PSY37
COST IMPACT OF BUPIVACAINE LIPOSOME INJECTABLE SUSPENSION (BLIS)
FOR THE MANAGEMENT OF POST-SURGICAL PAIN
V. Ektare 1, R. Scranton 2, M.F. Botteman 1
Pharmerit International, Bethesda, MD, USA, 2Pacira Pharmaceuticals, Parsippany, NJ, USA
1
Abstract
METHODS
Objective: Clinical trials in soft tissue surgery with BLIS have shown that a single
injection into the surgical site provides postsurgical pain control for up to 72 hours
while reducing the need for opioids. This study extrapolates via a simplified decision
tree the economic impact of bupivacaine liposome injectable suspension (BLIS) vs.
bupivacaine HCl (BH) in patients undergoing colectomy and cholecystectomy.
Methods: This simple model combined data from a claims database analysis with
literature. The incidence of opioid use (92%) and risk of opioid-related adverse events
(ORAEs, by ICD-9 diagnosis code) (16.32%) for the BH group were estimated via
retrospective analysis of the Premier hospital database. The incidence rate of opioid
use (68%) and ORAEs (1.86%) in the BLIS group were based on the observed relative
reduction between BLIS and BH in a hemorrhoidectomy trial. The excess cost per
patient with ORAE ($4,707) was estimated from Premier. The drug acquisition costs
of BLIS and BH, opioid costs (including inpatient pharmacy, administration, errors
and outpatient pharmacy) were literature based. Subgroup analyses by surgery types
(colectomy and cholecystectomy) and demographics were carried out.
Results: Compared to BH, the use of BLIS is projected to result in an increase in
analgesia drug acquisition cost of $249/patient. This was offset by reductions in
opioids (–$95/patient) and ORAE (–$680/patient) costs giving net cost savings of
$526/patient in the Premier population overall. BLIS resulted in modeled costs
savings in all of the 378 subgroups except one. These ranged from cost savings of
$1,633/patient in “open cholecystectomy/ admission source trauma” subgroup to a
net cost increase of $154/patient for those admitted with trauma and undergoing a
laparoscopic cholecystectomy.
Conclusion: The use of BLIS at the time of surgery may result in cost savings due to
better pain management and reduced usage of opioids for postsurgical pain relief.
RESULTS
Table 1. Key Model Aspects
Table 2. Clinical Inputs
Model description
Decision tree
Software
MS Excel 2010
Interventions
BLIS vs. BH
Time horizon
BH
BLIS
Absolute
Difference
Relative
Difference
% patients satisfied
73%7
95%7
+22%
+30%
One year (inpatient + long-term outpatient opioid related costs)
% patients pain-free
19%8
35%8
+16%
+84%
Target population
Patients undergoing colectomy and cholecystectomy
% patients with ORAE
(Clinical trial)*
35%6
4%6
–31%
–89%
Clinical outcomes
■
Incidence of opioid use
92%9
68%†
–24%
–26%
$600
16.32%9
1.86%†
–14%
–89%
$400
■
■
% Patients pain-free
% Patients satisfied
% Patients ORAE free
% patients with an ORAE
(Claims database)
Cost outcomes
Per patient per year costs, cost effectiveness
Analysis perspective
Payer’s perspective
Discounting
Discounting was not applied due to small time horizon
Data sources
■
■
■
% patients using PCA |
use of opioid
Clinical trials for efficacy data on BLIS
Administrative claims database for ORAEs cost,
outcomes with BH
Literature for drug acquisition costs and opioid
administration costs
■
Figure 2 presents the general model structure.
Cost of
Analgesia
Cost of
Opioids
BH
Cost of
ORAEs
Cost of
Analgesia
Cost of
Opioids
Cost of
ORAEs
Cost of
Administration
Inpatient/Outpatient
Drug Cost
Inpatient/Outpatient
Drug Cost
DepoFoam® is a multivesicular liposome technology that encapsulates drugs without
altering their molecular structure and then releases them over a desired time period
(from 1 to 30 days).
Cost of IV
PCA Errors
Cost of IV
PCA Errors
One intraoperative dose of BLIS provides up to three days of analgesia with reduced
opioid requirements.6*
BLIS Total Cost
Net Cost
BH Total Cost
Incremental Costeffectiveness Ratio
Percent patients satisfied
Percent patients without an ORAE
■ Percent patients pain-free
■
■
To calculate the potential cost savings associated with the use of Bupivacaine liposome
injectable suspension (BLIS) vs. Bupivacaine HCL (BH) in patients undergoing
colectomy and cholecystectomy.
