Is surveillance cost-effective for follow-up of patients with BO?
Is surveillance cost-effective for follow-up of patients with BO?
Australia’s health system faces increasing pressure to contain healthcare costs, while still maintaining high quality and optimal care. Cost-effectiveness analysis is a process that systematically compares the relative healthcare costs and benefits of alternative strategies to inform policy-makers of the strategies with the best value. There are a number of economic considerations in deciding whether the surveillance of Barrett’s Oesophagus is worthwhile. These include:
- A surveillance program involves repeated invasive endoscopies that are also costly when low-risk individuals will be examined frequently, although it is the only method to detect early stage oesophageal cancer and avoid death from advanced disease;
- Efficacy of surveillance should be established first before assessment of cost-effectiveness but no large-scale trial has been undertaken and it is unlikely one will be given that recruitment is usually slow, the yield of cancer cases is low and very high numbers of participants are required;
- To undertake a high-quality cost-effectiveness study, robust data on the natural history of disease progression, the effectiveness of surveillance, and evidence of health resources used are required. However, data on all of these has been scarce, until more recently;
- Treatment costs for oesophageal cancer are changing with newer less-invasive endoscopic technologies; and
- The cost-effectiveness of treatments for oesophageal cancer and high-grade dysplasia and the associated impact on the economic benefit of surveillance programs is unknown.
Whether surveillance of Barrett’s Oesophagus is cost-effective or not depends on if the incremental costs of surveillance (versus no surveillance) and the incremental health gains (versus no surveillance) are acceptable. Economic studies addressing this question have used mathematical modelling to synthesize the ‘best available’ evidence required for cost-effectiveness analysis and importantly address the uncertainty inherent in the model estimates.
Review of the evidence
One systematic review summarizes the evidence for cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett’s Oesophagus. The review included seven studies that met the inclusion criteria which were; 1) it had to be a comparison of surveillance for individuals with Barrett’s Oesophagus versus no surveillance, and 2) it had to include the key outcome of either quality-adjusted life year (QALY) or life-years saved (LYS) and 3) included both costs and health benefits in the analysis. Figure 1 illustrates the key results for the studies included in the review for the incremental cost per QALY/LYS ratios of endoscopic surveillance versus no surveillance strategy. Two studies by Sonnenberg et al. reported incremental cost per LYS.
Figure 1. Key findings of cost-effectiveness of surveillance versus no surveillance (incremental cost per QALY/LYS gained ratios)
Source: Data from Hirst et al. (2011)
All studies were US-based with the exception of one UK study and published from 1999-2009. All studies used decision-analytic Markov models to track hypothetical patient cohorts able to move between health states and reflect observed disease progression. The models were lifetime duration over 25-30 years or until death. The findings were inconsistent about the value of surveillance, ranging from being cost-effective to highly cost-ineffective. In addition, the studies in the review used data that is largely outdated now. New evidence is available on quality of life, proportion of patients progressing among dysplasia grades, improved mortality rates for oesophagectomy and estimates on the natural history of Barrett’s Oesophagus. Clinical practice has also improved with greater use of less invasive endoscopic techniques that promise to reduce treatment costs.
Key Limitations of the evidence in Hirst N et al. (2009) include:
- No randomised controlled trial for surveillance of Barrett’s Oesophagus
- Author assumptions made for key model estimates not based on robust data;
- Studies have only partially addressed key aspects of uncertainty in the analyses;
- Applicability to Australia is limited due to differences in practice patterns, health care prices and organisation of the health system.
- Heterogeneity in surveillance program delivery
- Endoscopic screening/surveillance methods were not always consistent
- Heterogeneity in definition of Barrett’s Oesophagus, i.e., confirmed intestinal metaplasia or other.
One study in the UK by Roberts KJ et al. that was published after the review period by Hirst claimed annual surveillance was cost-effective at £4,493 per life year gained. This study had ‘prevalent cases of cancer’ as the comparator and it is unclear if this is a suitable comparison. In addition, the analyses did not apply discounting or sensitivity analyses which are standard practice in health economic studies.
Current directions – surveillance of high-risk individuals
Patients who are most likely to benefit from surveillance programs are those at high-risk of developing malignancy. At the same time a targeted surveillance program will minimise unnecessary use of hospital resources. Three cost-effectiveness studies were identified that specifically addressed high-risk individuals; two involved biomarker testing and one involved individuals with long-segment Barrett's oesophagus.
Rubenstein’s approach was to determine how sensitive and specific a biomarker test would need to be, and how cheap, to be a cost-effective surveillance program. In Gordon et al, the cost-effectiveness of surveillance in Australia was favourable under the hypothetical scenario of biomarker testing and where patients testing negative for biomarkers did not receive surveillance in the following five years and received two-yearly surveillance thereafter. However, the model assumed that no cancers progress to advanced stage disease under such modified surveillance protocols, that is, all early cancers were successfully eradicated and there is only limited evidence available to support this. Most recently, Kastelein et al concluded that surveillance was cost-effective in the Dutch healthcare system among individuals with long-segment Barrett's oesophagus (median 4cm) at intervals of 5 years for patients with non-dysplasia and 3 years for low-grade dysplasia. These studies highlight the importance of the frequency of endoscopy surveillance which, if scheduled less frequently, can improve the cost-effectiveness of surveillance. However, currently surveillance intervals are consensus rather than evidence-based (see also How frequently should patients with BO undergo endoscopy?)
