Cost effectiveness analysis of intensive versus conventional follow up after curative resection for colorectal cancer
http://www.100md.com
《英国医生杂志》
1 Department of Surgery, Christie Hospital NHS Trust, Withington, Manchester M20 4BX, 2 Department of Economics, University of Nottingham, Nottingham NG7 2RD
Correspondence to: A G Renehan arenehan@picr.man.ac.uk
Abstract
More than 35 000 new cases of colorectal cancer occur in the United Kingdom each year, representing a major disease burden on health services.1 2 At initial presentation, around two thirds of patients undergo resection with curative intent, and most enter some type of long term follow up.3 The rationale behind this is threefold: psychological support, facilitation of audit, and the early detection and treatment of recurrent disease, with potential improvement in survival.4 The merits of early detection and treatment of recurrent disease have been vigorously debated. Recently, the present authors and a Cochrane review group independently reported two meta-analyses of all randomised trials of follow up strategies for patients treated for colorectal cancer and showed a significant improvement in all cause mortality in patients followed intensively.5 6 A further randomised trial has since been published supporting these findings.7 These data are the first direct evidence that intensive follow up improves survival.
Against the emerging evidence of the effectiveness of intensive follow up, follow up practice varies widely worldwide and, among these many different protocols, the costs to health services are considerable.8-10 We compared the cost effectiveness of intensive follow up with conventional follow up in patients treated for colorectal cancer.
Methods
Cost effectiveness
The figure shows the Forest plot for all cause mortality with absolute reductions in mortality, together with the calculated life years lost and gained for each patient for each study and associated incremental cost effectiveness ratios. For the five trial model, the lost and gained calculations favoured intensive follow up by 0.73 life years gained for each patient, increasing to 0.82 life years gained for each patient for the four trial model, consistent with the observations from our previous meta-analysis.5 In the five trial model, the adjusted net (extra) cost for each patient was ￡2479 and for each life year gained was ￡3402, substantially lower than the current NHS threshold of cost acceptability. The corresponding values for the four trial model were ￡2529 and ￡3077, suggesting that targeted surveillance is more cost effective.
Forest plot of randomised trials. Pooled analysis with summary estimates (Mantel-Haenszel fixed effects method) are for all cause mortality (adapted from Renehan et al 20025). Data are categorised into extramural and intramural detection groups. Positive difference indicates time gained (improved survival). See bmj.com for calculation of estimates. Incremental cost effectiveness ratio=/
Changes in benefit and discount rates and in false positive test rates made little impact on the incremental cost effectiveness ratios in both models (data for four trial model not shown; table 2). Changing the distributions of deaths yielded similar incremental cost effectiveness ratios, suggesting that the assumptions within the primary models were robust. Worst case scenario analyses showed that substituting with maximum surveillance costs produced greater increases in incremental cost effectiveness ratios compared with substituting with maximum treatment costs, indicating that surveillance cost is the most important determinant of cost effectiveness. All incremental cost effectiveness ratios for maximum cost estimates fell within the NHS cost acceptability threshold. The incremental cost threshold was near ninefold for both the five trial (￡30 620) and four trial (￡27 695) models. For both models the threshold of cost effectiveness was an absolute reduction in mortality of 3%.
Table 2 Sensitivity analyses
Discussion
Office of National Statistics. Cancer statistics: registrations, series MB1 for 1999. www.statistics.gov.uk (accessed 18 Mar 2003).
Information and Statistics Division (ISD) Scotland. Cancer: facts and figures for 1999. www.show.scot.nhs.uk/isd (accessed 18 Mar 2003).
Kievit J, Bruinvels DJ. Detection of recurrence after surgery for colorectal cancer. Eur J Cancer 1995;31a: 1222-5.
Scholefield JH, Steele RJ. Guidelines for follow up after resection of colorectal cancer. Gut 2002;51(Suppl 5): V3-5.
Renehan AG, Egger M, Saunders MP, O'Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002;324: 813.
Jeffrey GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. In: Cochrane Library, Issue 1. Oxford: Update Software, 2002.
Secco GB, Fardelli R, Gianquinto D, Bonfante P, Baldi E, Ravera G, et al. Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial. Eur J Surg Oncol 2002;28: 418-23.
Mella J, Datta SN, Biffin A, Radcliffe AG, Steele RJ, Stamatakis JD. Surgeons' follow-up practice after resection of colorectal cancer. Ann R Coll Surg Engl 1997;79: 206-9.
Bruinvels DJ, Stiggelbout AM, Klaassen MP, Kievit J, Dik J, Habbema F, et al. Follow-up after colorectal cancer: current practice in the Netherlands. Eur J Surg 1995;161: 827-31.
