Economic Impact of Oritavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in the Emergency Department or Observation Setting: Cost Savings Associated with Avoidable Hospitalizations

Clinical Therapeutics/Volume ], Number ], 2015

Economic Impact of Oritavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in the Emergency Department or Observation Setting: Cost Savings Associated with Avoidable Hospitalizations Thomas P. Lodise, PharmD, PhD1; Weihong Fan, MS2; and Katherine A. Sulham, MPH2 1

Albany College of Pharmacy and Health Sciences, Albany, New York; and 2The Medicines Company, Parsippany, New Jersey

ABSTRACT Purpose: Data indicate that acute bacterial skin and skin structure infection (ABSSSI) patients without major comorbidities can be managed effectively in the outpatient setting. Because most patients with ABSSSIs present to the emergency department, it is essential that clinicians identify candidates for outpatient treatment given the substantially higher costs associated with inpatient care. We examined the potential cost avoidance associated with shifting care from inpatient treatment with vancomycin to outpatient treatment with oritavancin for ABSSSI patients without major complications or comorbidities. Methods: A decision analytic, cost-minimization model was developed to compare costs of inpatient vancomycin versus outpatient oritavancin treatment of ABSSSI patients with few or no comorbidities (Charlson Comorbidity Index score r1) and no life-threatening conditions presenting to emergency department. Hospital discharge data from the Premier Research Database was used to determine the costs associated with inpatient vancomycin treatment. Findings: Mean costs for inpatient treatment with vancomycin ranged from $5973 to $9885, depending on Charlson Comorbidity Index score and presence of systemic symptoms. Switching an individual patient from inpatient vancomycin treatment to outpatient oritavancin treatment was estimated to save $1752.46 to $6475.87 per patient, depending on Charlson Comorbidity Index score, presence of systemic symptoms, and use of observation status. Assuming some patients may be admitted to the hospital after treatment with oritavancin, it is estimated that up to 38.12% of patients could be admitted while maintaining budget neutrality.

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Implications: This cost-minimization model indicates that use of oritavancin in the emergency department or observation setting is associated with substantial cost savings compared with inpatient treatment with vancomycin. (Clin Ther. 2015;]:]]]–]]]) & 2015 Elsevier HS Journals, Inc. All rights reserved. Key words: Acute Bacterial Skin and Skin Structure, Infections, ABSSSI, oritavancin vancomycin cost impact.

INTRODUCTION Acute bacterial skin and skin structure infections (ABSSSIs) are among the most common infections observed in the emergency department (ED).1,2 Although patients with ABSSSIs have historically received care in the hospital, which often includes multiday regimens of intravenous antibiotics, data suggest that many of these patients can be managed effectively in the outpatient setting.3–5 Because most patients with ABSSSIs present to the ED, clinicians in the ED essentially serve as ”gatekeepers” to hospital admission. This is a critical role in health care systems, given that mean hospitalization costs of patients with ABSSSI typically range from $6000 to $13,000 per patient (mean cost $8000 per patient), with multiday room and board expenses comprising 50% of total costs.6,7 Because inpatient care for ABSSSI costs approximately 2 to 4 times more than outpatient care,8 it is essential that ED clinicians identify candidates for outpatient parenteral antimicrobial treatment and utilize patient care strategies that can Accepted for publication November 18, 2015. http://dx.doi.org/10.1016/j.clinthera.2015.11.014 0149-2918/$ - see front matter & 2015 Elsevier HS Journals, Inc. All rights reserved.

