Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event of chemotherapy and may be associated with considerable health-.
Resource utilization and costs of chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting
Abstract #157 Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology 2009 International Symposium 25-27 June, 2009 Rome, Italy
Thomas A. Burke1, Tami Wisniewski1, Frank R. Ernst2 1
Outcomes Research, Merck & Co., Inc., Whitehouse Station, NJ, USA; 2Premier Research Services, Healthcare Informatics, Charlotte, NC, USA
Abstract • P urpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event of chemotherapy and may be associated with considerable healthcare resource utilization and costs. This study was conducted to describe CINVassociated healthcare visits and costs following a first cycle of highly or moderately emetogenic chemotherapy (HEC or MEC). • Methods: The Premier Perspective Database™ was used to identify adult patients with a first administration of HEC or MEC between January 2003 and December 2007 at 250 hospital-based outpatient facilities. Follow-up started after the chemotherapy administration and ended 30 days later or before the second chemotherapy, whichever was first. CINV costs were hospital-reported visit costs. • Results: Of 15,088 patients (HEC, 21%; MEC, 79%), mean (SD) age was 59 (14) years; 59% were female; 66% were white. CINV prophylaxis included 5-HT3 antagonists (92%), dexamethasone (82%), and NK-1 antagonists (2%). Overall, 10.4% of patients had a CINV visit (HEC, 13.5%; MEC, 9.5%): 0.1% for acute CINV (same day of chemotherapy, excluding chemotherapy administration visit), and 10.3% for delayed CINV; 63% were inpatient (IP), 27% were outpatient (OP), and 11% were emergency room (ER) visits. Mean (SD) costs of CINV visits were $4948 ($6087), and for IP, $7037 ($6690), OP, $1595 ($2232), and ER, $868 ($999); averaged over all patients, mean CINV costs were $513 (SD, $2473). • Conclusions: CINV visits in the first HEC or MEC cycle were common and costly, most notably inpatient hospitalizations in the delayed phase. Strategies to reduce CINV in the delayed phase could reduce healthcare utilization and costs.
Background
Methods
RESULTS
(continued)
Patient Characteristics HEC (N=3147)
Age, mean (std)
MEC (N=11,941)
55.3 (14.6)
59.5 (13.1)
Race – n (%)
Caucasian
2106 (66.9)
7907 (66.2)
African-American
464 (14.7)
108 (3.4)
2390 (20.0)
2498 (16.6)
Colorectal
26 (0.8)
1774 (14.9)
Lymphoma
426 (13.5)
1013 (8.5)
122 (3.9)
Other
1065 (8.9)
1924 (61.1)
Acute CINV Visit
3064 (25.7)
Delayed CINV - OP Visit
Delayed CINV Visit 6/15
No Delayed CINV Visit 9/15
Delayed CINV - IP Hospitalization 718/11,926
No Acute CINV Visit
2232 (14.8)
Breast
44/3140
2721/3140
10,013 (66.4)
1768 (14.8)
Delayed CINV - ER Visit
No Delayed CINV Visit
MEC (N=11,941)
3889 (25.8)
Ovarian
HEC or MEC
15/11,941
3280 (27.5)
11,926/11,941
Delayed CINV - ER Visit 121/11,926
Delayed CINV - OP Visit 285/11,926
No Delayed CINV Visit
Notes: IP = inpatient; ER = emergency room; OP = outpatient hospital visit. Costs are in US dollars.
10,802/11,926
$5066 $9596 $7361 $933 $1493 $0 $2311 $3716 $6921 $845 $1680 $0
Sensitivity analyses: alternative definitions of CINV hospital healthcare resource use and costs
1800 (11.9)
Alternative definition
CINV HCRU N (% of All)
Mean (SD) CINV Costs^ (All)
1439 (9.5)
Base case plus CINV on chemotherapy visit
1682 (11.1)
$616 ($2846)
1187 (7.9)
Restrictive ICD-9 definition*
979 (6.5)
$270 ($1761)
4988 (33.1)
Visits with primary ICD-9 CINV code§
544 (3.6)
$147 ($1199)
Restrictions of follow-up time for CINV visits post-chemotherapy~
Chemotherapies HEC N=3147 (20.9%)
MEC N=11,941 (79.1%)
All N=15,088 (100%)
Year of chemotherapy receipt – n (%) 2003
480 (15.3)
1883 (15.8)
2363 (15.7)
2004
510 (16.2)
1995 (16.7)
2505 (16.6)
2005
663 (21.1)
2578 (21.6)
3241 (21.5)
2006
764 (24.3)
2652 (22.2)
3416 (22.6)
2007
730 (23.2)
2833 (23.7)
3563 (23.6)
Common single agent HEC – n (% of All)
• The database contains information on patient demographics (age, sex, race, marital status), hospital characteristics, principal and secondary diagnoses, payer, cost of care, medication utilization (name, strength, quantity dispensed, day of administration), department cost and charge detail, length of stay, and physician specialty.