Virgo KS, Wade TP, Longo WE, Coplin MA, Vernava AM, Johnson FE. Surveillance after curative colon cancer resection: practice patterns of surgical subspecialists. Ann Surg Oncol 1995;2: 472-82.
Makela JT, Laitinen SO, Kairaluoma MI. Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial. Arch Surg 1995;130: 1062-7.
Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg KG. Follow-up after curative surgery for colorectal carcinoma: randomized comparison with no follow-up. Dis Colon Rectum 1995;38: 619-26.
Schoemaker D, Black R, Giles L, Toouli J. Yearly colonoscopy, liver CT, and chest radiography do not influence 5-year survival of colorectal cancer patients. Gastroenterology 1998;114: 7-14.
Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 1998;41: 1127-33.
Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomized study of follow-up after radical surgery for colorectal cancer. Br J Surg 1997;84: 666-9.
Department of Health NHS reference costs. www.doh.gov.uk/nhsexec/refcosts.htm (accessed 18 Mar 2003).
Gilbert RE, Augood C, Gupta R, Ades AE, Logan S, Sculpher M, et al. Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies. BMJ 2001;323: 423-5.
Multicentre aneurysm screening study (MASS): cost effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from randomised controlled trial. BMJ 2002;325: 1135.
UK Flexible Sigmoidoscopy Screening Trial Investigators. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002;359: 1291-300.
Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348: 883-90.
Kievit J. Follow-up of patients with colorectal cancer: numbers needed to test and treat. Eur J Cancer 2002;38: 986-99.
Fusai G, Davidson BR. Management of colorectal liver metastases. Colorectal Dis 2003;5: 2-23.
Wanebo HJ, Antoniuk P, Koness RJ, Levy A, Vezeridis M, Cohen SI, et al. Pelvic resection of recurrent rectal cancer: technical considerations and outcomes. Dis Colon Rectum 1999;42: 1438-48.
Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
UK Government Actuary's Department. Life tables. www.gad.uk/policy_and_stats/life_tables.htm (accessed 18 Mar 2003).
Raftery J. NICE: faster access to modern treatments? Analysis of guidance on health technologies. BMJ 2001;323: 1300-3.
Torgerson D, Raftery J. Economics notes: discounting. BMJ 1999;319: 914-5.
Virgo KS, Vernava AM, Longo WE, McKirgan LW, Johnson FE. Cost of patient follow-up after potentially curative colorectal cancer treatment. JAMA 1995;273: 1837-41.
Norum J, Olsen JA. A cost-effectiveness approach to the Norwegian follow-up programme in colorectal cancer. Ann Oncol 1997;8: 1081-7.
Edelman MJ, Meyers FJ, Siegel D. The utility of follow-up testing after curative cancer therapy: a critical review and economic analysis. J Gen Intern Med 1997;12: 318-31.
Graham RA, Wang S, Catalano PJ, Haller DG. Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg 1998;228: 59-63.
Beart RW Jr. Follow-up: does it work? Can we afford it? Surg Oncol Clin N Am 2000;9: 827-34.
Van den Hout WB, van den Brink M, Stiggelbout AM, van de Velde CJH, Kievit J. Cost-effectiveness analysis of colorectal cancer treatments. Eur J Cancer 2002;38: 953-63.
Stiggelbout AM, de Haes JC, Vree R, van de Velde CJ, Bruijninckx CM, van Groningen K, et al. Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up. Br J Cancer 1997;75: 914-20.
Renehan AG, Egger M, Saunders MP, Whynes D, O'Dwyer ST. Intensive follow-up after colorectal cancer. Recent successes and future challenges. In: Cunningham D, Topham C, Miles A, eds. The effective management of colorectal cancer, 4th ed. London: Aesculapius Medical Press, 2004.
Wang H, Karesen R, Hervik A, Thoresen SO. Mammography screening in Norway: results from the first screening round in four counties and cost-effectiveness of a modeled nationwide screening. Cancer Causes Control 2001;12: 39-45.
Whynes DK, Neilson AR, Walker AR, Hardcastle JD. Faecal occult blood screening for colorectal cancer: is it cost-effective? Health Econ 1998;7: 21-9.
Kjeldsen BJ, Thorsen H, Whalley D, Kronborg O. Influence of follow-up on health-related quality of life after radical surgery for colorectal cancer. Scand J Gastroenterol 1999;34: 509-15.
National Institute for Clinical Excellence. A review of the evidence for the clinical and cost-effectiveness of ironotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. www.nice.org.uk (accessed 18 Mar 2003).