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Clinical Therapeutics effectively shift site of care from the inpatient to the outpatient setting to reduce the overall cost of ABSSSI treatment. Any agent used in an effort to reduce the health care burden associated with inpatient treatment of patients with ABSSSIs must have reliable activity and efficacy against methicillin-resistant Staphylococcus aureus, given the high prevalence of this pathogen among these patients.2 Although no standard clinical criteria exist for outpatient parenteral antimicrobial treatment eligibility for patients with ABSSSIs, several expert panels suggest hospital admissions should be limited to patients with unstable comorbidities or those with more severe infections.9–11 Despite this recommendation, many of these patients continue to be treated in the inpatient setting. Cognizant of this, the present study examined the potential cost avoidance of shifting care from the inpatient to outpatient setting for patients without major complications or comorbidities, facilitated by use of oritavancin. Oritavancin is a recently approved singledose intravenous therapy for the treatment of ABSSSI caused or suspected to be caused by certain gram-positive pathogens, including methicillin-resistant S aureus.12 We hypothesized that outpatient use of oritavancin in patients with few or no comorbidities and no lifethreatening conditions would be associated with lower costs than inpatient treatment of these patients with vancomycin, the most common standard of care treatment used in this patient population.13–15 To explore this hypothesis, a cost-minimization model was developed from the hospital perspective to estimate the potential cost savings associated with treating adult ABSSSI patients with no or limited comorbidities and no life-threatening conditions with oritavancin in the outpatient setting relative to managing patients in the hospital with intravenous vancomycin. As part of the analysis, we also estimated the threshold for the proportion of patients initially receiving oritavancin in the outpatient setting that could be subsequently admitted while still conferring cost savings associated with oritavancin use relative to inpatient vancomycin therapy.

MATERIALS AND METHODS Model Structure and Population A decision analytic, cost-minimization model was developed to compare the costs of inpatient vancomycin versus outpatient oritavancin for the treatment

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of ABSSSI patients with few or no comorbidities (Charlson Comorbidity Index [CCI] score of 0 or 1) presenting to the ED (Figure 1). Patients with lifethreatening conditions were excluded from the analysis, as they would not be considered appropriate for outpatient treatment with oritavancin. Conditions considered life-threatening included necrotizing fasciitis or limb-threatening infections due to vascular compromise, bacteremia, neutropenia, sepsis and systemic inflammatory response syndrome. All vancomycin patients were assumed to be admitted as inpatients. For patients treated with oritavancin, it is anticipated that the intent is to treat patients as outpatients, either administering oritavancin in the ED and discharging directly, or administering oritavancin and observing the patient in a dedicated observation unit or under observation status. It is conservatively assumed, however, that some oritavancin-treated patients may be subsequently admitted to the hospital for factors such as worsening infection or hypersensitivity reaction. The impact of the rate of this potential subsequent hospitalization is explored in detail in this analysis. For hospitalized patients, 4 categories of disease severity were explored: CCI of 0 with and without systemic symptoms and CCI of 1 with and without systemic symptoms. Hypotension, mental status change, tachycardia, tachypnea, acute kidney failure, renal failure, fever, or abnormal glucose were considered systemic symptoms. As studies have reported no significant difference in treatment failure or rehospitalization rates between vancomycin and oritavancin, those parameters were excluded from the model.16–18 We focused the model structure on patient severity and site of care.

Model Inputs Costs Associated with Vancomycin Use To determine the costs associated with hospital inpatient treatment of ABSSSI patients receiving intravenous vancomycin, a retrospective, observational study was conducted using hospital discharge data from the Premier Research Database. The Premier Research Database contains clinical and economic data from >600 hospitals, representing all geographic regions within the United States over a broad range of health care facility sizes and architectures (ie, academic and nonacademic hospitals), located in both urban and rural settings. More than 5 million inpatient discharges and 35 million outpatient visits are recorded annually.

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No systemic Symptoms CCI = 0

Systemic Symptoms Vancomycin

Inpatient

No systemic Symptoms CCI = 1

Systemic Symptoms No systemic Symptoms

Patient presenting to ED with confirmed/suspected grampositive ABSSSI and risk of MRSA

CCI = 0

Systemic Symptoms

Inpatient No systemic Symptoms CCI = 1

Systemic Symptoms

Oritavancin

Discharge

Discharge No systemic Symptoms CCI = 0

Observation

Systemic Symptoms

Inpatient No systemic Symptoms CCI = 1

End of treatment

Systemic Symptoms

Figure 1. Decision Analytic Framework. ABSSSI ¼ acute bacterial skin and skin structure infections; CCI ¼ Charlson Comorbidity Index; ED ¼ emergency department; MRSA ¼ methicillin-resistant Staphylococcus aureus.

