Abstract
Background
With recent advances in the treatment of non-small-cell lung cancer (nsclc) and current fiscal constraints within publicly funded health care systems, understanding the real-world economic effect of lung cancer management has become important. The objective of the present study was to determine the costs and resources used in the management of nsclc cohorts in Ontario.
Methods
Patients diagnosed between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry and linked to provincial administrative databases, capturing resources such as hospitalizations, cancer clinic visits, physician services, and systemic therapies or radiotherapy. A cost-of-illness analysis using a bottom-up approach and the GETCOST macro available at ices determined the overall total and mean costs in 2017 Canadian dollars. Resource utilization results were analyzed according to the total number of encounters per resource, the number of patients using each resource, and the number of encounters per patient. A separate cost-and-resource analysis was conducted for radiotherapy.
Results
The 24,729 nsclc patients identified included 4542 with stage iii unresectable disease and 10,103 with stage iv nonsquamous disease. The overall total cost for all nsclc patients was $1.9 billion, with inpatient hospitalizations ($635.2 million), cancer clinic visits ($323.7 million), and physician services ($301.4 million) being the top cost contributors. The mean cost per patient was $76,816. The total cost of radiotherapy was $38.5 million.
Conclusions
Real-world costs for the management of nsclc during the 5-year period examined were substantial, despite the fact that median survival was poor and treatment information was limited.
Keywords: Lung cancer, costs, resource utilization, administrative data, Ontario
INTRODUCTION
Lung cancer is the most commonly diagnosed cancer in Canada, with an estimated 28,600 new cases in 2017; it is also the leading cause of cancer-related death (estimated at 21,000)1.
Non-small-cell lung cancer (nsclc) accounts for 80%–85% of lung cancers2,3. Approximately 50% of patients are diagnosed with stage iv disease4, and those patients have a short average survival1. The introduction of molecular testing, targeted therapies, and immunotherapy is changing the treatment paradigm for advanced nsclc and improving patient survival5–7. For example, durvalumab has been associated with improvements in both progression-free and overall survival in patients with unresectable stage iii disease5,8. In the metastatic setting, improved progression-free or overall survival has been observed when patients who are positive for mutations in EGFR receive targeted therapies9,10.
Previously published Canadian studies examining the overall costs of lung cancer have been based largely on simulation models11–13 or retrospective reviews of patient records14. As access to and use of administrative databases increase, large patient cohorts can be analyzed to accurately determine the real-world costs of cancers15,16. The objective of the present study was to use administrative data to determine the costs and resource utilization associated with the management of all stages of nsclc and of stage iii unresectable and stage iv nonsquamous nsclc cohorts in a real-world setting in Ontario. Ethics approval for the study was obtained from the Research Ethics Board at Sunnybrook Health Sciences Centre.
METHODS
Patients diagnosed with nsclc between 1 April 2010 and 31 March 2015 with disease stage known at diagnosis were identified in the Ontario Cancer Registry. Costing data were obtained up to 31 March 2016 to allow for at least 1 year of follow-up and to 31 March 2017 for resource utilization and survival. The data were analyzed and are presented in three separate cohorts. The main cohort consists of all nsclc patients defined by relevant diagnosis codes from the International Classification of Diseases, revision 10. Because of new therapies that are likely to be introduced soon, 2 subcohorts were specifically analyzed: unresectable stage iii nsclc (defined by excluding all lung-related surgeries) and stage iv nonsquamous nsclc (defined by excluding squamous-related diagnosis codes). Each cohort was linked to provincial administrative databases to capture health system resource use such as inpatient hospitalizations, cancer clinic visits, physician visits, radiotherapy, and systemic therapies. Radiotherapy data in the Cancer Care Ontario (cco) Activity Level Reporting system were not included in the main costing analysis, which used the GETCOST macro; however, a separate analysis using the National Hospital Productivity Improvement Project (nhpip) treatment codes as a proxy for radiotherapy fractions was conducted to estimate radiotherapy use (both curative and palliative). Use of systemic therapy drugs was captured from cco’s New Drug Funding Program (ndfp) and the Ontario Drug Benefit (odb) formularies. Based on defined criteria, newer systemic chemotherapies were accessed in the ndfp formulary, and oral therapies, in the odb formulary. In addition, costs for oral supportive drugs (for example, analgesics, antiemetics) were reported in the odb. Information about cancer clinic visits was collected separately from other outpatient clinic visits. Physician visits (from ohip, the Ontario Health Insurance Plan) comprised visits to general practitioners, medical oncologists, radiation oncologists, and all other specialists. All 3 cohorts had inpatient rehabilitation admissions, given that respiratory or exercise rehabilitation (or both) can often be required before and after lung surgery. Same-day surgical procedures might have included treatment-related insertions and removals of blood access ports and chest tubes.
