Curr Probl Cancer ] (2017) ]]]]]]

Contents lists available at ScienceDirect

Curr Probl Cancer

journal homepage: www.elsevier.com/locate/cpcancer

Direct medical cost associated with colorectal

cancer in north of Jordan
Qais Alefan, PhD*, Rana Malhees, MSc, Nizar Mhaidat, PhD

a r tic l e in f o a bs t r a c t

Colorectal cancer (CRC) is mainly characterized as the

Keywords: malignant and impaired growth of rectal cells in the
Colorectal cancer intestinal region. Direct medical cost is related to resources,
Growth which are directly used in treating the patient, that mainly
Impaired includes the cost of drugs, diagnostic, treatment, follow-up,
Rehabilitation rehabilitation, and hospital admission. The objective of
Hospital admission this study is to estimate and analyze direct medical costs
attributable to CRC in Jordan. A retrospective analysis of a
cohort patients treated for CRC data has been performed to
determine direct medical costs attributable to CRC in Jordan.
The prevalence-based approach has been used in addition to
the bottom up approach to accumulate 1-year time costs of
CRC. Demographic, clinical, and economic data have been
collected and analyzed using SPSS for windows. Costs were
estimated by a bottom-up approach, in which each service
component was identied and valued at the most detailed
level, to provide greater transparency and reliability in
economic evaluation of health care services. This study
quantied the economic burden associated with CRC by
Jordanian patients in King Abdullah University Hospital from
the perspective of health care providers (public sector). Total
CRC cost in the year 2014 was estimated to JD 695,608, and
the most expensive stage for all sites was stage 4 reaching a
cost of JD 5147. Advanced disease stages were associated
with an increase in total cost and chemotherapy costs. In
conclusion, results of this study propose that direct medical

Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

*Correspondence to: Qais Alefan, PhD, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid
22110, Jordan.
E-mail address: qmefan@just.edu.jo (Q. Alefan).

http://dx.doi.org/10.1016/j.currproblcancer.2017.05.001
0147-0272/& 2017 Elsevier Inc. All rights reserved.
2 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]]

costs associated with CRC are considerable. Most of the cost

was devoted for medications, primarily chemotherapy.
Advanced stages were associated with higher cost and
largest number of patients.
& 2017 Elsevier Inc. All rights reserved.

Introduction

Colon cancer or colorectal cancer (CRC) is usually characterized as the impaired growth of
cells within the structures of large intestines, colon, or rectum. The prevalence rate of CRC is
continuously increasing at a constant rate across the globe.1 Treatment of colon cancer includes
surgical procedures, chemotherapy, radiation therapy, monoclonal therapy, and after-care
treatments.2
The importance of dietary, lifestyle, and medication risk factors for CRC has been highlighted.
High intake of red and processed meats, rened grains and starches, and sugars are associated
with increased risk of CRC. On the contrary, ideal body weight, rational level of physical activity,
and avoidance of smoking and alcohol use are linked with lower risks of CRC. Medications such
as aspirin and nonsteroidal anti-inammatory drugs and postmenopausal hormones are related
to lower CRC risk. Therefore, changes in diet and lifestyle may signicantly decrease the risk of
CRC.2
A total of 14.1 million adults were diagnosed with cancer worldwide in 2012.3 If no action is
taken, deaths from cancer in the developing world are forecast to grow to 8.9 million in 2030. In
contrast, cancer deaths in wealthy countries are expected to remain stable over the next 20
years.4 The incidences of colon and rectum cancer in the Arab world are relatively low, although
in some of the more rich countries it is number 2 after breast.5 In Jordan, the total number of
cancer cases in 2012 was 3761. The total number of CRC casesthe second most common cancer
after lung cancerof male sex was 282 (12%) in 2012, and 285 (10.7%) for female of all CRC
cases.6,7
Cost-of-illness studies measure the economic burden of illness to society.8,9 These can be
described as prevalence-based or incidence-based approaches based on the way in which the
epidemiologic data are used. Being most commonly used, the prevalence approach estimates the
economic burden of a condition over a specic period, usually a year, whereas the incidence
approach estimates the lifetime costs of a condition from its onset until its disappearance
(usually by cure or death), which refers to the new number of cases arising in a predened time
period.10,11 Several studies have estimated direct medical costs of CRC and found that direct
costs of CRC present a signicant economic burden to health care systems.12-20 Most of
previously published studies on the topic of CRC surveillance in Jordan assessed its epidemiology
and related characteristics.21-24 However, none of these studies estimated the direct medical
costs of the disease. To the best of our knowledge, this study is the rst of its type in Jordan to
estimate direct medical cost of the second most common cancer in Jordan. Thus, the objective of
this study was to estimate the direct medical costs attributable to CRC in north of Jordan.

