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Are Endoscopic Antireflux Therapies Cost-Effective Compared with Laparoscopic Fundoplication? Background and Study Aims: A number of endoscopic antire- Results: Assuming that EAT has no impact on potential LF later flux therapies (EATs) have emerged as potential nonmedical on, the outcome of both strategies (LF, or EAT first with LF in treatment options for patients with gastroesophageal reflux dis- case of failure of EAT) is identical and preference is a simple ease (GERD). Concerns about clinical efficacy and costs have giv- question of costs. The sequential strategy in nonmedical GERD en rise to debate about their role in GERD management. The treatment would be preferable if the long-term relief rate with costs of laparoscopic fundoplication (LF) were compared with EAT exceeds the ratio of the cost of EAT to the cost of LF. Long- the costs of EAT when used in a sequential strategy that reserves term success rates of EAT do not exceed 0.65. At current prices EAT is clearly not cost-effective in Germany.
Methods: A simple mathematical criterion of direct medical Conclusion: Our simple criterion indicates that EAT would only costs was applied. Published articles concerning EAT were re- be cost-effective and beneficial in a sequential strategy if the viewed to assess its effectiveness, durability and costs, in order costs of EAT were to be decreased to around 30% of current retail to estimate the parameters of the model. The costs of EAT and prices. However, long-term studies and randomized controlled LF were evaluated from the perspective of a German third-party trials are necessary to finally determine the role of EAT in GERD payer. Only direct medical costs were considered.
treatment, and the preference may change in either direction.
antireflux surgery. The efficacy of GERD symptom control aswell as of prevention or treatment of complications is variable Gastroesophageal reflux disease (GERD) is a common disorder [8±11]. Since GERD is a chronic relapsing disorder [12] substan- with increasing incidence and prevalence in the industrialized tial healthcare resources are at stake.
countries and with a major impact on patient quality of life [1±4]. The prevalence of heartburn has been reported to be 29% of Proton-pump inhibitors (PPI) and (laparoscopic) antireflux sur- the population in the UK [5] and 22% in Finland [6]. Without gery are currently the accepted treatment modalities for man- treatment, potential sequelae of reflux esophagitis are ulcera- agement of GERD. Since 82% of patients relapse after 6 months tions, esophageal stricture, or precancerous changes (Barrett of PPI cessation [12] lifelong maintenance therapy is required esophagus) that are associated with a 30%±40 % increase in the [13]. A notable number of patients have relapsing GERD symp- risk of esophageal cancer [7]. GERD treatment options comprise toms or resent dependence on lifelong PPI medication. Antireflux lifestyle modifications, pharmacological acid suppression, and surgery is used as an alternative GERD therapy [14±16]. The 1 Department of Internal Medicine II, University of Leipzig, Leipzig, Germany 2 Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, 3 Department of Surgery II, University of Leipzig, Leipzig, Germany K. Caca, M.D. ´ Department of Medicine II, University of Leipzig ´ Philipp-Rosenthal-Straûe 27 ´ 04103 Leipzig ´ Germany ´ Fax: + 49-341-9712239 ´ E-mail: caca@medizin.uni-leipzig.de Submitted 26 October 2003 ´ Accepted after Revision 15 November 2003 Endoscopy 2005; 37 (3): 217±222  Georg Thieme Verlag KG Stuttgart ´ New York ´ ISSN 0013-726X open procedure has been replaced by the introduction of laparo-scopic fundoplication (LF) [17,18] which can achieve long-term Table 1 Comparison of costs of endoscopic antireflux therapy relief of symptoms [19] in about 90% of cases. However, LF re- (EAT) and laparoscopic fundoplication (LF) quires hospital admission and is associated with significant mor-bidity and with a mortality of 0.1%±0.3% [20±23]. Additionally, a comparative study has shown that after antireflux surgery 62% of patients were using antisecretory medication at a median fol- low-up of 6.3 years [10]. Comparing long-term PPI treatment with LF, the break-even point, where the costs of the two alterna- tives are equal, was calculated to be reached at 1.4 years of med- In view of these risks and costs, investigators have sought less in- vasive endoscopic methods to augment the function of the gas- troesophageal barrier and to prevent gastroesophageal reflux.