Descriptive statistics are used for baseline characteristics, costing, and resource utilization. Score on the Charlson comorbidity index17 and Johns Hopkins Aggregated Diagnosis Groups (Baltimore, MD, U.S.A.)18 describe comorbidities present before the nsclc diagnosis. A mean score of 0 indicates no comorbidities. The Aggregated Diagnosis Groups are also assigned to a simplified morbidity category called “predicted Resource Utilization Bands” (Johns Hopkins). The five neighbourhood income quintiles reported are based on a conversion of each individual’s postal code using Statistics Canada’s Postal Code Conversion File.
The cost-of-illness analysis, which calculated the overall total and mean cost per patient in 2017 Canadian dollars, used a macro-based costing methodology called GETCOST that is available at ices19. For total cost, the macro is programmed to determine the costs of short-term episodes (for example, hospital-based encounters) by multiplying the encounter’s resource intensity weight by an annual cost per weighted case. Long-term episode costs (for example, complex continuing care) are calculated by weighted days, and costs of visit-based encounters are determined at utilization (a bottom-up approach). As already mentioned, a separate analysis used the number of nhpip treatment codes as a proxy for radiotherapy fractions. Multiplying the total number of nhpip treatment codes by a unit cost previously published from a Canadian cancer centre ($137.72 in 1996)20 and inflated to 2017 dollars ($202.01) using the Consumer Price Index yielded radiotherapy costs for the 3 cohorts. Resource utilization results consisted of the total number of encounters per resource, the numbers of patients using each resource, and the number of encounters per patient (that is, a “per-treated” analysis).
RESULTS
Table I presents the baseline characteristics of the 3 cohorts: all-stage nsclc (n = 24,729), unresectable stage iii (n = 4542), and stage iv nonsquamous (n = 10,103). The median age in all groups was 70 years, and the sex distribution was approximately equal. Although the mean Charlson and Aggregated Diagnosis Groups scores before the nsclc diagnosis were found to be low, 95% of each cohort had at least moderate resource utilization based on the Resource Utilization Bands. A slightly higher rate of lung cancer was evident in the lowest neighbourhood income quintile, and the mean number of follow-up years after diagnosis was 1.7 for the all-stages nsclc cohort, but only 0.8 in the stage iv nonsquamous cohort. As expected, mean survival (calculated from date of diagnosis to date of death, if known) was poor for all 3 cohorts.
TABLE I.