Methodology

Study Design

This was a retrospective analysis of cohort CRC patients for 12 months starting from January
1, 2014 until December 31, 2014. The study protocol was approved by Institutional Review Board,
Jordan University of Science and Technology. As the study has estimated the direct medical costs
 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]] 3

attributable to CRC; this study applied the cost-of-illness approach.25-27 The prevalence-based
approach has been used in addition to the bottom up approach to accumulate 1-year time
costs of CRC.28,29 Prevalence-based studies quantify the costs incurred by all individuals due to
illness within a dened period, usually 1 year, regardless of the time of disease onset.

Settings

The study was conducted in King Abdullah University Hospital (KAUH) within the territories
of Ramtha, Jordan.

Study Population and Sampling Procedure

The sampling frame has included all CRC patients who have attended KAUH in the year 2014.
The list for patients diagnosed in 2014 was prepared by referring to the IT department by using
the code of (colon, rectal, and colorectal) cancers from CD19.0 until CD20 (n 62 patients).
According to International Classication of Diseases for Oncology we included patient cases
having the diagnosis of tumor site of colon (C18.0-C18.9 and C26.0) or rectum (C19.9 and C20.9).
Colon tumors were further designated by location as proximal (C18.0 and C18.2-C18.5), distal
(C18.6-C18.7), or other (C18.1, C18.8, C18.9, and C26.0). Then, a list was prepared for all patients
(n 1162 patients) who visited the oncology department for at least 1 time during the year 2014
and been hospitalized for at least 1 day in oncology and surgery departments. Afterwards, this
was cross-linked with the list of patients receiving chemotherapy that year (n 333 patients).
Finally, summation and cross-linking of all these patients lists yielded the nal patients list
(n 107) has been screened by inclusion and exclusion criteria to determine the direct medical
costs attributable to CRC.

Inclusion and Exclusion Criteria

The following inclusion and exclusion criteria were set for selecting study subjects. Patients
were included in the study, if

(1) The patient was diagnosed or has a history of CRC.

(2) The patient was receiving any kind of medical management for CRC (chemotherapy, surgery,
or at least investigational colonoscopy).
(3) The patient has been hospitalized in 2014 because of CRC.

Patients were excluded from the study, if

(1) The patient was a participant in a clinical trial.

(2) The patient was not receiving any kind of medical management for CRC (chemotherapy,
surgery, or at least investigational colonoscopy).
(3) The patient was not hospitalized during 2014 because of CRC.
(4) No medical le could have been reached for the patient.

On the basis of inclusion and exclusion criteria, 97 patients of 107 were included in the study.
Ten patients were excluded due to either not receiving any kind of medical management for CRC
or the patient was not hospitalized during 2014 because of CRC.
4 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]]

Study Variables

The demographic information on sex (male vs female) was considered as dichotomous

variables (ie, nominal level). Study subjects were divided into different groups according to CRC
primary site and stages. These groups were considered as dichotomous variables. Some of the
independent variables mentioned earlier can affect the cost. Therefore, in this study, direct
medical costs categories have been considered as dependent and continuous variables (ie, ratio
level).

