Medical or Surgical Therapy for Erosive Reflux Esophagitis: Cost-Utility Analysis Using a Markov Model

Joseph Romagnuolo, MD, FRCP(C), MSc, (Epid); Michael A. Meier, MD, FRCS(C); Daniel C. Sadowski, MD, FRCP(C)

Disclosures

Annals of Surgery. 2002;236(2) 

In This Article

Discussion

In this study we sought to determine the costs and consequences of long-term medical or surgical therapy for the subgroup of GERD patients with erosive (grade II or higher) reflux esophagitis. Our analysis illustrates that LNF is a cost-effective option for middle-aged patients with erosive esophagitis when the expected time of medical maintenance therapy is more than 3.1 years.

However, the results of our analysis differ significantly from those of a previous American study on this issue. Heudebert et al[76] found that while both strategies were similarly effective, omeprazole was significantly less expensive than LNF. While there are several important differences in methodology, the major distinction is the costs cited in the American model. Costs in Heudebert et al's study were strikingly higher for all interventions except drug therapy. For example, the cost of LNF was 7,500 U.S. dollars versus 3,091 Canadian dollars in our model. In comparison, most other published estimates of LNF costs have been less than that used in Heudebert et al's model. The Finnish hospital costs in a randomized prospective study comparing open and laparoscopic fundoplication were recently reported as $2,981.[77] A second study comparing open and laparoscopic surgery costs in Sweden showed that the direct costs of LNF were 27,693 SEK.[78] A third American estimate of hospital costs of LNF arrived at the figure of $6,000, which was about half that estimated for the open approach.[79] Lastly, one of the most recent American cost estimates, using an outpatient surgery program, was $4,588 for hospital costs. Also, the cost of gastroscopy was at least four times higher ($1,105 U.S. dollars) in Heudebert et al's study than in our analysis. While these differences reflect international variations in the cost of goods and services, they also indicate that medical economic models are not necessarily portable across political boundaries.

Two other studies have looked at quality of life after LNF. One examined this in terms of improvement in symptoms and reduction of medication use and found that by these measures, quality of life improved.[80] A second study, examining "psychological well-being" and the Gastrointestinal Symptoms Rating Scale, found that quality of life of patients was restored to normal with surgery by 12 months.[81]

A problem with previous analyses of this issue has been the assumption that the LNF failure rate is the major long-term adverse consequence of the intervention. However, as experience broadens, it is now increasingly recognized that some individuals will experience intermittent dysphagia and food impaction. In fact, a prematurely ended randomized trial comparing open and laparoscopic surgery has suggested a higher rate of dysphagia with laparoscopy.[48] Although the "gas-bloat" syndrome can also occur, these symptoms tend to abate within 3 to 6 months of surgery, can usually be treated conservatively and without dilatation, and will, therefore, not have as great an impact on the costs or utilities.[58,82,83] Incorporating factors such as ongoing adverse symptoms will bias any model against a surgical intervention but needs to be considered in future studies.

While the conclusions of our analysis are robust within the framework and constraints of the model, several issues should lend caution to the interpretation of the results. First, only one of the currently available PPIs (omeprazole) was modeled. While few head-to-head trials of lansoprazole and pantoprazole with omeprazole have been published, the available evidence suggests that all three PPIs have similar healing and maintenance efficacy in GERD.[84,85,86,87,88,89,90,91] While the newer PPIs have a slightly lower cost, a reduction of at least 50% is required before medical therapy is more cost effective in our model.

A second issue is the potential long-term complications of PPI therapy, which could not be modeled reliably simply because of lack of data. Until recently, carcinoid tumors in the setting of chronic PPI use had not been documented in humans, despite concerns raised by animal studies. However, a Japanese report may represent the first such human complication.[92] Although gastrin levels can occasionally become very high, they are not measured routinely as the clinical consequences of hypergastrinemia in this setting are unclear.[93] Fundic gland polyps may occur but are thought to have a benign prognosis and require neither surveillance nor treatment. Atrophic gastritis and argyrophil cell hyperplasia occurred in approximately 20% of patients in the 5-year follow-up study by Kuipers et al.[94] Most of the atrophy development was seen in Helicobacter pylori-positive patients, and none of these changes were seen in patients who had undergone fundoplication. Klinkenberg-Knol et al[95] have recently shown, in a study with a mean follow-up of 6.5 years, that atrophy occurs in 4.7% and 0.7% of H. pylori-positive and -negative patients, respectively, and that these rates were related to patient age and severity of gastritis at the beginning of therapy. No dysplasia or neoplasm was seen in over 1,000 patient-years of observation.[95] Although there remains a concern that H. pylori eradication may predispose to worsening of reflux symptoms, symptomatic relapse was not found to depend on H. pylori status in the large study by Klinkenberg-Knol et al.[95] These issues, although important and concerning, could not be addressed in this analysis as their impact on cost and clinical outcome is currently unknown.