Percent patients satisfied
Percent patients without an ORAE
■ Percent patients pain-free
■
Net Effectiveness
BLIS
■
BH
Figure 1. BLIS Clinical/Economic Impact
Reduction in patients
on opioids (26%)6
Better outcomes
Cost savings
Discussion
■
The cost/burden of administratively coded ORAEs is increasingly being well established.
■
Savings from reducing ORAEs drive value.
■
The risk of of ORAEs and the associated costs saving potential for BLIS varied across surgery
type and demographic and clinical characteristics. Specifically, higher savings for BLIS were
observed in the following groups:
– Open abdominal procedures
Reduction in risk
of ORAEs (89%)6
6.8%5,9
Cost savings
ORAE = constipation, nausea, vomiting, pruritus; Patients with more than one event may
be double counted.
$0
BLIS
BH
BLIS
BH
Cost of analgesia
$285
$36
Cost of ORAEs
$88
$768
Cost of administration of opioids
$98
$133
Pharmacy (Drug, Inpatient)
$131
$177
Cost of IV PCA errors
$3
$4
Outpatient cost of opioids
$37
$50
Total Cost
$642
$1,168
Table 4. Top 10 Sub-groups with High Cost Savings Potential for BLIS Compared to BH
Colectomy
Relative reductions in the use of opioids and incidence of ORAEs in BLIS vs. BH patients
(Table 2) were obtained from a randomized, active controlled clinical trial of BLIS in one
hundred hemorrhoidectomy patients.6
Cholecystectomy
All
Open
Laparoscopic
All
Open
Laparoscopic
All
Open
Laparoscopic
All
$1,296
NA
$1,296
$1,633
$154
$983
$1,327
$154
$1,253
Comorbidity: BPH
$1,611
$1,138
$1,455
$1,344
$613
$735
$1,554
$754
$1,081
Age: 71 and older
$1,486
$976
$1,347
$1,079
$452
$560
$1,411
$586
$962
Age 65+
$1,437
$883
$1,276
$1,040
$396
$502
$1,364
$525
$896
Comorbidity: CAD
$1,489
$1,069
$1,379
$1,099
$416
$521
$1,406
$541
$894
$998
$711
$922
$815
$131
$293
$990
$531
$837
■
These were applied to data from the Premier Perspective database to estimate per-patient
cost savings, using variables provided in Table 3.
■
The Premier Perspective database contains complete billing and coding history on more
than 45 million or 20% of all hospital inpatient discharges in the USA.
Comorbidity: Regional Enteritis
Comorbidity: Sleep Apnea
$1,516
$959
$1,316
$1,139
$361
$479
$1,422
$498
$826
Exploratory analyses were carried out to identify sub-groups where large cost savings may
be achieved. The sub-groups were defined by surgery types (colectomy/ cholecystectomy,
laparoscopic/open) and patient demographics.
Comorbidity: CHF
$1,188
$1,142
$1,180
$960
$423
$522
$1,140
$534
$824
Comorbidity: Osteoarthritis
$1,392
$818
$1,223
$975
$346
$437
$1,317
$460
$815
Comorbidity: COPD
$1,533
$967
$1,383
$948
$289
$371
$1,427
$417
$809
■
■
All costs are in 2012 US dollars.
Note: Red boxes represent subgroups where BLIS was not cost saving compared to BH.
OBJECTIVE
Better pain control
9.2%5,9
■
Cost of
Administration
* The clinical benefit of the attendant decrease in opioid consumption was not demonstrated.
■
% patients with long term
opioid use | use of opioids
5
Bupivacaine liposome injectable suspension (BLIS) (EXPAREL®, Pacira Pharmaceuticals,
Parsippany, NJ) is a non-opioid local analgesic indicated for administration into the
surgical site to produce postsurgical analgesia. BLIS combines bupivacaine with the
DepoFoam® drug delivery platform to provide postsurgical pain control with a single
intraoperative infiltration.
■
0.4%9,10
$200
Admitted as Trauma
Figure 2. Model Structure Elements
Opioid analgesics, used commonly to treat postsurgical pain, may cause opioidrelated adverse events (ORAEs), which can be associated with a significant clinical and
cost burden.1-4
Patients prescribed post-surgical opioids are at risk of long-term opioid use.
$642
Calculated based on relative reductions observed in clinical trials
| = given (conditional probability)
BLIS
■
■
0.6%9,10
■
The results described in Figure 3 showed that BLIS saved $526 per patient per year
compared to BH in patients undergoing colectomy and cholecystectomy.
The higher drug acquisition cost of BLIS compared to BH ($285 vs. $36) was offset
by cost savings in opioid related adverse event costs ($680) and opioid costs ($95).