Baseline characteristics of the study cohorts
| Characteristic | Non-small-cell lung cancer cohort | ||
|---|---|---|---|
|
| |||
| All | Stage III unresectable | Stage IV nonsquamous | |
| Patients (n) | 24,729 | 4,542 | 10,103 |
|
| |||
| Age (years) | |||
| Median | 70 | 70 | 69 |
| IQR | 62–77 | 63–77 | 61–77 |
|
| |||
| Sex [n (%)] | |||
| Women | 12,000 (48.5) | 2,081 (45.8) | 4,976 (49.3) |
| Men | 12,727 (51.5) | 2,460 (54.2) | 5,127 (50.7) |
|
| |||
| Stage at diagnosis [n (%)] | |||
| I | 5,120 (20.7) | NA | NA |
| II | 2,307 (9.3) | ||
| III | 5,143 (20.8) | ||
| IV | 12,159 (49.2) | ||
|
| |||
| Mean score on the CCI | 0.7±1.3 | 1.0±1.5 | 0.9±1.5 |
|
| |||
| Mean ADG score | 8.1±3.7 | 7.9±3.6 | 7.5±3.6 |
|
| |||
| Predicted RUB [n (%)] | |||
| Non-users | 303 (1.2) | 42 (0.9) | 182 (1.8) |
| Healthy users | 223 (0.9) | 40 (0.9) | 131 (1.3) |
| Low utilization | 721 (2.9) | 119 (2.6) | 425 (4.2) |
| Moderate utilization | 8,933 (36.1) | 1,663 (36.6) | 4,215 (41.7) |
| High utilization | 7,793 (31.5) | 1,468 (32.3) | 2,931 (29.0) |
| Very high utilization | 6,756 (27.3) | 1,210 (26.6) | 2,219 (22.0) |
|
| |||
| Income quintile [n (%)] | |||
| 1 (lowest) | 5,683 (23.1) | 1,102 (24.4) | 2,207 (22.0) |
| 2 | 5,367 (21.8) | 989 (21.9) | 2,175 (21.6) |
| 3 | 4,816 (19.6) | 869 (19.2) | 1,985 (19.7) |
| 4 | 4,640 (18.8) | 864 (19.1) | 1,938 (19.3) |
| 5 (highest) | 4,111 (16.7) | 699 (15.5) | 1,749 (17.4) |
|
| |||
| Mean follow-up (years) | 1.7 | 1.6 | 0.8 |
|
| |||
| Deaths [n (%)] | 18,840 (76.2) | 3,746 (82.5) | 9,538 (94.4) |
|
| |||
| Overall survival (years) | |||
| Median | 1.0 | 1.1 | 0.4 |
| IQR | 0.3–3.7 | 0.5–2.6 | 0.2–1.0 |
IQR = interquartile range; CCI = Charlson comorbidity index; ADG = Johns Hopkins (Baltimore, MD, U.S.A.) Aggregated Diagnosis Group system; RUB = Johns Hopkins Resource Utilization Band.
Table II shows the breakdown of costs for all years for each of the 3 cohorts. The overall total cost for all-stage nsclc was $1.9 billion; the stage iii unresectable and stage iv nonsquamous cohorts respectively accounted for 20.9% and 36.3% of that total. The overall mean cost per nsclc patient was $76,816 ± $67,789, but it was highest for unresectable stage iii patients at $87,393 ± $67,304. Inpatient hospitalizations, cancer clinic visits, and physician visits were the top three cost categories for all 3 cohorts. Oral medications listed on the odb formulary represented about 7% of the overall total cost for each of the 3 cohorts. Chemotherapies listed on the ndfp formulary accounted for only 3% of the overall total cost for the all-stage nsclc and stage iii unresectable cohorts, but were 6% for the stage iv nonsquamous cohort. Outpatient clinic visits and home care were high cost contributors. Because the overall total cost excluded radiotherapy costs, a separate analysis used nhpip treatment codes as a proxy for the number of fractions and applied a unit cost per fraction. For the all-stage nsclc cohort, the total radiotherapy cost was $38.5 million. The unresectable stage iii cohort had the highest mean cost, at $3,282 ± $3,319.
TABLE II.