Endoscopic antireflux therapies (EATs) have emerged as a poten- tial alternative to LF in patients with an incomplete response to PPIs and/or for whom lifelong medication is not an acceptable treatment option. Three minimally invasive endoscopic ap- proaches have recently been approved by the US Food and Drug Administration (FDA) for the management of GERD: endoscopic suturing (EndoCinch; CR BARD Endoscopic Technologies, Billeri-ca, Massachusetts, USA) [25 ±29], delivery of temperature-con-trolled radiofrequency energy (Stretta; Curon Medical Inc. Sun- nyvale, California, USA) [30±33], and injection of a biocompati- Most studies included patients with uncomplicated GERD. Pa- ble polymer (Enteryx; Boston Scientific, Natick, Massachusetts, tients considered here had to meet all of the following inclusion USA) [34±37]. The long-term relief rate after EAT is not fully criteria: moderate to severe reflux more than five times a week; comparable with that of LF. Follow-up reports of patients after at least a partial response to PPIs; abnormal findings at 24-hour LF have shown an 87% to 91% overall success rate after 3±5 years esophageal pH monitoring; hiatal hernia smaller than 3 cm; and [10,11,19,38]. For EAT the only available follow-up data are no significant co-morbidity. The hernia size criterion was im- scarce and short-term. Published data indicate that, after 6 posed in order to guarantee the applicability of all procedures.
months to 1year, the relief rate in terms of heartburn symptoms Patients who were aged less than 18 years or had dysphagia, pre- or reduction of PPI use is approximately 60 %±80% [26,27,30± vious thoracic surgery, or esophageal varices were excluded.
32,34±37]. On the other hand, EAT procedures (not includingthe cost of the device) are cheaper and have a considerably lower extent of side effects (with no operation, less mental and physi- To evaluate the costs, EAT was compared with LF from the per- cal strain, and no hospitalization). Two deaths have been report- spective of the third-party payer. Direct medical costs associated ed with the Stretta procedure during the introductory period of with EAT and LF consisted of those of uncomplicated operation the product, and for all EATs serious complications have been re- and of medication and the ªhotelº costs of hospitalization. The ported only very rarely, whereas LF shows a mortality of 0.2%± hotel costs for inpatient-days were obtained from the accounting center of the 20 participating hospitals by calculating the meanvalues (Table 1). For comparable costs, the GO¾ (GebührenOrd- As LF is still possible after EAT [41,42], it may be both beneficial nung für ¾rzte, 2.3-fold average cost multiplies in a national re- and cost-effective to adopt a conditional strategy, namely to car- imbursement schedule for German doctors) was used to provide ry out EAT as the first-line treatment and leave the option of LF as a nationwide cost-covering measuring unit. Direct nonmedical a last resort, only to be done if the results of EAT are unsatisfac- costs, for example transportation, and indirect costs such as loss tory. We used a simple decision-tree model scenario to elucidate of production due to endoscopy (1day) or operation (5 days) the circumstances under which long-term relief rates and costs were not included, to the disadvantage of EAT.
are optimal in the management of GERD patients. We deter-mined how great the rate of long-term relief after EAT needed to Our scenario was based on the following assumptions: be if the conditional strategy was to be beneficial, expressing this ± (i) that EAT does not affect the probability of success of a sec- rate as a function of the cost advantage of EAT over LF.
± (ii) that no patient could be cured by means of EAT who could not also be cured with an LF procedure. (This assumption was We reviewed all available publications regarding the efficacy, Figure 1 illustrates two treatment options in patients with mild and durability of the new EndoCinch, Stretta, and Enteryx antire- to moderate GERD, that is, LF as first-line treatment, or EAT as the first-line treatment with LF carried out only in those patientsin whom EAT failed.
