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PCN63
Systematic Literature Review of Cost of Adverse Events in Cancer Treatment in the US
Smeet Gala, Merena Nanavaty, John Proach
Market Access Solutions, LLC., Raritan, NJ
INTRODUCTION
 Adverse events (AEs) and dose-limiting toxicities in cancer patients are associated with increased
morbidity, mortality and cost.1
 AEs decrease patients’ compliance to chemotherapy and their quality-of-life, but also lead to significant
financial burden in form of direct and indirect costs.2
 Major clinical studies report the chemotherapy-related AEs, but there is very little literature on their costs.
 There is lack of reviews that summarizes the cost of various AEs across different cancers.
OBJECTIVES
 The objective of this systematic literature review was to provide an updated understanding of the cost of
AEs in cancer treatments in the US.
METHODS
 A systematic literature search was conducted in PubMed, and relevant articles published between January
2008 and October 2013, in English language were included.
 Primary search terms used were AE related; secondary search terms used were cost related.
 The inclusion criteria used:
• Studies evaluating cost of following AEs: neutropenia, thrombocytopenia, vomiting, nausea/vomiting,
peripheral neuropathy, sepsis, diarrhea and fatigue/asthenia due to cancer treatment
• US-based studies
 A total of 893 titles and abstracts were screened for eligibility by two researchers and discrepancies were
resolved by a third researcher. Any undetermined titles and abstracts were reviewed via full-text screening.
 Costs were extracted for case and control cohorts (if available) and the cost difference between the cohorts
was calculated to provide the additional cost due to the AEs.
Table 2. Cost of Adverse Events Related to Cancer Treatments
Cost
(difference
between
Study - year of
Type of cost
Unit of cost
case and
publication
controls
when
available)
Neutropenia
Elting 20083
Elting 20083
Inpatient cost
Outpatient cost
Per episode
Weycker 20084
Total healthcare cost
(hospitalizations,
outpatient encounters,
antibiotic therapy)
Hendricks 20115
Burudpakdee 20126
Burudpakdee 20126
Weycker 20127
Weycker 20127
Inpatient cost
Inpatient cost
Outpatient cost
Inpatient cost
Outpatient cost
Baroletti 20088
Smythe 20089
Eisenstein 201010
Per event
Thrombocytopenia
Per patient
Per patient
Per patient admission
Inpatient cost
Inpatient cost
Inpatient cost
 A PRISMA flow diagram was employed for study selection and inclusion (Figure 1).
Identify
Figure 1. Flow Diagram of Systematic Literature Search
Screen
PubMed (January 2008-October 2013)
(n = 893)
Abstracts excluded (n = 858)
1.Not US-based studies (n = 108)
2.Not cancer-based studies (n = 345)
3.Not evaluating cost of AEs (n = 405)
Abstracts screened
(n = 893)
Eligible
Include
Per event
Burke 201112
Inpatient cost
Burke 201112
Outpatient cost
Haiderali 201113
Direct medical cost
201314
Full-texts excluded (n = 20)
1.Not cancer-based studies (n = 8)
2.Not evaluating cost of AEs (n = 12)
Total Cost of medical care services
Healthcare cost
Inpatient cost
Outpatient cost
Neutropenia (n = 5)
Thrombocytopenia (n = 3)
29%
Vomiting (n = 1)
6%
Peripheral neuropathy (n = 1)
Sepsis (n = 1)
Diarrhea (n = 1)
18%
 Only 5 studies included type of
cancer reported
Fatigue/asthenia (n = 1)
6%
 Majority of studies (29%)
reported cost of treating
neutropenia, which is a major
AEs of chemotherapy.
 Majority of included studies
were either healthcare claims
database (n = 10) or registrybased studies (n = 2)
Nausea + vomiting (n = 4)
23%
Table 1. Characteristics of Included Studies
Study - year of
publication
Disease
Year of $
Data source in study
Neutropenia
20083
Solid tumor
A retrospective cohort consisting of consecutive
patients registered on the low-risk pathway
between 1997 and 2003
2006
Weycker 20084
Cancer
Hendricks 20115
Cancer
2008
Costs from a randomized trial
Metastatic
Medicare payments from the Healthcare Cost
2010
colorectal cancer
and Utilization Project database
Not specified
Cancer
(Database year
US Healthcare claims data
2003-2009)
Thrombocytopenia
Not specified
Heparin-induced (Database year
Single-center patient registry
2003-2006)
Financial / decision support database of
Heparin-induced Not specified
hospital
CATCH patients registry
Heparin-induced 2004
Burudpakdee
20126
Weycker 20127
Baroletti 20088
Smythe 20089
Eisenstein 201010
2003
US health-care claims database
Vomiting
Burudpakdee 20126
Metastatic
2010
colorectal cancer
Parra-Sanchez 201011 Post-operation
Burke 201112
Haiderali 201113
Hagiwara 201314
Pike 201215
Allareddy
201216
Cancer
Cancer
Renal cell
carcinoma
Cancer
Leukemia
Medicare payments from the Healthcare Cost
and Utilization Project database
Nausea and vomiting
Not specified
Economic data of ambulatory patients
Not specified
(Database year
Premier Perspective™Database
2003-2007)
2007
32 oncology specialty care settings in the USA
Linked Surveillance, Epidemiology and End
2007
Results (SEER) Medicare database
Peripheral neuropathy
Database of privately insured administrative
2006
claims record (Ingenix Employer
Database)
Sepsis
2008
Nationwide Inpatient Sample (NIS) of the
Healthcare Cost and Utilization Project
Diarrhea; Fatigue / Asthenia
Hagiwara
201314
Renal cell
carcinoma
2007
$17,117.10
$10,143.00
$12,606.00
$217.00
$12,554.00
$315.00
$11,664.45
$13,740.54
$236.53
$14,060.48
$352.80
$9,910.00
$32,872.00
$37,953.00
$11,991.10
NA
$48,200.31
$5,559.00
$195.00
$6,059.31
$212.55
$69.00
NA
$7,448.00
$8,788.64
$1,494.00
$1,762.92
$732.00
$863.76
$13,420.00
$15,835.60
$17,344.00
$7,552.00
$8,092.00
$20,986.24
$9,137.92
$9,791.32
Sepsis
Figure 2. Distribution of studies reporting AEs (total = 15)
6%
Per patient
Per patient (from patient’s 1st
chemotherapy date and
ending at the first of: 30 days
after the 1st chemotherapy
date or 1 day before the 2nd
chemotherapy)
Per patient (for the 5-day
period following
chemotherapy)
Per patient (over a period of
30 days following 1st mention
of the event)
Per patient per year
Studies included in qualitative review (n = 15)
6%
$13,167.00
Peripheral neuropathy
Allareddy 201216
Elting
Inpatient cost
Outpatient cost
Parra-Sanchez 201011 Total cost
Pike 201215
6%
$18,429.51
$9,412.59
Nausea and vomiting
Hagiwara
Full-text articles assessed for
eligibility (n = 35)
$15,231.00
$7,779.00
Vomiting
Burudpakdee 20126
Burudpakdee 20126
 A total of 35 full-text articles were assessed for eligibility, of which 15 were included.