Study Perspective

The health care providers perspective was considered in this study because this perspective
usually identies costs imposed on the hospitals and other health care providers in public sector.

Data Collection

To achieve the studys main objective, 3 types of data (ie, demographic, clinical, and
economic) were collected per patient using the case record form. The case record form included
items on patients age, sex, comorbidities, stage of CRC, size of tumor, site of metastasis, degree
of differentiation, drugs names, costs of drugs, hospitalization, surgery, and laboratory and
diagnostic procedures, etc. The case record form was initially tested on 10 subjects to assess its
suitability. Collected data were stored as binary numbers, normal numbers, and dates which
were stored in Microsoft Excel software on daily basis. Demographic data were collected using
the electronic system of KAUH and by reviewing medical le for each patient. Clinical data were
collected using the electronic system of KAUH and by reviewing medical le for each patient.
Moreover, body height and weight were recorded from patient medical le, and using
chemotherapy sheets that necessitate such information to be recorded. Body mass index was
calculated as body weight (kg) divided by the square of body height. Data on diagnosis, drugs,
chemotherapy regimens that were given to the patient were collected. Moreover, data on patient
hospitalization, operations, and hospital visits in addition to diagnostic and laboratory tests were
collected. Microcosting was used to collect economic data. Data that were considered for
economic evaluation included drug, investigational and diagnostic laboratory tests, treatment
procedures (surgery); and hospitalizations costs.

Costs Estimation

Median annual interval was chosen to present the direct medical costs. Only direct medical
costs were incorporated into the analysis. Costs were estimated by a bottom-up approach, in
which each service component was identied and valued at the most detailed level, to provide
greater transparency and reliability in economic evaluation of health care services. Costs of each
service use were derived by multiplication of the unit cost, and the number of respective
services used by the patients. The total estimated cost of each CRC was then computed by a
summation of all service use costs and categorized by stage of CRC stages I-IV CRC, tumor
primary site (colon and rectum) at diagnosis. Direct medical costs were calculated through the
summation of the cost produced by multiplying the quantities of each drug and other care
services by their unit cost.30,31
TCn J QLnj  ULj KQDnk  UDk M QMnm  UMm N QMnn  UMn FQCnf  UCf ,
where TCn is the total direct medical costs for patient n, QLnj is the number of laboratory test (j)
used by patient (n), ULj is the unit cost of laboratory test (j), QDnk is the number of drug k used
by patient n, UDk is the unit cost of drug k, QMnm is the number of clinic visit m encounter by
patient (n), UMm is the cost of the clinic visit m encounter, QMnn is the number of
hospitalization (n) encounter by patient (n), UMn is the unit cost of hospitalization encounter,
 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]] 5

QCnf is the number of chemotherapy doses f used by patient (n); UCf is the unit cost of
chemotherapy (f).
All costs were expressed in Jordanian Dinar (JD) (JD 0.708 1 US dollar for the year 2014).

Data Analysis

Statistical analysis was performed using SPSS for Windows, version 21. A variety of
descriptive statistics such as mean, standard deviation, median, and percentage was calculated
to describe some parts of the results. Kruskal-Wallis and Mann-Whitney tests were used to
determine the statistically signicant differences in median values of the CRC stages. A P o 0.05
was dened as statistically signicant.

Results

The total number of patients who were included in the study was 97 patients. More than half
of them were men (n 52, 53.6%) and the mean age of all patients was (57.31 7 13.3) years.
Most patients (85.6%) were nonsmokers and half of them (50.5%) did not have comorbidities.
More than half of the patients were at stage IV of the disease (n 56, 57.7%) (Table 1).

