[Financial restrictions in health care systems could affect treatment quality of GERD-patients]. / Wachsender Kostendruck im Gesundheitswesen kann zu einer Beeinträchtigung der Behandlungsqualität bei Refluxpatienten führen.

AIMS: To directly compare the efficacy and safety of pantoprazole 40 mg VS. omeprazole 20 mg in patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: 915 Patients suffering from symptomatic GERD B-D (Los Angeles classification) were included in a double-blind randomized multicenter clinical trial and treated with either pantoprazole 40 mg od or omeprazole 20 mg od for six weeks. Primary efficacy criterion was the first time to reach normal symptoms as assessed by the questionnaire ReQuest-GI. RESULTS: Compared to omeprazole 20 mg, pantoprazole 40 mg achieved a significantly faster rate of symptom relief (p = 0.0298). Thus, as assessed with the ReQuest questionnaire, patients treated with pantoprazole 40 mg experienced relief from the 7 leading GERD symptoms 2 days earlier than those treated with omeprazole 20 mg. Long-lasting sustained relief from symptoms was also achieved earlier with pantoprazole than with omeprazole; in patients treated with pantoprazole, the daily symptom load was lower than in those treated with omeprazole. After 6 weeks of treatment, over 90 percent of patients were free from symptoms in both treatment groups (93.7 % in the pantoprazole, vs. 91.8 % in the omeprazole group, PP). Both medications were well tolerated. CONCLUSIONS: GERD patients treated with pantoprazole 40 mg experience a significantly faster relief from their leading symptoms than those treated with omeprazole 20 mg.

"Proton-pump inhibitor-first" strategy versus "step-up" strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition, and acid-suppressing agents are the mainstays of treatment. For the acute medical management of GERD, two different strategies can be proposed: either the most effective therapy, i.e., proton-pump inhibitors (PPIs), can be given first, or histamine H2-receptor antagonists (H2RAs) can be attempted first (the "step-up" approach). METHODS: A clinical decision analysis comparing the PPI-first strategy and the H2RA-first "step-up" strategy for the acute treatment of reflux esophagitis in Japan was performed, using a Markov chain approach. RESULTS: The PPI-first strategy was consistently superior to the step-up strategy with regard to clinical outcomes for the patient and with regard to cost-effectiveness (direct cost per patient to achieve clinical success). This superiority was robust within the plausible range of probabilities according to the sensitivity analyses. CONCLUSIONS: The PPI-first strategy is superior to the H2RA-first "step-up" strategy with regard to both efficacy and cost-effectiveness and therefore, the PPI-first strategy is the preferred therapeutic approach for the acute medical treatment of reflux esophagitis.

A review of the clinical and economic impact of using esomeprazole or lansoprazole for the treatment of erosive esophagitis.

BACKGROUND: The use of proton pump inhibitors (PPIs) for the treatment of erosive esophagitis has had a major impact on the prescribing budgets of primary care organizations in the United Kingdom. Assessments of the clinical and economic effectiveness of PPIs would provide useful tools for decision-making. OBJECTIVE: The goal of this study was to review the available preclinical and clinical studies comparing esomeprazole with lansoprazole in the healing and maintenance of erosive esophagitis, and to compare the budgeting impact of the 2 strategies. Comparative tolerability was also reviewed. METHODS: MEDLINE (1966-September 2002) and EMBASE (1980-September 2002) were searched for abstracts and articles reporting comparative studies of esomeprazole and lansoprazole. The search terms used were gastroesophageal reflux disease, reflux esophagitis, and proton pump inhibitor; all comparisons of esomeprazole and lansoprazole at any dose were considered. The database search was supplemented based on the authors' familiarity with the literature. RESULTS: The comparative studies that were identified fell into 4 categories: (1) intragastric acid suppression studies; (2) randomized controlled trials in the healing of erosive esophagitis; (3) randomized controlled trials in the maintenance of erosive esophagitis; and (4) health economic analyses. Based on these studies, when healing doses (esomeprazole 40 mg once daily, lansoprazole 30 mg once daily) and low doses (20 and 15 mg once daily, respectively) were compared, esomeprazole was more efficacious than lansoprazole in suppressing acid in the intragastric compartment (both comparisons, P < 0.05). More patients with erosive esophagitis experienced healing at 4 and 8 weeks with esomeprazole 40 mg once daily than with lansoprazole 30 mg once daily (P < 0.001 at 4 and 8 weeks). At 6 months, remission was maintained in more patients receiving esomeprazole 20 mg once daily than in those receiving lansoprazole 15 mg once daily (P < 0.001). No significant differences in tolerability were noted in clinical trials that directly compared the 2 PPIs. When the cost-effectiveness of esomeprazole treatment was compared with that of lansoprazole treatment in the healing and maintenance of erosive esophagitis, the greater efficacy of esomeprazole translated into potential cost savings and better outcomes. CONCLUSION: The currently available comparative data for esomeprazole and lansoprazole indicate clinical and cost-effectiveness advantages for esomeprazole in the healing and maintenance of erosive esophagitis compared with lansoprazole.