Cost results
| Cost type | Summary measure | Cost, 2017 Canadian dollars, all years | ||
|---|---|---|---|---|
|
| ||||
| All NSCLC (n=24,729) | Stage III unresectable (n=4,542) | Stage IV nonsquamous (n=10,103) | ||
| Overall totala | Total | 1,899,571,969 | 396,939,652 | 689,980,195 |
| Mean per patient | 76,816±67,789 | 87,393±67,304 | 68,295±58,026 | |
|
| ||||
| Cancer clinic visits | Total | 323,705,991 | 107,512,095 | 116,622,466 |
| Mean per patient | 13,090±18,855 | 23,671±23,775 | 11,543±17,749 | |
|
| ||||
| Chemotherapy (NDFP) | Total | 61,505,575 | 10,770,008 | 41,604,143 |
| Mean per patient | 2,487±11,130 | 2,371±10,673 | 4,118±14,235 | |
|
| ||||
| Complex continuing care | Total | 67,325,154 | 12,533,873 | 28,597,180 |
| Mean per patient | 2,723±15,352 | 2,760±14,091 | 2,831±12,803 | |
|
| ||||
| Emergency department visits | Total | 41,248,095 | 8,371,551 | 14,818,783 |
| Mean per patient | 1,668±1,793 | 1,843±1,903 | 1,467±1,329 | |
|
| ||||
| Homecare services | Total | 102,209,907 | 21,049,530 | 46,081,212 |
| Mean per patient | 4,133±7,937 | 4,634±8,552 | 4,561±7,834 | |
|
| ||||
| Inpatient admissions | Total | 635,178,635 | 108,447,485 | 230,972,458 |
| Mean per patient | 25,686±36,641 | 23,877±33,863 | 22,862±24,699 | |
|
| ||||
| Long-term care admissions | Total | 27,531,680 | 4,797,990 | 3,768,451 |
| Mean per patient | 1,113±10,264 | 1,056±9,601 | 373±5,049 | |
|
| ||||
| Mental health admissions | Total | 4,631,966 | 976,528 | 382,312 |
| Mean per patient | 187±4,783 | 215±6,854 | 38±1,674 | |
|
| ||||
| Oral medications (ODB) | Total | 137,147,742 | 25,164,723 | 46,214,247 |
| Mean per patient | 5,546±12,483 | 5,540±11,683 | 4,574±11,830 | |
|
| ||||
| Outpatient clinic visits | Total | 123,842,902 | 25,683,802 | 42,354,018 |
| Mean per patient | 5,008±4,799 | 5,655±5,110 | 4,192±4,327 | |
|
| ||||
| Physician visits (OHIP) | Total | 301,438,705 | 56,890,288 | 103,193,961 |
| Mean per patient | 12,190±9,090 | 12,525±8,950 | 10,214±8,123 | |
|
| ||||
| Radiotherapy costs | Total | 38,458,866 | 14,907,328 | 12,835,311 |
| Mean per patient | 1,555±2,368 | 3,282±3,319 | 1,270±1,721 | |
|
| ||||
| Inpatient rehabilitation admissions | Total | 19,901,416 | 3,563,132 | 5,559,027 |
| Mean per patient | 805±4,623 | 784±4,543 | 550±3,860 | |
|
| ||||
| Same-day surgery admissions | Total | 27,341,937 | 6,685,664 | 5,384,093 |
| Mean per patient | 1,106±1,700 | 1,472±1,762 | 533±1,003 | |
Excludes radiotherapy costs because different methods were used.
NSCLC = non-small-cell lung cancer; NDFP = New Drug Funding Program; ODB = Ontario Drug Benefit; OHIP = Ontario Health Insurance Plan.
Four resource types (capitation, dialysis, laboratory, and non-physician costs) were not included in the results because they accounted for less than 2% of the overall cost.
In Table III, factors that were found to be resource-intensive were physician visits (general practitioners, medical or radiation oncologists), with minor differences between the stage iii and stage iv cohorts. Inpatient hospitalizations averaged only 2 per patient, at an estimated mean cost of $25,686 ± $36,641 for all-stage nsclc patients. Cancer clinic visits occurred most frequently, at 30.1, for patients with unresectable stage III disease. The stage iv nonsquamous and all-stages nsclc cohorts averaged 16.4 visits and 19.8 visits per patient respectively. Each patient in the all-stages nsclc cohort had an average of 121 claims for oral medications from the odb formulary. Patients in the stage iv nonsquamous cohort had half that number of claims (n = 63). In the stage iv nonsquamous cohort, 293 patients received targeted therapies (afatinib, erlotinib, gefitinib) as first-line treatment and were therefore assumed to be positive for EGFR mutation. The mean number of ndfp-funded chemotherapy drugs per patient was 8 for all 3 cohorts, and the mean number of nhpip treatment codes used for radiotherapy was highest (16.3) for the patients with unresectable stage iii disease.