Table 1
Sociodemographic characteristics of the sample (N 97).

n (%)

Age (mean 7 SD) 57.31 7 13.3

Sex
Male 52 (53.6)
Female 45 (46.4)

Nationality
Jordanian 94 (96.9)
Refugee 3 (3.1)

Smoking status
Smoker 14 (14.4)
Nonsmoker 83 (85.6)

Comorbidity
No 49 (50.5)
Hypertension 22 (22.7)
Diabetes 6 (6.2)
Diabetes and hypertension 6 (6.2)
Heart disease, diabetes and hypertension 1 (1.0)
Other 13 (13.4)

Death cases 22 (22.7)

Body mass index*

Underweight 7 (7.2)
Normal 38 (39.2)
Overweight 35 (36.1)
Obese 17 (17.5)

SD, standard deviation.

n
Underweight (o18.5), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese ( Z30 kg/m2).
6 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]]

Table 2
Disease-related characteristic of the sample (N 97).

n (%)

Stage of CRC at diagnosis

I 7 (7.2)
II 15 (15.5)
III 19 (19.6)
IV 56 (57.7)

Site of tumor
Colon 63 (64.3)
Rectal 18 (18.4)
Colorectal 16 (16.3)

Site of metastasis
No metastasis 46 (47.4)
Liver 19 (19.6)
Lung 5 (5.1)
Lymph node (distant) 15 (15.5)
Liver and lung 7 (7.2)
Liver, lung, and lymph node 3 (3.1)
Other 2 (2.1)

Degree of differentiation
Poorly 40 (41.2)
Moderately 39 (40.2)
Well 13 (13.4)
Unknown 5 (5.2)

Most of the patients (77.3%) were in advanced stages of CRC and about two-thirds of them
(64.3%) had colon as a primary site of tumor. Slightly less than half of the patients (47.4%) had no
metastasis (Table 2).

Categories of Direct Medical Cost of CRC

The total annual direct medical cost for all patients (N 97) was JD 695,608 with total
median JD 3981. Drugs were the main cost driver and contributed for 61% of total direct medical
costs Laboratory tests and diagnostic procedures came second as cost driver and contributed for
22% of total direct medical cost, followed by hospitalization cost (14%) and surgery cost (3%)
(Table 3).
Total annual direct medical costs attributable to colon, rectal, and CRC were calculated to be
JD 3838, JD 3623 and JD 5652, respectively (Table 4). However, there was no signicant
difference between total annual direct medical cost for the 3 cancers. Drugs costs were the main
cost driver for CRC and contributed for 38% of total cost. Hospitalization cost contributed for 34%

Table 3
Total annual direct medical cost of CRC stratied by cost category (N 97).

Cost category Total annual cost (%)

Drug cost 425,776 (61)

Hospitalization cost 98,280 (14)
Surgery cost 23,801 (3)
Laboratory tests and diagnostic procedures cost 147,751 (22)
Total cost 695,608 (100)
 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]] 7

Table 4
Difference in annual total direct medical cost stratied by cancer site.

Source/site Colon Rectal Colorectal P

value*
Median (IQR) [%]

Drug cost 1099 (234-3528) [54] 745 (92-16,584) [26] 1437 (27-15,340) [38] 0.826
Hospitalization cost 720 (315-1485) [16] 945 (428-1,541) [34] 1148 (304-1879) [30]
Surgery cost 276 (0-345) [5] 0 (0-414) [8] 147 (0-253) [4]
Laboratory test and 1144 (524-2596) [25] 871 (586-1923) [31] 1006 (693-2051) [27]
diagnostic procedures
Total cost 3838 (1649-7326) [100] 3623 (1407-18,881) [100] 5652 (1100-18,393) [100]

IQR, interquartile range.

n
Kruskal-Wallis test.

of total annual cost in rectal cancer and was the main cost driver. Although laboratory test and
diagnostic procedures were the main cost driver in colon cancer (25%).
Total annual direct medical costs attributable to stages I, II, III, and IV in CRC were estimated
to be JD 1159, JD 1835, JD 3132, and JD 5147, respectively. Additionally, it was noticed that direct
medical cost increased with disease stage and there was signicant difference in total annual
medical costs attributable to the 4 stages. The major portion of total costs was represented by
drugs costs (Table 5).
When post hoc analysis was conducted, statistical signicant difference was noted between
stages I & IV; II & IV; and III & IV (Table 6). Drugs categories contributions are illustrated in the
Figure. Chemotherapy was the main drugs cost driver with JD 407, 817 (96%).

