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Economic Studies in Colorectal Cancer: Challenges in Measuring and Comparing Costs

Economic Studies in Colorectal Cancer: Challenges in Measuring and Comparing Costs Abstract Estimates of the costs associated with cancer care are essential both for assessing burden of disease at the population level and for conducting economic evaluations of interventions to prevent, detect, or treat cancer. Comparisons of cancer costs between health systems and across countries can improve understanding of the economic consequences of different health-care policies and programs. We conducted a structured review of the published literature on colorectal cancer (CRC) costs, including direct medical, direct nonmedical (ie, patient and caregiver time, travel), and productivity losses. We used MEDLINE to identify English language articles published between 2000 and 2010 and found 55 studies. The majority were conducted in the United States (52.7%), followed by France (12.7%), Canada (10.9%), the United Kingdom (9.1%), and other countries (9.1%). Almost 90% of studies estimated direct medical costs, but few studies estimated patient or caregiver time costs or productivity losses associated with CRC. Within a country, we found significant heterogeneity across the studies in populations examined, health-care delivery settings, methods for identifying incident and prevalent patients, types of medical services included, and analyses. Consequently, findings from studies with seemingly the same objective (eg, costs of chemotherapy in year following CRC diagnosis) are difficult to compare. Across countries, aggregate and patient-level estimates vary in so many respects that they are almost impossible to compare. Our findings suggest that valid cost comparisons should be based on studies with explicit standardization of populations, services, measures of costs, and methods with the goal of comparability within or between health systems or countries. Expected increases in CRC prevalence and costs in the future highlight the importance of such studies for informing health-care policy and program planning. Estimates of the costs associated with cancer care are essential both for assessing burden of disease at the population level and for conducting economic evaluations of health-care policies and programs to prevent, detect, or treat cancer. Although considerable methodological progress has been made in disease costing (1), significant challenges remain. Importantly, existing data for cost determination in any given study are generally imperfect, sometimes missing, and often collected or analyzed in ways that make cross-study comparisons difficult. An underlying problem is that available data sources were generally created for other purposes (eg, paying bills) and are substantially influenced by features of the health-care system, including the structure of insurance plans and databases for tracking care (2). The alternative approach of collecting precisely the resource use data needed for a given economic evaluation can be expensive and time-consuming in practice, and there is wide variation in these “microcosting” studies (3). Thus, even within a single health system or country, studies with an identical purpose (eg, estimating the costs of chemotherapy in the year following cancer diagnosis) frequently use different methods, with data sources that vary in scope, population coverage, completeness, and capacity to examine patterns of service use. Internationally there is tremendous diversity in health-care systems, services covered, and availability of existing data sources relevant to health-care costing (4,5)—making comparisons of cancer costs across countries all the more difficult. Despite these challenges, comparisons within and between health systems and countries can enhance understanding of the economic consequences of differences in policies related to cancer care, as well as broader health-care programs, such as a coordinated hospice program for end-of-life care. Understanding the extent to which studies can be compared is also critical for economic evaluations of cancer prevention, screening, or treatment interventions, which may synthesize estimates from multiple sources as inputs to cost-effectiveness models. In this paper, we investigate the implications of this diversity in methods, health systems, and data sources for cost analyses through a structured review of the published literature on the economic burden associated with colorectal cancer (CRC) care. Worldwide approximately 2.1 million individuals were newly diagnosed with CRC in 2008, and CRC is the second most common cancer in women and the third most common in men (6). CRC prevalence is expected to increase appreciably in most developed countries as a result of population growth and aging, because CRC incidence increases with age (7). Additionally, ongoing efforts to improve early detection and treatment are expected to improve CRC survival and reduce CRC-related mortality, which will also result in increasing disease prevalence. Consequently, the societal burden of CRC is significant and is likely to increase over time (8,9). Important economic components of this burden include direct medical care costs, direct nonmedical costs (such as patient time involved with receiving medical care), and productivity losses among patients and caregivers. In this review, we build on and update prior work (10–13) describing the economic burden associated with CRC care. We then categorize the significant challenges in conducting valid, reliable, feasible, and comparable cancer costing analyses, with an emphasis on comparisons across studies, health systems, and countries. Methods Study Selection We used MEDLINE to identify English language articles about the costs of CRC published between 2000 and 2010. The search strategy used the Medical Subject Headings (MeSH) subject term “colorectal neoplasms” combined with MeSH major subject terms “health care costs,” or “cost of illness,” or “economics,” or “cost analysis.” The combination yielded 248 studies. Our focus was on CRC care, so we excluded studies of primary prevention and screening. We also excluded simulation models based on hypothetical cohorts with assumed patterns of care, because numerous studies have described patterns of CRC care in population-based samples that are inconsistent with treatment pathways or guidelines (14,15). Studies of costs of specific side effects of treatment (eg, nausea) or symptoms of disease were also excluded, because these studies represented only a small component of cancer care. Also excluded were small studies (with samples of fewer than 100 patients), as well as reviews, editorials, letters, and essays. Economic studies of cancer treatment trials were included only if they were based on primary patient-level data during and possibly after the trial period. Of the studies identified as potentially eligible for inclusion in our review, 30 met our eligibility criteria (16–43). Because electronic searches may not identify all relevant studies (44), we reviewed the reference lists of the selected studies as well as reviews of the costs of CRC care (10–13,45,46) and identified 25 additional studies (47–73). A total of 55 studies are included in this review. Data Abstraction Data were abstracted from each paper using a standardized abstraction format to describe the study characteristics, cancer patient characteristics, and study methods. Study characteristics included study publication year, country where study was conducted, geographic setting (single city, single state/province/region, multiple cities and/or states/provinces/regions, national, multiple countries), delivery setting (single institution or clinic, network of institutions or clinics, integrated system/insurance network, other), and the type of cost estimate evaluated (direct medical, direct nonmedical, including patient or caregiver time and travel, and productivity loss). Because health-care delivery in the United States is fragmented, we also abstracted information about the type of health insurance (fee-for-service, managed care, multiple types of insurance) and measurement of cost (insurance payments only, patient out-of-pocket payments, charges). Cancer patient characteristics included method of patient identification (medical record review, registry, claims, other), tumor stage (American Joint Committee on Cancer [AJCC] I/II or localized, AJCC III/IV or regional/distant, other, stage not reported), number of cancer patients (100–499, 500–999, 1000–4999, 5000–9999, 10 000+) and patient age groups (<40, 40–64, 65+, mean age <65, mean age 65+, patient age not stated). Study methods that were abstracted included study design (cross-sectional, cohort, based on a randomized controlled trial), phases of care evaluated (initial treatment, surveillance or continuing, last year of life, long-term/lifetime, all phases together [prevalent], other), use of a comparison group (noncancer controls, other comparison group, no comparison group), and use of price adjusters (time adjusters, other adjusters, not reported). Medical cost estimates for prevalent CRC patients (both incident and existing patients) were abstracted separately at the per-person and aggregate levels. Medical cost estimates were also abstracted separately for each phase of care. Studies that could not clearly define patients with incident disease, or that identified patients with metastatic disease but did not distinguish newly diagnosed from recurrent disease, or that were based on receipt of specific treatment, were classified as cost estimates of prevalent cancer patients. Studies based on patterns of care observed in clinical trials of cancer treatment were abstracted separately, as were studies of other aspects of the burden of illness, including patient and caregiver time and productivity loss. Consistent with the diverse approaches found in the literature, we use the term “cost” broadly to reflect either expenditures, insurance payments, charges, actual costs of care, or wages, and we abstracted data as reported in the underlying studies. The “reference year” used to adjust for monetary inflation (eg, in 2000 dollars) was abstracted as reported, or noted as not reported when the reference year was not available in the underlying study. We did not attempt to standardize studies to a single reference year, because it would not be meaningful to do so given the heterogeneity across health systems and countries in cancer care delivery settings, data sources, patient populations, measurement of cost, types of medical services, use of comparison groups, and other methodological differences. Finally, findings are reported as either total costs or cancer-related costs. Total costs reflect the cost of all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or else the net cost of all services among cancer patients compared with similar individuals without cancer. Nonmedical costs are also reported as either total or cancer-related based on comparisons with similar individuals without cancer. Results Study Characteristics The number of published studies of the costs of CRC care increased throughout the study period, with almost half being published between 2008 and 2010 (Table 1). The majority of studies were conducted in the United States (52.7%), followed by France (12.7%), Canada (9.1%), and the United Kingdom (9.1%). Studies were also conducted in Brazil, Germany, Greece, Hungary, Italy, Japan, and Norway. Almost 90% of studies estimated direct medical costs, and few estimated patient or caregiver time costs (14.5%), travel costs (7.3%), or productivity losses (7.3%). In the United States, the dominant health insurance type was fee-for-service, with few studies conducted in managed care or across multiple types of payers/providers. The most commonly used data source was the linked SEER–Medicare data, which include only fee-for-service insurance predominantly for patients aged 65 and older. Studies varied in the comprehensiveness of estimates, ranging from Medicare payments only, to adjusting also for patient out-of-pocket payments, to using Medicare charges as a proxy for cost. Few studies in the United States included patients without any health insurance at all. Table 1. Study summary (N = 55)*     No.  Percent  Study characteristics  Study publication year    2000–2003  14  25.5      2004–2007  16  29.1    2008–2010  25  45.5  Country    Canada    5    9.1    France    7  12.7    Italy    2    3.6    Japan    2    3.6    United Kingdom    5    9.1    United States  29  52.7    Other    5    9.1  Geographic setting†    Single city    4    7.2    Single state/province/region    9  16.4    Multiple cities and/or states/provinces/regions  21  38.2    National  18  32.7    Multiple countries    3    5.5  Delivery setting†    Single institution or clinic    3    5.5    Network of institutions or clinics    3    5.5    Integrated system/insurance network  18  32.7    National health-care system  12  21.8    Other  19  34.5  Cost domain†    Direct medical costs  49  89.1    Direct nonmedical costs  10  18.2     Patient or caregiver time    8  14.5     Travel    5    7.3    Lost productivity    5    7.3  Cancer patient characteristics  Cancer patient identification†    Medical record review    6  10.9    Registry  23  41.8    Claims    9  16.4    Other  21  38.2  Tumor stage†    AJCC I/II or localized  24  43.6    AJCC III/IV or regional/distant  29  52.7    Other    5    9.1    Stage not reported  21  38.2  No. of cancer patients†    100–499  17  30.9    500–999    9  16.4    1000–4999  10  18.2    5000–9999    5    9.1    10 000+  13  23.6  Patient age groups†    <40  18  32.7    40–64  30  54.5    65+  42  76.4    Mean age <65    1    1.8    Mean age 65+    5    9.1    Patient ages not stated    7  12.7  Study methods  Study design      Cross-sectional  18  32.7    Cohort  24  43.6    Based on randomized controlled trial  13  25.5  Phase of cancer care†    Initial treatment of incident disease  19  34.5      Surveillance, continuing, or monitoring  12  21.8      Last year of life  10  18.8      Long-term/lifetime costs  13  23.6      Prevalence (all patients ever diagnosed)  22  40.0      Other    5    9.1    Comparison group†          Noncancer controls  15  27.3      Other comparison group  22  40.0      No comparison group  18  32.7    Use of price adjusters†          Time adjusters for inflation  32  58.2      Other adjusters (eg, geographic)  10  18.2      Not reported  15  27.3      No.  Percent  Study characteristics  Study publication year    2000–2003  14  25.5      2004–2007  16  29.1    2008–2010  25  45.5  Country    Canada    5    9.1    France    7  12.7    Italy    2    3.6    Japan    2    3.6    United Kingdom    5    9.1    United States  29  52.7    Other    5    9.1  Geographic setting†    Single city    4    7.2    Single state/province/region    9  16.4    Multiple cities and/or states/provinces/regions  21  38.2    National  18  32.7    Multiple countries    3    5.5  Delivery setting†    Single institution or clinic    3    5.5    Network of institutions or clinics    3    5.5    Integrated system/insurance network  18  32.7    National health-care system  12  21.8    Other  19  34.5  Cost domain†    Direct medical costs  49  89.1    Direct nonmedical costs  10  18.2     Patient or caregiver time    8  14.5     Travel    5    7.3    Lost productivity    5    7.3  Cancer patient characteristics  Cancer patient identification†    Medical record review    6  10.9    Registry  23  41.8    Claims    9  16.4    Other  21  38.2  Tumor stage†    AJCC I/II or localized  24  43.6    AJCC III/IV or regional/distant  29  52.7    Other    5    9.1    Stage not reported  21  38.2  No. of cancer patients†    100–499  17  30.9    500–999    9  16.4    1000–4999  10  18.2    5000–9999    5    9.1    10 000+  13  23.6  Patient age groups†    <40  18  32.7    40–64  30  54.5    65+  42  76.4    Mean age <65    1    1.8    Mean age 65+    5    9.1    Patient ages not stated    7  12.7  Study methods  Study design      Cross-sectional  18  32.7    Cohort  24  43.6    Based on randomized controlled trial  13  25.5  Phase of cancer care†    Initial treatment of incident disease  19  34.5      Surveillance, continuing, or monitoring  12  21.8      Last year of life  10  18.8      Long-term/lifetime costs  13  23.6      Prevalence (all patients ever diagnosed)  22  40.0      Other    5    9.1    Comparison group†          Noncancer controls  15  27.3      Other comparison group  22  40.0      No comparison group  18  32.7    Use of price adjusters†          Time adjusters for inflation  32  58.2      Other adjusters (eg, geographic)  10  18.2      Not reported  15  27.3  * AJCC = American Joint Committee on Cancer. † Studies may be included in more than one category. View Large Cancer patients were identified by medical record review (10.9%), tumor registries (41.8%), billing or claims data (16.4%), or other approaches, including clinical trial participation. Many studies included patients with all stages of disease at diagnosis, whereas about 25% included only patients with metastatic disease (recurrent or late-stage disease at diagnosis), and few studies restricted patients to early-stage disease (data not shown). Stage was not reported in 38% of studies. Most studies included patients aged 65 and older, either because they included patients of all ages and CRC incidence was higher in the elderly, or because they were conducted in the United States using SEER–Medicare data. Age was not stated in seven studies. Of the 55 studies included in the review, 32.7% were cross-sectional, 43.6% were conducted in observational cohorts, and 25.5% were clinical trial–based. The majority of observational studies were conducted in the United States, whereas the majority of clinical trial–based studies were conducted in other countries. Many studies assessed the costs of CRC in prevalent samples of patients (40%), including clinical trial–based studies of treatment for metastatic disease. Many observational studies assessed either costs of initial treatment of incident disease or the initial phase of care (34.5%), or long-term/lifetime costs (23.6%), or both. Fewer observational studies assessed care at the end of life (18.8%). About one-third of the studies did not include a comparison group. Most studies used inflation price adjusters to standardize costs over the study period, but a sizable portion did not report use of any price adjusters (27.3%). Direct Medical Costs of CRC Care in Observational Studies National estimates of the direct medical costs of CRC were conducted in France, the United States, Canada, Brazil, and Hungary (20,30,31,34,39,66,69) (Table 2). Estimates were for either the entire population with cancer in a given year or for a subset of newly diagnosed patients in a given year over some defined time period, ranging from the first year following cancer diagnosis up to the patient’s lifetime. Although several studies included the entire population of CRC patients, others were restricted to only the elderly. Finally, the scope of care included in these estimates varied widely—one study included only hospitalizations, whereas others included all care following diagnosis. Table 2. National estimates of direct medical costs of colorectal cancer (CRC) care* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Boncz, 2010 (20)  Hungary; National Cancer Registry–National Health Insurance Fund  All patients  Inpatient, outpatient, drugs, and sickness pay  The National Health Insurance Fund Administration spent €32.2 million and €0.8 million on the treatment of malignant and in situ CRC, respectively in 2001  Torres, 2010 (30)  Brazil; Hospital Information Systems of the Brazilian Unified Health System  297 108 hospital admissions 1996–2008 with a primary diagnosis of CRC  Hospitalizations  Overall costs of CRC hospitalizations $16.5 million in 1996 and $33.5 million in 2008; the average cost of each admission, however, decreased from $1283 to $954; estimates in 2007 US dollars  Lejeune, 2009 (66)  France  36 000 patients diagnosed in 2000 with potentially curative surgery  Surveillance up to 3 years  3-year cost of surveillance €42.4 million; year of euros not reported  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Aggregate 5-year net costs for patients diagnosed in 2004 to Medicare were estimated to be $3101 million; estimates in 2004 US dollars  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older with all stages 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Total 2002 Medicare payments for CRC care in year following diagnosis in the United States was estimated to be $2.04 billion (in 2003 US dollars)  Maroun, 2003 (39)  Canada  16 856 patients diagnosed with colon or rectal cancer in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Total aggregate lifetime treatment cost for patients in 2000 estimated to be $333 million and $187 million for colon and rectal cancer, respectively (in 1988 Canadian dollars)  Selke, 2003 (69)  France  All patients in 1999  Hospital inpatient and outpatient, physician, and prescription costs  Total direct medical costs of CRC to the health insurance system was €469.7 million  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Boncz, 2010 (20)  Hungary; National Cancer Registry–National Health Insurance Fund  All patients  Inpatient, outpatient, drugs, and sickness pay  The National Health Insurance Fund Administration spent €32.2 million and €0.8 million on the treatment of malignant and in situ CRC, respectively in 2001  Torres, 2010 (30)  Brazil; Hospital Information Systems of the Brazilian Unified Health System  297 108 hospital admissions 1996–2008 with a primary diagnosis of CRC  Hospitalizations  Overall costs of CRC hospitalizations $16.5 million in 1996 and $33.5 million in 2008; the average cost of each admission, however, decreased from $1283 to $954; estimates in 2007 US dollars  Lejeune, 2009 (66)  France  36 000 patients diagnosed in 2000 with potentially curative surgery  Surveillance up to 3 years  3-year cost of surveillance €42.4 million; year of euros not reported  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Aggregate 