Third, esophageal complications of reflux, such as the development of peptic stricture while on medical therapy, are not modeled mainly because rates of occurrence of these outcomes are not accurately known. The dilatations modeled into the surgical group were for complications of the surgical procedure and not for reflux-induced strictures. As well, the outcome of Barrett's esophagus could not be accurately modeled. While surgical therapy may be more effective than medical therapy in preventing complications such as Barrett's esophagus, no long-term trials directly comparing the effectiveness of these therapeutic approaches have yet been published.[96] A recent study demonstrated a decrease in the frequency of adenocarcinoma in those undergoing surgery in a Veterans Administration multicenter randomized trial (n = 248).[28] As well, the issue of squamous epithelial regrowth over underlying Barrett's in the patients with apparently successful regression renders even the existing literature regarding success rates too unreliable to use in our model.[97]

A fourth limitation of our model is the validity of the available data on long-term LNF success. Unfortunately, a well-known bias in the literature leans toward the reporting of favorable results. We acknowledge that the literature likely reflects the experience of the best centers and may not apply specifically to every surgeon. A significant bias in the opposite direction, however, is the inclusion of results from early in the LNF era. Because of the long learning curve,[52,98,99] these results are likely slightly worse than current practice, since complication rates appear to continue to fall even after 100 procedures.[52,98,99] Surgical costs may vary slightly from center to center just as length of stay may vary from surgeon to surgeon. However, despite these possible discrepancies, sensitivity analyses verified that our conclusions were reliable up to five times the reported failure rate, up to $2,000 above our surgical costs, and up to a mean length of stay that would not be currently acceptable (4.2 days).

The last limitation we will discuss is related to the choice of the model itself. As outlined earlier, the Markov technique is one method among a group of dynamic models that allow the modeling of events over time. This characteristic is essential for the problem at hand as relapse occurs gradually with time, and the costs and disutility of medical therapy also accrue with time. Given that time and the current clinical state are likely the most powerful predictors of outcome, and that previous events have little impact, we felt this model was appropriate. The main limitation of the model, lack of memory, makes it impossible to model the "snowballing" effect wherein a patient who, for example, receives a dilatation for gas-bloat symptoms is more likely than others to require a subsequent dilatation, or that a patient who requires a conversion to an open laparotomy is more or less likely to go on to require medications. This argument can be made in the opposite direction, since patients who have fared well in the first year after surgery, for example, may tend to be at lower risk for subsequent complications. However, since costs and utilities are bounded below but unbounded above, there remains the possibility of a bias against the medical arm. The model inherently makes the groups more homogeneous and thereby tends to overestimate precision by not taking into account these rare outliers. Regardless, the degree to which these previous events influence most future events is not accurately known, and so modeling memory for these type of events, even if it were possible, would not have borne much validity.

Mathematical simulations must be regarded as such and are in no way meant to replace life experience. In addition, one is reminded from the upper end of the 95% interpercentile ranges derived from Monte Carlo analysis that surgical therapy can be debilitating and expensive when serious complications occur. Although in our model the laparoscopic approach appears to be on average more cost effective than long-term medical therapy, this does not predict the best approach for the individual. From a societal perspective, however, our model's conclusions are highly relevant. Clinical judgment, patient preference, and patient selection are all of obvious importance.

While it is possible to model, from a macroeconomic perspective, the choices available in the long-term management of GERD, patients and their physicians will make the ultimate decision. They will derive their preferences from considering the adverse effects, costs, and anticipated long-term outcomes. To date, little work has been done on patient and physician attitudes to surgical versus medical management of GERD. In our experience, most primary care physicians regard LNF as expensive, invasive, and excessive.[100] Our work has clearly demonstrated that these attitudes should be re-examined. In Canada, antireflux surgery is increasing in frequency in regions where the majority of procedures are performed laparoscopically.[101] We maintain that LNF is a cost-effective option for the treatment of erosive reflux esophagitis. One must be cautioned that these results cannot and should not be extrapolated to patients with either endoscopy-negative GERD or mild (grade I) esophagitis. When situations require long-term PPI maintenance and patient-specific factors such as age, surgical risk, and individual preference are favorable, LNF should be considered. Final data from several randomized trials in progress comparing medical therapy and antireflux surgery in the laparoscopic era are awaited.

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