Presently, the appropriateness of biomarker testing, its efficacy within a surveillance program, its feasibility and its acceptance are yet to be determined. Further clinical and economic research involving patients with positive biomarkers and additional high-risk factors (e.g., male, the presence of oesophagitis, length of Barrett’s Oesophagus, and length of time with Barrett’s Oesophagus) is required to assess outcomes from a more targeted high-risk surveillance population.
Economic evaluations are designed to assist with efficiently allocating scarce health care resources, that is, to minimise costs for given health outputs. Therefore, the cost-effectiveness of appropriate management strategies for patients with Barrett’s oesophagus should be considered. Based on the evidence of the malignant potential of Barrett’s Oesophagus in the general population versus those reported in surveillance program audits, surveillance of all patients with non-dysplastic Barrett’s oesophagus may not be cost-effective. Further work to identify high-risk individuals, those with long-segment Barrett's or positive biomarkers, appear promising to improve the economic efficiency of endoscopy-based surveillance of Barrett’s oesophagus.
Implications for practice
- Cost-effectiveness of endoscopic surveillance of patients with Barrett’s Oesophagus is limited in the absence of a randomised clinical trial to confirm the efficacy of surveillance
- Mathematical modelling studies estimate that endoscopic surveillance of patients with non-dysplastic Barrett’s Oesophagus is likely not be cost-effective and remains controversial
- Identifying patients at high-risk of progression to adenocarcinoma substantially improves cost-effectiveness
- Using Clinical Practice Guidelines and consensus statements to guide practice around surveillance protocols will increase the cross-comparison of research audits and could be used to feed into cost-effectiveness analyses.
Issues requiring more clinical research study
- New technologies used in the treatment pathways for patients identified for surveillance of Barrett’s oesophagus need to be assessed for their cost-effectiveness
- Identification of high-risk individuals via positive biomarkers, long-segment Barrett's oesophagus or other known risk-factors shows promise in improving the cost-effectiveness of endoscopic surveillance and clinical research evidence to confirm this is required.
- Stinnett AA, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998 Apr;18(2 Suppl):S68-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9566468.
- Gordon LG, Eckermann S, Hirst NG, Watson DI, Mayne GC, Fahey P, et al. Healthcare resource use and medical costs for the management of oesophageal cancer. Br J Surg 2011 Nov;98(11):1589-98 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22059235.
- Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med 2011 Oct 13;365(15):1375-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21995385.
- Briggs AH, Claxton K, Sculpher MJ. Decision Modelling for Health Economic Evaluation. Oxford: Gray A, Briggs AH, editors. Oxford University Press; 2006.
- Hirst NG, Gordon LG, Whiteman DC, Watson DI, Barendregt JJ. Is endoscopic surveillance for non-dysplastic Barrett's esophagus cost-effective? Review of economic evaluations. J Gastroenterol Hepatol 2011 Feb;26(2):247-54 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21261712.
- Das A, Wells C, Kim HJ, Fleischer DE, Crowell MD, Sharma VK. An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett's esophagus. Endoscopy 2009 May;41(5):400-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19418393.
- Garside R, Pitt M, Somerville M, Stein K, Price A, Gilbert N. Surveillance of Barrett's oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling. Health Technol Assess 2006 Mar;10(8):1-142, iii-iv Available from: http://www.ncbi.nlm.nih.gov/pubmed/16545207.
- Inadomi JM, Sampliner R, Lagergren J, Lieberman D, Fendrick AM, Vakil N. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med 2003 Feb 4;138(3):176-86 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12558356.
- Inadomi JM, Somsouk M, Madanick RD, Thomas JP, Shaheen NJ. A cost-utility analysis of ablative therapy for Barrett's esophagus. Gastroenterology 2009 Jun;136(7):2101-2114.e1-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19272389.
- Provenzale D, Schmitt C, Wong JB. Barrett's esophagus: a new look at surveillance based on emerging estimates of cancer risk. Am J Gastroenterol 1999 Aug;94(8):2043-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10445526.
- Sonnenberg A, Fennerty MB. Medical decision analysis of chemoprevention against esophageal adenocarcinoma. Gastroenterology 2003 Jun;124(7):1758-66 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12806608.
- Sonnenberg A, Soni A, Sampliner RE. Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma. Aliment Pharmacol Ther 2002 Jan;16(1):41-50 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11856077.
- Amamra N, Touzet S, Colin C, Ponchon T. Current practice compared with the international guidelines: endoscopic surveillance of Barrett's esophagus. J Eval Clin Pract 2007 Oct;13(5):789-94 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17824873.
- Abrams JA, Kapel RC, Lindberg GM, Saboorian MH, Genta RM, Neugut AI, et al. Adherence to biopsy guidelines for Barrett's esophagus surveillance in the community setting in the United States. Clin Gastroenterol Hepatol 2009 Jul;7(7):736-42; quiz 710 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19268726.
- Roberts KJ, Harper E, Alderson D, Hallissey M. Long-term survival and cost analysis of an annual Barrett's surveillance programme. Eur J Gastroenterol Hepatol 2010 Apr;22(4):399-403 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19858726.
- Rubenstein JH, Vakil N, Inadomi JM. The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma. Aliment Pharmacol Ther 2005 Jul 15;22(2):135-46 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16011672.
- Gordon LG, Mayne GC, Hirst NG, Bright T, Whiteman DC, Watson DI, et al. Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's esophagus. Gastrointest Endosc 2014 Feb 1;79(2):242-56 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24079411.
- Kastelein F, van Olphen S, Steyerberg EW, Sikkema M, Spaander MC, Looman CW, et al. Surveillance in patients with long-segment Barrett's oesophagus: a cost-effectiveness analysis. Gut 2014 Jul 18 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25037191.
- Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011 Jul 6;103(13):1049-57 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21680910.