5-year net costs for patients diagnosed in 2004 to Medicare were estimated to be $3101 million; estimates in 2004 US dollars  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older with all stages 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Total 2002 Medicare payments for CRC care in year following diagnosis in the United States was estimated to be $2.04 billion (in 2003 US dollars)  Maroun, 2003 (39)  Canada  16 856 patients diagnosed with colon or rectal cancer in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Total aggregate lifetime treatment cost for patients in 2000 estimated to be $333 million and $187 million for colon and rectal cancer, respectively (in 1988 Canadian dollars)  Selke, 2003 (69)  France  All patients in 1999  Hospital inpatient and outpatient, physician, and prescription costs  Total direct medical costs of CRC to the health insurance system was €469.7 million  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Ten studies estimated the cost of cancer care in prevalent patients, the combination of newly diagnosed and existing cancer patients (17,19,21,27,36,42,54,57,63,70) (Table 3). These studies were conducted exclusively in the United States, but the number of patients, age distribution, data source, types of costs included, and reference year varied widely. For example, two studies assessed ambulatory care, but one reported cancer-related costs for chemotherapy ranging from $1028 to $38 027 for different regimens (57), and the other reported payments for all care of $946 among individuals with cancer (27). Neither reported the year of dollars, patient age distribution, or period during which costs were accrued. Table 3. Direct medical costs of colorectal cancer (CRC) care among prevalent cancer patients* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Chu, 2009 (70); Chu, 2010 (17)  United States; Medstat MarketScan  3333 patients identified from diagnosis codes received chemotherapy 2003–2006 and subset of 1396 patients who received chemotherapy within 90 days of surgery  Chemotherapy-related  Monthly cancer-related chemotherapy cost from $6683 to $14 320 for capecitabine and 5-FU/LV/oxaliplatin, respectively; for chemotherapy within 90 days of surgery, monthly costs $8003 and $7263 for 5-FU and capecitabine, respectively (in 2006 US dollars)  Dinan, 2010 (54)  United States; 5% Medicare sample  7039 patients aged 67 and older identified from claims for CRC in 1999, 2003, and 2006  All care  Total costs over 2 years in 1999, 2003, and 2006: $38 724, $51 715, and $56 839, respectively; imaging costs 1999, 2003, and 2006: $1009, $1686, and $1918, respectively (in 2008 US dollars)  Yabroff, 2009 (42)  United States; SEER–Medicare, 5% Medicare sample, MEPS  Patients aged 65 and older; SEER–Medicare: 73 050 diagnosed 1973–2002 with costs 1998–2002; 5% Medicare sample: 3575 patients 1996–2002 with costs 1998–2002; MEPS: 196 patients treated 1996–2004 with costs 1996–2004  All care  Annual cancer-related costs were $5341, $8736, and $11 614 in SEER–Medicare, 5% Medicare sample, and MEPS, respectively (in 2004 US dollars)  Ferro, 2008 (57)  United States; 115 ambulatory centers  421 CRC patients receiving chemotherapy 2002–2005  Ambulatory chemotherapy  Costs of cancer-related chemotherapy ranged from $1028 to $38 027 per regimen; year of dollars not reported  Paramore, 2006 (19)  United States; PharMetrics Database  699 patients with a code for metastases identified from claims, 1998–2004  All care  Cancer-related payments over average of 12.8 months were $97 031 (in 2005 dollars)  Chang, 2004 (21)  United States; Medstat MarketScan  2858 patients identified from claims, 1999–2000  All care  Cancer-related payments were $3742 per month and $30 939 over study; year of dollars not reported  Mullins, 2004 (27)  United States; MD Medicaid  1904 patients identified from claims, 1999–2000; patient age not stated  Ambulatory care  Total mean ambulatory payments were $946; year of dollars not reported  Ray, 2000 (63)  United States; KP–Northern CA  2613 patients of all ages identified from billing 1995–1996  All care  Total annual adjusted and unadjusted cost per capita were $10 506 and $15 253, respectively (in 1996 dollars)  Polednak, 2000 (36)  United States; CT registry and hospitals  11 023 patients all ages diagnosed 1992–1996, with first hospital admission 1992–1996  Hospital care  Total mean charges for first hospital admission after diagnosis were $32 061 for initial emergency department admission and $20 130 for admitted directly to the hospital; year of dollars not reported  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Chu, 2009 (70); Chu, 2010 (17)  United States; Medstat MarketScan  3333 patients identified from diagnosis codes received chemotherapy 2003–2006 and subset of 1396 patients who received chemotherapy within 90 days of surgery  Chemotherapy-related  Monthly cancer-related chemotherapy cost from $6683 to $14 320 for capecitabine and 5-FU/LV/oxaliplatin, respectively; for chemotherapy within 90 days of surgery, monthly costs $8003 and $7263 for 5-FU and capecitabine, respectively (in 2006 US dollars)  Dinan, 2010 (54)  United States; 5% Medicare sample  7039 patients aged 67 and older identified from claims for CRC in 1999, 2003, and 2006  All care  Total costs over 2 years in 1999, 2003, and 2006: $38 724, $51 715, and $56 839, respectively; imaging costs 1999, 2003, and 2006: $1009, $1686, and $1918, respectively (in 2008 US dollars)  Yabroff, 2009 (42)  United States; SEER–Medicare, 5% Medicare sample, MEPS  Patients aged 65 and older; SEER–Medicare: 73 050 diagnosed 1973–2002 with costs 1998–2002; 5% Medicare sample: 3575 patients 1996–2002 with costs 1998–2002; MEPS: 196 patients treated 1996–2004 with costs 1996–2004  All care  Annual cancer-related costs were $5341, $8736, and $11 614 in SEER–Medicare, 5% Medicare sample, and MEPS, respectively (in 2004 US dollars)  Ferro, 2008 (57)  United States; 115 ambulatory centers  421 CRC patients receiving chemotherapy 2002–2005  Ambulatory chemotherapy  Costs of cancer-related chemotherapy ranged from $1028 to $38 027 per regimen; year of dollars not reported  Paramore, 2006 (19)  United States; PharMetrics Database  699 patients with a code for metastases identified from claims, 1998–2004  All care  Cancer-related payments over average of 12.8 months were $97 031 (in 2005 dollars)  Chang, 2004 (21)  United States; Medstat MarketScan  2858 patients identified from claims, 1999–2000  All care  Cancer-related payments were $3742 per month and $30 939 over study; year of dollars not reported  Mullins, 2004 (27)  United States; MD Medicaid  1904 patients identified from claims, 1999–2000; patient age not stated  Ambulatory care  Total mean ambulatory payments were $946; year of dollars not reported  Ray, 2000 (63)  United States; KP–Northern CA  2613 patients of all ages identified from billing 1995–1996  All care  Total annual adjusted and unadjusted cost per capita were $10 506 and $15 253, respectively (in 1996 dollars)  Polednak, 2000 (36)  United States; CT registry and hospitals  11 023 patients all ages diagnosed 1992–1996, with first hospital admission 1992–1996  Hospital care  Total mean charges for first hospital admission after diagnosis were $32 061 for initial emergency department admission and $20 130 for admitted directly to the hospital; year of dollars not reported  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. CA = California; CT = Connecticut; FU = fluorouracil; KP = Kaiser Permanente, LV = leucovorin; MarketScan = Coordination of Benefits and Health and Productivity Management; MD = Maryland; MEPS = Medical Expenditure Panel Survey; SEER = Surveillance, Epidemiology, and End Results tumor registry. View Large Fourteen studies assessed the costs of CRC care by phase of cancer care (Table 4), including 10 in the initial phase or initial care period (16,18,31,32,34,39,41,48,55,67), five in the continuing phase (16,24,34,41,66), and five in the last year of life (16,29,34,41,58). The majority of these studies were conducted in the United States, with three in France and one each in Canada and Norway. There was notable variation across studies in the number of patients, age distribution, definition of phase, type of costs, and reference year. For example, even among the US studies using the SEER–Medicare linked data for patients aged 65 and older, estimates ranged from mean cancer-related costs in 12 months of the initial phase of $29 609 in men and $29 930 in women in 2004 dollars (34) to total costs of $41 134 in the first year following diagnosis in 2003 dollars (31). The latter study reported total costs incurred by those diagnosed with CRC, whereas the former estimated cancer-related costs. These studies also differed in the calendar years of observation and definitions of the initial period of treatment (12 months following diagnosis vs initial phase of care). Table 4. Direct medical costs of colorectal cancer (CRC) care by phase of care and/or care period*   First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Initial care  Luo, 2010 (55)  United States; MI Registry–Medicare claims  6462 colon cancer patients aged 66 and older diagnosed 1997–2000  All care (including patient and third-party payer)  Mean cost attributable to cancer 1 year after diagnosis was $29 196 (in 2000 dollars), due to higher inpatient costs in cancer patients than controls  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in first year after diagnosis greater for late stage than early stage ($28 500 vs $20 200 in men), and for cancer patients with heart disease or diabetes compared with no comorbid conditions ($33 700, $34 100, and $25 200, respectively, for men with late-stage disease); estimates in 2001 dollars  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related costs in year after diagnosis were $33 294; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Clerc, 2008 (67)  France, two areas in Burgundy  384 patients of all ages diagnosed in 2004 with information from three public health insurance funds  Hospital, outpatient, including drugs and chemotherapy, transportation  Total costs in 12 months after diagnosis were €24 966, of which transportation costs were €623; costs were higher for stage IV (€35 059) than stage I (€17 596) or stage II (€20 472)  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older diagnosed with all stages of invasive CRC 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Average total Medicare payments in the 12 months following diagnosis in 2002 was $41 134 (in 2003 dollars); inflation-adjusted increase of $5345 from 1991; hospitalization accounted for the largest portion of payments  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1999–2002 with cost data 1999–2003  All care  Mean cancer-related Medicare costs in 12 months of initial phase of care were $29 609 in men and $29 930 in women; estimates in 2004 dollars  Wright, 2007 (32)  United States; SEER–Medicare  6108 patients aged 66 and older with stage II–III rectal and stage III colon cancer 1992–1996 with cost data 1992–1998  All care (including patient and other insurer)  Unadjusted charges in 16 months following diagnosis higher for African Americans than whites ($44 199 vs $38 378); adjusted estimates similar in the two groups ($34 588 vs $33 614); estimates in 2000 dollars  Ramsey, 2003 (18)  United States; SEER–GHC  923 patients aged 50+ diagnosed 1993–1999, with costs 1993–2000  All care year after diagnosis  Total costs for screen and symptom detected were $23 344 and $29 384 in 2002 dollars  Bouvier, 2003 (48)  France; Caisse Nationale d’Assurance Maladie des Travailleurs Salaries  142 patients of all ages and stages diagnosed 1997–1998 affiliated with health insurance fund  Hospital, outpatient, transportation, medical purchases, and patient assistance (disability)  Mean cost of care was €21 918 in first year after diagnosis; costs were lower in older ages and mean costs per month of survival were higher in higher stages; year of euro estimates not reported  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Initial treatment costs were $14 375 and $16 951 for colon and rectal cancers, respectively; estimates in 1988 Canadian dollars  Continuing phase of care  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean annual cancer-related cost in 12 months of continuing care was $4280; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Lejeune, 2009 (66)  France, two areas in Burgundy  385 patients diagnosed in 1998 with potentially curative surgery  Surveillance (physician, imaging, tumor markers)  Average surveillance cost per patient €713 over 3 years; year of euros not reported  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total annual costs in continuing phase greater for late than early stage ($3300 vs $3800 in men), but similar for cancer patients with heart disease or diabetes compared with no comorbid conditions; estimates in 2001 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  82 559 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs of CRC care $2254 in men and $1595 in women in 12 months of continuing phase; estimates in 2004 dollars  Körner, 2005 (24)  Norway; single institution  194 patients younger than 76 years with curative surgery for Dukes A-C 1996–1999  Surveillance  The total cost of postoperative surveillance was €20 530 per patient in 2003 euros  Last year of life  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in last year of life similar by stage, but higher for patients with heart disease or diabetes compared with no comorbid conditions ($28 900, $28 200, and $20 000, respectively, for men with late-stage disease); estimates in 2001 dollars  Koroukian, 2009 (58)  United States; OH Medicaid Program  4573 patients with CRC as underlying cause of death 1992–2002, with cost data in 12 months before death 1992–2002  All care  Mean and median per-person month expenditures were $2109 and $1754, respectively, during the 12 months before death; year of dollars not reported  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related cost in final year was $14 538; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  38 636 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs in 12 months of last-year-of-life phase of care were $36 483 in men and $33 610 in women; estimates in 2004 dollars  Shugarman, 2007 (29)  United States; 5% sample of Medicare beneficiaries  6657 patients aged 68 and older who died 1996–1999 with a diagnosis code for CRC within 3 years of death; costs reported 1995–1999  All care  Total per-person payments were $33 560 in the last year of life (in 1999 dollars); largest portion was inpatient care ($18 832), followed by physician services ($5633); payments for older patients lower than for younger patients    First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Initial care  Luo, 2010 (55)  United States; MI Registry–Medicare claims  6462 colon cancer patients aged 66 and older diagnosed 1997–2000  All care (including patient and third-party payer)  Mean cost attributable to cancer 1 year after diagnosis was $29 196 (in 2000 dollars), due to higher inpatient costs in cancer patients than controls  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in first year after diagnosis greater for late stage than early stage ($28 500 vs $20 200 in men), and for cancer patients with heart disease or diabetes compared with no comorbid conditions ($33 700, $34 100, and $25 200, respectively, for men with late-stage disease); estimates in 2001 dollars  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related costs in year after diagnosis were $33 294; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Clerc, 2008 (67)  France, two areas in Burgundy  384 patients of all ages diagnosed in 2004 with information from three public health insurance funds  Hospital, outpatient, including drugs and chemotherapy, transportation  Total costs in 12 months after diagnosis were €24 966, of which transportation costs were €623; costs were higher for stage IV (€35 059) than stage I (€17 596) or stage II (€20 472)  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older diagnosed with all stages of invasive CRC 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Average total Medicare payments in the 12 months following diagnosis in 2002 was $41 134 (in 2003 dollars); inflation-adjusted increase of $5345 from 1991; hospitalization accounted for the largest portion of payments  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1999–2002 with cost data 1999–2003  All care  Mean cancer-related Medicare costs in 12 months of initial phase of care were $29 609 in men and $29 930 in women; estimates in 2004 dollars  Wright, 2007 (32)  United States; SEER–Medicare  6108 patients aged 66 and older with stage II–III rectal and stage III colon cancer 1992–1996 with cost data 1992–1998  All care (including patient and other insurer)  Unadjusted charges in 16 months following diagnosis higher for African Americans than whites ($44 199 vs $38 378); adjusted estimates similar in the two groups ($34 588 vs $33 614); estimates in 2000 dollars  Ramsey, 2003 (18)  United States; SEER–GHC  923 patients aged 50+ diagnosed 1993–1999, with costs 1993–2000  All care year after diagnosis  Total costs for screen and symptom detected were $23 344 and $29 384 in 2002 dollars  Bouvier, 2003 (48)  France; Caisse Nationale d’Assurance Maladie des Travailleurs Salaries  142 patients of all ages and stages diagnosed 1997–1998 affiliated with health insurance fund  Hospital, outpatient, transportation, medical purchases, and patient assistance (disability)  Mean cost of care was €21 918 in first year after diagnosis; costs were lower in older ages and mean costs per month of survival were higher in higher stages; year of euro estimates not reported  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Initial treatment costs were $14 375 and $16 951 for colon and rectal cancers, respectively; estimates in 1988 Canadian dollars  Continuing phase of care  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean annual cancer-related cost in 12 months of continuing care was $4280; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Lejeune, 2009 (66)  France, two areas in Burgundy  385 patients diagnosed in 1998 with potentially curative surgery  Surveillance (physician, imaging, tumor markers)  Average surveillance cost per patient €713 over 3 years; year of euros not reported  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total annual costs in continuing phase greater for late than early stage ($3300 vs $3800 in men), but similar for cancer patients with heart disease or diabetes compared with no comorbid conditions; estimates in 2001 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  82 559 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs of CRC care $2254 in men and $1595 in women in 12 months of continuing phase; estimates in 2004 dollars  Körner, 2005 (24)  Norway; single institution  194 patients younger than 76 years with curative surgery for Dukes A-C 1996–1999  Surveillance  The total cost of postoperative surveillance was €20 530 per patient in 2003 euros  Last year of life  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in last year of life similar by stage, but higher for patients with heart disease or diabetes compared with no comorbid conditions ($28 900, $28 200, and $20 000, respectively, for men with late-stage disease); estimates in 2001 dollars  Koroukian, 2009 (58)  United States; OH Medicaid Program  4573 patients with CRC as underlying cause of death 1992–2002, with cost data in 12 months before death 1992–2002  All care  Mean and median per-person month expenditures were $2109 and $1754, respectively, during the 12 months before death; year of dollars not reported  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related cost in final year was $14 538; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  38 636 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs in 12 months of last-year-of-life phase of care were $36 483 in men and $33 610 in women; estimates in 2004 dollars  Shugarman, 2007 (29)  United States; 5% sample of Medicare beneficiaries  6657 patients aged 68 and older who died 1996–1999 with a diagnosis code for CRC within 3 years of death; costs reported 1995–1999  All care  Total per-person payments were $33 560 in the last year of life (in 1999 dollars); largest portion was inpatient care ($18 832), followed by physician services ($5633); payments for older patients lower than for younger patients  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. Estimates are in US dollars, unless otherwise noted. GHC = Group Health Cooperative; MI = Michigan; OH = Ohio; RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Eleven studies reported long-term or lifetime costs associated with CRC care (16,22,23,34,38–41,59,62,68) (Table 5). Again, studies were conducted predominantly in the United States, with two in Canada and one each in the United Kingdom and France, and varied substantially in the samples, settings, types of care and costs included, and time periods covered postdiagnosis (eg, 2 years, 6–11 years, 25 years, lifetime). Despite these differences, lifetime cancer-related costs were generally higher in younger patients compared with older patients, as might be expected (16). Additionally, costs were generally higher among patients with more advanced disease at diagnosis (39), although lifetime costs were lower in patients with stage IV disease than stage I disease, reflecting shorter life expectancy in this group (22,40). One study evaluated trends in lifetime costs and survival in patients treated with chemotherapy and found that, compared with 1995–1996, patients treated in 2005–2006 had greater lifetime costs ($63 200 vs $100 300) as well as greater survival (16.5 months vs 23.4 months) (59). Table 5. Lifetime or long-term costs of colorectal cancer (CRC) care* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Howard, 2010 (59)  United States; SEER–Medicare  12 473 patients aged 66 and older diagnosed with stage IV CRC 1995–2005  All care  Among patients treated with chemotherapy, lifetime costs increased from $63 200 during 1995–1996 to $100 300 during 2004–2005 in 2006 dollars; life expectancy increased from 16.5 months to 23.4 months; lifetime costs among patents who did not receive chemotherapy were more stable in 1995–1996 and 2004–2005 ($40 500 and $42 300) as was life expectancy (7.6 months and 7.5 months, respectively)  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Lifetime medical costs lower in patients with detected vs undetected adenomatous polyps and higher in patients with screen-detected vs undetected early-stage cancer across most age groups and types of comorbidities; lifetime costs for screen-detected early-stage cancer ranged from $59 600 to $44 500 in men aged 65 and 85, respectively, and undetected early-stage cancer costs ranged from $57 700 to $42 200 in men aged 65 and 85, respectively (in 2001 dollars)  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Cancer-related lifetime costs were $28 626 (in 2006 dollars); lifetime costs higher in younger patients aged 66–74 than older patients aged 75–84 and 85+ ($36 401, $21 167, and $23 799, respectively); net lifetime costs were lower in patients with stage IV compared with earlier stage, reflecting lower life expectancy  Macafee, 2009 (68)  United Kingdom; single hospital in Nottingham  227 patients, median age 70.3 diagnosed with all stages 1981–2002 admitted to the hospital for treatment  Cancer-related hospital costs  Median cost up to 2 years following admission was £4479 in 2001 pounds, and higher for Dukes B and C than Dukes A and D  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages 1973–2002 with cost data 1999–2003  All care  Mean 5-year cancer-related Medicare costs of CRC care in the elderly following diagnosis were $36 621 in men and $35 037 in women; estimates in 2004 dollars  Kerrigan, 2005 (23)  United States; SEER–GHC, SEER–Blue Shield  Patients aged 20–64 with all stages diagnosed 1996–1998, costs 1996–2000; SEER–GHC: 136 patients, SEER–Blue Shield: 201 patients  All care  Mean 2-year cancer-related costs for women and men were $42 837 and $36 673, and $44 208 and $44 376, for SEER–GHC and SEER–Blue Shield, respectively; estimates in 2003 dollars  Borie, 2004 (62)  France; registry: physician records  256 patients diagnosed with Dukes A-C in 1992 undergoing resection  Follow-up tests  Mean cumulative 5-year cost was €842 per patient; reported in 1998 euros  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Average lifetime costs were $29 110 and $34 475 for colon and rectal cancer, respectively; generally higher lifetime costs for higher stage; hospitalization was the largest component (65% and 61% for colon and rectal); estimates in 1988 Canadian dollars  Ramsey, 2002 (40)  United States; SEER–Medicare  Patients aged 65+ with all stages diagnosed 1984–1994  All care  Mean cancer-related payments years 6–11 in men and women were $13 134 and $9180 for stage I and $3147 and $3731 for stage IV; all in 2000 dollars  Etzioni, 2001 (22)  United States; SEER–Medicare  71 519 patients aged 65+ with all stages diagnosed 1983–1993  All care  Mean 11-year cancer-related payments in men and women were $29 635 and $25 444 for stage I and $3006 and $3665 for stage IV (in 2000 dollars); discounted costs lower for stage IV lower than controls  O’Brien, 2001 (38)  Nova Scotia, Canada; registry: Department of Health  553 patients of all ages and all stages diagnosed 1990  Hospital care  Total hospital costs were $9.8 million dollars ($1300 per person annually), representing 22 460 hospital days in 3 years following diagnosis; year of dollars not stated  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Howard, 2010 (59)  United States; SEER–Medicare  12 473 patients aged 66 and older diagnosed with stage IV CRC 1995–2005  All care  Among patients treated with chemotherapy, lifetime costs increased from $63 200 during 1995–1996 to $100 300 during 2004–2005 in 2006 dollars; life expectancy increased from 16.5 months to 23.4 months; lifetime costs among patents who did not receive chemotherapy were more stable in 1995–1996 and 2004–2005 ($40 500 and $42 300) as was life expectancy (7.6 months and 7.5 months, respectively)  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Lifetime medical costs lower in patients with detected vs undetected adenomatous polyps and higher in patients with screen-detected vs undetected early-stage cancer across most age groups and types of comorbidities; lifetime costs for screen-detected early-stage cancer ranged from $59 600 to $44 500 in men aged 65 and 85, respectively, and undetected early-stage cancer costs ranged from $57 700 to $42 200 in men aged 65 and 85, respectively (in 2001 dollars)  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Cancer-related lifetime costs were $28 626 (in 2006 dollars); lifetime costs higher in younger patients aged 66–74 than older patients aged 75–84 and 85+ ($36 401, $21 167, and $23 799, respectively); net lifetime costs were lower in patients with stage IV compared with earlier stage, reflecting lower life expectancy  Macafee, 2009 (68)  United Kingdom; single hospital in Nottingham  227 patients, median age 70.3 diagnosed with all stages 1981–2002 admitted to the hospital for treatment  Cancer-related hospital costs  Median cost up to 2 years following admission was £4479 in 2001 pounds, and higher for Dukes B and C than Dukes A and D  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages 1973–2002 with cost data 1999–2003  All care  Mean 5-year cancer-related Medicare costs of CRC care in the elderly following diagnosis were $36 621 in men and $35 037 in women; estimates in 2004 dollars  Kerrigan, 2005 (23)  United States; SEER–GHC, SEER–Blue Shield  Patients aged 20–64 with all stages diagnosed 1996–1998, costs 1996–2000; SEER–GHC: 136 patients, SEER–Blue Shield: 201 patients  All care  Mean 2-year cancer-related costs for women and men were $42 837 and $36 673, and $44 208 and $44 376, for SEER–GHC and SEER–Blue Shield, respectively; estimates in 2003 dollars  Borie, 2004 (62)  France; registry: physician records  256 patients diagnosed with Dukes A-C in 1992 undergoing resection  Follow-up tests  Mean cumulative 5-year cost was €842 per patient; reported in 1998 euros  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Average lifetime costs were $29 110 and $34 475 for colon and rectal cancer, respectively; generally higher lifetime costs for higher stage; hospitalization was the largest component (65% and 61% for colon and rectal); estimates in 1988 Canadian dollars  Ramsey, 2002 (40)  United States; SEER–Medicare  Patients aged 65+ with all stages diagnosed 1984–1994  All care  Mean cancer-related payments years 6–11 in men and women were $13 134 and $9180 for stage I and $3147 and $3731 for stage IV; all in 2000 dollars  Etzioni, 2001 (22)  United States; SEER–Medicare  71 519 patients aged 65+ with all stages diagnosed 1983–1993  All care  Mean 11-year cancer-related payments in men and women were $29 635 and $25 444 for stage I and $3006 and $3665 for stage IV (in 2000 dollars); discounted costs lower for stage IV lower than controls  O’Brien, 2001 (38)  Nova Scotia, Canada; registry: Department of Health  553 patients of all ages and all stages diagnosed 1990  Hospital care  Total hospital costs were $9.8 million dollars ($1300 per person annually), representing 22 460 hospital days in 3 years following diagnosis; year of dollars not stated  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. All estimates are in US dollars unless otherwise noted. GHC = Group Health Cooperative; MI = Michigan; RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Medical Costs of CRC Care Among Patients Participating in Clinical Trials Fourteen studies reported the costs of CRC care among patients participating in clinical trials (26,35,37,43,47,49–53,65,71,72) (Table 6). Studies were conducted mainly outside of the United States, in the United Kingdom, France, Italy, Japan, Germany, and Greece. These studies generally measured patterns of care during the period of the trial and applied standardized cost multipliers to the services and procedures observed to estimate patient-level costs. Several studies were multinational and estimated costs for a single country based on all patients in the trial (across countries), whereas others were single-country trials and yielded cost estimates for that country only. Even though the majority of studies reviewed here assessed chemotherapy, and most evaluated metastatic disease, there was significant variability in the choice of comparators, period of evaluation, types of costs included, and level of detail reported. Table 6. Costs of colorectal cancer (CRC) care among patients in clinical trials* First author, y (ref.)  Country and setting  Sample characteristics  Components of health-care after identification  Findings  De Portu, 2010 (53)  Italy; multisite trial unit costs from National Health Service tariffs, DRGs, and formulary  231 metastatic patients in trial of capecitabine vs 5-FU-based treatment, 2001–2006  Medical-care use for 6 months  Costs of care for patients receiving capecitabine and 5-FU were €1002 and €3173 per month, respectively; differences reflect aministration and drug cost (in 2007 euros)  Mittman, 2009 (35)  Canada; multicountry trial unit costs from standardized estimates from Ontario and study hospital  557 chemorefractory patients in trial of cetuximab + best supportive care vs best supportive care alone  Medical-care use up to 19 months  Overall, incremental cost with cetuximab compared with best supportive care was $23 969, and ICER was $199 742 per life-year gained; for patients with wild-type KRAS, the incremental cost with cetuximab was $33 617, and ICER was $120 061 per life-year gained (in 2007 Canadian dollars)  Shiroiwa, 2009 (43)  Japan; multinational trials  1923 metastatic patients in trial of capecitabine plus oxaliplatin (XELOX) or 5-FU/folinic acid and oxaliplatin (FOLFOX4)  Chemotherapy and other drugs over 1 year  Total costs of first and second line outpatient chemotherapy for FOLFOX4 and XELOX were €21 300 and €18 300 and €14 900 and €12 000, respectively; in 2007 euros  Hisashige, 2008 (65)  Japan; trial with standard costs  274 stage-III rectal patients in trial of uracil-tegafur vs no adjuvant treatment following curative resection  Chemotherapy, tests, imaging, AEs, recurrence for 5.6 years  Costs were $8742 for patients treated with uracil-tegafur and $11 199 for surgery alone; estimates in 2005 dollars  Lopatriello, 2008 (26)  Italy; trial in five oncology centers with Italian Healthcare Service tariffs and market retail prices  202 metastatic patients randomized to firstline infusional 5-FU or oral capecitabine  Chemotherapy, AEs, lab tests, and supportive agents  From the Italian health-care service perspective, mean total costs per patient for 5-FU and oral capecitabine were €12 029 and €5781, respectively; €7338 and €4688 from the hospital perspective; differences in the two perspectives reflect national tariffs and market retail prices and payment for infusion administration; year of euros not reported  Maniadakis, 2007 (37)  Greece; multisite trial with unit costs from the National Health Service  276 patients with advanced CRC randomized to FOLFIRI or FOLFOXIRI  Chemotherapy, radiation therapy, AEs  Total cost of therapy in the FOLFOXIRI was significantly higher than the FOLFIRI group (€18 344 vs €12 201); differences in mean chemotherapy costs, second line drugs, and hospitalizations; estimates reported in 2006 euros  Borget, 2006 (71)  France; multicenter trial with unit costs from National Health System reimbursement, cost accounting systems  294 metastatic patients in trial of HD-LV5-FU2, raltitrexed, LD-LV5-FU2, or weekly infusional 5-FU.  Chemotherapy and toxicity or complications, follow-up and travel until disease progression or death  Total costs were €15 970, €14 888, €13 760, and €10 687 for HD-LV5-FU2, LD-LV5-FU2, weekly 5-FU, and raltitrexed, respectively; estimates in 2001 euros  Cassidy, 2006 (47)  United Kingdom; multinational trial standardized costs applied to service use  1987 patients with Dukes C colon cancer randomized to either oral capecitabine or infusional LV + 5-FU  Chemotherapy, AEs, travel over 6 months  Chemotherapy administration higher for 5-FU/LV vs capecitabine (₤5151 vs ₤419), but mean cost of AEs and travel lower in capecitabine as compared to 5-FU-LV; year not stated  Franks, 2006 (72)  United Kingdom; multicenter trial with unit costs from published sources and single hospital  682 patients in trial of conventional vs laparoscopic-assisted surgery  Hospital, treatment for complications, and outpatient  3-month medical and lost productivity costs for patients treated with laparoscopic vs conventional surgery were ₤6899 vs ₤6631; year not stated  Earle, 2004 (52)  United States; multicenter trial with unit costs from Medicare reimbursement and billing data from a single center  291 CRC patients with metastatic disease refractory to 5-FU randomized to either weekly or every 3-week irinotecan  Hospital, ER, chemotherapy, physician up to 1 year  Major cost drivers were chemotherapy, hospitalization, and chemotherapy administration; every 3-week administration of irinotecan associated with cost–utility ratio of $78 627 per QALY; costs reported in 2001 dollars  Monz, 2003 (49)  Germany; multisite trial, unit costs from the perspective German Social Health Insurance based on fee scale, reports, and Red Book  563 patients with UICC II/III in trial of 5-FU + levamisole vs 5-FU + levamisole + FA following surgery  Chemotherapy and follow-up over 5 years of trial  Cancer-related costs were €4909 and €11 085 for patients without and with progression receiving FU + levamisole and €17 122 and €21 330 for patients without and with progression receiving 5-FU + levamisole + FA; ICER of €51 225 for 5-FU + levamisole + FA vs 5-FU + levamisole; cost reported in 2000 euros  Cunningham, 2002 (51)  United Kingdom; multinational trial with standard costs from formulary and hospital tariffs  385 patients with metastatic disease randomized to 5-FU/FA vs irinotecan and 5-FU/FA  In-study treatment and additional chemotherapy up to 3 years  Mean cumulative costs £3767 vs £4220 for irinotecan and 5-FU/FA vs 5-FU/FA, respectively, with incremental cost per LYG £14 794 reflecting improved survival; year of pounds not stated  Levy-Piedbois, 2000 (50)  France; trial with costs from single hospital in Paris  256 patients in trial of irinotecan vs infusional 5-FU  Chemotherapy, clinic and complications up to 1 year  Total cost of treatment for irinotecan vs infusional 5-FU ($14 135 vs $12 192–$12 344); incorporating survival difference, cost-effectiveness ratios ranged from $9344 to $10 137 per additional year of survival; estimates in 1999 dollars  First author, y (ref.)  Country and setting  Sample characteristics  Components of health-care after identification  Findings  De Portu, 2010 (53)  Italy; multisite trial unit costs from National Health Service tariffs, DRGs, and formulary  231 metastatic patients in trial of capecitabine vs 5-FU-based treatment, 2001–2006  Medical-care use for 6 months  Costs of care for patients receiving capecitabine and 5-FU were €1002 and €3173 per month, respectively; differences reflect aministration and drug cost (in 2007 euros)  Mittman, 2009 (35)  Canada; multicountry trial unit costs from standardized estimates from Ontario and study hospital  557 chemorefractory patients in trial of cetuximab + best supportive care vs best supportive care alone  Medical-care use up to 19 months  Overall, incremental cost with cetuximab compared with best supportive care was $23 969, and ICER was $199 742 per life-year gained; for patients with wild-type KRAS, the incremental cost with cetuximab was $33 617, and ICER was $120 061 per life-year gained (in 2007 Canadian dollars)  Shiroiwa, 2009 (43)  Japan; multinational trials  1923 metastatic patients in trial of capecitabine plus oxaliplatin (XELOX) or 5-FU/folinic acid and oxaliplatin (FOLFOX4)  Chemotherapy and other drugs over 1 year  Total costs of first and second line outpatient chemotherapy for FOLFOX4 and XELOX were €21 300 and €18 300 and €14 900 and €12 000, respectively; in 2007 euros  Hisashige, 2008 (65)  Japan; trial with standard costs  274 stage-III rectal patients in trial of uracil-tegafur vs no adjuvant treatment following curative resection  Chemotherapy, tests, imaging, AEs, recurrence for 5.6 years  Costs were $8742 for patients treated with uracil-tegafur and $11 199 for surgery alone; estimates in 2005 dollars  Lopatriello, 2008 (26)  Italy; trial in five oncology centers with Italian Healthcare Service tariffs and market retail prices  202 metastatic patients randomized to firstline infusional 5-FU or oral capecitabine  Chemotherapy, AEs, lab tests, and supportive agents  From the Italian health-care service perspective, mean total costs per patient for 5-FU and oral capecitabine were €12 029 and €5781, respectively; €7338 and €4688 from the hospital perspective; differences in the two perspectives reflect national tariffs and market retail prices and payment for infusion administration; year of euros not reported  Maniadakis, 2007 (37)  Greece; multisite trial with unit costs from the National Health Service  276 patients with advanced CRC randomized to FOLFIRI or FOLFOXIRI  Chemotherapy, radiation therapy, AEs  Total cost of therapy in the FOLFOXIRI was significantly higher than the FOLFIRI group (€18 344 vs €12 201); differences in mean chemotherapy costs, second line drugs, and hospitalizations; estimates reported in 2006 euros  Borget, 2006 (71)  France; multicenter trial with unit costs from National Health System reimbursement, cost accounting systems  294 metastatic patients in trial of HD-LV5-FU2, raltitrexed, LD-LV5-FU2, or weekly infusional 5-FU.  Chemotherapy and toxicity or complications, follow-up and travel until disease progression or death  Total costs were €15 970, €14 888, €13 760, and €10 687 for HD-LV5-FU2, LD-LV5-FU2, weekly 5-FU, and raltitrexed, respectively; estimates in 2001 euros  Cassidy, 2006 (47)  United Kingdom; multinational trial standardized costs applied to service use  1987 patients with Dukes C colon cancer randomized to either oral capecitabine or infusional LV + 5-FU  Chemotherapy, AEs, travel over 6 months  Chemotherapy administration higher for 5-FU/LV vs capecitabine (₤5151 vs ₤419), but mean cost of AEs and travel lower in capecitabine as compared to 5-FU-LV; year not stated  Franks, 2006 (72)  United Kingdom; multicenter trial with unit costs from published sources and single hospital  682 patients in trial of conventional vs laparoscopic-assisted surgery  Hospital, treatment for complications, and outpatient  3-month medical and lost productivity costs for patients treated with laparoscopic vs conventional surgery were ₤6899 vs ₤6631; year not stated  Earle, 2004 (52)  United States; multicenter trial with unit costs from Medicare reimbursement and billing data from a single center  291 CRC patients with metastatic disease refractory to 5-FU randomized to either weekly or every 3-week irinotecan  Hospital, ER, chemotherapy, physician up to 1 year  Major cost drivers were chemotherapy, hospitalization, and chemotherapy administration; every 3-week administration of irinotecan associated with cost–utility ratio of $78 627 per QALY; costs reported in 2001 dollars  Monz, 2003 (49)  Germany; multisite trial, unit costs from the perspective German Social Health Insurance based on fee scale, reports, and Red Book  563 patients with UICC II/III in trial of 5-FU + levamisole vs 5-FU + levamisole + FA following surgery  Chemotherapy and follow-up over 5 years of trial  Cancer-related costs were €4909 and €11 085 for patients without and with progression receiving FU + levamisole and €17 122 and €21 330 for patients without and with progression receiving 5-FU + levamisole + FA; ICER of €51 225 for 5-FU + levamisole + FA vs 5-FU + levamisole; cost reported in 2000 euros  Cunningham, 2002 (51)  United Kingdom; multinational trial with standard costs from formulary and hospital tariffs  385 patients with metastatic disease randomized to 5-FU/FA vs irinotecan and 5-FU/FA  In-study treatment and additional chemotherapy up to 3 years  Mean cumulative costs £3767 vs £4220 for irinotecan and 5-FU/FA vs 5-FU/FA, respectively, with incremental cost per LYG £14 794 reflecting improved survival; year of pounds not stated  Levy-Piedbois, 2000 (50)  France; trial with costs from single hospital in Paris  256 patients in trial of irinotecan vs infusional 5-FU  Chemotherapy, clinic and complications up to 1 year  Total cost of treatment for irinotecan vs infusional 5-FU ($14 135 vs $12 192–$12 344); incorporating survival difference, cost-effectiveness ratios ranged from $9344 to $10 137 per additional year of survival; estimates in 1999 dollars  * All estimates are in US dollars unless otherwise noted. AE = adverse event; DRG = diagnosis-related group; ER = emergency room; FA = folinic acid; FU = fluorouracil; HD = high-dose; ICER = incremental cost-effectiveness ratio; LD = low-dose; LV = leucovorin; LYG = life-year gained; QALY = quality-adjusted life-year; UICC = Union for International Cancer Control. View Large Nonmedical Costs of CRC Care Ten studies estimated patient or caregiver time costs or productivity loss associated with cancer (21,25,28,33,56,60,61,64,69,73) (Table 7). Studies were conducted in the United States, Canada, France, and the United Kingdom. Nine were observational studies and one was conducted among a subset of patients from a clinical trial. As in the studies of medical costs associated with CRC care, there was wide variation in the methods for identifying patients or caregivers, components of time or productivity measured, evaluation periods, and approaches for valuing time or lost productivity. Standard approaches for estimating time costs or productivity loss combine wage rates or other measures of the value of time with measures of time, either as self-reported by patients or caregivers through surveys or else derived empirically from medical care utilization data combined with standard service-specific time estimates or actual sick leave records. There was, however, significant variation observed within this general approach. For example, one study surveyed elderly individuals and asked about the number of hours in a recent week they required informal care and compared estimates for those with and without a self-reported diagnosis of cancer (61). Another study of informal caregiving used registries to identify newly diagnosed cancer patients, who then identified a caregiver who was surveyed about the amount of time they had provided informal care to the patient in the years following cancer diagnosis (56). Table 7. Direct nonmedical costs of colorectal cancer (CRC) care* First author, y (ref.)  