Patients were included in the study if they had a medical encounter with primary diagnosis of ABSSSI* between January 1, 2012 and December 30, 2012 and intravenous vancomycin use on day 1 or 2 of hospital admission. Presence of comorbid conditions was based on the CCI noted during the qualifying admission.19,20 Patients were included for analysis if they had a CCI score of 0 or 1 without any life-threatening condition (Table I), as those could be considered potentially avoidable hospital *

The following International Classification of Diseases 9th revision, clinical modification codes were used to define an ABSSSI: 035 (erysipelas), 681.00 (cellulitis/abscess of finger), 681.10 (cellulitis/abscess of toe), 681.9 (cellulitis/abscess), 958.3 (post-traumatic wound infection), 998.5 (post-procedural wound infection), and 686.8 (other specified local infections of skin and subcutaneous tissue), 686.9 (other unspecified local infections of skin and subcutaneous tissue).

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admissions and therefore patients eligible to receive outpatient treatment with oritavancin. Infections were further classified as having either presence or absence of systemic symptoms, which included hypotension, mental status change, tachycardia, tachypnea, acute kidney failure, renal failure, fever, or abnormal glucose. International Classification of Diseases, Ninth Revision, Clinical Modification codes for those clinical conditions were summarized in Table I. Database elements used in this analysis included hospitalization length of stay, hospitalization costs, medications, laboratory, diagnostic and therapeutic services delivered to the patient during hospitalization. Descriptive statistics were used to characterize the population included for analysis and the associated costs of hospitalization.

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Clinical Therapeutics

Table I. Infection severity categories. Infection Severity

Classification

ICD-9-CM

Life-threatening Necrotizing fasciitis or limb-threatening conditions infections due to vascular compromise

Bacteremia

Neutropenia

Systemic inflammatory response syndrome (SIRS) and sepsis syndrome

Systemic symptoms

728.86: Necrotizing fasciitis 040.0: Gas gangrene 785.4: Gangrene 440.24: Atherosclerosis of native arteries of the extremities with gangrene 790.7X: Bacteremia 038.XX: Septicemia 421.XX: Acute and subacute endocarditis 424.9X: Endocarditis valve unspecified 288.0X: Neutropenia 288.1: Functional disorders of polymorphonuclear neutrophils 785.5X: Shock without mention of trauma 995.9X: SIRS, unspecified 995.91: Sepsis 995.92: Severe sepsis 040.83: Toxic shock syndrome 458.XX: Hypotension 796.3: Nonspecific low blood pressure reading 780.97: Altered mental status 785.0: Tachycardia unspecified 785.1: Palpitations 786.0X: Dyspnea and respiratory abnormalities 584.XX: Acute kidney failure 586.XX: Renal failure, unspecified 780.6x: Fever, unspecified 790.2X: Abnormal glucose

ICD-9-CM = International Classification of Disease, Ninth Revision, Clinical Modification.

Costs Associated with Oritavancin Use For patients treated with oritavancin, ED treatment costs were assumed to be equal to those derived from the Premier analysis of vancomycin costs as described. Aside from drug acquisition costs and costs associated with intravenous drug administration, additional costs associated with inpatient treatment were also assumed to be equal between patients receiving oritavancin and vancomycin. The wholesale acquisition cost of oritavancin was used for the drug acquisition cost, and

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Medicare National Limitation amounts were used as a proxy for the direct hospital costs of the 3-hour intravenous therapy administration for oritavancin. Cost associated with observation care for oritavancin were similarly derived from Medicare National Limitation amounts (Table II).