Discussion

This study quantied the economic burden associated with direct medical services used by
CRC patients admitted at KAUH in the north of Jordan. In this study and similar to another study,
the main cost driver in all stages of the disease was the cost of drugs.32 Although the price of
treatment protocol observed in this study is relatively close to the price shown in a previous
study,9 total drugs costs in this study was lower. Prescribing cheaper regimens in Jordan may
explain, to a certain extent, the lower total direct medical cost of CRC in this study.15,32,33 Other
explanations behind the lower direct medical costs in Jordan may be that many patients in
Jordan present at the hospital with advanced stages and die before receiving treatment

Table 5
Difference in total annual direct medical cost stratied by colorectal cancer stage at diagnosis.

Stage I II III IV P value*

Median (IQR) [%]

Drug cost 67(19-1016) 552 (41-1578) 339 (41-1558) 1627 (478-11,077) 0.016
[38] [58] [50] [63]
Hospitalization 315 (45-495) 630 (180-1125) 765 (315-1395) 1080 (461-1710)
cost [16] [10] [22] [13]
Surgery cost 238 (0-966) 276 (0-552) 184 (0-345) 0 (0-345)
[16] [6] [6] [2]
Laboratory test 740 (349-837) 813 (365-2178) 900 (562-1182) 1759 (627-2922)
and diagnostic [29] [26] [22] [22]
procedures
Total cost/stage 1159 (801-2526) 1835 (1522-6143) 3132 (983-4826) 5147 (5147-16231)
(% to the total) [100] [100] [100] [100]

IQR, interquartile range.

n
Kruskal-Wallis test.
8 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]]

Table 6
Difference in total annual costs of stages of colorectal cancer.

Stage Stage P value*

I II 0.185
I III 0.236
I IV 0.003
II III 0.849
II IV 0.04
III IV 0.012

n
Mann-Whitney test.

(premature death); some patients refuse to receive any medical treatment either because of
social or economic reasons; and the unregistered number of CRC cases in Jordan.
Similar to another study,34 laboratory tests cost came second as cost driver after drugs in this
study. Normally, laboratory tests, investigational procedures and follow-up tests are conducted
continuously during hospitalization periods because of the use of diagnostic procedures and
tests along the treatment journey, which ultimately increases the cost. According to this study,
the cost weight was shifted from surgery and diagnostic procedures in early stages to
chemotherapy, palliative care, and follow-up procedures in the late stages. Similarly, a study by
Carrol et al35 found that advanced disease stages were associated with a decrease in the relative
weight of surgical, inpatient care costs, and an increase in chemotherapy costs. The relation of
hospitalization cost to the total direct medical costs is signicant. It affects the total cost along
with stage at diagnosis. In this study, hospitalization cost was ranked third (14%). Nevertheless, it
was much less than what Egger and colleagues (2005)36 found in their study. Surgery cost was
the least cost driver of direct medical cost. This may be rationalized partially by the low
number of patients who underwent surgery. In addition, the review of patients proles
conrmed that some of the patients had left the hospital and refused to receive treatment
services, especially surgery. Moreover, low income and cheap insurance plans might not allow
patients to undergo surgery options. Further, the study has shown that more than half of
patients presented to the hospital in stage IV when chemotherapy or palliative care are the best
management options. In contrast, a study in Switzerland36 found that surgery was the main cost
driver because most of the patients had undergone surgery that led to higher surgery cost in
rectal cancer due to the early detection of cancer.
Several studies found that direct medical cost associated with rectal cancer care was more
expensive than that of colon cancer.16,17,19,34,36-38 These studies ndings were attributed to the
additional services used for diagnosis, preoperative investigation, and tumor-specic treatment
of rectal cancer. This means that rectal cancer costs more than colon cancer due to the higher

Fig. Drugs categories contributions for total sample cost.

