|
Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis |
Suleiman S, Rex D K, Sonnenberg A |
|
|
Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Three strategies for the prevention of colorectal cancer (CRC) were examined:
colonoscopy (COL) once every 10 years or, in case of adenomatous polyps, every 3 years until polyps were no longer found;
chemoprevention (CHE) with 325 mg/day aspirin; and
a combination of the first and second strategies (i.e. COL every 10 or 3 years plus 325 mg/day aspirin).
Type of intervention Diagnosis and primary prevention.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised individuals aged 50 years.
Setting The setting was primary and secondary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were derived from studies published between 1982 and 2001. Some resources used were derived from studies published from 1988 to 2000. The price year could have been 2000.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of completed studies.
Modelling A published decision model was used to examine the lifetime costs and benefits of the four alternative strategies in a hypothetical cohort of 100,000 individuals aged 50 years of age, who were followed until death. The model was based on a Markov process. The cycle length was one year. In the COL branch, all patients started with a COL at age 50 and moved across four possible health states. These were a state after a negative colonoscopy without polyps, a state after COL plus polypectomy, a state after developing CRC, and death from CRC or other causes. In the aspirin branch, all patients started on a daily dose of aspirin and moved among three different states. These were remain disease-free on aspirin prophylaxis, develop a CRC, or die from CRC or other causes.
Outcomes assessed in the review The outcomes estimated from the literature were:
surveillance intervals for COL and after polypectomy;
the efficacy of COL in preventing CRC;
the efficacy of aspirin in preventing CRC;
the efficacy of COL plus aspirin;
the annual incidence rate of adenomas;
the bleeding rate of COL;
the bleeding rate of polypectomy;
the perforation rate of COL;
the perforation rate of polypectomy;
the perforation rate of sigmoidoscopy; and
mortality from CRC.
Study designs and other criteria for inclusion in the review It appears that the authors have not carried out a systematic review of the literature to identify relevant primary studies. Limited information on the design of the studies was provided. The authors stated that the transition probabilities used were the same as those in prior models of CRC. Some data came from the Surveillance, Epidemiology, and End Results Program, while other data came from the annual age-specific death rate of the US population.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Approximately 12 primary studies provided evidence.
Methods of combining primary studies When different values were available from the literature, the authors chose intermediate values.
Investigation of differences between primary studies Results of the review The surveillance interval was 10 years for COL and 3 years after polypectomy (range: 1 - 5).
The efficacy of COL in preventing CRC was 75% (range: 50 - 75).
The efficacy of aspirin in preventing CRC was 50% (range: 25 - 75).
The efficacy of Col plus aspirin was 87.5% (range: 50 - 100).
The incidence rate of adenomas per year was 1%.
The bleeding rate of colonoscopy was 0.15%.
The bleeding rate of polypectomy was 2.00%.
The perforation rate of COL was 0.20%.
The perforation rate of polypectomy was 0.38%.
The perforation rate of sigmoidoscopy was 0.011%.
The mortality from CRC was 40%.
Measure of benefits used in the economic analysis The summary benefit measure used was the number of expected life-years associated with each strategy. The expected survival was estimated using a modelling approach and an annual discount rate of 3% was applied. Other model outputs included the number of CRC cases prevented and the proportion of cases prevented of the total number of CRC cases.
Direct costs An annual discount rate of 3% was applied as the lifetime costs were estimated. The unit costs were presented separately from the quantities of resources used for only some cost items. The health services included in the economic evaluation were aspirin prevention, aspirin prevention and management of gastrointestinal side effects, COL, polypectomy, bleeding, perforation and medical care for incurable CRC. The latter (medical care) covered expenses for diagnosis, surgery, radiation and chemotherapy. The cost/resource boundary of the third-party payer was used. The costs were estimated from several sources, including published studies and Medicare reimbursement rates. Some costs and resource use data were derived from studies published between 1988 and 2000. Other resource use data were probably based on authors' assumptions (e.g. patterns of diagnostic tests). The price year appears to have been 2000.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were not included in the economic evaluation.
Sensitivity analysis Some two-way sensitivity analyses were carried out to examine the robustness of the base-case cost-effectiveness ratios to variations in model inputs. The pairs of model inputs investigated were the cost of CHE and preventive efficacy of both COL and CHE, and the efficacy of COL and efficacy of CHE. The ranges of values used were often derived from published data.
Estimated benefits used in the economic analysis In the cohort of 100,000 persons, the estimated number of cases of CRC prevented was 0 with no intervention, 4,428 with COL, 2,952 with CHE, and 5,166 with a combination of COL and CHE.
The estimated proportion of cases prevented over the total number of CRC cases was 0% with no intervention, 75% with COL, 50% with CHE, and 87.5% with a combination of COL and CHE.