Model Outputs Key outputs of the model included mean perpatient total and component costs by setting of care

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Table II. Oritavancin model inputs. Input

Cost, US$

Observation

810.81

IV therapy administration

238.75

Drug acquisition

2900.00

Description

Source

Calculated observation cost (APC OPPS Addendum A (Final OPPS APCs 8009, reimbursement rate of for CY 2015): https://www.cms. $1234.70) is inclusive of ED visit, gov/Medicare/Medicare-Fee-forCPT 99284/APC 615 ($333.80) Service-Payment/Hospital OutpatientPPS/Addendum-Aand-Addendum-B-Updates-Items/ 2015-Jan-Addendum-A.html Mean time in OBS has been AMA Code Manager (accessed June reported to be 21.6 h for ABSSSI 2015); https://ocm.ama-assn.org/ ([$1234.70  $333.80)  (21.6 / OCM/CPTRelativeValueSearch. 24)] ¼ $810.81 do?submitbutton=accept Schrock et al5 CPT code 96365 and 96366. AMA Code Manager (accessed June $173.59 first hour, $32.58 2015) subsequent hours Oritavancin requires a single 3-h infusion ($173.59 þ $32.58 þ $32.58 ¼ $238.75) WAC Medi-Span Price Rx (accessed June 2015); https://pricerx.medispan. com/

AMA ¼ American Medical Association; APC ¼ Ambulatory Payment Classification; ED ¼ emergency department; CPT ¼ Current Procedural Technology; OBS ¼ observation; OPPS ¼ Outpatient Prospective Payment System; WAC ¼ wholesale acquisition cost.

and treatment. Per patient cost differences between treatment with vancomycin and oritavancin were calculated for both ED treatment only and use of observation for oritavancin-treated patients. Cost differences under a variety of treatment settings and hospitalization scenarios were considered to understand the economic impact of oritavancin among patients who were subsequently admitted from the ED or observation.

Sensitivity Analysis To determine the impact of varying model inputs on the total hospital costs, a univariate sensitivity analysis was conducted. Total costs of inpatient vancomycin treatment derived from the Premier Research Database varied by ⫾20%. Drug acquisition costs of oritavancin varied by 20% to account for potential discounts at the hospital level; it was

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assumed that the wholesale acquisition cost represented the highest likely acquisition cost. Costs associated with ED treatment for oritavancin varied by ⫾20%, and costs of observation care for oritavancin varied between $327.85 and $1234.70, representing the likely minimum and maximum reimbursement amounts for observation care based on Medicare national limitation amounts.† Costs associated with intravenous therapy administration for oritavancin were varied between the corresponding vancomycin intravenous administration data derived from Premier †

Calculation based on Ambulatory Payment Classification (APC) 8009 is inclusive of ED visit APC 616 (Observation cost ¼ APC8009  APC616). 2015 APC 8009 ¼ 1229. Rates from American Medical Association Code Manager (accessed May 2014) (alternative: direct admission of patient for hospital observation care, Current Procedural Terminology code G0379 $327.85).

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Clinical Therapeutics

Table III. Costs and length of stay for hospitalized patients receiving vancomycin. Total Costs, US$ Population CCI ¼ 0 No systemic symptoms Systemic symptoms CCI ¼ 1 No systemic symptoms Systemic symptoms Total

Length of Stay, d

n (%)

Mean (SD)

Median

Mean (SD)

Median

33,366 (62.31) 3968 (7.41)

5972.73 (6051.41) 7658.06 (7984.89)

4525.26 5451.21

3.7 (2.89) 4.7 (3.99)

3 4

14,098 (26.33) 2113 (3.95) 53,545 (100)

6959.26 (6783.68) 9885.33 (10,217.38) 6511.89 (6675.05)

5308.41 6791.75 4861.34

4.4 (3.39) 6.0 (5.12) 4.0 (3.27)

4 5 3

CCI ¼ Charlson Comorbidity Index.

($85.60$101.29) and $238.75, the Medicare national limitation reimbursement amount for administration of a 3-hour intravenous infusion in the hospital setting.‡

RESULTS Vancomycin Inpatient Costs A total of 84,562 hospitalized patients with a diagnosis of ABSSSI and a CCI score of 0 or 1 without life-threatening condition were identified in the Premier Research Database. Of those, 53,545 (63.32%) had vancomycin use on day 1 or 2 of hospitalization and were included for analysis. Mean costs ranged from $5973 for patients with a CCI score of 0 and no systemic symptoms, to $9885 for patients with a CCI score of 1 with systemic symptoms. Mean length of stay followed a similarly increasing pattern, with means of 3.7 and 6.0 days for patients with a CCI score of 0 (no systemic symptoms) and 1 (systemic symptoms), respectively (Table III).