 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]] 9

incidence of rectal cancer over the colon cancer and the use of radiotherapy that contributes
signicantly to the cost. In contrast, this study found that cost of colon cancer was higher than
that of rectal cancer but with no signicant difference. Although in another study17 it was shown
that although the early and the very late stages (ie, I & IV) of colon cancer cost was higher than
rectal cancer cost, the continuous phases of treatment and middle stages of the rectal cancer cost
(ie, II & III) was higher.
One of the most important factors affecting the total annual direct medical cost of CRC is the
stage at diagnosis.13,39 Similar to other studies,12,14,16,17,40,41 this study found that the total direct
medical costs attributable to late stages of CRC (ie, stages III and IV) were higher than total direct
medical costs attributable to early stages. In addition, there was signicance difference in total
direct medical costs between all stages of CRC. Furthermore, the post hoc analysis found a
statistical difference between the stages I & IV; II & IV; and III & IV. This can be explained by the
presence of higher number of patients in stage IV compared to other stages. Moreover, stage IV
involved more of chemotherapy; hepatic resection; and other metastatic parts. A recent study
found that stage IV corresponds to higher expenditures in any facility.42 However, there are wide
discrepancies in the absolute medical costs of the same stage of disease in different populations.
This is because health care systems, disease management protocols and staff, drug, and other
service unit costs are different among different countries.34
Several factors should be considered when interpreting this studys ndings. This study
represents the rst to include detailed direct medical, tumor-specic cost information for
CRC in Jordan. Further, the patient population was a convenience sample (ie, all patients
with CRC diagnosis and were receiving treatment in KAUH). Data on cancer treatments
were retrieved retrospectively from medical records. Additionally, the study did not measure
the cost of radiotherapy treatment because there is no radiotherapy treatment unit in KAUH.
This has resulted in lower total annual cost of rectal cancer. Metastatic CRC with K-Ras wild
type tumor which may be treated with another option of targeted therapy such as cetuximab
was not considered in this study. Such treatment option is not provided by KAUH and patients
have to buy it from private sector. Finally, cost analysis adopting the societal perspective
and accounting for all direct (medical and nonmedical) and indirect costs should be
evaluated. However, estimating direct nonmedical and indirect costs were beyond the scope
of this study.

Conclusion

Results of this study propose that direct medical costs associated with CRC are considerable.
Most of the cost was devoted for medications, primarily chemotherapy. Advanced stages were
associated with higher cost and largest number of patients. This study can be used in cost-
effectiveness studies of preventive measures, screening programs and therapeutic interventions.
It will also help decision makers when deciding about resources allocation for patients with CRC.
Future studies evaluating the possible budget savings from early diagnosis of CRC should be
encouraged.

Role of authors

Q.A. concepulized study idea and manuscript drafting. R.M. collected and analyzed data. N.M.
recruited patients and manuscript revision.

Acknowledgment

The authors are very thankful to all the associated personnel in any reference who
contributed in/for the purpose of this research.
10 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]]