TABLE III.
Resource results
| Resource type | All NSCLC (n=24,729) | Stage III unresectable (n=4,542) | Stage IV nonsquamous (n=10,103) | ||||||
|---|---|---|---|---|---|---|---|---|---|
|
|
|
|
|||||||
| Encounters (all years) | Pts (n) | Encounters per pta (n) | Encounters (all years) | Pts (n) | Encounters per pta (n) | Encounters (all years) | Pts (n) | Encounters per pta (n) | |
| Cancer clinic visits | 352,226 | 17,816 | 19.8 | 115,373 | 3,830 | 30.1 | 125,053 | 7,612 | 16.4 |
|
| |||||||||
| Chemotherapies (NDFP) | 55,740 | 6,607 | 8.4 | 9,978 | 1,311 | 7.6 | 27,804 | 3,207 | 8.7 |
|
| |||||||||
| Complex continuing care | 6,996 | 3,541 | 2.0 | 1,261 | 611 | 2.1 | 3,382 | 1,843 | 1.8 |
|
| |||||||||
| Emergency department visits | 88,663 | 21,899 | 4.0 | 17,846 | 4,112 | 4.3 | 29,398 | 9,024 | 3.3 |
|
| |||||||||
| Homecare services | 1,101,176 | 18,319 | 60.1 | 226,110 | 3,534 | 64.0 | 463,383 | 8,127 | 57.0 |
|
| |||||||||
| Inpatient admissions | 53,542 | 22,325 | 2.4 | 9,738 | 3,922 | 2.5 | 19,900 | 9,064 | 2.2 |
|
| |||||||||
| Long-term care admissions | 5,331 | 774 | 6.9 | 926 | 139 | 6.7 | 857 | 185 | 4.6 |
|
| |||||||||
| Mental health admissions | 215 | 131 | 1.6 | 36 | 22 | 1.6 | 26 | 20 | 1.3 |
|
| |||||||||
| Oral medications (ODB) | 2,707,976 | 22,327 | 121.3 | 492,571 | 4,215 | 116.9 | 545,737 | 8,714* | 62.6 |
|
| |||||||||
| Outpatient clinic visits | 343,659 | 24,158 | 14.2 | 71,080 | 4,448 | 16.0 | 116,401 | 9,793 | 11.9 |
|
| |||||||||
| Primary care physician visits (OHIP) | 1,379,774 | 24,483 | 56.4 | 262,578 | 4,490 | 58.5 | 494,060 | 9,987 | 49.5 |
|
| |||||||||
| Other specialist physician visits (OHIP) | 3,417,541 | 24,713 | 138.3 | 638,180 | 4,541 | 140.5 | 1,074,628 | 10,091 | 106.5 |
|
| |||||||||
| Medical oncologist visits (OHIP) | 294,100 | 14,034 | 21.0 | 70,716 | 3,067 | 23.1 | 143,987 | 6,187 | 23.3 |
|
| |||||||||
| Radiation oncologist visits (OHIP) | 160,840 | 18,457 | 8.7 | 44,248 | 4,124 | 10.7 | 59,726 | 7,985 | 7.5 |
|
| |||||||||
| Radiotherapy encounters (NHPIP codes) | 190,381 | 24,729 | 7.7 | 73,795 | 4,542 | 16.3 | 63,538 | 10,103 | 6.3 |
|
| |||||||||
| Inpatient rehabilitation admissions | 1,125 | 963 | 1.2 | 190 | 169 | 1.1 | 298 | 272 | 1.1 |
|
| |||||||||
| Same-day surgery admissions | 22,725 | 12,407 | 1.8 | 5,081 | 2,917 | 1.7 | 4,657 | 3,426 | 1.4 |
The encounters for all years divided by the patients who used the resource.