Individual Cost Components by Treatment Setting Costs were further examined by individual cost component and treatment setting, and compared with estimated costs associated with use of oritavancin (Table IV). ‡

Current Procedural Terminology code 96365, 96366, 96374. $172.18 first hour, $29.50 subsequent hours, $105.90 IV bolus push. Oritavancin requires a single 3-hour infusion.

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Model Output Cost Comparisons between Oritavancin and Vancomycin Costs associated with use of oritavancin in the ED ($3409.46) and observation unit ($4220.27) were estimated to be substantially lower than costs associated with inpatient vancomycin treatment ($5972.73$9885.33). Switching any individual patient from inpatient vancomycin treatment to outpatient oritavancin treatment could be estimated to save approximately $1752.46 to $6475.87, depending on CCI score, presence of systemic symptoms, and use of observation (Figure 2). If all vancomycin inpatients were treated with oritavancin in the ED only, per-patient cost savings would be $3102.43. Assuming some patients may be admitted to the hospital after treatment with oritavancin in the ED, it is estimated that up to 51.61% of patients could be admitted while maintaining budget neutrality. If patient care was shifted to use of oritavancin in the observation unit instead of inpatient treatment with vancomycin, the corresponding cost savings is expected to be $2291.62 per patient, with a budget-neutral break-even hospitalization rate of 38.12% (Figure 3). Alternatively, assuming a treatment distribution in which all patients with a CCI score of 0 (69.72%) were treated in the ED only and patients with a CCI score of 1 (30.28%) were treated in observation, use of oritavancin in the outpatient setting compared with inpatient vancomycin use would be associated with a cost savings of $2856.80 per patient. Under these distribution assumptions, up to 43.44% of patients could subsequently be hospitalized before the costs associated with oritavancin use would become cost-

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Table IV. Total costs by cost component associated with use of vancomycin and oritavancin. Vancomycin Outpatient

Inpatient CCI ¼ 0

CCI ¼ 1

Cost Component, ED No Systemic Systemic No Systemic Systemic Total (CCI 0 and 1, US$ Only Observation Symptoms Symptoms Symptoms Symptoms Inpatient Only) ED Observation IV therapy administration Drug acquisition* Other pharmacy costs Room and board Other† Total costs

  

  

269.29  91.17

276.63  89.76

270.44  85.60

284.11  101.29

270.71  90.00

 

 

136.64 625.64

149.55 913.55

141.29 849.91

158.57 1306.02

139.68 732.88

  

  

3101.51 1748.48 5972.73

3979.04 2249.53 7658.06

3593.27 2018.76 6959.26

5061.92 2973.42 9885.33

3373.39 1905.23 6511.89

Oritavancin Outpatient

Inpatient CCI ¼ 0

CCI ¼ 1

Total (CCI 0 and No No 1, Inpatient Systemic Systemic Systemic Systemic ED only Observation Symptoms Symptoms Symptoms Symptoms Only) ED Observation IV therapy administration Drug acquisition* Other pharmacy costs Room and board Other† Total costs, patients treated in the ED or OBS Total costs, patients admitted from ED‡ Total costs, patients admitted from OBS

270.71  238.75

270.71 810.81 238.75

269.29 810.81 238.75

276.63 810.81 238.75

270.44 810.81 238.75

284.11 810.81 238.75

270.71 810.81 238.75

2900.00    3409.46

2900.00    4220.27

2900.00 625.64 3101.51 1748.48

2900.00 913.55 3979.04 2249.53

2900.00 849.91 3593.27 2018.76

2900.00 1306.02 5061.92 2973.42

2900.00 732.88 3373.39 1905.23

8883.67

10,557.50

9871.13

12,764.22

9420.96

9694.48

11,368.31 10,681.94 13,575.03

10,231.77

CCI ¼ Charlson Comorbidity Index; ED ¼ emergency department; IV ¼ intravenous; OBS ¼ observation. * Drug acquisition costs include only the costs attributed to vancomycin or oritavancin; all other pharmacy-related costs are included in the “other pharmacy costs” category. † Includes operating room, central supplies, cardiology or ECG, laboratory, radiology, and respiratory costs. ‡ Excludes costs associated with observation.