Frew E, Wolstenholme JL, Atkin W, Whynes DK. Estimating time and travel costs incurred in clinic based screening: flexible sigmoidoscopy screening for colorectal cancer. J Med Screen 1999;6: 119-23.(Andrew G Renehan, senior )
Correspondence to: A G Renehan arenehan@picr.man.ac.uk
Abstract
More than 35 000 new cases of colorectal cancer occur in the United Kingdom each year, representing a major disease burden on health services.1 2 At initial presentation, around two thirds of patients undergo resection with curative intent, and most enter some type of long term follow up.3 The rationale behind this is threefold: psychological support, facilitation of audit, and the early detection and treatment of recurrent disease, with potential improvement in survival.4 The merits of early detection and treatment of recurrent disease have been vigorously debated. Recently, the present authors and a Cochrane review group independently reported two meta-analyses of all randomised trials of follow up strategies for patients treated for colorectal cancer and showed a significant improvement in all cause mortality in patients followed intensively.5 6 A further randomised trial has since been published supporting these findings.7 These data are the first direct evidence that intensive follow up improves survival.
Against the emerging evidence of the effectiveness of intensive follow up, follow up practice varies widely worldwide and, among these many different protocols, the costs to health services are considerable.8-10 We compared the cost effectiveness of intensive follow up with conventional follow up in patients treated for colorectal cancer.
Methods
Cost effectiveness
The figure shows the Forest plot for all cause mortality with absolute reductions in mortality, together with the calculated life years lost and gained for each patient for each study and associated incremental cost effectiveness ratios. For the five trial model, the lost and gained calculations favoured intensive follow up by 0.73 life years gained for each patient, increasing to 0.82 life years gained for each patient for the four trial model, consistent with the observations from our previous meta-analysis.5 In the five trial model, the adjusted net (extra) cost for each patient was ￡2479 and for each life year gained was ￡3402, substantially lower than the current NHS threshold of cost acceptability. The corresponding values for the four trial model were ￡2529 and ￡3077, suggesting that targeted surveillance is more cost effective.
Forest plot of randomised trials. Pooled analysis with summary estimates (Mantel-Haenszel fixed effects method) are for all cause mortality (adapted from Renehan et al 20025). Data are categorised into extramural and intramural detection groups. Positive difference indicates time gained (improved survival). See bmj.com for calculation of estimates. Incremental cost effectiveness ratio=/
Changes in benefit and discount rates and in false positive test rates made little impact on the incremental cost effectiveness ratios in both models (data for four trial model not shown; table 2). Changing the distributions of deaths yielded similar incremental cost effectiveness ratios, suggesting that the assumptions within the primary models were robust. Worst case scenario analyses showed that substituting with maximum surveillance costs produced greater increases in incremental cost effectiveness ratios compared with substituting with maximum treatment costs, indicating that surveillance cost is the most important determinant of cost effectiveness. All incremental cost effectiveness ratios for maximum cost estimates fell within the NHS cost acceptability threshold. The incremental cost threshold was near ninefold for both the five trial (￡30 620) and four trial (￡27 695) models. For both models the threshold of cost effectiveness was an absolute reduction in mortality of 3%.
Table 2 Sensitivity analyses
Discussion
Office of National Statistics. Cancer statistics: registrations, series MB1 for 1999. www.statistics.gov.uk (accessed 18 Mar 2003).
Information and Statistics Division (ISD) Scotland. Cancer: facts and figures for 1999. www.show.scot.nhs.uk/isd (accessed 18 Mar 2003).
Kievit J, Bruinvels DJ. Detection of recurrence after surgery for colorectal cancer. Eur J Cancer 1995;31a: 1222-5.
Scholefield JH, Steele RJ. Guidelines for follow up after resection of colorectal cancer. Gut 2002;51(Suppl 5): V3-5.
Renehan AG, Egger M, Saunders MP, O'Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002;324: 813.
Jeffrey GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. In: Cochrane Library, Issue 1. Oxford: Update Software, 2002.
Secco GB, Fardelli R, Gianquinto D, Bonfante P, Baldi E, Ravera G, et al. Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial. Eur J Surg Oncol 2002;28: 418-23.
Mella J, Datta SN, Biffin A, Radcliffe AG, Steele RJ, Stamatakis JD. Surgeons' follow-up practice after resection of colorectal cancer. Ann R Coll Surg Engl 1997;79: 206-9.
Bruinvels DJ, Stiggelbout AM, Klaassen MP, Kievit J, Dik J, Habbema F, et al. Follow-up after colorectal cancer: current practice in the Netherlands. Eur J Surg 1995;161: 827-31.
Virgo KS, Wade TP, Longo WE, Coplin MA, Vernava AM, Johnson FE. Surveillance after curative colon cancer resection: practice patterns of surgical subspecialists. Ann Surg Oncol 1995;2: 472-82.