$800
19.7%9,10
% patients experiencing
PCA errors | (use of PCA |
use of opioids)
■
$1,000
†
INTRODUCTION
■
26.6%9,10
Base Case
$1,168
$1,200
* p < 0.007 6
Patient
■
Figure 3. Base Case Results
– Laparoscopic colectomy
– Other laparoscopic procedures if age >60 years of age or if history of respiratory disease such
as COPD, sleep apnea which carry a higher risk for costly opioid related AE
Table 3. Cost Inputs
Exploratory Subgroup Analysis
Cost
■
Drug Acquisition Cost 11
Bupivacaine liposome injectable suspension (BLIS)
Bupivacaine HCL
Additional cost of ORAEs per patient per year 9
$285 (per 266 mg dose)
$12 (per dose)
■
$4,707
Cost of Opioids
Opioid inpatient cost 11
Opioid outpatient cost*
Cost of opioid administration †
Cost of errors in PCA use 10
■
$192
$547
$145
$643
* Calculated based on % of long term opioid users given in Alam et al.5
† Micro-costed assuming 29% PCA use among opioid users (divided equally in PCA with and
without elastomeric pump users) based on Meissner et al.10 PCA costs taken from Frost
and Sullivan Survey.12
■
■
Exploratory sub-group analyses by surgery type were carried out by varying the incidence of
ORAEs while assuming 92% of patients used opioids and $4,707 as the cost of ORAEs.
Potential cost savings with BLIS were dependent upon the incidence of ORAEs and ranged from
cost savings of $1,633/patient in “open cholecystectomy/admission source trauma” subgroup
to a net cost increase of $154/patient for those admitted with trauma and undergoing a
laparoscopic cholecystectomy.
Per-patient cost savings for BLIS compared to BH were $133 for laparascopic cholecystectomy,
$676 for laparascopic colectomy, $746 for open cholecystecomy, and $1,225 for open colectomy.
Table 4 shows sub-groups with the highest cost-savings potential for BLIS owing to a high
assumed ORAE incidence when receiving BH.
Sub-groups that are among top ten cost savers for at least two surgery types:
– Admission source: trauma
– Age groups: 65+, 71+
– Comorbidities:
● Benign prostatic hyperplasia, (BPH)
● Congestive heart failure (CHF)
● Coronary artery disease (CAD)
● Chronic obstructive pulmonary disease (COPD)
● Sleep apnea
CONCLUSIONS
■
Based on this model, BLIS may be cost saving compared to BH in patients undergoing colectomy
and cholecystectomy.
■
BLIS may be cost-saving in a wide range of sub groups.
■
Cost-savings are driven by reduction in costly ORAE.
■
BLIS was shown to be better than BH in terms of percent patients without pain and ORAE and
percent patients satisfied with postsurgical pain treatment.
■
This analysis provides information whereby a postsurgical opioid sparing pain management
strategy may lead to cost savings and improved quality of care over a strategy that relies heavily
upon the use of opioids to manage postsurgical pain.
Table 5. Cost-effectiveness Ratios
Cost per satisfied patient
BLIS is dominant
Cost per patient
without ORAE
BLIS is dominant
Cost per pain-free patient
BLIS is dominant
■
For all outcomes included in the analysis, BLIS was
found to be the dominant treatment compared to BH.
■
This is the result of higher efficacy (in each of the
three included outcomes) and lower costs of BLIS
compared with BH.
REFERENCES
01. Oderda GM et al. J Pain Palliat Care Pharmacother. 2013;27(1):62-70.
02. Oderda GM et al: The Annals of Pharmacotherapy 2007;41(3):400-406.
03. Panchal S et al. International Journal of Clinical Practice 2007;61(7):1181-1187.
04. Kessler ER, Shah M, K Gruschkus S, Raju A. Pharmacotherapy. 2013 Apr;33(4):383-91.
05. Alam A et al. Archives of Internal Medicine 2012;172(5):425.
06. Haas E et al. Am Surg. 2012;78(5):574-81.
07. Gorfine SR et al. Diseases of the Colon & Rectum 2011;54(12):1552.
08. Golf M et al. Advances in Therapy 2011:1-13.
09. Claims database analysis using Premier Perspective Database, 2012 (Data on file).
10. Meissner B et al. Hospital Pharmacy 2009;44(4):312-324.
11. Thomson Redbook online, WAC prices, 2012.
12. Frost and Sullivan White Paper 2011: New opportunities for hospitals to improve economic efficiency and patient outcomes:
The case of EXPAREL®, a long-acting, non-opioid local analgesic. www.frost.com/prod/servlet/cpo/252218999.
Funding for this research was provided in part by Pacira Pharmaceuticals, Parsippany, NJ, USA.
Presented at ISPOR 2013, 18th Annual International Meeting, May 18–22, 2013, New Orleans, LA, USA.