Schiefke I et al. Costs of Endoscopic Antireflux Therapies ´ Endoscopy 2005; 37: 217±222 for gastroesophageal reflux disease (GERD): laparoscopic fundoplication (LF) as first-line treatment, or endoscopic antireflux therapy Long-term
? Treatment
(EAT) as first-line treatment followed by LF in those patients in whom EAT fails.
long-term relief rate following LF after EAT failed The costs of EAT and LF are designated by CEAT and CLF, respective- If one disregards Csecond, the conditional strategy is cheaper, i.e.
ly and the costs of the conditional strategy by CEAT<fail>®LF. The CLF > CEAT<fail>®LFlong-term relief rates for EAT and for LF are denoted by pEAT andpLF, respectively.
In the discussion, costs may be interpreted from two perspec-tives: a) the monetary costs for the procedures, or b) the subjec- tive ªcostsº, which include side effects and the stress caused to the patient by the procedures. While monetary costs can be as-sessed by adding the expense of the material used, operations, Thus the conditional strategy would be preferable if the long- and hospitalization etc., the assessment of subjective costs de- term relief rate provided by EAT exceeds the ratio of the cost of pends on clinical judgment. Both perspectives are important and the equations in their general form apply to both.
In order to have a rough upper boundary for pEAT, we set the ad-ditional costs Csecond of needing a second procedure as being equal to CEAT. Thus assuming that the additional expense of need-ing a second procedure is in the order of the costs for EAT, the conditional procedure is cost-effective if Applying the assumptions of the model, the final long-term relief rates of both strategies, that is, LF or EAT with LF only in case offailure, are identical. As the outcomes may thus be assumed to be eventually the same, preference between the strategies is a The main conceptual insight from this result is that, given the The monetary cost of the conditional strategy is simply: costs of the procedures, we can calculate a break-even threshold CEAT<fail>®LF = CEAT + (1 ± pEAT) * (Csecond + CLF).
for pEAT. Also, given values for CLF and pEAT, we can calculate valuesfor the cost CEAT at which the sequential procedure would be- Here Csecond denotes the additional cost or stress associated with come cost-effective.
the experience and the diagnosis of failure of EAT and the need toface a second intervention.
Monetary CostsThe costs CEAT and CLF can be crudely estimated by adding the cost Thus the conditional strategy is cheaper, i.e.
of performing the procedures to the costs for hospitalization (Ta- ble 1). LF is clearly cheaper than any of the EAT alternatives. A for-tiori, the sequential strategy is far from cost-effective at current pEAT > (Csecond + CEAT)/(Csecond + CLF).
In order to determine at what price EAT might become cost-ef- Monetary values for CEAT and CLF are estimated below. Csecond is fective we assessed effectiveness as the percentage of patientsmore difficult to assess.
who were satisfied at 6 months without PPI (Table 2). Less opti- Schiefke I et al. Costs of Endoscopic Antireflux Therapies ´ Endoscopy 2005; 37: 217±222 with great caution because only a few studies with a limited Table 2 Economic evaluation of alternative strategies in (GERD), number of patients and limited follow-up have been published.
data from [19,26,31,38,44] and non-published data At this point it remains unclear whether one or all of the EATswill evolve into an evidence-based treatment approach for GERD. Although the EndoCinch, Stretta, and Enteryx methods vary in their mechanism of action and potential side effects, the sequential model of cost-effectiveness is applicable since LF can be performed after all three EAT procedures in the case of treat- ment failure [41,42; personal communication, P. Meier, Hann-over, May 2004].
We modelled the trade-off between higher long-term relief rates with LF versus lower hospitalization costs and less side effects with EAT, using simple conditional probability calculations andassuming that LF was a backup treatment option after failed * 94/118 were available for follow-up.