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Clinical Therapeutics

A

Costs associated with inpatient vancomycin compared to use of oritavancin in the emergency department

$12,000.00

$6,476 $9,885

$10,000.00 $8,000.00

$4,249 $3,550

$7,658 $2,563

$6,959

$5,973 $6,000.00 $4,000.00

$3,409

$3,409

$3,409

$3,409

CCI=0, No SS

CCI=0, SS

CCI-1, No SS

CCI=1, SS

$2,000.00 $-

VAN

B

ORI

Costs associated with inpatient vancomycin compared to use of oritavancin in the observation unit

$12,000.00

$5,665 $9,885

$10,000.00

$3,438 $2,739

$8,000.00

$1,752

$7,658 $6,959

$5,973 $6,000.00 $4,220

$4,220

$4,220

$4,220

$4,000.00 $2,000.00 $CCI=0, No SS

CCI=1, No SS

CCI=0, SS VAN

CCI=1, SS

ORI

Figure 2. Costs associated with inpatient vancomycin (VAN) use compared with use of outpatient oritavancin (ORI) for the treatment of acute bacterial skin and skin structure infections.

additive (assuming an equal rate of hospital admission from both the ED and observation). Similarly, if all patients with no systemic symptoms (regardless of CCI score, 88.64%) were treated in the ED only and patients with systemic symptoms (regardless of CCI score, 11.36%) were treated in observation, cost savings associated with use of oritavancin would be $3010.20 per patient, with budget neutrality maintained at up to a 44.73% hospital admission rate (Table V).

Sensitivity Analysis In sensitivity analysis, cost savings associated with shifting inpatient vancomycin to outpatient

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oritavancin ranged from $1383.15 (with use of observation) to $4769.19 (ED treatment only). Oritavancin was associated with cost savings in 100% of tested scenarios. Incremental costs associated with subsequent inpatient treatment of oritavancin compared with inpatient vancomycin ranged from $1242.31 (admission from the ED) to $4628.35 (admission from observation) (Table VI). These results suggest that, under assumptions associated with the highest total oritavancin costs (which include use of observation), up to 23.01% of patients treated as outpatients with oritavancin could subsequently be hospitalized while still

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$3,102

Cost difference (VAN-ORI)

$3,000.00

Favors oritavancin

$2,000.00 $1,000.00 $-

$2,292

0%

10%

20%

30%

40%

50%

60%

80%

70%

90%

100%

ED

$(1,000.00)

Des

$(2,000.00)

-$2,909

$(3,000.00)

Favors vancomycin

-$3,720

$(4,000.00) $(5,000.00)

Proportion of oritavancin-treated patients hospitalized

Figure 3. Mean per-patient cost difference (vancomycin  oritavancin) as a function of proportion of oritavancin patients subsequently hospitalized as inpatients, by oritavancin treatment location. ED ¼ emergency department; OBS ¼ observation.

Table V. Per patient cost savings associated with use of oritavancin compared with vancomycin. Outpatient, %

Inpatient, % CCI ¼ 0

Treatment VAN ORI, scenario 1 (all patients are treated in ED with ORI) ORI, scenario 2 (all patients are treated in OBS with ORI) ORI, scenario 3 (all patients with CCI ¼ 0 are treated in ED with ORI, all with CCI ¼ 1 are treated in OBS with ORI) ORI, scenario 4 (all patients with no SS are treated in ED with ORI, all with SS are treated in OBS with ORI)

SS

CCI ¼ 1 No SS

SS

Total Cost Savings, per Patient (VAN  ORI), US$

ED Only

OBS

No SS

 100.00

 

62.31 



100.00









2291.62

69.72

30.28









2856.80

88.64

11.36









3010.20

7.41 26.33 3.95   

 3102.31

CCI ¼ Charlson Comorbidity Index; ED ¼ emergency department; OBS ¼ observation; ORI ¼ oritavancin; SS ¼ systemic symptoms; VAN ¼ vancomycin.