Cisplatin
2542 (16.8)
Common single MEC – n (% of All)
Carboplatin
5185 (34.4)
Anthracycline
3677 (24.4)
Study Cohort
Cyclophosphamide
2507 (16.6)
• The study population comprised patients aged 18 years or older who received a first highly or moderately emetogenic single-day chemotherapy (HEC or MEC) and at least 1 antiemetic for prophylaxis at an outpatient hospital facility between January 1, 2003, and December 31, 2007.
Etoposide
1495 (9.9)
Oxaliplatin
1367 (9.1)
Irinotecan
1130 (7.5)
• We collected patient demographic characteristics (age, sex, marital status, race), payer type, cancer diagnosis (based on ICD-9 codes recorded at the chemotherapy administration visit), and chemotherapy and antiemetic therapies that were administered from the hospital pharmacy during the chemotherapy administration visit. Other recorded sample characteristics included geographic region and type of hospital (teaching hospital, urban hospital) and physician specialty for outpatient visits.
Antiemetics
6 days
574 (3.8)
$122 ($964)
10 days
913 (6.1)
$219 ($1302)
14 days
1162 (7.7)
$315 ($1770)
Restrictions of follow-up time for CINV visits post-chemotherapy and inclusion of chemotherapy visit costs when CINV was ICD-9 diagnosis
6 days
778 (5.2)
$249 ($1790)
10 days
1085 (7.2)
$341 ($1982)
14 days
1314 (8.7)
$430 ($2299)
Notes: ^Costs presented in US dollars. *ICD-9 codes 787.01-787.03 (nausea and/or vomiting) and excluding 276.5 (volume depletion; including dehydration, depletion of volume of plasma or extracellular fluid, hypovolemia). §Including only primary CINV codes, excluding those visits with CINV coded as secondary ICD-9 code. ~Includes only those CINV costs within indicated time period after chemotherapy.
Strengths • This study consisted of a large, ethnically diverse sample from hospitals throughout the US. • The study time frame is recent and therefore reflects use of newer antiemetics that have improved CINV control. • CINV coded on the chemotherapy administration visit was excluded from the analysis, thereby potentially not including resource use, rescue medication, and nursing time associated with acute CINV.
Limitations
Antiemetic – n (%)
HEC (N=3147)
MEC (N=11,941)
All (N=15,088)
5-HT3 antagonists
3000 (95.3)
10,844 (90.8)
13,844 (91.8)
2855 (90.7)
9533 (79.8)
12,388 (82.1)
8 (0.3)
86 (0.7)
94 (0.6)
Corticosteroids Dexamethasone Other
• Average US values for body surface area for adult women (1.6) and adult men (1.9) were used.12-15
Antihistamines
708 (22.5)
4585 (38.4)
5293 (35.1)
Benzodiazapines
576 (18.3)
1277 (10.7)
1853 (12.3)
• Antiemetic prophylaxis was defined by the following classes of medications: 5-HT3 antagonists, corticosteroids, benzodiazepines, antihistamines, NK-1 receptor antagonists, butyrophenones, phenothiazines, and cannabinoids.
NK-1 antagonists
161 (5.1)
142 (1.2)
303 (2.0)
• Hospital visits were classified as inpatient admission, emergency room visits, and outpatient hospital visits (non-emergency room). Patients with multiple visits for CINV were classified into a single mutually exclusive healthcare resource use category according to the following hierarchy: inpatient > emergency room > outpatient hospital visit. This classification was applied overall and separately for the acute and delayed phases.