The estimated life-years saved were 0 with no intervention, 7,951 with COL, 5,301 with CHE, and 9,277 with a combination of COL and CHE.
Cost results In the cohort of 100,000 persons, the estimated costs were $136,452,922 with no intervention, $223,780,829 with COL, $386,920,810 with CHE, and $525,418,563 with a combination of COL and CHE.
Synthesis of costs and benefits An incremental cost-effectiveness ratio (ICER; i.e. the cost per additional life-year saved) was calculated to combine the costs and benefits of the alternative strategies. Average cost-effectiveness ratios were also calculated.
The average cost per life-year saved was $28,143 with COL, $72,990 with CHE, and $56,638 with a combination of COL and CHE.
The ICER over no intervention was $10,983 with COL, $47,249 with CHE, and $41,929 with a combination of COL and CHE. The ICER with a combination of COL and CHE was $227,607 over COL and $34,836 over CHE. The incremental analysis showed that CHE was dominated by COL, which was both more effective and less costly.
The sensitivity analysis showed that under baseline conditions, the cost of CHE needed to fall below $70 to become more cost-effective than COL. Even under the assumption of highly efficacious (75%) CHE and a comparatively inefficacious (50%) COL, the threshold was only $150 (actual cost for CHE $172).
When using plausible ranges of values for the efficacy of CHE and COL, the ICER of CHE over COL fell into the $100,000 to $200,000 range.
Authors' conclusions Colonoscopy (COL) once every 10 years saved more lives at lower overall costs than daily aspirin. The high cost of chemoprevention (CHE) and its relatively low efficacy rendered COL the more cost-effective option to reduce morbidity and mortality related to colorectal cancer (CRC). CHE used in addition to COL provided a viable strategy to save more lives than through COL alone, although this benefit was associated with a relatively high cost per life-year saved.
CRD COMMENTARY - Selection of comparators The selection of the comparators was appropriate given the objective of the study. Other diagnostic options for the detection of CRC were not considered because COL was considered the most cost-effective. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence came from published studies. It was not stated whether a systematic review of the literature had been undertaken and the primary studies appear to have been identified selectively. Limited information on the design of the primary studies was reported. The methods used to extract and combine the data were not described clearly, although intermediate estimates were presumably selected when multiple data were available. Key model inputs were varied in the sensitivity analysis.
Validity of estimate of measure of benefit The use of survival as a summary benefit measure was appropriate since this was the most relevant dimension of health affected by the interventions examined in the study. The impact of the preventive strategies on quality of life was not investigated, which would have been interesting given the frequency of side effects of CHE. Discounting was applied, as US guidelines recommend.
Validity of estimate of costs The cost analysis was consistent with the perspective explicitly adopted in the study. A detailed breakdown of the cost items was not provided, as some costs (i.e. medical care for incurable CRC) were presented as macro-categories. The source of the data was reported. Resource use was partially derived from authors' assumptions on the care patterns that were modelled in the decision analysis. The source of the data was given for all items. The price year was reported, although not explicitly, which enhances the possibility of conducting reflation exercises in other settings. The cost estimates were specific to the study setting and only the cost of CHE was varied in the sensitivity analysis.
Other issues The authors did not compare their findings with those from other studies, although they presented published findings on the use of aspirin for the prevention of cardiovascular diseases. The issue of the generalisability of the study results to other settings was not addressed. In addition, limited sensitivity analyses were carried out. In general, the external validity of the study was low.
Implications of the study The study results supported the use of COL to prevent CRC in patients in the general population. In patients already taking aspirin to prevent cardiovascular disease, COL improved the overall cost-effectiveness of the preventive strategy.
Bibliographic details Suleiman S, Rex D K, Sonnenberg A. Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis. Gastroenterology 2002; 122(1): 78-84 Other publications of related interest Greenberg ER, Baron JA, Freeman DH Jr, et al. Reduced risk of large bowel adenomas among aspirin users. Journal of the National Cancer Institute 1993;85:912-6.
Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. New England Journal of Medicine 1993;329:1977-81.
Muller A D, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy: a case control study of 32,702 veterans. Annals of Internal Medicine 1995;123:904-10.
Comment: Gastroenterology 2002;122:230-3.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Anti-Inflammatory Agents, Non-Steroidal /economics /therapeutic use; Aspirin /economics /therapeutic use; Colonoscopy; Colorectal Neoplasms /drug therapy /economics /prevention & Cost-Benefit Analysis; Humans; Markov Chains; Middle Aged; control AccessionNumber 22002000194 Date bibliographic record published 31/10/2005 Date abstract record published 31/10/2005 |
|
|
|