Per patient (from date of
initial hospitalization for
neutropenic complications
through end of
chemotherapy)
NR
Per event
 The difference in cost was adjusted to 2013 USD assuming a discounting rate of 3%.
RESULTS
Cost for
2013 $
(inflated by
3% every
year)
Linked Surveillance, Epidemiology and End
Results (SEER) Medicare database
Hospitalization charges Per patient
$165,787.00 $190,655.05
Diarrhea
Hagiwara
201314
Total Cost of medical care services
Per patient (over a period of
30 days following 1st mention
of the event)
$12,356.00
$14,580.08
$12,552.00
$14,811.36
Fatigue / Asthenia
Hagiwara
201314
Total Cost of medical care services
Per patient (over a period of
30 days following 1st mention
of the event)
 The type of costs identified included inpatient-outpatient costs and total healthcare costs.
 The units of costs reported varied as: per patient, per-patient per-year (PPPY), per event and per episode.
 Inpatient costs ranged from $6,000 per event to $48,000 per patient admission and outpatient costs varied
from $213 per event to $9,800 PPPY.
 The inpatient cost per patient of treating thrombocytopenia was the highest as compared to the inpatient
costs of treating other AEs.
 The total healthcare cost ranged from $15,000 per patient per 30-day post-event to $21,000 PPPY.
 An economic burden is observed on cancer patients due to the AEs related to chemotherapy.
STRENGTHS
 This is the first literature review to systematically assess the cost of various cancer treatment-related AEs in
the US.
 This study highlights the excessive economic burden of treatment-related AEs a cancer patient faces in
addition to the expensive oncology treatments.
LIMITATIONS
 Comparisons should be made with extreme cautions owing to the differences in type of cancer, grade of
AEs, type of costs, population in case and control groups and data sources.
 Cost data on some AEs such as fatigue, fertility and sexual side effects, pain, xerostomia, etc. were not
available through the current search. Additional searches may be needed to obtain such cost data.
 Grey literature and various conferences, not searched in the current review, may provide deeper insight in
the cost of cancer treatment-related AEs.
CONCLUSION
 The adverse events in cancer treatment remain a common and an expensive problem.
 The direct healthcare cost reviewed in this study, along with the indirect cost (not in study) of these AEs
pose a tremendous economic burden on healthcare.
 In the future, it is important to compare the costs of treating AEs resulting from various cancer treatments,
in order to efficiently allocate the healthcare budget.
REFERENCES
1. Kuderer NM et al. Cancer. 2006;106(10):2258-2266.
2. Hurvitz S et al. The oncologist. 2014;19(9).
3. Elting LS et al. Journal of clinical oncology : official journal of
the American Society of Clinical Oncology. Feb 1
2008;26(4):606-611.
4. Weycker D et al. 2008;19(3):454-460.
5. Hendricks AM et al. Journal of clinical oncology : official
journal of the American Society of Clinical Oncology. Oct 20
2011;29(30):3984-3989.
6. Burudpakdee C et al. Journal of medical economics.
2012;15(2):371-377.
7. Weycker D et al. Chemotherapy. 2012;58(1):8-18.
8. Baroletti S et al. Thrombosis and haemostasis. 2008.
9. Smythe MA et al. Chest. Sep 2008;134(3):568-573
10.Eisenstein EL et al. Journal of medical systems.
2009;34(3):379-386.
11.Parra-Sanchez I et al. Canadian Journal of
Anesthesia/Journal canadien d'anesthésie. 2012;59(4):366375
International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting,
Philadelphia, PA, USA, May 16 - 20, 2015
12. Burke TA et al. Supportive care in cancer : official journal
of the Multinational Association of Supportive Care in
Cancer. Jan 2011;19(1):131-140.
13. Haiderali A et al. Supportive care in cancer : official
journal of the Multinational Association of Supportive Care
in Cancer. Jun 2011;19(6):843-851
14. Hagiwara M et al. Journal of medical economics. Nov
2013;16(11):1300-1306.
15. Pike CT et al. Chemotherapy research and practice.
2012;2012:913848.
16. Allareddy V et al. World journal of pediatrics : WJP. Aug
2012;8(3):222-228.