EAT, as suggested by the literature [43]. We considered both a monetary and a subjective patient-centred perspective. We de- rived an order of magnitude value for the break-even threshold for the long-term relief rate with EAT as a function of the costsof EAT and LF, and vice versa. Our simple trade-off scenario con- mistic long-term rates would be preferable, but are currently un- ceptualizes what is involved in choosing between LF or a condi- tional strategy with EAT as the first-line treatment. The cost esti-mates provided suggest that there may only be a role for EAT in Since the mean success rates of all EAT do not exceed 0.63 (mean the management of GERD patients requiring intervention if pric- PEAT = 0.63; range 0.60±0.68) and CLF = C = 511.38 if it is assumed that Csecond = CEAT. Thus current prices The short-term results of limited trials with EATs and our own experience with 43 patients with EndoCinch (64 % success at 3months) suggest that the mean long-term relief rate following Subjective Costs: the Patient's Perspective EAT treatments does not exceed 0.63 (range 0.60±0.68) (for ex- The side effects of an ambulatory EAT compare favorably with ample, EndoCinch, 64% patients with reduced medication at 12 those associated with a full operation and 5 days of hospitaliza- months [27]; Enteryx, 70 % with no medication at 12 months tion with LF. The subjective cost ratio is probably more favorable [37]; Stretta, 61% with no medication at 12 months [31]). Based for EAT than is the monetary cost ratio. Although experiencing a on the crude cost estimates that we provide and the published failure of EAT is certainly stressful, we think that the subjective success rates, a conditional strategy would appear to be both break-even threshold is smaller than or equal to the monetary cost-efficient and beneficial only if costs of EAT were to decrease Cost assessment is notoriously difficult. Nevertheless we think that our estimates define well the order of magnitude of thebreak-even threshold. All the cost estimations were done on the We derived a simple criterion for the cost-effectiveness of endo- basis of current wholesale prices for EAT and published cost esti- scopic antireflux therapy used within a sequential treatment mates for LF. Since costs for the EAT devices will probably decline strategy. Based on success rates published so far, EAT could be a in the future, the potential cost-effectiveness of EAT may rise.
cost-effective initial treatment option compared with laparo-scopic fundoplication if costs of EAT decreased to around 30% of Several general comments about this conceptual model need to be emphasized:a) The time horizon of our model is limited by the currently pub- Endoscopic antireflux therapies are an innovative treatment ap- lished data on EAT which do not relate to follow-up of more proach to GERD. Due to their minimal invasiveness EATs are associated with less morbidity and require a shorter hospital b) The values assigned to the model parameters were based on the best available evidence. There are no data from random-ized controlled clinical trials to support the response rates Although several endoscopic techniques are under investigation, EndoCinch, Stretta, and Enteryx are the most advanced devices c) The morbidity, mortality and efficacy estimates for EAT are and are FDA approved, and therefore only these three techniques based on limited data of relatively small series from centers were considered here. Success rates have been reported for all where experience is considerable, to the extent that when three EATs (on the basis of symptom relief and PPI reduction of EAT procedures are performed by less skilled endoscopic op- at least 50 %), that range from 60 % to 80% [26,27,30±32,34± erators, the results may be less favorable.
37]. Although these results are promising, they should be viewed Schiefke I et al. Costs of Endoscopic Antireflux Therapies ´ Endoscopy 2005; 37: 217±222 We took the perspective of a third-party payer and calculated the 6 Voutilainen M, Sipponen P, Mecklin JP et al. Gastroesophageal reflux cost based on customary reimbursement by a German health in- disease: prevalence, clinical, endoscopic and histopathological find- surance company using a nationwide cost-covering measuring ings in 1,128 consecutive patients referred for endoscopy due to dys- peptic and reflux symptoms. Digestion 2000; 61: 6±13 unit (the GO¾). Although the cost structure of reimbursement 7 Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastro- for gastrointestinal procedures has undergone several changes, esophageal reflux as a risk factor for esophageal adenocarcinoma. N the GO¾ values represent the average payments in the present German healthcare system. However, relative reimbursements Klinkenberg-Knol EC, Festen HP, Jansen JB et al. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety.
for EAT and LF procedures in the United States followed an oppo- site pattern, with LF being more expensive [44] (Table 2). Our 9 Vigneri S, Termini R, Leandro G et al. A comparison of five mainte- model allows country-specific calculations of cost estimates by nance therapies for reflux esophagitis. N Engl J Med 1995; 333: simple replacement of regional reimbursement parameters.