Setting  Sample characteristics  Components included  Findings  Hopkins, 2011 (73)  Canada; Canadian Community Health Survey  929 individuals with cancer aged 19–65 in 2005  Household wage loss  Annual mean cancer-related wage loss of $17 729 and national household cancer-related wage loss of $2.95 billion; wages in 2009 Canadian dollars  Van Houtven, 2010 (60)  United States; CanCORS survey about caregiving and wages  1629 caregivers of patients of all stages and ages surveyed in 2005 either 6 months–1 year or 1–2 years following patient diagnosis  Time caregiving and out-of-pocket costs  Mean cumulative time and out-of-pocket costs were $12 618 and $1442 over periods ranging from 6 months to 2 years since patient diagnosis; costs reported in 2005 dollars  Yabroff, 2009 (56)  United States; survey of caregivers of patients from registries  688 caregivers surveyed about 2-year period following patient diagnosis, 2003–2006  Time providing informal care to the patient since diagnosis  Average of 13.7 months and 8.3 hours per day providing informal care after patient diagnosis; time costs ranged from $28 363 to $50 060 with approach for valuing time  Yabroff, 2007 (64); Yabroff, 2005 (33)  United States; SEER–Medicare, multiple data sources for time  213 278 patients with all stages of disease, diagnosed 1973–1999 aged 65 and older 1995–2001  Service counts, estimates of service time, and wage rates  Cancer-related patient time in initial phase of care was 243.5 hours and time cost ranged from $3432 to $5279 depending on approach to value time; in last year of life, 282.3 hours and time cost ranged from $3986 to $6325  Longo, 2006 (25)  Ontario, Canada; outpatient cancer clinics  261 patients of all ages with breast, colorectal, lung, and prostate cancers 2002–2003  Out-of-pocket costs and days missed from work  The mean monthly out-of-pocket and travel costs were $213 and $372, respectively; in the previous 30 days, caregivers and employed patients lost 7 days and 12.6 days from work, respectively, at $101 per day of work missed  Chang, 2004 (21)  United States; MarketScan  Employed patients with a cancer diagnosis code and workplace absence and short-term disability in 1999  Absenteeism, copays, and deductibles  Cancer patients had more absenteeism ($373 vs $101 per month) and short-term disability days ($698 vs $25 per month); employee caregivers had higher absenteeism ($255 vs $161 costs per month) and copays and deductibles ($302 vs $29 per month); year of wages not stated  Selke, 2003 (69)  France; GAZEL cohort, health insurance payments  All patients in 1999  Disability allowance and work days lost in year after diagnosis  Costs to French social security system were €85.9 million in 1999  Hayman, 2001 (61)  United States; 1993 AHEAD Survey  303 individuals receiving cancer treatment, 718 with cancer history, but not in treatment, and 6422 without cancer; all aged 70+ in 1993  Caregiving hours, valued with wage rates  Adjusted weekly hours of informal caregiving were 6.9, 6.8, and 10.0 for individuals without cancer, with a cancer history, and undergoing cancer treatment, respectively; annual cost of informal caregiving estimated to be $3000, $2900, and $4200, respectively; wages in 1998 dollars  Sculpher, 2000 (28)  United Kingdom; multicountry trial with patient and caregiver travel and time  270 patients with advanced disease in a trial of raltitrexed and 5-FU + LV treatment until progression  Travel and time costs during the trial  Total mean time cost per patient higher for 5-FU + LV vs raltitrexed (₤486 vs ₤378), reflecting greater travel and longer treatment times for patients receiving 5-FU + LV; estimates with 1997 prices  First author, y (ref.)  Setting  Sample characteristics  Components included  Findings  Hopkins, 2011 (73)  Canada; Canadian Community Health Survey  929 individuals with cancer aged 19–65 in 2005  Household wage loss  Annual mean cancer-related wage loss of $17 729 and national household cancer-related wage loss of $2.95 billion; wages in 2009 Canadian dollars  Van Houtven, 2010 (60)  United States; CanCORS survey about caregiving and wages  1629 caregivers of patients of all stages and ages surveyed in 2005 either 6 months–1 year or 1–2 years following patient diagnosis  Time caregiving and out-of-pocket costs  Mean cumulative time and out-of-pocket costs were $12 618 and $1442 over periods ranging from 6 months to 2 years since patient diagnosis; costs reported in 2005 dollars  Yabroff, 2009 (56)  United States; survey of caregivers of patients from registries  688 caregivers surveyed about 2-year period following patient diagnosis, 2003–2006  Time providing informal care to the patient since diagnosis  Average of 13.7 months and 8.3 hours per day providing informal care after patient diagnosis; time costs ranged from $28 363 to $50 060 with approach for valuing time  Yabroff, 2007 (64); Yabroff, 2005 (33)  United States; SEER–Medicare, multiple data sources for time  213 278 patients with all stages of disease, diagnosed 1973–1999 aged 65 and older 1995–2001  Service counts, estimates of service time, and wage rates  Cancer-related patient time in initial phase of care was 243.5 hours and time cost ranged from $3432 to $5279 depending on approach to value time; in last year of life, 282.3 hours and time cost ranged from $3986 to $6325  Longo, 2006 (25)  Ontario, Canada; outpatient cancer clinics  261 patients of all ages with breast, colorectal, lung, and prostate cancers 2002–2003  Out-of-pocket costs and days missed from work  The mean monthly out-of-pocket and travel costs were $213 and $372, respectively; in the previous 30 days, caregivers and employed patients lost 7 days and 12.6 days from work, respectively, at $101 per day of work missed  Chang, 2004 (21)  United States; MarketScan  Employed patients with a cancer diagnosis code and workplace absence and short-term disability in 1999  Absenteeism, copays, and deductibles  Cancer patients had more absenteeism ($373 vs $101 per month) and short-term disability days ($698 vs $25 per month); employee caregivers had higher absenteeism ($255 vs $161 costs per month) and copays and deductibles ($302 vs $29 per month); year of wages not stated  Selke, 2003 (69)  France; GAZEL cohort, health insurance payments  All patients in 1999  Disability allowance and work days lost in year after diagnosis  Costs to French social security system were €85.9 million in 1999  Hayman, 2001 (61)  United States; 1993 AHEAD Survey  303 individuals receiving cancer treatment, 718 with cancer history, but not in treatment, and 6422 without cancer; all aged 70+ in 1993  Caregiving hours, valued with wage rates  Adjusted weekly hours of informal caregiving were 6.9, 6.8, and 10.0 for individuals without cancer, with a cancer history, and undergoing cancer treatment, respectively; annual cost of informal caregiving estimated to be $3000, $2900, and $4200, respectively; wages in 1998 dollars  Sculpher, 2000 (28)  United Kingdom; multicountry trial with patient and caregiver travel and time  270 patients with advanced disease in a trial of raltitrexed and 5-FU + LV treatment until progression  Travel and time costs during the trial  Total mean time cost per patient higher for 5-FU + LV vs raltitrexed (₤486 vs ₤378), reflecting greater travel and longer treatment times for patients receiving 5-FU + LV; estimates with 1997 prices  * All estimates in US dollars unless otherwise noted. AHEAD = Asset and Health Dynamics; CanCORS = Cancer Care Outcomes Research and Surveillance Consortium; FU = fluorouracil; GAZEL = GAZ and ELectricité; LV = leucovorin; MarketScan = Coordination of Benefits and Health and Productivity Management; SEER = Surveillance, Epidemiology, and End Results. View Large Discussion In this study, we conducted a systematic review of recently published studies of the economic burden associated with CRC care to assess data, methods, scope, and the extent to which estimates from these studies can be used in “head-to-head” comparisons. As might be expected, the economic cost associated with CRC care within study generally varied by stage(s) of disease at diagnosis, patient age, observation time (eg, 12 months following diagnosis vs lifetime), types of medical services included, and the scope of costs considered. Depending on the study, included costs ranged from single components of medical care only (eg, hospitalizations) to more comprehensive economic measures of resource use that might include patient time, travel for care, and productivity losses associated with cancer and its treatment. Even within country, we found great heterogeneity across studies in the settings, data sources, populations, means of patient identification, types of medical services, and study methods. Each of these study characteristics can significantly influence the estimation of cancer costs. When they vary together across studies, as is typically the case, even cost calculations with seemingly the same objective are difficult to compare. Complicating factors include features of the health-care delivery system, accompanying payer model, and data availability, all of which vary by country. Across countries, published aggregate and patient-level cost estimates vary in so many respects that accurate international comparisons are almost impossible. Our findings suggest that valid cost comparisons must be developed de novo with explicit standardization of patient populations, types of medical services included, measures of cost, and choice of methods, whether the context is within or between health systems or countries. Further, the design of such studies should reflect a detailed understanding of health-system payment and reimbursement policies and their impact on available data (74,75). Despite these challenges, improving our understanding of how best to measure and report the economic burden of cancer is critical because the aggregate economic burden of cancer, including direct medical costs, direct nonmedical costs, and productivity losses, is expected to increase in the future (8,9,76). To improve comparability across studies, we need more detailed reporting of patient characteristics, methods, and cost estimates by patient subgroups associated with the cost of care (eg, age, stage at diagnosis), the setting of care (eg, inpatient hospitalizations), and the type of cancer-related service (eg, chemotherapy) in both newly diagnosed and prevalent samples. Additionally, because variation in cancer prevalence and population sizes across countries limits national comparisons, reporting of per-person estimates by age, health-care setting, and components of care will allow better national comparisons. Expected increases in the burden of cancer highlight the importance of evaluating the transferability and economic consequences of effective care delivery and payment models used in other health-care delivery settings and countries. A key component of this rising cost burden is the growing use of more effective, but dramatically more expensive cancer treatments. Cost-effectiveness analyses of alternative cancer treatment interventions clearly require sound estimates of each intervention’s associated costs, as well as its benefits in terms of survival or health-related quality of life. Moreover, when cost-effectiveness analyses are focused on cancer prevention or screening, the cost of cancer care is still a pivotal input. Specifically, to prevent or delay the onset of a cancer, or to detect it at an earlier stage, is to alter the expected lifetime cost profile of cancer treatment for the individual. Changes in the costs and benefits of CRC treatments also necessarily affect the cost-effectiveness of cancer prevention and screening strategies (77), such that they may become either more or less cost-effective, or even cost-saving. Updating these analyses to reflect changes in CRC costs and benefits may impact policies in countries that use cost-effectiveness to inform formulary policy decisions. Increased standardization of methods to estimate the economic burden of cancer over time, conditional on choice of intervention, can improve the comparability and consistency of information for setting priorities among competing cancer control interventions (76). The majority of studies we reviewed included just one component of the burden of cancer—direct medical care costs. Fewer studies assessed costs associated with patient and caregiver time or productivity losses associated with cancer and its treatment, but findings in those studies suggest such costs can be substantial and important for understanding the societal burden of cancer (21,25,60,61,64,69,73,76). Additionally, patient time costs are a recommended component of cost-effectiveness analysis of prevention, screening, and treatment interventions (78), but are still rarely included in these studies, in part because these data are not routinely collected. However, their exclusion may bias estimates of cost-effectiveness towards interventions that place a greater time burden on patients and their families (79). As with studies of direct medical costs, reporting of per-person estimates by age, health-care setting, and components of care will allow better comparisons across studies. Further, reporting of intermediate estimates (eg, time, days lost from work) will allow comparisons across studies where the “cost” component is based on different wage structures or different assumptions about the value of time for the underlying populations. Studies conducted in countries with comprehensive data describing cancer incidence and survival and employment and population characteristics (ie, Sweden, Norway) have reported lower incomes for individuals diagnosed with cancer and also their spouses (80) and increased use of sick leave among spouses (81), although these studies did not quantify the impact on employment in economic terms. Thus, to strengthen the data available for estimating the nonmedical economic burden of cancer, increased attention should be devoted to linking data on cancer incidence and survival with longitudinal information on labor market participation and earnings and the allocation of time to medical care–related activities and, in parallel, to developing additional sources of information on the nonmedical burden of cancer. These could include targeted enhancements to existing population-based surveys, such as the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement in the United States (82). Developing a more comprehensive picture of the economic burden of cancer for the patient and family could inform decisions in the workplace. In particular, these data can be important for employers interested in minimizing the impact of cancer on patient and caregiver employment outcomes, including presenteeism and workplace productivity, absenteeism, and overall retention. Including other components of the burden of cancer, such as patient time costs, caregiver burden, and productivity losses, will improve our understanding of the societal impact of cancer and may inform further development of employment policies. We observed clearly discernible relationships between the country where a study was performed, study design, and the approaches used for estimating either the prevalence or incidence cost of care. The majority of US studies were observational, whereas the majority of studies in other countries were based on clinical trials focusing on the cost or cost-effectiveness of treatment interventions, presumably to inform coverage decisions by national formularies (ie, NICE) or other purchasers. Other differences in health-care systems, and hence the nature of the data available for cost analyses, influenced the types of studies conducted. For example, the majority of CRC cost studies in the United States were conducted among patients aged 65 and older, using the linked SEER registry–Medicare claims data. By implication, very few studies were conducted in the under-65 population, which leaves an important research gap because cancer care is typically more aggressive in younger compared with older patients within stage at diagnosis (83). In addition, the difference in comorbidity between cancer patients and noncancer controls is greater in the under-65 population compared with the elderly. In the United States, information about health-care use and payments is available primarily from health insurance claims, and the largest population with comprehensive and longitudinal claims and enrollment information currently consists of Medicare enrollees, aged 65 and older. Current efforts to estimate the longitudinal costs of CRC care for patients of all ages in the managed care population and state-based efforts to link population-based cancer registry with multiple public and private claims databases may help address these important data gaps (84–86). The studies based on clinical trials used service frequencies collected as part of the trial, and actual costs or standardized service-specific costs that were then applied to service use, to estimate CRC treatment costs. An important advantage of this microcosting approach is that it allows country-specific and importantly comparable estimates to be generated from multinational trials. Also, cost estimates are based on actual care received, rather than hypothesized treatment pathways or patterns of care derived from treatment guidelines. Yet, cost studies that capture trial-based service use and apply unit cost multipliers to reflect local circumstances may have other limitations (87–89). Microcosting has also been used in some observational studies, particularly in countries where health coverage is applied centrally (thus, no individual billing). However, the care provided in clinical trials does not reflect typical care in community settings, including “induced costs” for some care that would not occur outside the trial setting. There are, however, processes for defining similar populations of patients, standardizing service and procedure definitions, and taking other steps to promote comparability of cost estimates across observational studies (75,90,91). Prior reviews have described methodological limitations with descriptive economic studies (12) as well as cost-effectiveness analyses (92). We observed many of the same limitations here. Patient characteristics that influence care and costs, such as age distribution and stage of disease at diagnosis, were frequently not reported, nor were methods used to estimate costs always clearly stated. Many economic studies based on treatment trials did not report the number of patients providing data for the economic study compared with the underlying treatment trial, or reported a smaller sample in the economic study than in the treatment trial, suggesting the potential for bias in the included sample (ie, not conducted in a truly randomized population). Several studies based on multinational trials did not report the number of patients from the country of interest. Reporting of patient characteristics that influence care and costs is critical for evaluation of the study and any comparisons across studies. We also identified a number of specific methodological concerns in the studies reviewed here, related to sample selection and representativeness, phase of care definitions, and the analysis of cost data over time. Several observational studies used diagnostic or procedure codes from health-care claims to identify patients—an approach that identifies prevalent rather than incident patients, overidentifies individuals without cancer from “rule-out” diagnostic procedures, and underidentifies patients whose cancer care lacks detailed coding or does not indicate receipt of specific procedures or treatments. Additionally, diagnostic codes may reflect metastatic rather than primary tumor sites. Finally, we identified concerns with aspects of the cost data analysis and reporting, including omission of inflation price adjusters and inadequate (or inadequately explained) methods for handling missing, censored, or highly skewed cost data. Standards for conducting and reporting cost-effectiveness analyses have been published (78), but we were not able to identify any published standards for conducting and reporting cost analyses in observational studies. Developing standards for observational studies and encouraging adherence to existing standards for cost-effectiveness analyses will be important for future efforts (1,93,94), particularly with expected increases in targeted therapies that are both more effective and more expensive than current regimens. Importantly, the methodological limitations for specific studies also constrain the comparisons that can be made between studies. We used MEDLINE, one of the largest publications databases devoted to biomedicine and health (ie, more than 5500 journals in 39 languages), to identify studies for inclusion in our review. We then reviewed the reference lists of included studies to identify additional eligible studies. 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J Natl Cancer Inst Monogr . 2013; 46( 1): 124– 130 Published by Oxford University Press 2013. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI Monographs Oxford University Press

Economic Studies in Colorectal Cancer: Challenges in Measuring and Comparing Costs

JNCI Monographs , Volume 2013 (46) – Aug 16, 2013

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References (101)

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Oxford University Press
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Published by Oxford University Press 2013.