References

1. Dipiro CV. Colorectal cancer. In: Wells BG, DiPiro JT, Schwinghammer TL, Dipiro CV, eds. Pharmacotherapy:
A Pathophysiologic Approach. New York, NY: McGraw-Hill Medical; 2007:689698.
2. National Collaborating Centre for Cancer (UK). Colorectal Cancer: The Diagnosis and Management of Colorectal
Cancer. Cardiff: National Collaborating Centre for Cancer (UK); 2011 (NICE Clinical Guidelines, No. 131.) Available
from http://www.ncbi.nlm.nih.gov/books/NBK116638/; 2016 (accessed 25.10.16).
3. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major
patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):E359E386. http://dx.doi.org/10.1002/ijc.29210.
4. Colon cancer, King Hussein Cancer Foundation. Available at: http://www.khcc.jo/section/colon-cancer, 2016
(accessed 25.10.16).
5. Al-Shamsi SR, Bener A, Al-Sharhan M, et al. Clinicopathological pattern of colorectal cancer in the United Arab
Emirates. Saudi Med J 2003;24(5):518522.
6. Al-Sayaideh A, Nimri O, Arqoub K, Al-Zaghal M. Cancer Incidence in Jordan-2012. pp 4041.
7. Stewart BW, Wild CP. World Cancer Report. IARC Publications; 2014; p 392402.
8. Jo C. Cost-of-illness studies: concepts, scopes, and methods. Clin Mol Hepatol 2014;20(4):327337.
9. Jefferson T, Demicheli V, Mugford M. Cost-of-Illness Studies, Elementary Economic Evaluation in Health Care. 2nd ed.
London: BMJ Publishing Group; 2000; p 1729.
10. Byford S, Torgerson DJ, James R. Economic note: cost of illness studies. Br Med J 2000;320(7245):1335.
11. Tarricone R. Cost-of-illness: what room in health economics? Health Policy 2006;77(1):5163.
12. Kriza C, Emmert M, Wahlster P, Niederlnder C, Kolominsky-Rabas P. Cost of Illness in Colorectal Cancer: an
international review. Pharmacoeconomics 2013;31(7):577588.
13. Cilleachair AJO, Hanly P, Skally M, et al. Cost comparisons and methodological heterogeneity in cost-of-illness
studies. Med Care 2013;51(4):339350.
14. Yabroff KR, Borowski L, Lipscomb J. Economic studies in colorectal cancer: challenges in measuring and comparing
costs. J Natl Cancer Inst Monog 2013;2013(46):6278. http://dx.doi.org/10.1093/jncimonographs/lgt001.
15. Ray S, Bonthapally V, Meyer NM, Miller JD, Bonafede MM, Curkendall SM. Direct medical costs associated with
different lines of therapy for colorectal cancer patients. Colorectal Cancer 2013;2(2):121134.
16. Haug U, Engel S, Verheyen F, Linder R. Estimating colorectal cancer treatment costs: a pragmatic approach
exemplied by health insurance data from Germany. PLoS One 2014;9(2):e88407.
17. Lang K, Lines LM, Lee DW, Korn JR, Earle CC, Menzin J. Lifetime and treatment-phase costs associated with colorectal
cancer: evidence from SEER-medicare data. Clin Gastroenterol Hepatol 2009;7(2):198204.
18. Seifeldin R, Hantsch JJ. The economic burden associated with colon cancer in the United States. Clin Ther 1999;21(8):
13701379.
19. Hall PS, Hamilton P, Hulme CT, et al. Costs of cancer care for use in economic evaluation: a UK analysis of patient-
level routine health system data. Br J Cancer 2015;112(5):948956. http://dx.doi.org/10.1038/bjc.2014.644.
20. Maroun J, Ng E, Berthelot JM, et al. Lifetime costs of colon and rectal cancer management in Canada. Chronic Dis Can
2003;24(4):91101.
21. Dajani YF, Zayid I, Dikran A, Malatjalian DA, Kamal MF. Colorectal cancer in Jordan and Nova Scotia a comparative
epidemiologic and histopathologic study. Cancer 1980;46(2):420426.
22. Arafa MA, Waly MI, Jriesat S, Al Khafajei A, Sallam S. Dietary and lifestyle characteristics of colorectal cancer in