NSCLC = non-small-cell lung cancer; Pt[s] = patient[s]; NDFP = New Drug Funding Program; ODB = Ontario Drug Benefit; OHIP = Ontario Health Insurance Plan; NHPIP = National Hospital Productivity Improvement Program.
DISCUSSION AND CONCLUSIONS
This cost analysis of an all-stage nsclc cohort found that, in a 5-year period, the total cost of care was $1.9 billion, at a mean cost of $76,816 ± $67,789 per patient. The mean cost was higher for the stage iii unresectable cohort ($87,393 ± $67,304) than for the stage iv nonsquamous cohort ($68,295 ± $58,026), possibly reflecting the longer survival of those patients. Another Canadian study using administrative data reported that the mean 5-year net cost per patient for lung cancer was approximately $30,000 (2009 Canadian dollars) or $34,132 in 2017 dollars16. However, unlike our study, the latter study used a case–control design to ensure that the costs incurred were attributable to lung cancer. Our resource utilization results were similar for all 3 cohorts, with the exception of cancer clinic visits and oral medications (odb), for which utilization was lower in the stage iv nonsquamous cohort.
The strengths of our study include the large cohort size, known stage distributiona, and representation of all adults diagnosed with nsclc living in both rural and urban areas. One limitation was whether the reported costs and resources were attributable to nsclc, thus possibly resulting in an overestimation, given that the resources and costs could not be allocated to a specific diagnosis (that is, lung cancer). On the other hand, because the GETCOST macro from ices does not calculate Activity Level Reporting costs, systemic therapy costs have been underestimated. A separate analysis to estimate Activity Level Reporting radiotherapy costs was conducted, however. Another limitation is the 31 March 2016 cut-off date for the costing analysis, because the use of new drugs (immuno-oncology and targeted therapy agents) would not be captured in this cost-of-illness study.
In conclusion, although the 3 cohorts all experienced poor survival, total management costs were large. The uptake of new and effective systemic therapies will result in new practice patterns and affect both resource utilization and costs.
ACKNOWLEDGMENTS
The Ontario Institute for Cancer Research (oicr) is funded by the Government of Ontario through the Ministry of Economic Development, Job Creation and Trade. The Canadian Centre for Applied Research in Cancer Control (arcc) receives core funding from the Canadian Cancer Society (grant no. 2015-703549). Both oicr and arcc are proud to support the publication of this costing series.
This study was funded by an unrestricted research grant from AstraZeneca Canada Inc. The study made use of de-identified data from the ices Data Repository, which is managed by ices with support from its funders and partners: Canada’s Strategy for Patient-Oriented Research (spor), the Ontario spor Support Unit, the Canadian Institutes of Health Research, and the Government of Ontario. The opinions, results, and conclusions reported here are those of the authors. No endorsement by ices or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (cihi). However, the analyses, conclusions, opinions, and statements expressed herein are those of the authors and not necessarily those of cihi. Parts of this material are based on data and information provided by cco. The opinions, results, views, and conclusions reported in this paper are those of the authors and do not necessarily reflect those of cco. No endorsement by cco is intended or should be inferred. This work was presented as a poster at ispor Europe 2018; Barcelona, Spain; 10–14 November 2018.
Footnotes
The Canadian Partnership Against Cancer’s National Staging Initiative has resulted in the consistent and reliable collection of staging information by 9 provinces (including Ontario) for Canadians diagnosed with breast, colorectal, lung, and prostate cancers.
CONFLICT OF INTEREST DISCLOSURES
We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: SJS and SH declare consultancies through the hope Research Centre, a group that consults to the pharmaceutical industry; MH and RW are employees of AstraZeneca Canada; WKE reports personal fees from AstraZeneca during the conduct of the study.
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