Medical or surgical therapy for erosive reflux esophagitis: cost-utility analysis using a Markov model.

OBJECTIVE: To compare the cost and utility of healing and maintenance regimens of omeprazole and laparoscopic Nissen fundoplication (LNF) in the framework of the Canadian medical system. SUMMARY BACKGROUND DATA: Medical therapy with proton pump inhibitors for endoscopically proven reflux esophagitis is a safe and effective treatment option. Of late, the surgical treatment of choice for this disease has become LNF. METHODS: The authors' base case was a 45-year-old man with erosive reflux esophagitis refractory to H2-blockers. A cost-utility analysis was performed comparing the two strategies. A two-stage Markov model (healing and maintenance phases) was used to estimate costs and utilities with a time horizon of 5 years. Discounted direct costs were estimated from the perspective of a provincial health ministry, and discounted quality-of-life estimates were derived from the medical literature. Sensitivity analyses were performed to test the robustness of the model to the authors' assumptions and to determine thresholds. A Monte Carlo simulation of 10,000 patients was used to estimate variances and 95% interpercentile ranges. RESULTS: For the 5-year period studied, LNF was less expensive than omeprazole (3519.89 dollars vs. 5464.87 dollars per patient) and became the more cost-effective option at 3.3 years of follow-up. The authors found that 20 mg/day omeprazole would have to cost less than 38.60 dollars per month before medical therapy became cost effective; conversely, the cost of LNF would have to be more than 5,273.70 dollars or the length of stay more than 4.2 days for medical therapy to be cost effective. Estimates of quality-adjusted life-years did not differ significantly between the two treatment options, and the incremental cost for medical therapy was 129,665 dollars per quality-adjusted life-years gained. CONCLUSIONS: For patients with severe esophagitis, LNF is a cost-effective alternative to long-term maintenance therapy with proton pump inhibitors.

Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK.

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.

Cost-effectiveness of proton-pump inhibitors for maintenance therapy of erosive reflux esophagitis.

The relative cost-effectiveness of proton-pump inhibitors (PPIs) in the maintenance therapy of erosive reflux esophagitis was studied. Decision analysis was used to model the cost-effectiveness of PPIs on the basis of clinical trial results. Management decisions in the model were based on published U.S. guidelines and recommendations. Probability estimates were derived from a systematic review of the literature. The model's base-case scenario compared rabeprazole, lansoprazole, and omeprazole for the prevention of symptom recurrence over one year. Meta-analyzed estimates of efficacy were derived from trials by using a generalized logistic regression model with random effects. Medical costs for hospitalization, procedures, and office visits reflected 2000 Medicare payment; drug costs were based on 2000 average wholesale prices. Average costs per patient were comparable among the PPIs (rabeprazole, $1414; lansoprazole, $1671; and omeprazole, $1599). Rabeprazole prevented symptom recurrence in 86% of rabeprazole recipients, versus 68% for lansoprazole and 81% for omeprazole, and yielded the lowest average cost-effectiveness ratio (rabeprazole, $1637 per recurrence prevented; lansoprazole, $2439; and omeprazole, $1968). The model was robust to changes in key variables. When evaluated by decision analysis over a wide range of assumptions, rabeprazole was comparable to other PPIs in terms of cost and offered improved effectiveness for maintenance therapy of erosive reflux esophagitis.