Makela JT, Laitinen SO, Kairaluoma MI. Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial. Arch Surg 1995;130: 1062-7.
Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg KG. Follow-up after curative surgery for colorectal carcinoma: randomized comparison with no follow-up. Dis Colon Rectum 1995;38: 619-26.
Schoemaker D, Black R, Giles L, Toouli J. Yearly colonoscopy, liver CT, and chest radiography do not influence 5-year survival of colorectal cancer patients. Gastroenterology 1998;114: 7-14.
Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 1998;41: 1127-33.
Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomized study of follow-up after radical surgery for colorectal cancer. Br J Surg 1997;84: 666-9.
Department of Health NHS reference costs. www.doh.gov.uk/nhsexec/refcosts.htm (accessed 18 Mar 2003).
Gilbert RE, Augood C, Gupta R, Ades AE, Logan S, Sculpher M, et al. Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies. BMJ 2001;323: 423-5.
Multicentre aneurysm screening study (MASS): cost effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from randomised controlled trial. BMJ 2002;325: 1135.
UK Flexible Sigmoidoscopy Screening Trial Investigators. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002;359: 1291-300.
Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348: 883-90.
Kievit J. Follow-up of patients with colorectal cancer: numbers needed to test and treat. Eur J Cancer 2002;38: 986-99.
Fusai G, Davidson BR. Management of colorectal liver metastases. Colorectal Dis 2003;5: 2-23.
Wanebo HJ, Antoniuk P, Koness RJ, Levy A, Vezeridis M, Cohen SI, et al. Pelvic resection of recurrent rectal cancer: technical considerations and outcomes. Dis Colon Rectum 1999;42: 1438-48.
Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
UK Government Actuary's Department. Life tables. www.gad.uk/policy_and_stats/life_tables.htm (accessed 18 Mar 2003).
Raftery J. NICE: faster access to modern treatments? Analysis of guidance on health technologies. BMJ 2001;323: 1300-3.
Torgerson D, Raftery J. Economics notes: discounting. BMJ 1999;319: 914-5.
Virgo KS, Vernava AM, Longo WE, McKirgan LW, Johnson FE. Cost of patient follow-up after potentially curative colorectal cancer treatment. JAMA 1995;273: 1837-41.
Norum J, Olsen JA. A cost-effectiveness approach to the Norwegian follow-up programme in colorectal cancer. Ann Oncol 1997;8: 1081-7.
Edelman MJ, Meyers FJ, Siegel D. The utility of follow-up testing after curative cancer therapy: a critical review and economic analysis. J Gen Intern Med 1997;12: 318-31.
Graham RA, Wang S, Catalano PJ, Haller DG. Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg 1998;228: 59-63.
Beart RW Jr. Follow-up: does it work? Can we afford it? Surg Oncol Clin N Am 2000;9: 827-34.
Van den Hout WB, van den Brink M, Stiggelbout AM, van de Velde CJH, Kievit J. Cost-effectiveness analysis of colorectal cancer treatments. Eur J Cancer 2002;38: 953-63.
Stiggelbout AM, de Haes JC, Vree R, van de Velde CJ, Bruijninckx CM, van Groningen K, et al. Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up. Br J Cancer 1997;75: 914-20.
Renehan AG, Egger M, Saunders MP, Whynes D, O'Dwyer ST. Intensive follow-up after colorectal cancer. Recent successes and future challenges. In: Cunningham D, Topham C, Miles A, eds. The effective management of colorectal cancer, 4th ed. London: Aesculapius Medical Press, 2004.
Wang H, Karesen R, Hervik A, Thoresen SO. Mammography screening in Norway: results from the first screening round in four counties and cost-effectiveness of a modeled nationwide screening. Cancer Causes Control 2001;12: 39-45.
Whynes DK, Neilson AR, Walker AR, Hardcastle JD. Faecal occult blood screening for colorectal cancer: is it cost-effective? Health Econ 1998;7: 21-9.
Kjeldsen BJ, Thorsen H, Whalley D, Kronborg O. Influence of follow-up on health-related quality of life after radical surgery for colorectal cancer. Scand J Gastroenterol 1999;34: 509-15.
National Institute for Clinical Excellence. A review of the evidence for the clinical and cost-effectiveness of ironotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. www.nice.org.uk (accessed 18 Mar 2003).
Frew E, Wolstenholme JL, Atkin W, Whynes DK. Estimating time and travel costs incurred in clinic based screening: flexible sigmoidoscopy screening for colorectal cancer. J Med Screen 1999;6: 119-23.(Andrew G Renehan, senior )