Subject
Article
ISSN
1052-6773
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1745-6614
DOI
10.1093/jncimonographs/lgt001
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23962510
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Abstract

Abstract Estimates of the costs associated with cancer care are essential both for assessing burden of disease at the population level and for conducting economic evaluations of interventions to prevent, detect, or treat cancer. Comparisons of cancer costs between health systems and across countries can improve understanding of the economic consequences of different health-care policies and programs. We conducted a structured review of the published literature on colorectal cancer (CRC) costs, including direct medical, direct nonmedical (ie, patient and caregiver time, travel), and productivity losses. We used MEDLINE to identify English language articles published between 2000 and 2010 and found 55 studies. The majority were conducted in the United States (52.7%), followed by France (12.7%), Canada (10.9%), the United Kingdom (9.1%), and other countries (9.1%). Almost 90% of studies estimated direct medical costs, but few studies estimated patient or caregiver time costs or productivity losses associated with CRC. Within a country, we found significant heterogeneity across the studies in populations examined, health-care delivery settings, methods for identifying incident and prevalent patients, types of medical services included, and analyses. Consequently, findings from studies with seemingly the same objective (eg, costs of chemotherapy in year following CRC diagnosis) are difficult to compare. Across countries, aggregate and patient-level estimates vary in so many respects that they are almost impossible to compare. Our findings suggest that valid cost comparisons should be based on studies with explicit standardization of populations, services, measures of costs, and methods with the goal of comparability within or between health systems or countries. Expected increases in CRC prevalence and costs in the future highlight the importance of such studies for informing health-care policy and program planning. Estimates of the costs associated with cancer care are essential both for assessing burden of disease at the population level and for conducting economic evaluations of health-care policies and programs to prevent, detect, or treat cancer. Although considerable methodological progress has been made in disease costing (1), significant challenges remain. Importantly, existing data for cost determination in any given study are generally imperfect, sometimes missing, and often collected or analyzed in ways that make cross-study comparisons difficult. An underlying problem is that available data sources were generally created for other purposes (eg, paying bills) and are substantially influenced by features of the health-care system, including the structure of insurance plans and databases for tracking care (2). The alternative approach of collecting precisely the resource use data needed for a given economic evaluation can be expensive and time-consuming in practice, and there is wide variation in these “microcosting” studies (3). Thus, even within a single health system or country, studies with an identical purpose (eg, estimating the costs of chemotherapy in the year following cancer diagnosis) frequently use different methods, with data sources that vary in scope, population coverage, completeness, and capacity to examine patterns of service use. Internationally there is tremendous diversity in health-care systems, services covered, and availability of existing data sources relevant to health-care costing (4,5)—making comparisons of cancer costs across countries all the more difficult. Despite these challenges, comparisons within and between health systems and countries can enhance understanding of the economic consequences of differences in policies related to cancer care, as well as broader health-care programs, such as a coordinated hospice program for end-of-life care. Understanding the extent to which studies can be compared is also critical for economic evaluations of cancer prevention, screening, or treatment interventions, which may synthesize estimates from multiple sources as inputs to cost-effectiveness models. In this paper, we investigate the implications of this diversity in methods, health systems, and data sources for cost analyses through a structured review of the published literature on the economic burden associated with colorectal cancer (CRC) care. Worldwide approximately 2.1 million individuals were newly diagnosed with CRC in 2008, and CRC is the second most common cancer in women and the third most common in men (6). CRC prevalence is expected to increase appreciably in most developed countries as a result of population growth and aging, because CRC incidence increases with age (7). Additionally, ongoing efforts to improve early detection and treatment are expected to improve CRC survival and reduce CRC-related mortality, which will also result in increasing disease prevalence. Consequently, the societal burden of CRC is significant and is likely to increase over time (8,9). Important economic components of this burden include direct medical care costs, direct nonmedical costs (such as patient time involved with receiving medical care), and productivity losses among patients and caregivers. In this review, we build on and update prior work (10–13) describing the economic burden associated with CRC care. We then categorize the significant challenges in conducting valid, reliable, feasible, and comparable cancer costing analyses, with an emphasis on comparisons across studies, health systems, and countries. Methods Study Selection We used MEDLINE to identify English language articles about the costs of CRC published between 2000 and 2010. The search strategy used the Medical Subject Headings (MeSH) subject term “colorectal neoplasms” combined with MeSH major subject terms “health care costs,” or “cost of illness,” or “economics,” or “cost analysis.” The combination yielded 248 studies. Our focus was on CRC care, so we excluded studies of primary prevention and screening. We also excluded simulation models based on hypothetical cohorts with assumed patterns of care, because numerous studies have described patterns of CRC care in population-based samples that are inconsistent with treatment pathways or guidelines (14,15). Studies of costs of specific side effects of treatment (eg, nausea) or symptoms of disease were also excluded, because these studies represented only a small component of cancer care. Also excluded were small studies (with samples of fewer than 100 patients), as well as reviews, editorials, letters, and essays. Economic studies of cancer treatment trials were included only if they were based on primary patient-level data during and possibly after the trial period. Of the studies identified as potentially eligible for inclusion in our review, 30 met our eligibility criteria (16–43). Because electronic searches may not identify all relevant studies (44), we reviewed the reference lists of the selected studies as well as reviews of the costs of CRC care (10–13,45,46) and identified 25 additional studies (47–73). A total of 55 studies are included in this review. Data Abstraction Data were abstracted from each paper using a standardized abstraction format to describe the study characteristics, cancer patient characteristics, and study methods. Study characteristics included study publication year, country where study was conducted, geographic setting (single city, single state/province/region, multiple cities and/or states/provinces/regions, national, multiple countries), delivery setting (single institution or clinic, network of institutions or clinics, integrated system/insurance network, other), and the type of cost estimate evaluated (direct medical, direct nonmedical, including patient or caregiver time and travel, and productivity loss). Because health-care delivery in the United States is fragmented, we also abstracted information about the type of health insurance (fee-for-service, managed care, multiple types of insurance) and measurement of cost (insurance payments only, patient out-of-pocket payments, charges). Cancer patient characteristics included method of patient identification (medical record review, registry, claims, other), tumor stage (American Joint Committee on Cancer [AJCC] I/II or localized, AJCC III/IV or regional/distant, other, stage not reported), number of cancer patients (100–499, 500–999, 1000–4999, 5000–9999, 10 000+) and patient age groups (<40, 40–64, 65+, mean age <65, mean age 65+, patient age not stated). Study methods that were abstracted included study design (cross-sectional, cohort, based on a randomized controlled trial), phases of care evaluated (initial treatment, surveillance or continuing, last year of life, long-term/lifetime, all phases together [prevalent], other), use of a comparison group (noncancer controls, other comparison group, no comparison group), and use of price adjusters (time adjusters, other adjusters, not reported). Medical cost estimates for prevalent CRC patients (both incident and existing patients) were abstracted separately at the per-person and aggregate levels. Medical cost estimates were also abstracted separately for each phase of care. Studies that could not clearly define patients with incident disease, or that identified patients with metastatic disease but did not distinguish newly diagnosed from recurrent disease, or that were based on receipt of specific treatment, were classified as cost estimates of prevalent cancer patients. Studies based on patterns of care observed in clinical trials of cancer treatment were abstracted separately, as were studies of other aspects of the burden of illness, including patient and caregiver time and productivity loss. Consistent with the diverse approaches found in the literature, we use the term “cost” broadly to reflect either expenditures, insurance payments, charges, actual costs of care, or wages, and we abstracted data as reported in the underlying studies. The “reference year” used to adjust for monetary inflation (eg, in 2000 dollars) was abstracted as reported, or noted as not reported when the reference year was not available in the underlying study. We did not attempt to standardize studies to a single reference year, because it would not be meaningful to do so given the heterogeneity across health systems and countries in cancer care delivery settings, data sources, patient populations, measurement of cost, types of medical services, use of comparison groups, and other methodological differences. Finally, findings are reported as either total costs or cancer-related costs. Total costs reflect the cost of all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or else the net cost of all services among cancer patients compared with similar individuals without cancer. Nonmedical costs are also reported as either total or cancer-related based on comparisons with similar individuals without cancer. Results Study Characteristics The number of published studies of the costs of CRC care increased throughout the study period, with almost half being published between 2008 and 2010 (Table 1). The majority of studies were conducted in the United States (52.7%), followed by France (12.7%), Canada (9.1%), and the United Kingdom (9.1%). Studies were also conducted in Brazil, Germany, Greece, Hungary, Italy, Japan, and Norway. Almost 90% of studies estimated direct medical costs, and few estimated patient or caregiver time costs (14.5%), travel costs (7.3%), or productivity losses (7.3%). In the United States, the dominant health insurance type was fee-for-service, with few studies conducted in managed care or across multiple types of payers/providers. The most commonly used data source was the linked SEER–Medicare data, which include only fee-for-service insurance predominantly for patients aged 65 and older. Studies varied in the comprehensiveness of estimates, ranging from Medicare payments only, to adjusting also for patient out-of-pocket payments, to using Medicare charges as a proxy for cost. Few studies in the United States included patients without any health insurance at all. Table 1. Study summary (N = 55)*     No.  Percent  Study characteristics  Study publication year    2000–2003  14  25.5      2004–2007  16  29.1    2008–2010  25  45.5  Country    Canada    5    9.1    France    7  12.7    Italy    2    3.6    Japan    2    3.6    United Kingdom    5    9.1    United States  29  52.7    Other    5    9.1  Geographic setting†    Single city    4    7.2    Single state/province/region    9  16.4    Multiple cities and/or states/provinces/regions  21  38.2    National  18  32.7    Multiple countries    3    5.5  Delivery setting†    Single institution or clinic    3    5.5    Network of institutions or clinics    3    5.5    Integrated system/insurance network  18  32.7    National health-care system  12  21.8    Other  19  34.5  Cost domain†    Direct medical costs  49  89.1    Direct nonmedical costs  10  18.2     Patient or caregiver time    8  14.5     Travel    5    7.3    Lost productivity    5    7.3  Cancer patient characteristics  Cancer patient identification†    Medical record review    6  10.9    Registry  23  41.8    Claims    9  16.4    Other  21  38.2  Tumor stage†    AJCC I/II or localized  24  43.6    AJCC III/IV or regional/distant  29  52.7    Other    5    9.1    Stage not reported  21  38.2  No. of cancer patients†    100–499  17  30.9    500–999    9  16.4    1000–4999  10  18.2    5000–9999    5    9.1    10 000+  13  23.6  Patient age groups†    <40  18  32.7    40–64  30  54.5    65+  42  76.4    Mean age <65    1    1.8    Mean age 65+    5    9.1    Patient ages not stated    7  12.7  Study methods  Study design      Cross-sectional  18  32.7    Cohort  24  43.6    Based on randomized controlled trial  13  25.5  Phase of cancer care†    Initial treatment of incident disease  19  34.5      Surveillance, continuing, or monitoring  12  21.8      Last year of life  10  18.8      Long-term/lifetime costs  13  23.6      Prevalence (all patients ever diagnosed)  22  40.0      Other    5    9.1    Comparison group†          Noncancer controls  15  27.3      Other comparison group  22  40.0      No comparison group  18  32.7    Use of price adjusters†          Time adjusters for inflation  32  58.2      Other adjusters (eg, geographic)  10  18.2      Not reported  15  27.3      No.  Percent  Study characteristics  Study publication year    2000–2003  14  25.5      2004–2007  16  29.1    2008–2010  25  45.5  Country    Canada    5    9.1    France    7  12.7    Italy    2    3.6    Japan    2    3.6    United Kingdom    5    9.1    United States  29  52.7    Other    5    9.1  Geographic setting†    Single city    4    7.2    Single state/province/region    9  16.4    Multiple cities and/or states/provinces/regions  21  38.2    National  18  32.7    Multiple countries    3    5.5  Delivery setting†    Single institution or clinic    3    5.5    Network of institutions or clinics    3    5.5    Integrated system/insurance network  18  32.7    National health-care system  12  21.8    Other  19  34.5  Cost domain†    Direct medical costs  49  89.1    Direct nonmedical costs  10  18.2     Patient or caregiver time    8  14.5     Travel    5    7.3    Lost productivity    5    7.3  Cancer patient characteristics  Cancer patient identification†    Medical record review    6  10.9    Registry  23  41.8    Claims    9  16.4    Other  21  38.2  Tumor stage†    AJCC I/II or localized  24  43.6    AJCC III/IV or regional/distant  29  52.7    Other    5    9.1    Stage not reported  21  38.2  No. of cancer patients†    100–499  17  30.9    500–999    9  16.4    1000–4999  10  18.2    5000–9999    5    9.1    10 000+  13  23.6  Patient age groups†    <40  18  32.7    40–64  30  54.5    65+  42  76.4    Mean age <65    1    1.8    Mean age 65+    5    9.1    Patient ages not stated    7  12.7  Study methods  Study design      Cross-sectional  18  32.7    Cohort  24  43.6    Based on randomized controlled trial  13  25.5  Phase of cancer care†    Initial treatment of incident disease  19  34.5      Surveillance, continuing, or monitoring  12  21.8      Last year of life  10  18.8      Long-term/lifetime costs  13  23.6      Prevalence (all patients ever diagnosed)  22  40.0      Other    5    9.1    Comparison group†          Noncancer controls  15  27.3      Other comparison group  22  40.0      No comparison group  18  32.7    Use of price adjusters†          Time adjusters for inflation  32  58.2      Other adjusters (eg, geographic)  10  18.2      Not reported  15  27.3  * AJCC = American Joint Committee on Cancer. † Studies may be included in more than one category. View Large Cancer patients were identified by medical record review (10.9%), tumor registries (41.8%), billing or claims data (16.4%), or other approaches, including clinical trial participation. Many studies included patients with all stages of disease at diagnosis, whereas about 25% included only patients with metastatic disease (recurrent or late-stage disease at diagnosis), and few studies restricted patients to early-stage disease (data not shown). Stage was not reported in 38% of studies. Most studies included patients aged 65 and older, either because they included patients of all ages and CRC incidence was higher in the elderly, or because they were conducted in the United States using SEER–Medicare data. Age was not stated in seven studies. Of the 55 studies included in the review, 32.7% were cross-sectional, 43.6% were conducted in observational cohorts, and 25.5% were clinical trial–based. The majority of observational studies were conducted in the United States, whereas the majority of clinical trial–based studies were conducted in other countries. Many studies assessed the costs of CRC in prevalent samples of patients (40%), including clinical trial–based studies of treatment for metastatic disease. Many observational studies assessed either costs of initial treatment of incident disease or the initial phase of care (34.5%), or long-term/lifetime costs (23.6%), or both. Fewer observational studies assessed care at the end of life (18.8%). About one-third of the studies did not include a comparison group. Most studies used inflation price adjusters to standardize costs over the study period, but a sizable portion did not report use of any price adjusters (27.3%). Direct Medical Costs of CRC Care in Observational Studies National estimates of the direct medical costs of CRC were conducted in France, the United States, Canada, Brazil, and Hungary (20,30,31,34,39,66,69) (Table 2). Estimates were for either the entire population with cancer in a given year or for a subset of newly diagnosed patients in a given year over some defined time period, ranging from the first year following cancer diagnosis up to the patient’s lifetime. Although several studies included the entire population of CRC patients, others were restricted to only the elderly. Finally, the scope of care included in these estimates varied widely—one study included only hospitalizations, whereas others included all care following diagnosis. Table 2. National estimates of direct medical costs of colorectal cancer (CRC) care* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Boncz, 2010 (20)  Hungary; National Cancer Registry–National Health Insurance Fund  All patients  Inpatient, outpatient, drugs, and sickness pay  The National Health Insurance Fund Administration spent €32.2 million and €0.8 million on the treatment of malignant and in situ CRC, respectively in 2001  Torres, 2010 (30)  Brazil; Hospital Information Systems of the Brazilian Unified Health System  297 108 hospital admissions 1996–2008 with a primary diagnosis of CRC  Hospitalizations  Overall costs of CRC hospitalizations $16.5 million in 1996 and $33.5 million in 2008; the average cost of each admission, however, decreased from $1283 to $954; estimates in 2007 US dollars  Lejeune, 2009 (66)  France  36 000 patients diagnosed in 2000 with potentially curative surgery  Surveillance up to 3 years  3-year cost of surveillance €42.4 million; year of euros not reported  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Aggregate 5-year net costs for patients diagnosed in 2004 to Medicare were estimated to be $3101 million; estimates in 2004 US dollars  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older with all stages 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Total 2002 Medicare payments for CRC care in year following diagnosis in the United States was estimated to be $2.04 billion (in 2003 US dollars)  Maroun, 2003 (39)  Canada  16 856 patients diagnosed with colon or rectal cancer in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Total aggregate lifetime treatment cost for patients in 2000 estimated to be $333 million and $187 million for colon and rectal cancer, respectively (in 1988 Canadian dollars)  Selke, 2003 (69)  France  All patients in 1999  Hospital inpatient and outpatient, physician, and prescription costs  Total direct medical costs of CRC to the health insurance system was €469.7 million  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Boncz, 2010 (20)  Hungary; National Cancer Registry–National Health Insurance Fund  All patients  Inpatient, outpatient, drugs, and sickness pay  The National Health Insurance Fund Administration spent €32.2 million and €0.8 million on the treatment of malignant and in situ CRC, respectively in 2001  Torres, 2010 (30)  Brazil; Hospital Information Systems of the Brazilian Unified Health System  297 108 hospital admissions 1996–2008 with a primary diagnosis of CRC  Hospitalizations  Overall costs of CRC hospitalizations $16.5 million in 1996 and $33.5 million in 2008; the average cost of each admission, however, decreased from $1283 to $954; estimates in 2007 US dollars  Lejeune, 2009 (66)  France  36 000 patients diagnosed in 2000 with potentially curative surgery  Surveillance up to 3 years  3-year cost of surveillance €42.4 million; year of euros not reported  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Aggregate 5-year net costs for patients diagnosed in 2004 to Medicare were estimated to be $3101 million; estimates in 2004 US dollars  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older