Jordan: a case-control study. Asian Pac J Cancer Prev 2011;12(8):19311936.
23. Salem OA. Colon cancer in North Jordan. RMJ 2010;35(2):129132.
24. Ajlouni Y, Halloush A, Ghazzawi I, et al. Retrospective review of epidemiological, pathological and clinical features of
colorectal cancer diagnosed by colonoscopy at King Hussein Medical Center. J R Med Serv 2011;18(2):4955.
25. Drummond M. Cost of illness studies: a major headache? Pharmacoeconomics 1992;2(1):14.
26. Hodgson TA. The state of the art of cost-of-illness estimates. Adv Health Econ Health Serv Res 1983;4(4):129164.
27. Alefan Q, Izham MM, Razak AT, Ayub A. Cost of treating hypertension in Malaysia. Am J Pharma Clin Res 2009;2(1):
15.
28. Choi BC, Robson L, Single E. Estimating the economic costs of the abuse of tobacco, alcohol and illicit drugs: a review
of methodologies and Canadian data sources. Chronic Dis Can 1997;18(4):149165.
29. Rice DP, Hodgson TA, Kopstein AN. The economic costs-of-illness: a replication and update. Health Care Financ Rev
1985;7(1):6180.
30. Alefan Q, Ibrahim MIM, Razak TA. The impact of poorly controlled hypertension on ambulatory care resources in
Malaysia. J Clin Diagn Res 2010;4(6):33713377.
31. Riewpaiboon A, Pornlertwadee P, Pongsawat K. Diabetes cost model of a hospital in Thailand. Value Health 2007;10
(4):223230.
32. Davari M, Maracy MR, Emami MH, et al. The direct medical costs of colorectal cancer in Iran; analyzing the patients
level data from a cancer specic hospital in Isfahan. Int J Prev Med 2012;3(12):887892.
33. Davari M, Ashra F, Maracy M, Aslani A, Tabatabei M. Cost-effectiveness analysis of cetuximab in treatment of
metastatic colorectal cancer in Iranian pharmaceutical market. Int J Prev Med 2015;6(1):63.
34. Wong C, Lam CL, Poon JT, et al. Direct medical costs of care for Chinese patients with colorectal neoplasia: a health
care service provider perspective. J Eval Clin Pract 2011;18(6):12031210.
35. Corral J, Borrs JM, Chiarello P, et al. Estimation of hospital costs of colorectal cancer in Catalonia (Spain). Gac Sanit
2015;29(6):437444.
36. Delco F, Egger R, Bauerfeind P, Beglinger C. Hospital health care resource utilization and costs of colorectal cancer
during the rst 3-year period following diagnosis in Switzerland. Aliment Pharmacol Ther 2005;21(5):615622.
37. Giuliani J, Bonetti A. The pharmacological costs of rst-line therapies in unselected patients with advanced colorectal
cancer: a review of published phase III trials. Clin Colorectal Cancer 2016;(4):19. pii: S1533-0028(16)30083-4.
 Q. Alefan et al. / Curr Probl Cancer ] (2017) ]]]]]] 11

38. Riesco-Martnez MC, Berry SR, Ko YJ, et al. Cost-effectiveness analysis of different sequences of the use of epidermal
growth factor receptor inhibitors for wild-type kras unresectable metastatic colorectal cancer. J Onc Prac 2016;12(6):
e710e723.
39. Taplin SH, Barlow W, Urban N, et al. Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer
care. J Natl Cancer Inst 1995;87(6):417426.
40. Macafee DAL, West J, Scholeeld JH, Whynes DK. Hospital costs of colorectal cancer care. Clin Med Oncol 2009;3(1):
2737.
41. Torres Udos S, Almeida TE, Netinho JG. Increasing hospital admission rates and economic burden for colorectal
cancer in Brazil, 1996-2008. Rev Panam Salud Publica 2010;28(4):244248.
42. Chastek B, Kulakodlu M, Valluri S, Seal B. Impact of metastatic colorectal cancer stage and number of treatment
courses on patient health care costs and utilization. Postgrad Med 2013;125(2):7382.