No Delayed CINV Visit
120/3140
58.9 (13.5)
609 (19.4)
• Acute CINV hospital visits were those on the day of chemotherapy administration, excluded in the chemotherapy visit, and delayed CINV hospital visits were those on days following chemotherapy administration.
4/7
Delayed CINV - IP Hospitalization
3140/3147
All (N=15,088)
Lung
• The analysis of CINV-related healthcare resource use was descriptive.
$800
3/7
No Acute CINV Visit
Statistical Analysis
$600
255/3140
• Costs for CINV-associated hospitalizations included those categorized as emergency room or outpatient visit; and costs for inpatient CINV visits included total costs for the inpatient hospitalization as reported by the hospital.
$400
HEC (N=3147)
Cancer diagnosis – n (%)
• Costs of healthcare resource use were the hospital costs as reported in the database.
$200
7/3147
• Prevention of CINV from the acute phase (0-24 hours post-chemotherapy) in the first cycle of chemotherapy remains an important goal of treatment because it can help to minimize CINV on subsequent cycles1,2 and decrease the incidence of delayed CINV3 (25-120 hours post-chemotherapy). Nonetheless, recent studies indicate that CINV control is incomplete, particularly control of nausea and delayed CINV.4 -10
• CINV-associated healthcare resource use was defined as any hospital visit with a primary or secondary ICD-9 code of 787.0 (nausea and vomiting), 787.01 (nausea with vomiting), 787.02 (nausea alone), 787.03 (vomiting alone), 276.5 (volume depletion), or 276.50 (volume depletion, unspecified).
$41
Delayed CINV Visit
1983 (13.1)
• Healthcare resource use was assessed starting on the patient’s first chemotherapy administration date and ending 30 days after the chemotherapy administration date or 1 day before the second chemotherapy administration, whichever occurred first.
$9
Acute CINV Visit
1586 (11.3)
Resource Use and Costs
MEC
Decision Tree
397 (11.0)
• Antiemetic drugs given on the same day as chemotherapy were assumed to be CINV prophylaxis rather than CINV treatment.
$682
Notes: HV = hospital visit; IP = inpatient admission; ER = emergency room visit; OP = outpatient hospital visit. Costs in US dollars.
Other
• We defined HEC and MEC regimens according to the Multinational Association of Supportive Care in Cancer (MASCC) guidelines.11
OP
$469 $419
$0
• Substantial progress has been made over the past 2 decades in the prophylaxis and treatment of chemotherapy-induced nausea and vomiting (CINV).
• This was a retrospective cohort study using the Premier Perspective™ Database, a hospital service database that includes detailed patient-level data, differentiated by inpatient stay versus visits to outpatient hospital facilities, from over 600 US hospitals.
ER
$13 $57
N = 11,941
RESULTS
IP
$611
N = 3147
• Analyses were conducted using SAS version 9.1.
860 (5.7)
Data Source
HEC
Any HV
$513 $459
$10 $44
N = 15,088
• We also combined sensitivity analyses 1 and 4.
680 (5.7)
Methods
All
• Sensitivity analyses were conducted using alternative definitions of CINV-related healthcare resource utilization to explore the impact of: 1) including costs of the chemotherapy administration as CINV costs; 2) using a more narrow CINV ICD-9 definition that excluded volume depletion codes; 3) excluding CINV costs when CINV was the secondary diagnosis code on the visit claim; and 4) restricting CINV healthcare resource use to a shorter period after the chemotherapy administration visit (6-14 days).
180 (5.7)
• The objectives of this study were to describe the percentage of patients who have a hospital visit (inpatient, outpatient, and emergency room) secondary to uncontrolled CINV and to report the associated costs.
CINV-related hospital costs, for those with and without CINV, after a first cycle of HEC or MEC
• Costs associated with CINV were summed across visits for each patient for the overall study, the acute phase, and the delayed phase. Mean cost (SD) per CINV visit was calculated for patients with at least 1 event, as well as across all patients with and without CINV visits.