with all stages 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Total 2002 Medicare payments for CRC care in year following diagnosis in the United States was estimated to be $2.04 billion (in 2003 US dollars)  Maroun, 2003 (39)  Canada  16 856 patients diagnosed with colon or rectal cancer in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Total aggregate lifetime treatment cost for patients in 2000 estimated to be $333 million and $187 million for colon and rectal cancer, respectively (in 1988 Canadian dollars)  Selke, 2003 (69)  France  All patients in 1999  Hospital inpatient and outpatient, physician, and prescription costs  Total direct medical costs of CRC to the health insurance system was €469.7 million  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Ten studies estimated the cost of cancer care in prevalent patients, the combination of newly diagnosed and existing cancer patients (17,19,21,27,36,42,54,57,63,70) (Table 3). These studies were conducted exclusively in the United States, but the number of patients, age distribution, data source, types of costs included, and reference year varied widely. For example, two studies assessed ambulatory care, but one reported cancer-related costs for chemotherapy ranging from $1028 to $38 027 for different regimens (57), and the other reported payments for all care of $946 among individuals with cancer (27). Neither reported the year of dollars, patient age distribution, or period during which costs were accrued. Table 3. Direct medical costs of colorectal cancer (CRC) care among prevalent cancer patients* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Chu, 2009 (70); Chu, 2010 (17)  United States; Medstat MarketScan  3333 patients identified from diagnosis codes received chemotherapy 2003–2006 and subset of 1396 patients who received chemotherapy within 90 days of surgery  Chemotherapy-related  Monthly cancer-related chemotherapy cost from $6683 to $14 320 for capecitabine and 5-FU/LV/oxaliplatin, respectively; for chemotherapy within 90 days of surgery, monthly costs $8003 and $7263 for 5-FU and capecitabine, respectively (in 2006 US dollars)  Dinan, 2010 (54)  United States; 5% Medicare sample  7039 patients aged 67 and older identified from claims for CRC in 1999, 2003, and 2006  All care  Total costs over 2 years in 1999, 2003, and 2006: $38 724, $51 715, and $56 839, respectively; imaging costs 1999, 2003, and 2006: $1009, $1686, and $1918, respectively (in 2008 US dollars)  Yabroff, 2009 (42)  United States; SEER–Medicare, 5% Medicare sample, MEPS  Patients aged 65 and older; SEER–Medicare: 73 050 diagnosed 1973–2002 with costs 1998–2002; 5% Medicare sample: 3575 patients 1996–2002 with costs 1998–2002; MEPS: 196 patients treated 1996–2004 with costs 1996–2004  All care  Annual cancer-related costs were $5341, $8736, and $11 614 in SEER–Medicare, 5% Medicare sample, and MEPS, respectively (in 2004 US dollars)  Ferro, 2008 (57)  United States; 115 ambulatory centers  421 CRC patients receiving chemotherapy 2002–2005  Ambulatory chemotherapy  Costs of cancer-related chemotherapy ranged from $1028 to $38 027 per regimen; year of dollars not reported  Paramore, 2006 (19)  United States; PharMetrics Database  699 patients with a code for metastases identified from claims, 1998–2004  All care  Cancer-related payments over average of 12.8 months were $97 031 (in 2005 dollars)  Chang, 2004 (21)  United States; Medstat MarketScan  2858 patients identified from claims, 1999–2000  All care  Cancer-related payments were $3742 per month and $30 939 over study; year of dollars not reported  Mullins, 2004 (27)  United States; MD Medicaid  1904 patients identified from claims, 1999–2000; patient age not stated  Ambulatory care  Total mean ambulatory payments were $946; year of dollars not reported  Ray, 2000 (63)  United States; KP–Northern CA  2613 patients of all ages identified from billing 1995–1996  All care  Total annual adjusted and unadjusted cost per capita were $10 506 and $15 253, respectively (in 1996 dollars)  Polednak, 2000 (36)  United States; CT registry and hospitals  11 023 patients all ages diagnosed 1992–1996, with first hospital admission 1992–1996  Hospital care  Total mean charges for first hospital admission after diagnosis were $32 061 for initial emergency department admission and $20 130 for admitted directly to the hospital; year of dollars not reported  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included after patient identification  Findings  Chu, 2009 (70); Chu, 2010 (17)  United States; Medstat MarketScan  3333 patients identified from diagnosis codes received chemotherapy 2003–2006 and subset of 1396 patients who received chemotherapy within 90 days of surgery  Chemotherapy-related  Monthly cancer-related chemotherapy cost from $6683 to $14 320 for capecitabine and 5-FU/LV/oxaliplatin, respectively; for chemotherapy within 90 days of surgery, monthly costs $8003 and $7263 for 5-FU and capecitabine, respectively (in 2006 US dollars)  Dinan, 2010 (54)  United States; 5% Medicare sample  7039 patients aged 67 and older identified from claims for CRC in 1999, 2003, and 2006  All care  Total costs over 2 years in 1999, 2003, and 2006: $38 724, $51 715, and $56 839, respectively; imaging costs 1999, 2003, and 2006: $1009, $1686, and $1918, respectively (in 2008 US dollars)  Yabroff, 2009 (42)  United States; SEER–Medicare, 5% Medicare sample, MEPS  Patients aged 65 and older; SEER–Medicare: 73 050 diagnosed 1973–2002 with costs 1998–2002; 5% Medicare sample: 3575 patients 1996–2002 with costs 1998–2002; MEPS: 196 patients treated 1996–2004 with costs 1996–2004  All care  Annual cancer-related costs were $5341, $8736, and $11 614 in SEER–Medicare, 5% Medicare sample, and MEPS, respectively (in 2004 US dollars)  Ferro, 2008 (57)  United States; 115 ambulatory centers  421 CRC patients receiving chemotherapy 2002–2005  Ambulatory chemotherapy  Costs of cancer-related chemotherapy ranged from $1028 to $38 027 per regimen; year of dollars not reported  Paramore, 2006 (19)  United States; PharMetrics Database  699 patients with a code for metastases identified from claims, 1998–2004  All care  Cancer-related payments over average of 12.8 months were $97 031 (in 2005 dollars)  Chang, 2004 (21)  United States; Medstat MarketScan  2858 patients identified from claims, 1999–2000  All care  Cancer-related payments were $3742 per month and $30 939 over study; year of dollars not reported  Mullins, 2004 (27)  United States; MD Medicaid  1904 patients identified from claims, 1999–2000; patient age not stated  Ambulatory care  Total mean ambulatory payments were $946; year of dollars not reported  Ray, 2000 (63)  United States; KP–Northern CA  2613 patients of all ages identified from billing 1995–1996  All care  Total annual adjusted and unadjusted cost per capita were $10 506 and $15 253, respectively (in 1996 dollars)  Polednak, 2000 (36)  United States; CT registry and hospitals  11 023 patients all ages diagnosed 1992–1996, with first hospital admission 1992–1996  Hospital care  Total mean charges for first hospital admission after diagnosis were $32 061 for initial emergency department admission and $20 130 for admitted directly to the hospital; year of dollars not reported  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. CA = California; CT = Connecticut; FU = fluorouracil; KP = Kaiser Permanente, LV = leucovorin; MarketScan = Coordination of Benefits and Health and Productivity Management; MD = Maryland; MEPS = Medical Expenditure Panel Survey; SEER = Surveillance, Epidemiology, and End Results tumor registry. View Large Fourteen studies assessed the costs of CRC care by phase of cancer care (Table 4), including 10 in the initial phase or initial care period (16,18,31,32,34,39,41,48,55,67), five in the continuing phase (16,24,34,41,66), and five in the last year of life (16,29,34,41,58). The majority of these studies were conducted in the United States, with three in France and one each in Canada and Norway. There was notable variation across studies in the number of patients, age distribution, definition of phase, type of costs, and reference year. For example, even among the US studies using the SEER–Medicare linked data for patients aged 65 and older, estimates ranged from mean cancer-related costs in 12 months of the initial phase of $29 609 in men and $29 930 in women in 2004 dollars (34) to total costs of $41 134 in the first year following diagnosis in 2003 dollars (31). The latter study reported total costs incurred by those diagnosed with CRC, whereas the former estimated cancer-related costs. These studies also differed in the calendar years of observation and definitions of the initial period of treatment (12 months following diagnosis vs initial phase of care). Table 4. Direct medical costs of colorectal cancer (CRC) care by phase of care and/or care period*   First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Initial care  Luo, 2010 (55)  United States; MI Registry–Medicare claims  6462 colon cancer patients aged 66 and older diagnosed 1997–2000  All care (including patient and third-party payer)  Mean cost attributable to cancer 1 year after diagnosis was $29 196 (in 2000 dollars), due to higher inpatient costs in cancer patients than controls  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in first year after diagnosis greater for late stage than early stage ($28 500 vs $20 200 in men), and for cancer patients with heart disease or diabetes compared with no comorbid conditions ($33 700, $34 100, and $25 200, respectively, for men with late-stage disease); estimates in 2001 dollars  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related costs in year after diagnosis were $33 294; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Clerc, 2008 (67)  France, two areas in Burgundy  384 patients of all ages diagnosed in 2004 with information from three public health insurance funds  Hospital, outpatient, including drugs and chemotherapy, transportation  Total costs in 12 months after diagnosis were €24 966, of which transportation costs were €623; costs were higher for stage IV (€35 059) than stage I (€17 596) or stage II (€20 472)  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older diagnosed with all stages of invasive CRC 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Average total Medicare payments in the 12 months following diagnosis in 2002 was $41 134 (in 2003 dollars); inflation-adjusted increase of $5345 from 1991; hospitalization accounted for the largest portion of payments  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1999–2002 with cost data 1999–2003  All care  Mean cancer-related Medicare costs in 12 months of initial phase of care were $29 609 in men and $29 930 in women; estimates in 2004 dollars  Wright, 2007 (32)  United States; SEER–Medicare  6108 patients aged 66 and older with stage II–III rectal and stage III colon cancer 1992–1996 with cost data 1992–1998  All care (including patient and other insurer)  Unadjusted charges in 16 months following diagnosis higher for African Americans than whites ($44 199 vs $38 378); adjusted estimates similar in the two groups ($34 588 vs $33 614); estimates in 2000 dollars  Ramsey, 2003 (18)  United States; SEER–GHC  923 patients aged 50+ diagnosed 1993–1999, with costs 1993–2000  All care year after diagnosis  Total costs for screen and symptom detected were $23 344 and $29 384 in 2002 dollars  Bouvier, 2003 (48)  France; Caisse Nationale d’Assurance Maladie des Travailleurs Salaries  142 patients of all ages and stages diagnosed 1997–1998 affiliated with health insurance fund  Hospital, outpatient, transportation, medical purchases, and patient assistance (disability)  Mean cost of care was €21 918 in first year after diagnosis; costs were lower in older ages and mean costs per month of survival were higher in higher stages; year of euro estimates not reported  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Initial treatment costs were $14 375 and $16 951 for colon and rectal cancers, respectively; estimates in 1988 Canadian dollars  Continuing phase of care  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean annual cancer-related cost in 12 months of continuing care was $4280; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Lejeune, 2009 (66)  France, two areas in Burgundy  385 patients diagnosed in 1998 with potentially curative surgery  Surveillance (physician, imaging, tumor markers)  Average surveillance cost per patient €713 over 3 years; year of euros not reported  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total annual costs in continuing phase greater for late than early stage ($3300 vs $3800 in men), but similar for cancer patients with heart disease or diabetes compared with no comorbid conditions; estimates in 2001 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  82 559 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs of CRC care $2254 in men and $1595 in women in 12 months of continuing phase; estimates in 2004 dollars  Körner, 2005 (24)  Norway; single institution  194 patients younger than 76 years with curative surgery for Dukes A-C 1996–1999  Surveillance  The total cost of postoperative surveillance was €20 530 per patient in 2003 euros  Last year of life  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in last year of life similar by stage, but higher for patients with heart disease or diabetes compared with no comorbid conditions ($28 900, $28 200, and $20 000, respectively, for men with late-stage disease); estimates in 2001 dollars  Koroukian, 2009 (58)  United States; OH Medicaid Program  4573 patients with CRC as underlying cause of death 1992–2002, with cost data in 12 months before death 1992–2002  All care  Mean and median per-person month expenditures were $2109 and $1754, respectively, during the 12 months before death; year of dollars not reported  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related cost in final year was $14 538; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  38 636 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs in 12 months of last-year-of-life phase of care were $36 483 in men and $33 610 in women; estimates in 2004 dollars  Shugarman, 2007 (29)  United States; 5% sample of Medicare beneficiaries  6657 patients aged 68 and older who died 1996–1999 with a diagnosis code for CRC within 3 years of death; costs reported 1995–1999  All care  Total per-person payments were $33 560 in the last year of life (in 1999 dollars); largest portion was inpatient care ($18 832), followed by physician services ($5633); payments for older patients lower than for younger patients    First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Initial care  Luo, 2010 (55)  United States; MI Registry–Medicare claims  6462 colon cancer patients aged 66 and older diagnosed 1997–2000  All care (including patient and third-party payer)  Mean cost attributable to cancer 1 year after diagnosis was $29 196 (in 2000 dollars), due to higher inpatient costs in cancer patients than controls  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in first year after diagnosis greater for late stage than early stage ($28 500 vs $20 200 in men), and for cancer patients with heart disease or diabetes compared with no comorbid conditions ($33 700, $34 100, and $25 200, respectively, for men with late-stage disease); estimates in 2001 dollars  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related costs in year after diagnosis were $33 294; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Clerc, 2008 (67)  France, two areas in Burgundy  384 patients of all ages diagnosed in 2004 with information from three public health insurance funds  Hospital, outpatient, including drugs and chemotherapy, transportation  Total costs in 12 months after diagnosis were €24 966, of which transportation costs were €623; costs were higher for stage IV (€35 059) than stage I (€17 596) or stage II (€20 472)  Warren, 2008 (31)  United States; SEER–Medicare  64 554 patients aged 65 and older diagnosed with all stages of invasive CRC 1991–2002 with cost data for year following diagnosis 1991–2003  All care  Average total Medicare payments in the 12 months following diagnosis in 2002 was $41 134 (in 2003 dollars); inflation-adjusted increase of $5345 from 1991; hospitalization accounted for the largest portion of payments  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1999–2002 with cost data 1999–2003  All care  Mean cancer-related Medicare costs in 12 months of initial phase of care were $29 609 in men and $29 930 in women; estimates in 2004 dollars  Wright, 2007 (32)  United States; SEER–Medicare  6108 patients aged 66 and older with stage II–III rectal and stage III colon cancer 1992–1996 with cost data 1992–1998  All care (including patient and other insurer)  Unadjusted charges in 16 months following diagnosis higher for African Americans than whites ($44 199 vs $38 378); adjusted estimates similar in the two groups ($34 588 vs $33 614); estimates in 2000 dollars  Ramsey, 2003 (18)  United States; SEER–GHC  923 patients aged 50+ diagnosed 1993–1999, with costs 1993–2000  All care year after diagnosis  Total costs for screen and symptom detected were $23 344 and $29 384 in 2002 dollars  Bouvier, 2003 (48)  France; Caisse Nationale d’Assurance Maladie des Travailleurs Salaries  142 patients of all ages and stages diagnosed 1997–1998 affiliated with health insurance fund  Hospital, outpatient, transportation, medical purchases, and patient assistance (disability)  Mean cost of care was €21 918 in first year after diagnosis; costs were lower in older ages and mean costs per month of survival were higher in higher stages; year of euro estimates not reported  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Initial treatment costs were $14 375 and $16 951 for colon and rectal cancers, respectively; estimates in 1988 Canadian dollars  Continuing phase of care  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean annual cancer-related cost in 12 months of continuing care was $4280; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Lejeune, 2009 (66)  France, two areas in Burgundy  385 patients diagnosed in 1998 with potentially curative surgery  Surveillance (physician, imaging, tumor markers)  Average surveillance cost per patient €713 over 3 years; year of euros not reported  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total annual costs in continuing phase greater for late than early stage ($3300 vs $3800 in men), but similar for cancer patients with heart disease or diabetes compared with no comorbid conditions; estimates in 2001 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  82 559 patients aged 65 and older diagnosed with all stages (including in situ) of CRC 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs of CRC care $2254 in men and $1595 in women in 12 months of continuing phase; estimates in 2004 dollars  Körner, 2005 (24)  Norway; single institution  194 patients younger than 76 years with curative surgery for Dukes A-C 1996–1999  Surveillance  The total cost of postoperative surveillance was €20 530 per patient in 2003 euros  Last year of life  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients in all phases of care aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Total costs in last year of life similar by stage, but higher for patients with heart disease or diabetes compared with no comorbid conditions ($28 900, $28 200, and $20 000, respectively, for men with late-stage disease); estimates in 2001 dollars  Koroukian, 2009 (58)  United States; OH Medicaid Program  4573 patients with CRC as underlying cause of death 1992–2002, with cost data in 12 months before death 1992–2002  All care  Mean and median per-person month expenditures were $2109 and $1754, respectively, during the 12 months before death; year of dollars not reported  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients in all phases of care aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Mean cancer-related cost in final year was $14 538; costs were higher for later compared with earlier stage and younger compared with older age; estimates in 2006 dollars  Yabroff, 2008 (34)  United States; SEER–Medicare  38 636 patients aged 65 and older diagnosed with all stages (including in situ) 1973–2002 with cost data 1999–2003  All care  Mean net Medicare costs in 12 months of last-year-of-life phase of care were $36 483 in men and $33 610 in women; estimates in 2004 dollars  Shugarman, 2007 (29)  United States; 5% sample of Medicare beneficiaries  6657 patients aged 68 and older who died 1996–1999 with a diagnosis code for CRC within 3 years of death; costs reported 1995–1999  All care  Total per-person payments were $33 560 in the last year of life (in 1999 dollars); largest portion was inpatient care ($18 832), followed by physician services ($5633); payments for older patients lower than for younger patients  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. Estimates are in US dollars, unless otherwise noted. GHC = Group Health Cooperative; MI = Michigan; OH = Ohio; RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Eleven studies reported long-term or lifetime costs associated with CRC care (16,22,23,34,38–41,59,62,68) (Table 5). Again, studies were conducted predominantly in the United States, with two in Canada and one each in the United Kingdom and France, and varied substantially in the samples, settings, types of care and costs included, and time periods covered postdiagnosis (eg, 2 years, 6–11 years, 25 years, lifetime). Despite these differences, lifetime cancer-related costs were generally higher in younger patients compared with older patients, as might be expected (16). Additionally, costs were generally higher among patients with more advanced disease at diagnosis (39), although lifetime costs were lower in patients with stage IV disease than stage I disease, reflecting shorter life expectancy in this group (22,40). One study evaluated trends in lifetime costs and survival in patients treated with chemotherapy and found that, compared with 1995–1996, patients treated in 2005–2006 had greater lifetime costs ($63 200 vs $100 300) as well as greater survival (16.5 months vs 23.4 months) (59). Table 5. Lifetime or long-term costs of colorectal cancer (CRC) care* First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Howard, 2010 (59)  United States; SEER–Medicare  12 473 patients