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Clinical Therapeutics

Table VI. Sensitivity analysis results: total cost difference. Cost Difference (VAN  ORI) VAN Inpatients  ORI Patients Treated in the ED Input Variable

Min, $

Max, $

Range, $

Explained Variation,* %

Total costs of inpatient treatment with VAN ORI drug acquisition ORI IV therapy administration ED cost for ORI patients

2164.42 4769.19

2604.76

94.83

Input, $ Min

Max

Base Case

5209.51 7814.27 6511.89

3756.81 3176.81 580.00 99.53 2320.00 2900.00 2900.00 3541.18 3392.43 148.75 99.84 90.00 238.75 164.38 3520.95 3412.67 108.28 100.00 216.57 324.85 270.71 VAN inpatients  ORI patients treated in OBS Input, $ Total costs of inpatient treatment 1383.15 3987.91 2604.76 85.05 5209.51 7814.27 6511.89 with VAN OBS cost for ORI patients 3138.96 2232.11 906.85 95.36 327.85 1234.70 781.28 ORI drug acquisition 2975.53 2395.53 580.00 99.58 2320.00 2900.00 2900.00 ORI IV therapy administration 2759.91 2611.16 148.75 99.85 90.00 238.75 164.38 ED cost for ORI patients 2739.67 2631.39 108.28 100.00 216.57 324.85 270.71

ED ¼ emergency department; Min ¼ minimum; Max ¼ maximum; OBS ¼ observation; ORI ¼ oritavancin; VAN ¼ vancomycin. * Explained variation is cumulative.

maintaining budget neutrality, compared with treating those patients as inpatients with vancomycin.

DISCUSSION The intent of this analysis was to assess the potential cost savings associated with treating adult patients with ABSSSIs with oritavancin in the outpatient setting as an alternative to managing these patients as inpatients with intravenous vancomycin. When evaluating the economic utility (ie, cost-saving potential) of any new treatment that offers the potential to avoid hospital admissions, several important considerations must be taken into account when constructing the economic model. First, it is critical to identify the appropriate target population for use. Clearly, there is a subset of patients with ABSSSIs for whom hospital admission is required. Typically, these patients are those with unstable comorbidities and life-threatening conditions. Although hospitalization is reasonable for unstable patients with comorbidities that may require inpatient services or those with more severe infections, data indicate that ABSSSI patients without major

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complications or comorbidities can be managed successfully in the outpatient setting.3,4,21,22 As such, these patients were designated as the target population for use in this model. In addition, observed real-world costs associated with intravenous vancomycin use in the target population may present more accurate model inputs rather than literature estimates; the use of direct cost data from Premier as opposed to assumptions based on published literature or other models is a key strength of this analysis. Alternative cost input scenarios should also be considered to account for the variability in ABSSSI patient populations and costing structures present across US hospitals. Finally, the model should account for the costs associated with the subsequent and presumably unplanned admission of a patient who initially received oritavancin in the outpatient setting. It is critical to determine how many patients initially receiving oritavancin in the outpatient setting could be subsequently admitted and still confer overall cost savings to the hospital. To determine the subset of hospitalized ABSSSI patients treated with vancomycin who potentially could be managed in the outpatient setting (potentially