[Cost-effectiveness of the treatment of reflux esophagitis: proton pump inhibitor versus histamine-2-receptor antagonist].

Gastroesophageal reflux disease(GERD) is a common condition and acid-suppressing agents are the mainstays of treatment. A clinical decision analysis comparing a proton pump inhibitor(PPI), lansoprazole and a histamine H2-receptor antagonist (H2RA), ranitidine for the treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The PPI was consistently superior to the H2RA with regard to both clinical effectiveness and cost-effectiveness. Prescription of PPIs for a one-month period would further enhance the cost-effectiveness of PPI treatment. The PPI first strategy is the preferred therapeutic approach for medical treatment of reflux esophagitis. We also recommend that prescription of PPIs for a one-month period be approved by the Japanese health insurance scheme.

Economic considerations in the treatment of gastroesophageal reflux disease: a review.

Gastroesophageal reflux disease is a common problem. Most patients with erosive GERD require long-term treatment, without which relapse is common. The cost of ongoing medical care for GERD is substantial, and patients with symptomatic GERD have impaired quality of life. Treatment strategies for GERD should aim to improve patient outcome at a reasonable cost. Cost-effectiveness methodology facilitates the integration of costs and patient outcomes, enabling the clinician to choose the most cost-effective therapy in a variety of clinical circumstances. The published studies reviewed in this paper show that proton pump inhibitors are the most cost-effective initial and maintenance medical therapy for GERD under most circumstances. However, variations in drug acquisition costs, such as may occur in managed care practice settings, may lead to H2-receptor antagonists being preferred under some circumstances. In the long-term management of GERD, laparoscopic surgery is effective, but its high initial cost makes it less cost-effective than proton pump inhibitors in the early treatment years. Also, recent data suggest that the long-term morbidity is higher than previously suspected. Finally, appropriate application of cost-effectiveness analyses to clinical practice requires critical appraisal of model design and the perspective adopted. The purpose of this article is to describe the interpretation and application of the results of cost-effectiveness analyses in clinical practice, and to examine the published literature on the cost-effectiveness of treatment options for GERD.

Sample size calculation in economic evaluations.

A simulation method is presented for sample size calculation in economic evaluations. As input the method requires: the expected difference and variance of costs and effects, their correlation, the significance level (alpha) and the power of the testing method and the maximum acceptable ratio of incremental effectiveness to incremental costs. The method is illustrated with data from two trials. The first compares primary coronary angioplasty with streptokinase in the treatment of acute myocardial infarction, in the second trial, lansoprazole is compared with omeprazole in the treatment of reflux oesophagitis. These case studies show how the various parameters influence the sample size. Given the large number of parameters that have to be specified in advance, the lack of knowledge about costs and their standard deviation, and the difficulty of specifying the maximum acceptable ratio of incremental effectiveness to incremental costs, the conclusion of the study is that from a technical point of view it is possible to perform a sample size calculation for an economic evaluation, but one should wonder how useful it is.

Proton pump inhibitors or histamine-2 receptor antagonists for the prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis.

OBJECTIVES: Erosive esophagitis is a recurring condition for which many patients require preventive therapy. If maintenance therapy must be provided, the most cost-effective treatment strategy should be established. We evaluated the costs and benefits associated with three treatment strategies: 1) maintenance therapy with a proton pump inhibitor (PPI) strategy, 2) maintenance therapy with a high-dose histamine-2 receptor antagonist (H2RA) strategy, and 3) maintenance therapy with a standard-dose H2RA. If patients experience a symptomatic recurrence on the H2RA strategies, they then receive PPI maintenance. METHODS: We used a cost-effectiveness model with a 1-yr time frame; data were obtained from randomized trials of lansoprazole and ranitidine, from case series, and expert opinion. RESULTS: In most situations, the high-dose H2RA strategy is the most costly, yet it is less effective than the PPI strategy. Among the remaining two options, the PPI strategy is more costly and more effective than the standard-dose H2RA strategy, requiring an additional $52-688 per recurrence prevented, depending on drug acquisition costs. The greater the degree to which esophagitis decreases quality of life, the more cost effective is the PPI strategy. For example, with a $50,000 per quality-adjusted life year cost-effectiveness threshold and a market-weighted average of drug costs, the PPI strategy appears cost effective for those patients who report that symptoms of esophagitis cause greater than a 9% decrement in quality of life. CONCLUSIONS: The high-dose H2RA strategy is not preferred in terms of either costs or benefits. The PPI strategy appears cost effective relative to the standard-dose H2RA strategy in the following situations: when patients are significantly bothered by esophagitis and in institutional settings where the difference in drug costs between PPIs and H2RAs is small.

Prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis of maintenance proton pump inhibition.

PURPOSE: To determine the cost-effectiveness of three management strategies for healed erosive reflux esophagitis: maintenance therapy with a proton pump inhibitor (PPI) from the outset; no maintenance therapy unless a patient's symptoms recur once over a year; and no maintenance therapy unless a patient's symptoms recur twice over a year. MATERIALS AND METHODS: Decision analysis using data from randomized trials of lansoprazole, case series, and expert opinion. RESULTS: For patients with grade 4 esophagitis, maintenance from the outset is the most efficient approach. For all other patients, providing maintenance PPI after a patient experiences two recurrences is the least costly but least effective approach. The other two approaches prevent more recurrences: waiting to initiate maintenance therapy until symptoms recur once requires an additional $73 for each recurrence prevented whereas maintenance PPI from the outset requires an additional $819 for each recurrence prevented. Maintenance therapy from the outset is cost effective if symptoms of esophagitis cause a 22% or greater decrement in quality of life (using $50,000 per quality-adjusted life year gained as a cost-effectiveness definition). However, withholding maintenance until the time of a first recurrence is cost effective if symptoms cause a 2% or greater decrement in quality of life. CONCLUSION: For grades 2 and 3 esophagitis, providing maintenance therapy after a patient experiences a further recurrence is a preferred option that appears cost-effective across a wide array of assumptions. Maintenance therapy from the outset, however, appears cost-effective only for those patients who report a significant decline in quality of life associated with esophagitis or for those patients with baseline grade 4 esophagitis.

Contingent valuation with an open-ended follow-up question: a test of scope effects.

It has been suggested that an open-ended follow-up question should be added to the binary contingent valuation question. Before this is generally recommended, it is important to evaluate the properties of such follow-up questions. Using a split sample approach, we test whether the open-ended follow-up is sensitive to the scope of the commodity being valued. No significant scope effects were detected. It is concluded that the results obtained do not support the use of an open-ended follow-up in contingent valuation applications.

Valuation of health changes with the contingent valuation method: a test of scope and question order effects.

In recent years, there has been a growing interest in the contingent valuation method for measurement of monetary values of various commodities. However, the validity and reliability of the method need to be examined thoroughly. This paper reports results of a test of scope and question order effects in a contingent valuation experiment in the health care field. Using three binary valuation questions, data were collected on willingness to pay for superior treatment of reflux oesophagitis. To test for scope effects, different probabilities of successful short- and long-term treatments were evaluated using a split sample approach. The presence of question order effects was tested by assigning respondents to different question orders. The contingent valuation method proved sensitive to changes in scope in that the willingness to pay increased with the probability of being free from symptoms and with a reduced risk of having a relapse once recovered. Also, regression analysis indicate that people who suffer from severe reflux oesophagitis are more willing to pay for more effective treatment. No question order effects were detected in the data.

Economic evaluation in gastrointestinal disease.