10 Spechler SJ, Lee E, Ahnen D et al. Long-term outcome of medical and Since we did not explicitly consider indirect medical costs (e.g.
surgical therapies for gastroesophageal reflux disease: follow-up of a transport, days of work lost) in our calculation, the overall cost randomized controlled trial. JAMA 2001; 285: 2331±2338 estimate may be biased towards LF as hospital stay and number 11 Lundell L. Laparoscopic fundoplication is the treatment of choice for of working days lost are greater after LF. The aim of our analysis gastro-oesophageal reflux disease. Protagonist. Gut 2002; 51: 468± was to increase awareness of the cost of modern interventions in 12 Hetzel DJ, Dent J, Reed WD et al. Healing and relapse of severe peptic the early stages of clinical use, and we wished to analyse the pro- esophagitis after treatment with omeprazole. Gastroenterology 1988; cedures themselves, not taking indirect or nonmedical costs into McDougall NI, Johnston BT, Kee F et al. Natural history of reflux oe- sophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life. Gut 1996; 38: 481 ± 486 Although medical PPI therapy is the gold standard of treatment 14 Donahue PE, Samelson S, Nyhus LM, Bombeck CT. The floppy Nissen for GERD, our calculations did not include a comparison with fundoplication. Effective long-term control of pathologic reflux. Arch medical treatment. According to existing opinion in the litera- 15 DeMeester TR, Bonavina L, Albertucci M. Nissen fundoplication for ture, EAT and LF are considered to be a treatment option for gastroesophageal reflux disease. Evaluation of primary repair in 100 GERD only in patients with a partial response to PPIs, with side consecutive patients. Ann Surg 1986; 204: 9±20 effects from PPI, or, most commonly, who reject long-term med- 16 Thor KB, Silander T. A long-term randomized prospective trial of the Nissen procedure versus a modified Toupet technique. Ann Surg 17 Dallemagne B, Weerts JM, Jehaes C et al. Laparoscopic Nissen fundo- In summary, this simple sequential model of nonmedical GERD plication: preliminary report. Surg Laparosc Endosc 1991; 1: 138±143 treatment suggests that EAT as a first-line treatment, followed 18 Fuchs KH, Feussner H, Bonavina L et al. Current status and trends in by LF if needed, may be cost-effective in patients with mild to laparoscopic antireflux surgery: results of a consensus meeting. The European Study Group for Antireflux Surgery (ESGARS). Endoscopy moderate reflux, if costs of EAT decrease to around 30 % of cur- rent retail prices (in the German healthcare system). Alongside 19 Lafullarde T, Watson DI, Jamieson GG et al. Laparoscopic Nissen fun- its potential clinical superiority, due to lower morbidity, im- doplication: five-year results and beyond. Arch Surg 2001; 136: 180± proved patient satisfaction, and shorter hospital stay, EAT is not 20 Pelissier EP, Ottignon Y, Deschamps JP, Carayon P. Fundoplication superior from the perspective of health economics, even assum- avoiding complications of the Nissen procedure: prospective evalua- ing favorable long-term efficacy data. Given that long-term data tion. World J Surg 1997; 21: 611 ±616; discussion 616±617 are awaited, as well as data from randomised controlled trials, 21 Wetscher GJ, Glaser K, Wieschemeyer T et al. Tailored antireflux sur- the results from our simple model could change in either direc- gery for gastroesophageal reflux disease: effectiveness and risk of postoperative dysphagia. World J Surg 1997; 21: 605 ±610 22 Bais JE, Bartelsman JF, Bonjer HJ et al. Laparoscopic or conventional Nissen fundoplication for gastro- oesophageal reflux disease: ran- Based on our findings, further cost-effectiveness analyses of EAT domised clinical trial. The Netherlands Antireflux Surgery Study versus LF should be performed as part of clinical trials.
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