aged 66 and older diagnosed with stage IV CRC 1995–2005  All care  Among patients treated with chemotherapy, lifetime costs increased from $63 200 during 1995–1996 to $100 300 during 2004–2005 in 2006 dollars; life expectancy increased from 16.5 months to 23.4 months; lifetime costs among patents who did not receive chemotherapy were more stable in 1995–1996 and 2004–2005 ($40 500 and $42 300) as was life expectancy (7.6 months and 7.5 months, respectively)  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Lifetime medical costs lower in patients with detected vs undetected adenomatous polyps and higher in patients with screen-detected vs undetected early-stage cancer across most age groups and types of comorbidities; lifetime costs for screen-detected early-stage cancer ranged from $59 600 to $44 500 in men aged 65 and 85, respectively, and undetected early-stage cancer costs ranged from $57 700 to $42 200 in men aged 65 and 85, respectively (in 2001 dollars)  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Cancer-related lifetime costs were $28 626 (in 2006 dollars); lifetime costs higher in younger patients aged 66–74 than older patients aged 75–84 and 85+ ($36 401, $21 167, and $23 799, respectively); net lifetime costs were lower in patients with stage IV compared with earlier stage, reflecting lower life expectancy  Macafee, 2009 (68)  United Kingdom; single hospital in Nottingham  227 patients, median age 70.3 diagnosed with all stages 1981–2002 admitted to the hospital for treatment  Cancer-related hospital costs  Median cost up to 2 years following admission was £4479 in 2001 pounds, and higher for Dukes B and C than Dukes A and D  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages 1973–2002 with cost data 1999–2003  All care  Mean 5-year cancer-related Medicare costs of CRC care in the elderly following diagnosis were $36 621 in men and $35 037 in women; estimates in 2004 dollars  Kerrigan, 2005 (23)  United States; SEER–GHC, SEER–Blue Shield  Patients aged 20–64 with all stages diagnosed 1996–1998, costs 1996–2000; SEER–GHC: 136 patients, SEER–Blue Shield: 201 patients  All care  Mean 2-year cancer-related costs for women and men were $42 837 and $36 673, and $44 208 and $44 376, for SEER–GHC and SEER–Blue Shield, respectively; estimates in 2003 dollars  Borie, 2004 (62)  France; registry: physician records  256 patients diagnosed with Dukes A-C in 1992 undergoing resection  Follow-up tests  Mean cumulative 5-year cost was €842 per patient; reported in 1998 euros  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Average lifetime costs were $29 110 and $34 475 for colon and rectal cancer, respectively; generally higher lifetime costs for higher stage; hospitalization was the largest component (65% and 61% for colon and rectal); estimates in 1988 Canadian dollars  Ramsey, 2002 (40)  United States; SEER–Medicare  Patients aged 65+ with all stages diagnosed 1984–1994  All care  Mean cancer-related payments years 6–11 in men and women were $13 134 and $9180 for stage I and $3147 and $3731 for stage IV; all in 2000 dollars  Etzioni, 2001 (22)  United States; SEER–Medicare  71 519 patients aged 65+ with all stages diagnosed 1983–1993  All care  Mean 11-year cancer-related payments in men and women were $29 635 and $25 444 for stage I and $3006 and $3665 for stage IV (in 2000 dollars); discounted costs lower for stage IV lower than controls  O’Brien, 2001 (38)  Nova Scotia, Canada; registry: Department of Health  553 patients of all ages and all stages diagnosed 1990  Hospital care  Total hospital costs were $9.8 million dollars ($1300 per person annually), representing 22 460 hospital days in 3 years following diagnosis; year of dollars not stated  First author, y (ref.)  Country and setting  Sample characteristics  Components of health care included  Findings  Howard, 2010 (59)  United States; SEER–Medicare  12 473 patients aged 66 and older diagnosed with stage IV CRC 1995–2005  All care  Among patients treated with chemotherapy, lifetime costs increased from $63 200 during 1995–1996 to $100 300 during 2004–2005 in 2006 dollars; life expectancy increased from 16.5 months to 23.4 months; lifetime costs among patents who did not receive chemotherapy were more stable in 1995–1996 and 2004–2005 ($40 500 and $42 300) as was life expectancy (7.6 months and 7.5 months, respectively)  Howard, 2009 (41)  United States; SEER–Medicare  71 397 cancer patients aged 65 and older diagnosed 1991–1999 with claims 1991–2001  All care  Lifetime medical costs lower in patients with detected vs undetected adenomatous polyps and higher in patients with screen-detected vs undetected early-stage cancer across most age groups and types of comorbidities; lifetime costs for screen-detected early-stage cancer ranged from $59 600 to $44 500 in men aged 65 and 85, respectively, and undetected early-stage cancer costs ranged from $57 700 to $42 200 in men aged 65 and 85, respectively (in 2001 dollars)  Lang, 2009 (16)  United States; SEER–Medicare  56 838 patients aged 66 and older diagnosed 1996–2002  All care (including patient and other insurer)  Cancer-related lifetime costs were $28 626 (in 2006 dollars); lifetime costs higher in younger patients aged 66–74 than older patients aged 75–84 and 85+ ($36 401, $21 167, and $23 799, respectively); net lifetime costs were lower in patients with stage IV compared with earlier stage, reflecting lower life expectancy  Macafee, 2009 (68)  United Kingdom; single hospital in Nottingham  227 patients, median age 70.3 diagnosed with all stages 1981–2002 admitted to the hospital for treatment  Cancer-related hospital costs  Median cost up to 2 years following admission was £4479 in 2001 pounds, and higher for Dukes B and C than Dukes A and D  Yabroff, 2008 (34)  United States; SEER–Medicare  22 935 patients aged 65 and older diagnosed with all stages 1973–2002 with cost data 1999–2003  All care  Mean 5-year cancer-related Medicare costs of CRC care in the elderly following diagnosis were $36 621 in men and $35 037 in women; estimates in 2004 dollars  Kerrigan, 2005 (23)  United States; SEER–GHC, SEER–Blue Shield  Patients aged 20–64 with all stages diagnosed 1996–1998, costs 1996–2000; SEER–GHC: 136 patients, SEER–Blue Shield: 201 patients  All care  Mean 2-year cancer-related costs for women and men were $42 837 and $36 673, and $44 208 and $44 376, for SEER–GHC and SEER–Blue Shield, respectively; estimates in 2003 dollars  Borie, 2004 (62)  France; registry: physician records  256 patients diagnosed with Dukes A-C in 1992 undergoing resection  Follow-up tests  Mean cumulative 5-year cost was €842 per patient; reported in 1998 euros  Maroun, 2003 (39)  Canada  Estimated 16 856 patients with colon or rectal cancer in Canada diagnosed in 2000  Diagnosis and staging, surgery, hospital, RT, chemotherapy  Average lifetime costs were $29 110 and $34 475 for colon and rectal cancer, respectively; generally higher lifetime costs for higher stage; hospitalization was the largest component (65% and 61% for colon and rectal); estimates in 1988 Canadian dollars  Ramsey, 2002 (40)  United States; SEER–Medicare  Patients aged 65+ with all stages diagnosed 1984–1994  All care  Mean cancer-related payments years 6–11 in men and women were $13 134 and $9180 for stage I and $3147 and $3731 for stage IV; all in 2000 dollars  Etzioni, 2001 (22)  United States; SEER–Medicare  71 519 patients aged 65+ with all stages diagnosed 1983–1993  All care  Mean 11-year cancer-related payments in men and women were $29 635 and $25 444 for stage I and $3006 and $3665 for stage IV (in 2000 dollars); discounted costs lower for stage IV lower than controls  O’Brien, 2001 (38)  Nova Scotia, Canada; registry: Department of Health  553 patients of all ages and all stages diagnosed 1990  Hospital care  Total hospital costs were $9.8 million dollars ($1300 per person annually), representing 22 460 hospital days in 3 years following diagnosis; year of dollars not stated  * Total costs reflect all services received by cancer patients. Cancer-related costs reflect either the cost of services presumed to be related to cancer treatment or the net cost of all services among cancer patients compared with similar individuals without cancer. All estimates are in US dollars unless otherwise noted. GHC = Group Health Cooperative; MI = Michigan; RT = radiation therapy; SEER = Surveillance, Epidemiology, and End Results. View Large Medical Costs of CRC Care Among Patients Participating in Clinical Trials Fourteen studies reported the costs of CRC care among patients participating in clinical trials (26,35,37,43,47,49–53,65,71,72) (Table 6). Studies were conducted mainly outside of the United States, in the United Kingdom, France, Italy, Japan, Germany, and Greece. These studies generally measured patterns of care during the period of the trial and applied standardized cost multipliers to the services and procedures observed to estimate patient-level costs. Several studies were multinational and estimated costs for a single country based on all patients in the trial (across countries), whereas others were single-country trials and yielded cost estimates for that country only. Even though the majority of studies reviewed here assessed chemotherapy, and most evaluated metastatic disease, there was significant variability in the choice of comparators, period of evaluation, types of costs included, and level of detail reported. Table 6. Costs of colorectal cancer (CRC) care among patients in clinical trials* First author, y (ref.)  Country and setting  Sample characteristics  Components of health-care after identification  Findings  De Portu, 2010 (53)  Italy; multisite trial unit costs from National Health Service tariffs, DRGs, and formulary  231 metastatic patients in trial of capecitabine vs 5-FU-based treatment, 2001–2006  Medical-care use for 6 months  Costs of care for patients receiving capecitabine and 5-FU were €1002 and €3173 per month, respectively; differences reflect aministration and drug cost (in 2007 euros)  Mittman, 2009 (35)  Canada; multicountry trial unit costs from standardized estimates from Ontario and study hospital  557 chemorefractory patients in trial of cetuximab + best supportive care vs best supportive care alone  Medical-care use up to 19 months  Overall, incremental cost with cetuximab compared with best supportive care was $23 969, and ICER was $199 742 per life-year gained; for patients with wild-type KRAS, the incremental cost with cetuximab was $33 617, and ICER was $120 061 per life-year gained (in 2007 Canadian dollars)  Shiroiwa, 2009 (43)  Japan; multinational trials  1923 metastatic patients in trial of capecitabine plus oxaliplatin (XELOX) or 5-FU/folinic acid and oxaliplatin (FOLFOX4)  Chemotherapy and other drugs over 1 year  Total costs of first and second line outpatient chemotherapy for FOLFOX4 and XELOX were €21 300 and €18 300 and €14 900 and €12 000, respectively; in 2007 euros  Hisashige, 2008 (65)  Japan; trial with standard costs  274 stage-III rectal patients in trial of uracil-tegafur vs no adjuvant treatment following curative resection  Chemotherapy, tests, imaging, AEs, recurrence for 5.6 years  Costs were $8742 for patients treated with uracil-tegafur and $11 199 for surgery alone; estimates in 2005 dollars  Lopatriello, 2008 (26)  Italy; trial in five oncology centers with Italian Healthcare Service tariffs and market retail prices  202 metastatic patients randomized to firstline infusional 5-FU or oral capecitabine  Chemotherapy, AEs, lab tests, and supportive agents  From the Italian health-care service perspective, mean total costs per patient for 5-FU and oral capecitabine were €12 029 and €5781, respectively; €7338 and €4688 from the hospital perspective; differences in the two perspectives reflect national tariffs and market retail prices and payment for infusion administration; year of euros not reported  Maniadakis, 2007 (37)  Greece; multisite trial with unit costs from the National Health Service  276 patients with advanced CRC randomized to FOLFIRI or FOLFOXIRI  Chemotherapy, radiation therapy, AEs  Total cost of therapy in the FOLFOXIRI was significantly higher than the FOLFIRI group (€18 344 vs €12 201); differences in mean chemotherapy costs, second line drugs, and hospitalizations; estimates reported in 2006 euros  Borget, 2006 (71)  France; multicenter trial with unit costs from National Health System reimbursement, cost accounting systems  294 metastatic patients in trial of HD-LV5-FU2, raltitrexed, LD-LV5-FU2, or weekly infusional 5-FU.  Chemotherapy and toxicity or complications, follow-up and travel until disease progression or death  Total costs were €15 970, €14 888, €13 760, and €10 687 for HD-LV5-FU2, LD-LV5-FU2, weekly 5-FU, and raltitrexed, respectively; estimates in 2001 euros  Cassidy, 2006 (47)  United Kingdom; multinational trial standardized costs applied to service use  1987 patients with Dukes C colon cancer randomized to either oral capecitabine or infusional LV + 5-FU  Chemotherapy, AEs, travel over 6 months  Chemotherapy administration higher for 5-FU/LV vs capecitabine (₤5151 vs ₤419), but mean cost of AEs and travel lower in capecitabine as compared to 5-FU-LV; year not stated  Franks, 2006 (72)  United Kingdom; multicenter trial with unit costs from published sources and single hospital  682 patients in trial of conventional vs laparoscopic-assisted surgery  Hospital, treatment for complications, and outpatient  3-month medical and lost productivity costs for patients treated with laparoscopic vs conventional surgery were ₤6899 vs ₤6631; year not stated  Earle, 2004 (52)  United States; multicenter trial with unit costs from Medicare reimbursement and billing data from a single center  291 CRC patients with metastatic disease refractory to 5-FU randomized to either weekly or every 3-week irinotecan  Hospital, ER, chemotherapy, physician up to 1 year  Major cost drivers were chemotherapy, hospitalization, and chemotherapy administration; every 3-week administration of irinotecan associated with cost–utility ratio of $78 627 per QALY; costs reported in 2001 dollars  Monz, 2003 (49)  Germany; multisite trial, unit costs from the perspective German Social Health Insurance based on fee scale, reports, and Red Book  563 patients with UICC II/III in trial of 5-FU + levamisole vs 5-FU + levamisole + FA following surgery  Chemotherapy and follow-up over 5 years of trial  Cancer-related costs were €4909 and €11 085 for patients without and with progression receiving FU + levamisole and €17 122 and €21 330 for patients without and with progression receiving 5-FU + levamisole + FA; ICER of €51 225 for 5-FU + levamisole + FA vs 5-FU + levamisole; cost reported in 2000 euros  Cunningham, 2002 (51)  United Kingdom; multinational trial with standard costs from formulary and hospital tariffs  385 patients with metastatic disease randomized to 5-FU/FA vs irinotecan and 5-FU/FA  In-study treatment and additional chemotherapy up to 3 years  Mean cumulative costs £3767 vs £4220 for irinotecan and 5-FU/FA vs 5-FU/FA, respectively, with incremental cost per LYG £14 794 reflecting improved survival; year of pounds not stated  Levy-Piedbois, 2000 (50)  France; trial with costs from single hospital in Paris  256 patients in trial of irinotecan vs infusional 5-FU  Chemotherapy, clinic and complications up to 1 year  Total cost of treatment for irinotecan vs infusional 5-FU ($14 135 vs $12 192–$12 344); incorporating survival difference, cost-effectiveness ratios ranged from $9344 to $10 137 per additional year of survival; estimates in 1999 dollars  First author, y (ref.)  Country and setting  Sample characteristics  Components of health-care after identification  Findings  De Portu, 2010 (53)  Italy; multisite trial unit costs from National Health Service tariffs, DRGs, and formulary  231 metastatic patients in trial of capecitabine vs 5-FU-based treatment, 2001–2006  Medical-care use for 6 months  Costs of care for patients receiving capecitabine and 5-FU were €1002 and €3173 per month, respectively; differences reflect aministration and drug cost (in 2007 euros)  Mittman, 2009 (35)  Canada; multicountry trial unit costs from standardized estimates from Ontario and study hospital  557 chemorefractory patients in trial of cetuximab + best supportive care vs best supportive care alone  Medical-care use up to 19 months  Overall, incremental cost with cetuximab compared with best supportive care was $23 969, and ICER was $199 742 per life-year gained; for patients with wild-type KRAS, the incremental cost with cetuximab was $33 617, and ICER was $120 061 per life-year gained (in 2007 Canadian dollars)  Shiroiwa, 2009 (43)  Japan; multinational trials  1923 metastatic patients in trial of capecitabine plus oxaliplatin (XELOX) or 5-FU/folinic acid and oxaliplatin (FOLFOX4)  Chemotherapy and other drugs over 1 year  Total costs of first and second line outpatient chemotherapy for FOLFOX4 and XELOX were €21 300 and €18 300 and €14 900 and €12 000, respectively; in 2007 euros  Hisashige, 2008 (65)  Japan; trial with standard costs  274 stage-III rectal patients in trial of uracil-tegafur vs no adjuvant treatment following curative resection  Chemotherapy, tests, imaging, AEs, recurrence for 5.6 years  Costs were $8742 for patients treated with uracil-tegafur and $11 199 for surgery alone; estimates in 2005 dollars  Lopatriello, 2008 (26)  Italy; trial in five oncology centers with Italian Healthcare Service tariffs and market retail prices  202 metastatic patients randomized to firstline infusional 5-FU or oral capecitabine  Chemotherapy, AEs, lab tests, and supportive agents  From the Italian health-care service perspective, mean total costs per patient for 5-FU and oral capecitabine were €12 029 and €5781, respectively; €7338 and €4688 from the hospital perspective; differences in the two perspectives reflect national tariffs and market retail prices and payment for infusion administration; year of euros not reported  Maniadakis, 2007 (37)  Greece; multisite trial with unit costs from the National Health Service  276 patients with advanced CRC randomized to FOLFIRI or FOLFOXIRI  Chemotherapy, radiation therapy, AEs  Total cost of therapy in the FOLFOXIRI was significantly higher than the FOLFIRI group (€18 344 vs €12 201); differences in mean chemotherapy costs, second line drugs, and hospitalizations; estimates reported in 2006 euros  Borget, 2006 (71)  France; multicenter trial with unit costs from National Health System reimbursement, cost accounting systems  294 metastatic patients in trial of HD-LV5-FU2, raltitrexed, LD-LV5-FU2, or weekly infusional 5-FU.  Chemotherapy and toxicity or complications, follow-up and travel until disease progression or death  Total costs were €15 970, €14 888, €13 760, and €10 687 for HD-LV5-FU2, LD-LV5-FU2, weekly 5-FU, and raltitrexed, respectively; estimates in 2001 euros  Cassidy, 2006 (47)  United Kingdom; multinational trial standardized costs applied to service use  1987 patients with Dukes C colon cancer randomized to either oral capecitabine or infusional LV + 5-FU  Chemotherapy, AEs, travel over 6 months  Chemotherapy administration higher for 5-FU/LV vs capecitabine (₤5151 vs ₤419), but mean cost of AEs and travel lower in capecitabine as compared to 5-FU-LV; year not stated  Franks, 2006 (72)  United Kingdom; multicenter trial with unit costs from published sources and single hospital  682 patients in trial of conventional vs laparoscopic-assisted surgery  Hospital, treatment for complications, and outpatient  3-month medical and lost productivity costs for patients treated with laparoscopic vs conventional surgery were ₤6899 vs ₤6631; year not stated  Earle, 2004 (52)  United States; multicenter trial with unit costs from Medicare reimbursement and billing data from a single center  291 CRC patients with metastatic disease refractory to 5-FU randomized to either weekly or every 3-week irinotecan  Hospital, ER, chemotherapy, physician up to 1 year  Major cost drivers were chemotherapy, hospitalization, and chemotherapy administration; every 3-week administration of irinotecan associated with cost–utility ratio of $78 627 per QALY; costs reported in 2001 dollars  Monz, 2003 (49)  Germany; multisite trial, unit costs from the perspective German Social Health Insurance based on fee scale, reports, and Red Book  563 patients with UICC II/III in trial of 5-FU + levamisole vs 5-FU + levamisole + FA following surgery  Chemotherapy and follow-up over 5 years of trial  Cancer-related costs were €4909 and €11 085 for patients without and with progression receiving FU + levamisole and €17 122 and €21 330 for patients without and with progression receiving 5-FU + levamisole + FA; ICER of €51 225 for 5-FU + levamisole + FA vs 5-FU + levamisole; cost reported in 2000 euros  Cunningham, 2002 (51)  United Kingdom; multinational trial with standard costs from formulary and hospital tariffs  385 patients with metastatic disease randomized to 5-FU/FA vs irinotecan and 5-FU/FA  In-study treatment and additional chemotherapy up to 3 years  Mean cumulative costs £3767 vs £4220 for irinotecan and 5-FU/FA vs 5-FU/FA, respectively, with incremental cost per LYG £14 794 reflecting improved survival; year of pounds not stated  Levy-Piedbois, 2000 (50)  France; trial with costs from single hospital in Paris  256 patients in trial of irinotecan vs infusional 5-FU  Chemotherapy, clinic and complications up to 1 year  Total cost of treatment for irinotecan vs infusional 5-FU ($14 135 vs $12 192–$12 344); incorporating survival difference, cost-effectiveness ratios ranged from $9344 to $10 137 per additional year of survival; estimates in 1999 dollars  * All estimates are in US dollars unless otherwise noted. AE = adverse event; DRG = diagnosis-related group; ER = emergency room; FA = folinic acid; FU = fluorouracil; HD = high-dose; ICER = incremental cost-effectiveness ratio; LD = low-dose; LV = leucovorin; LYG = life-year gained; QALY = quality-adjusted life-year; UICC = Union for International Cancer Control. View Large Nonmedical Costs of CRC Care Ten studies estimated patient or caregiver time costs or productivity loss associated with cancer (21,25,28,33,56,60,61,64,69,73) (Table 7). Studies were conducted in the United States, Canada, France, and the United Kingdom. Nine were observational studies and one was conducted among a subset of patients from a clinical trial. As in the studies of medical costs associated with CRC care, there was wide variation in the methods for identifying patients or caregivers, components of time or productivity measured, evaluation periods, and approaches for valuing time or lost productivity. Standard approaches for estimating time costs or productivity loss combine wage rates or other measures of the value of time with measures of time, either as self-reported by patients or caregivers through surveys or else derived empirically from medical care utilization data combined with standard service-specific time estimates or actual sick leave records. There was, however, significant variation observed within this general approach. For example, one study surveyed elderly individuals and asked about the number of hours in a recent week they required informal care and compared estimates for those with and without a self-reported diagnosis of cancer (61). Another study of informal caregiving used registries to identify newly diagnosed cancer patients, who then identified a caregiver who was surveyed about the amount of time they had provided informal care to the patient in the years following cancer diagnosis (56). Table 7. Direct nonmedical costs of colorectal cancer (CRC) care* First author, y (ref.)  