Safety and efficacy are not the only parameters of interest in the choice of medical technology--costs are playing an increasingly important role. There is growing interest in 'value for money', which can be assessed economically by comparing the costs and consequences of alternative courses of action. A number of different economic evaluation methods may be used: cost-minimization (only costs examined with no consideration given to consequences); cost-effectiveness (in which a unidimensional clinical outcome is assessed, for example, life-years gained); cost-utility (multidimensional outcomes measured, for example quantity and quality of life); and cost-benefit (where outcome is considered in monetary terms). Ulcer disease offers several examples of how economic evaluation can be used to address issues related to efficiency and value for money in healthcare. In a study of reflux oesophagitis, omeprazole was shown to be more cost-effective than ranitidine in a 12-week treatment study. With omeprazole the costs were lower and the effectiveness better than with the H2-receptor antagonist. In a later study the cost-effectiveness of omeprazole and ranitidine are compared for both intermittent and maintenance treatment in reflux oesophagitis. Using a Markov chain approach, Swedish cost data and studying a time period of 12 months, it found that omeprazole is both more effective in providing healthy days and less costly than ranitidine for both treatment strategies. The comparison between intermittent treatment and maintenance treatment with omeprazole shows that the latter is more effective but also more costly. It is concluded that the relative cost-effectiveness of omeprazole maintenance treatment increases with the risk of relapse when off treatment, the severity of symptoms following relapse, and the value of healthy days, i.e. days free from reflux oesophagitis. A model analysis comparing Helicobacter pylori eradication with conventional treatments in patients with duodenal ulcer disease has shown H. pylori eradication to be cost-effective when compared with either episodic therapy using omeprazole or maintenance therapy with ranitidine. The study used a Markov chain approach, and included the cost of treatment, in Swedish crowns, in a Swedish primary care setting over a period of 5 years. In the analysis, patients receiving conventional therapy were initially healed with omeprazole, 20-40 mg once daily. Following healing patients were either treated with further courses of omeprazole upon relapse or were given maintenance treatment with ranitidine, 150 mg once daily. The patients who were assigned to the H. pylori eradication therapy group were initially given an H. pylori test. Those patients who proved positive for the bacterium received omeprazole, 20 mg twice daily, plus amoxicillin, 2000 mg daily in divided doses, for 2 weeks, followed by omeprazole, 20 mg once daily, for a further 2 weeks to ensure healing. Patients who were H. pylori-negative were assigned to receive either episodic or maintenance therapy as described above. The model assumption applied in the H. pylori eradication group was that, following successful healing and H. pylori eradication, virtually all patients were cured and experienced no relapse during the following 5 years. by contrast, almost all the patients assigned to episodic therapy relapsed, and during maintenance therapy with H2-receptor antagonists, most patients experienced at least one relapse. Although H. pylori eradication resulted in initial higher costs than the alternative strategies, it reduced the risk of recurrence and for most patients there were no future costs. The investment therefore paid off within a relatively short period of time. Even when unfavourable assumptions were made, such as an H. pylori eradication rate of only 50%, the H. pylori eradication strategy had a pay-off period of less than 1.3 years compared with maintenance treatment, and 3 years compared with episodic

Cost and quality effects of treating erosive oesophagitis. A re-evaluation.

The objective of this study was to re-evaluate the clinical and economic effects of common therapies for erosive oesophagitis in the light of a newly approved treatment regimen. A previously constructed 7-month community practice decision analytical model was revised to include the latest published data on efficacy and symptomatic outcomes. The original results of phase I therapy (antacids plus dietary, sleeping and lifestyle changes) alone or combined with ranitidine 150mg bid or omeprazole 20mg od were reassessed by adding new clinical data on the efficacy of and symptomatic response to ranitidine 150mg qid. The same payment data used in the first analysis were applied here as well, with the addition of the US price of ranitidine 150mg qid. The study perspective was that of the payer or insurer. Omeprazole-based therapy remained a dominant strategy for symptomatic care during the 7-month model. It was 14% less costly per patient, led to 23% fewer symptomatic months, and had 21% lower cost per symptom-free month than ranitidine 150mg qid, the next best alternative. Evolving treatment strategies necessitate rapid assessment and reassessment so that clinical practice can remain current, patients can be assured of the best quality, and insurers can be aware of treatment cost and budgetary impact given limited resources in all countries. Only by consistent and continuous re-evaluation of new or changing medical interventions can clinicians and insurers adapt patient management to new scientifically derived results. This is the best manner by which to meet patients' care needs and the clinical needs of practitioners, as well as the financial needs of payers.