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T.P. Lodise et al. avoidable hospital admissions), we examined the distribution of hospital admissions categorized by CCI and the presence or absence of other systemic symptoms. Based on the mounting data that found ABSSSI patients without major complications or comorbidities can be successfully managed in the outpatient setting, we identified adult, hospitalized vancomycin-treated ABSSSI patients with nonlifethreatening ABSSSIs with 0 or 1 comorbid conditions as a subset of patients who could likely be managed in the outpatient rather than the inpatient setting (ie, population of potentially avoidable hospital admissions). Interestingly, we found that vancomycintreated patients with a CCI score of 0 or 1 and no life-threatening conditions represented nearly 40% of all patients admitted. Among these 53,545 hospitalized vancomycin-treated patients with ABSSSIs, the majority (62%) had a CCI score of 0 and only 12% had coded systemic symptoms. On average, hospitalization costs were approximately $6500 dollars and varied moderately as a function of the CCI score and presence of systemic symptoms. Using patients with a CCI score r1 and no lifethreatening conditions as the target population for the base case scenario, the model indicated that outpatient use of oritavancin would result in a cost savings of approximately $2291.62 to $3102.43 per patient relative to inpatient use of vancomycin. When different treatment setting scenarios and parameter variations were considered in the sensitivity analysis, the model indicated that the cost savings ranged from $1383.15 to $4769.19. More importantly, the model indicated that cost savings would be realized by the hospital, even under conservative model estimates, if nearly 1 out of every 4 (23%) of patients who received oritavancin in the outpatient setting were subsequently admitted. Limited research is available to estimate the actual expected rates of hospitalization of patients intended to be treated in an outpatient setting; this likely is a result of the lack of standard criteria used to identify patients for outpatient treatment. However, this number is expected to be substantially lower than the cost-savings thresholds identified in this analysis (23%-45% hospital admission). Several published cohort studies that examined the use of outpatient parenteral antimicrobial treatment reported unplanned admission rates between 6% and 12%.23–26 As a result, it is unlikely that use of oritavancin in the outpatient setting would result in an

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unplanned hospital admission rate high enough to become cost-additive to the hospital.

Limitations Several potential limitations should be considered when interpreting these findings. The model inputs were derived from the Premier Research Database. Although it contains coding and billing information for approximately 50 million admissions from approximately 500 US acute-care hospitals, it may not be generalizable to all other US hospitals. As such, hospitals should rely on institution-specific costs and treatment patterns when determining the potential cost savings associated with oritavancin in the outpatient setting relative to inpatient vancomycin use. We relied on International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and the CCI disease severity scoring system to both categorize the patients with ABSSSIs that could potentially be managed with oritavancin in the outpatient setting, and to identify appropriate comparator costs for inpatients treated with vancomycin. It is possible that not all systemic symptoms and comorbid conditions present in a given individual were either coded accurately or fully captured in the CCI disease severity scoring system. The literature suggests that mean inpatient costs for the treatment of ABSSSI are approximately $8000, which is substantially higher than the cost estimates employed in our model.6 In addition, Medicare National Limitation payment amounts were used to represent observation and drug administration costs associated with oritavancin use. This may have over- or underestimated the actual total cost of care for these health resource components. Finally, this analysis considers direct costs to the hospital only, including costs incurred in the ED, observation, and inpatient settings. Treatment of ABSSSI frequently involved continued ambulatory outpatient treatment after admission; these costs were not considered in the model and therefore may underestimate the actual total cost savings associated with use of outpatient oritavancin compared with inpatient vancomycin.

CONCLUSIONS This cost-minimization analysis indicates that use of oritavancin in the ED or observation setting is

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Clinical Therapeutics associated with cost savings of $3102.43 and $2291.62, respectively, compared with inpatient treatment with vancomycin. As with any model, these findings need to be validated in the clinical arena. However, this analysis points to substantial costs savings achievable when oritavancin is used to shift the site of care from the inpatient to outpatient setting for the treatment of ABSSSIs in patients with few or no unstable comorbidities.

ACKNOWLEDGMENTS The authors would like to acknowledge Kevin Xiang for his contributions to the Premier data analysis, and Caitlin Rothermel for her professional editing contributions to the manuscript. The authors confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. T. Lodise and K. Sulham conceived of and designed this analysis. T. Lodise provided expert clinical insight on model assumptions. K. Sulham draft the manuscript. W. Fan designed and conducted the analysis of the Premier database.

CONFLICTS OF INTEREST This work was funded by The Medicines Company. Weihong Fan and Katherine A. Sulham are employees and shareholders of The Medicines Company. Thomas P. Lodise is a consultant, speaker, and contractor for The Medicines Company. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

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Address correspondence to: Thomas Lodise, PharmD, PhD, Albany College of Pharmacy and Health Sciences, Albany, New York 12208-3492. E-mail: [email protected]

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