Hispanic/Latino
• CINV also has potential economic consequences, as patients may require additional medical care to treat symptoms related to uncontrolled CINV, such as dehydration. One study demonstrated the most frequently used resources for uncontrolled CINV were the need for rescue medication, additional office and outpatient hospital visits, and hospitalization.4
(continued)
• There was no control group to provide a background rate of visits and costs associated with nausea, vomiting, and dehydration in patients with cancer not receiving chemotherapy. • The time period to capture CINV, of up to 30 days or until the next chemotherapy visit, may have captured nausea and vomiting unrelated to chemotherapy. This time frame, however, was selected to capture adverse consequences of CINV requiring a hospital visit or admission that may have extended beyond the delayed phase, such as dehydration. • We may have not captured all resource use if patients returned to nonparticipating outpatient or hospital facilities for uncontrolled CINV management.
Percentage of patients with CINV-related hospital healthcare resource utilization after a first cycle of HEC or MEC All
1.1%
N = 15,088
HEC
2.8%
MEC
1.0%
N = 11,941
13.5%
8.3%
1.4%
N = 3147
Any HV IP ER OP
10.4%
6.5%
Conclusions • Over 1 in 10 patients had a follow-up hospital visit associated with CINV in this study. • The average cost of uncontrolled CINV is $500 per patient receiving HEC and MEC in the first chemotherapy cycle. • The majority of healthcare resource use and cost burden for CINV occur during the delayed phase post-chemotherapy.
3.9%
6.1%
9.5%
• Appropriate use of newer antiemetic regimens that reduce CINV in the delayed phase may help to reduce the overall cost burden of CINV.
3.0%
0.0%
5.0%
10.0%
15.0%
20.0%
References
Notes: HV = hospital visit; IP = inpatient admission; ER = emergency room visit; OP = outpatient hospital visit.
CINV-related hospital costs, for those with CINV, after a first cycle of HEC or MEC $4948
All
$868
N = 1565
HEC
OP
$844
$0
$7400
$6907
$1655
$2000
$4914
MEC
IP ER
$934 $1454
N = 1139
$7037
$1595 $5038
N = 426
Any HV
$4000
$6000
$8000
Notes: HV = hospital visit; IP = inpatient admission; ER = emergency room visit; OP = outpatient hospital visit. Costs in US dollars.
1. M orrow GR, Roscoe JA, Hickok JT, et al. Initial control of chemotherapy-induced nausea and vomiting in patient quality of life. Oncology (Williston Park). 1998;12:32-37. 2. Kris MG. Why do we need another antiemetic? Just ask. J Clin Oncol. 2003;21:4077-4080. 3. Liau CT, Chu NM, Liu HE, Deuson R, Lien J, Chen JS. Incidence of chemotherapy-induced nausea and vomiting in Taiwan: physicians’ and nurses’ estimation vs. patients’ reported outcomes. Support Care Cancer. 2005;13:277-286. 4. Ihbe-Heffinger A, Ehlken B, Bernard R, et al. The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol. 2004;15:526-536. 5. Molassiotis A, Saunders MP, Valle J, et al. A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre. Support Care Cancer. 2008;16:201-208. 6. Glaus A, Knipping C, Morant R, et al. Chemotherapy-induced nausea and vomiting in routine practice: a European perspective. Support Care Cancer. 2004;12:708-715. 7. Cohen L, de Moor CA, Eisenberg P, Ming EE, Hu H. Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer. 2007;15:497-503. 8. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006;24:4472-4478. 9. Grunberg SM, Deuson RR, Mavros P, et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer. 2004;100:22612268. 10. Ballatori E, Roila F, Ruggeri B, et al. The impact of chemotherapy-induced nausea and vomiting on health-related quality of life. Support Care Cancer. 2007;15:179-185. 11. Roila F, Hesketh PJ, Herrstedt J; Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference. Ann Oncol. 2006;17:20-28. 12. Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med. 1916;17:863-871. 13. Gehan EA, George SL. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970;54:225-235. 14. Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr. 1978;93:62-66. 15. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317:1098. Editorial assistance was provided by Elizabeth V. Hillyer with financial support from Merck & Co. Inc. Thomas A Burke and Tami Wisniewski are employees of Merck & Co. Inc. Frank Ernst is an employee of Premier Research Services and conducted this research for Merck & Co., Inc.
This study was sponsored by Merck & Co., Inc.