Setting  Sample characteristics  Components included  Findings  Hopkins, 2011 (73)  Canada; Canadian Community Health Survey  929 individuals with cancer aged 19–65 in 2005  Household wage loss  Annual mean cancer-related wage loss of $17 729 and national household cancer-related wage loss of $2.95 billion; wages in 2009 Canadian dollars  Van Houtven, 2010 (60)  United States; CanCORS survey about caregiving and wages  1629 caregivers of patients of all stages and ages surveyed in 2005 either 6 months–1 year or 1–2 years following patient diagnosis  Time caregiving and out-of-pocket costs  Mean cumulative time and out-of-pocket costs were $12 618 and $1442 over periods ranging from 6 months to 2 years since patient diagnosis; costs reported in 2005 dollars  Yabroff, 2009 (56)  United States; survey of caregivers of patients from registries  688 caregivers surveyed about 2-year period following patient diagnosis, 2003–2006  Time providing informal care to the patient since diagnosis  Average of 13.7 months and 8.3 hours per day providing informal care after patient diagnosis; time costs ranged from $28 363 to $50 060 with approach for valuing time  Yabroff, 2007 (64); Yabroff, 2005 (33)  United States; SEER–Medicare, multiple data sources for time  213 278 patients with all stages of disease, diagnosed 1973–1999 aged 65 and older 1995–2001  Service counts, estimates of service time, and wage rates  Cancer-related patient time in initial phase of care was 243.5 hours and time cost ranged from $3432 to $5279 depending on approach to value time; in last year of life, 282.3 hours and time cost ranged from $3986 to $6325  Longo, 2006 (25)  Ontario, Canada; outpatient cancer clinics  261 patients of all ages with breast, colorectal, lung, and prostate cancers 2002–2003  Out-of-pocket costs and days missed from work  The mean monthly out-of-pocket and travel costs were $213 and $372, respectively; in the previous 30 days, caregivers and employed patients lost 7 days and 12.6 days from work, respectively, at $101 per day of work missed  Chang, 2004 (21)  United States; MarketScan  Employed patients with a cancer diagnosis code and workplace absence and short-term disability in 1999  Absenteeism, copays, and deductibles  Cancer patients had more absenteeism ($373 vs $101 per month) and short-term disability days ($698 vs $25 per month); employee caregivers had higher absenteeism ($255 vs $161 costs per month) and copays and deductibles ($302 vs $29 per month); year of wages not stated  Selke, 2003 (69)  France; GAZEL cohort, health insurance payments  All patients in 1999  Disability allowance and work days lost in year after diagnosis  Costs to French social security system were €85.9 million in 1999  Hayman, 2001 (61)  United States; 1993 AHEAD Survey  303 individuals receiving cancer treatment, 718 with cancer history, but not in treatment, and 6422 without cancer; all aged 70+ in 1993  Caregiving hours, valued with wage rates  Adjusted weekly hours of informal caregiving were 6.9, 6.8, and 10.0 for individuals without cancer, with a cancer history, and undergoing cancer treatment, respectively; annual cost of informal caregiving estimated to be $3000, $2900, and $4200, respectively; wages in 1998 dollars  Sculpher, 2000 (28)  United Kingdom; multicountry trial with patient and caregiver travel and time  270 patients with advanced disease in a trial of raltitrexed and 5-FU + LV treatment until progression  Travel and time costs during the trial  Total mean time cost per patient higher for 5-FU + LV vs raltitrexed (₤486 vs ₤378), reflecting greater travel and longer treatment times for patients receiving 5-FU + LV; estimates with 1997 prices  First author, y (ref.)  Setting  Sample characteristics  Components included  Findings  Hopkins, 2011 (73)  Canada; Canadian Community Health Survey  929 individuals with cancer aged 19–65 in 2005  Household wage loss  Annual mean cancer-related wage loss of $17 729 and national household cancer-related wage loss of $2.95 billion; wages in 2009 Canadian dollars  Van Houtven, 2010 (60)  United States; CanCORS survey about caregiving and wages  1629 caregivers of patients of all stages and ages surveyed in 2005 either 6 months–1 year or 1–2 years following patient diagnosis  Time caregiving and out-of-pocket costs  Mean cumulative time and out-of-pocket costs were $12 618 and $1442 over periods ranging from 6 months to 2 years since patient diagnosis; costs reported in 2005 dollars  Yabroff, 2009 (56)  United States; survey of caregivers of patients from registries  688 caregivers surveyed about 2-year period following patient diagnosis, 2003–2006  Time providing informal care to the patient since diagnosis  Average of 13.7 months and 8.3 hours per day providing informal care after patient diagnosis; time costs ranged from $28 363 to $50 060 with approach for valuing time  Yabroff, 2007 (64); Yabroff, 2005 (33)  United States; SEER–Medicare, multiple data sources for time  213 278 patients with all stages of disease, diagnosed 1973–1999 aged 65 and older 1995–2001  Service counts, estimates of service time, and wage rates  Cancer-related patient time in initial phase of care was 243.5 hours and time cost ranged from $3432 to $5279 depending on approach to value time; in last year of life, 282.3 hours and time cost ranged from $3986 to $6325  Longo, 2006 (25)  Ontario, Canada; outpatient cancer clinics  261 patients of all ages with breast, colorectal, lung, and prostate cancers 2002–2003  Out-of-pocket costs and days missed from work  The mean monthly out-of-pocket and travel costs were $213 and $372, respectively; in the previous 30 days, caregivers and employed patients lost 7 days and 12.6 days from work, respectively, at $101 per day of work missed  Chang, 2004 (21)  United States; MarketScan  Employed patients with a cancer diagnosis code and workplace absence and short-term disability in 1999  Absenteeism, copays, and deductibles  Cancer patients had more absenteeism ($373 vs $101 per month) and short-term disability days ($698 vs $25 per month); employee caregivers had higher absenteeism ($255 vs $161 costs per month) and copays and deductibles ($302 vs $29 per month); year of wages not stated  Selke, 2003 (69)  France; GAZEL cohort, health insurance payments  All patients in 1999  Disability allowance and work days lost in year after diagnosis  Costs to French social security system were €85.9 million in 1999  Hayman, 2001 (61)  United States; 1993 AHEAD Survey  303 individuals receiving cancer treatment, 718 with cancer history, but not in treatment, and 6422 without cancer; all aged 70+ in 1993  Caregiving hours, valued with wage rates  Adjusted weekly hours of informal caregiving were 6.9, 6.8, and 10.0 for individuals without cancer, with a cancer history, and undergoing cancer treatment, respectively; annual cost of informal caregiving estimated to be $3000, $2900, and $4200, respectively; wages in 1998 dollars  Sculpher, 2000 (28)  United Kingdom; multicountry trial with patient and caregiver travel and time  270 patients with advanced disease in a trial of raltitrexed and 5-FU + LV treatment until progression  Travel and time costs during the trial  Total mean time cost per patient higher for 5-FU + LV vs raltitrexed (₤486 vs ₤378), reflecting greater travel and longer treatment times for patients receiving 5-FU + LV; estimates with 1997 prices  * All estimates in US dollars unless otherwise noted. AHEAD = Asset and Health Dynamics; CanCORS = Cancer Care Outcomes Research and Surveillance Consortium; FU = fluorouracil; GAZEL = GAZ and ELectricité; LV = leucovorin; MarketScan = Coordination of Benefits and Health and Productivity Management; SEER = Surveillance, Epidemiology, and End Results. View Large Discussion In this study, we conducted a systematic review of recently published studies of the economic burden associated with CRC care to assess data, methods, scope, and the extent to which estimates from these studies can be used in “head-to-head” comparisons. As might be expected, the economic cost associated with CRC care within study generally varied by stage(s) of disease at diagnosis, patient age, observation time (eg, 12 months following diagnosis vs lifetime), types of medical services included, and the scope of costs considered. Depending on the study, included costs ranged from single components of medical care only (eg, hospitalizations) to more comprehensive economic measures of resource use that might include patient time, travel for care, and productivity losses associated with cancer and its treatment. Even within country, we found great heterogeneity across studies in the settings, data sources, populations, means of patient identification, types of medical services, and study methods. Each of these study characteristics can significantly influence the estimation of cancer costs. When they vary together across studies, as is typically the case, even cost calculations with seemingly the same objective are difficult to compare. Complicating factors include features of the health-care delivery system, accompanying payer model, and data availability, all of which vary by country. Across countries, published aggregate and patient-level cost estimates vary in so many respects that accurate international comparisons are almost impossible. Our findings suggest that valid cost comparisons must be developed de novo with explicit standardization of patient populations, types of medical services included, measures of cost, and choice of methods, whether the context is within or between health systems or countries. Further, the design of such studies should reflect a detailed understanding of health-system payment and reimbursement policies and their impact on available data (74,75). Despite these challenges, improving our understanding of how best to measure and report the economic burden of cancer is critical because the aggregate economic burden of cancer, including direct medical costs, direct nonmedical costs, and productivity losses, is expected to increase in the future (8,9,76). To improve comparability across studies, we need more detailed reporting of patient characteristics, methods, and cost estimates by patient subgroups associated with the cost of care (eg, age, stage at diagnosis), the setting of care (eg, inpatient hospitalizations), and the type of cancer-related service (eg, chemotherapy) in both newly diagnosed and prevalent samples. Additionally, because variation in cancer prevalence and population sizes across countries limits national comparisons, reporting of per-person estimates by age, health-care setting, and components of care will allow better national comparisons. Expected increases in the burden of cancer highlight the importance of evaluating the transferability and economic consequences of effective care delivery and payment models used in other health-care delivery settings and countries. A key component of this rising cost burden is the growing use of more effective, but dramatically more expensive cancer treatments. Cost-effectiveness analyses of alternative cancer treatment interventions clearly require sound estimates of each intervention’s associated costs, as well as its benefits in terms of survival or health-related quality of life. Moreover, when cost-effectiveness analyses are focused on cancer prevention or screening, the cost of cancer care is still a pivotal input. Specifically, to prevent or delay the onset of a cancer, or to detect it at an earlier stage, is to alter the expected lifetime cost profile of cancer treatment for the individual. Changes in the costs and benefits of CRC treatments also necessarily affect the cost-effectiveness of cancer prevention and screening strategies (77), such that they may become either more or less cost-effective, or even cost-saving. Updating these analyses to reflect changes in CRC costs and benefits may impact policies in countries that use cost-effectiveness to inform formulary policy decisions. Increased standardization of methods to estimate the economic burden of cancer over time, conditional on choice of intervention, can improve the comparability and consistency of information for setting priorities among competing cancer control interventions (76). The majority of studies we reviewed included just one component of the burden of cancer—direct medical care costs. Fewer studies assessed costs associated with patient and caregiver time or productivity losses associated with cancer and its treatment, but findings in those studies suggest such costs can be substantial and important for understanding the societal burden of cancer (21,25,60,61,64,69,73,76). Additionally, patient time costs are a recommended component of cost-effectiveness analysis of prevention, screening, and treatment interventions (78), but are still rarely included in these studies, in part because these data are not routinely collected. However, their exclusion may bias estimates of cost-effectiveness towards interventions that place a greater time burden on patients and their families (79). As with studies of direct medical costs, reporting of per-person estimates by age, health-care setting, and components of care will allow better comparisons across studies. Further, reporting of intermediate estimates (eg, time, days lost from work) will allow comparisons across studies where the “cost” component is based on different wage structures or different assumptions about the value of time for the underlying populations. Studies conducted in countries with comprehensive data describing cancer incidence and survival and employment and population characteristics (ie, Sweden, Norway) have reported lower incomes for individuals diagnosed with cancer and also their spouses (80) and increased use of sick leave among spouses (81), although these studies did not quantify the impact on employment in economic terms. Thus, to strengthen the data available for estimating the nonmedical economic burden of cancer, increased attention should be devoted to linking data on cancer incidence and survival with longitudinal information on labor market participation and earnings and the allocation of time to medical care–related activities and, in parallel, to developing additional sources of information on the nonmedical burden of cancer. These could include targeted enhancements to existing population-based surveys, such as the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement in the United States (82). Developing a more comprehensive picture of the economic burden of cancer for the patient and family could inform decisions in the workplace. In particular, these data can be important for employers interested in minimizing the impact of cancer on patient and caregiver employment outcomes, including presenteeism and workplace productivity, absenteeism, and overall retention. Including other components of the burden of cancer, such as patient time costs, caregiver burden, and productivity losses, will improve our understanding of the societal impact of cancer and may inform further development of employment policies. We observed clearly discernible relationships between the country where a study was performed, study design, and the approaches used for estimating either the prevalence or incidence cost of care. The majority of US studies were observational, whereas the majority of studies in other countries were based on clinical trials focusing on the cost or cost-effectiveness of treatment interventions, presumably to inform coverage decisions by national formularies (ie, NICE) or other purchasers. Other differences in health-care systems, and hence the nature of the data available for cost analyses, influenced the types of studies conducted. For example, the majority of CRC cost studies in the United States were conducted among patients aged 65 and older, using the linked SEER registry–Medicare claims data. By implication, very few studies were conducted in the under-65 population, which leaves an important research gap because cancer care is typically more aggressive in younger compared with older patients within stage at diagnosis (83). In addition, the difference in comorbidity between cancer patients and noncancer controls is greater in the under-65 population compared with the elderly. In the United States, information about health-care use and payments is available primarily from health insurance claims, and the largest population with comprehensive and longitudinal claims and enrollment information currently consists of Medicare enrollees, aged 65 and older. Current efforts to estimate the longitudinal costs of CRC care for patients of all ages in the managed care population and state-based efforts to link population-based cancer registry with multiple public and private claims databases may help address these important data gaps (84–86). The studies based on clinical trials used service frequencies collected as part of the trial, and actual costs or standardized service-specific costs that were then applied to service use, to estimate CRC treatment costs. An important advantage of this microcosting approach is that it allows country-specific and importantly comparable estimates to be generated from multinational trials. Also, cost estimates are based on actual care received, rather than hypothesized treatment pathways or patterns of care derived from treatment guidelines. Yet, cost studies that capture trial-based service use and apply unit cost multipliers to reflect local circumstances may have other limitations (87–89). Microcosting has also been used in some observational studies, particularly in countries where health coverage is applied centrally (thus, no individual billing). However, the care provided in clinical trials does not reflect typical care in community settings, including “induced costs” for some care that would not occur outside the trial setting. There are, however, processes for defining similar populations of patients, standardizing service and procedure definitions, and taking other steps to promote comparability of cost estimates across observational studies (75,90,91). Prior reviews have described methodological limitations with descriptive economic studies (12) as well as cost-effectiveness analyses (92). We observed many of the same limitations here. Patient characteristics that influence care and costs, such as age distribution and stage of disease at diagnosis, were frequently not reported, nor were methods used to estimate costs always clearly stated. Many economic studies based on treatment trials did not report the number of patients providing data for the economic study compared with the underlying treatment trial, or reported a smaller sample in the economic study than in the treatment trial, suggesting the potential for bias in the included sample (ie, not conducted in a truly randomized population). Several studies based on multinational trials did not report the number of patients from the country of interest. Reporting of patient characteristics that influence care and costs is critical for evaluation of the study and any comparisons across studies. We also identified a number of specific methodological concerns in the studies reviewed here, related to sample selection and representativeness, phase of care definitions, and the analysis of cost data over time. Several observational studies used diagnostic or procedure codes from health-care claims to identify patients—an approach that identifies prevalent rather than incident patients, overidentifies individuals without cancer from “rule-out” diagnostic procedures, and underidentifies patients whose cancer care lacks detailed coding or does not indicate receipt of specific procedures or treatments. Additionally, diagnostic codes may reflect metastatic rather than primary tumor sites. Finally, we identified concerns with aspects of the cost data analysis and reporting, including omission of inflation price adjusters and inadequate (or inadequately explained) methods for handling missing, censored, or highly skewed cost data. Standards for conducting and reporting cost-effectiveness analyses have been published (78), but we were not able to identify any published standards for conducting and reporting cost analyses in observational studies. Developing standards for observational studies and encouraging adherence to existing standards for cost-effectiveness analyses will be important for future efforts (1,93,94), particularly with expected increases in targeted therapies that are both more effective and more expensive than current regimens. Importantly, the methodological limitations for specific studies also constrain the comparisons that can be made between studies. We used MEDLINE, one of the largest publications databases devoted to biomedicine and health (ie, more than 5500 journals in 39 languages), to identify studies for inclusion in our review. We then reviewed the reference lists of included studies to identify additional eligible studies. 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J Natl Cancer Inst Monogr . 2013; 46( 1): 124– 130 Published by Oxford University Press 2013.

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Published: Aug 16, 2013

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