this
`manuscript have received honorarium for their review work, but
`have no other relevant financial relationships to disclose.
`
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