|Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies
|Wahlqvist P, Junghard O, Higgins A, Green J
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
Three strategies for the treatment of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis were examined:
on-demand treatment with esomeprazole 20 mg (ESO);
intermittent 4-week acute treatment courses of omeprazole 20 mg once daily (prescribed in response to relapse while on no drug therapy; OME-INT); and
continuous omeprazole treatment (20 mg once daily) following acute treatment of first relapse (OME-CONT).
Economic study type
The study population comprised a hypothetical cohort of patients with GORD without oesophagitis.
The setting was primary and secondary care. The economic study was conducted in the UK.
Dates to which data relate
The effectiveness data were derived from studies published between 1998 and 2001. The resource use data were mainly derived from a study published in 2001. The price year was not reported.
Source of effectiveness data
The effectiveness evidence was derived from a review of completed studies.
A simple Markov model was used to assess the long-term costs and effectiveness of the three alternative treatment strategies under evaluation. The time horizon of the model was 6 months and each Markov cycle lasted 2 weeks. The structure of the model was reported in the article. The model was based on several assumptions concerning the structure and patterns of care. The assumptions were, in part, derived from a survey of physicians (including 10 gastroenterologists and 15 general physicians). The model appears to have been deterministic.
Outcomes assessed in the review
The outcomes assessed from published studies were the probabilities of relapse associated with the three treatments. These values were estimated from the rate of discontinuation (due to an unwillingness to continue) for ESO. For the OME strategies, the rate of relapse associated with placebo (in the study comparing ESO with placebo) was used as the lower limit, while that associated with no treatment was used as the upper limit. Therefore, two different scenarios were considered. The rate of relapse associated with no treatment was obtained from a study where patients did not receive placebo and were not provided with antacids as rescue medication.
Study designs and other criteria for inclusion in the review
The evidence on ESO and placebo (lower limit) came from two randomised, double-blind, parallel group, 6-month, clinical trials. The information on the relapse rate with no treatment came from a clinical trial, the design of which was not described. A literature search was conducted in December 2000 only to identify data on relapse rate with no treatment. The two trials on ESO and placebo were identified selectively.
Sources searched to identify primary studies
Criteria used to ensure the validity of primary studies
The validity of the study was implicitly ensured by the robust design (randomisation, double-blind, etc.).
Methods used to judge relevance and validity, and for extracting data
Number of primary studies included
The effectiveness data were mainly derived from three primary studies.
Methods of combining primary studies
The two trials on ESO and placebo were pooled as if they were one large single study.
Investigation of differences between primary studies
The authors stated that the two studies had identical treatment protocols and the unique difference was that the patients were randomised in different proportions.
Results of the review
The rate of discontinuation was 10% (95% confidence interval, CI: 7 - 13) for ESO and 47% (95% CI: 41 - 52) for placebo (lower limit). The reasons for discontinuation were insufficient control of heartburn (8% versus 44%), adverse event (1% versus 2%), and other reasons (1% versus 0%).
The rate of relapse during no drug therapy (upper limit) was 75%.
Measure of benefits used in the economic analysis
The summary benefit measure used was the relapse rate over a 6-month period. It was derived using modelling. No discounting was applied. Side effects were considered in the measure.
Discounting was not relevant since the costs were incurred during a 6-month timeframe. The unit costs were reported separately from the quantities of resources used for most categories of costs. The health services included in the economic evaluation were primary care visit, gastroenterologist visit, endoscopy and study drugs. The cost/resource boundary of the study was that of the NHS. The resource use data were estimated using information retrieved from the trials used to provide the clinical data and from the same survey of physicians as that used to define treatment patterns in the decision model. Several assumptions were also reported to define the clinical treatment of patients with GORD without oesophagitis. The costs came from standard NHS sources. The price year was not reported.
Statistical analysis of costs
The costs were treated deterministically.
The indirect costs were not included in the economic evaluation.
A threshold analysis was conducted to assess the value at which the treatment strategies became cost neutral in terms of the medical costs. The cost of relapse in the on-demand strategy was considered as a separate unit cost. Further, the effect of substituting continuous treatment with OME 10 mg for OME 20 mg was also investigated.
Estimated benefits used in the economic analysis
Using the lower limit (47%) for probability of relapse while on no drug treatment, the expected number of relapses per patient over the 6-month period was 0.10 with ESO, 0.57 with OME-INT, and 0.47 with OME-CONT.
Using the upper limit (75%) for probability of relapse while on no drug treatment, the expected number of relapses per patient over the 6-month period was 0.10 with ESO, 1.12 with OME-INT, and 0.75 with OME-CONT.
Using the lower limit (47%) for probability of relapse while on no drug treatment, the expected costs per patient over the 6-month period were 63 with ESO, 75 with OME-INT, and 96 with OME-CONT.
The use of ESO led to reductions of 16% relative to OME-INT and 34% relative to OME-CONT.
Using the upper limit (75%) for probability of relapse while on no drug treatment, the expected costs per patient over the 6-month period were 63 with ESO, 147 with OME-INT, and 162 with OME-CONT.
The use of ESO led to reductions of 57% relative to OME-INT and 61% relative to OME-CONT.
Synthesis of costs and benefits
A synthesis of the costs and benefits was not relevant since ESO was dominant over both OME strategies, which were less effective and more expensive. The dominance of ESO was confirmed in all the sensitivity analyses conducted to test the robustness of the base-case results.
Compared with the omeprazole continuous and intermittent strategies (OME-CONT and OME-INT, respectively), on-demand esomeprazole (ESO) 20 mg led to better effectiveness and lower costs in the treatment of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis in the UK.
CRD COMMENTARY - Selection of comparators
The authors justified the choice of the comparators. OME-CONT represented conventional care, while OME-INT was included to cover all possible treatment strategies for patients with GORD without oesophagitis. The authors noted that other treatment options for GORD were lifestyle modifications, antacids, alginates, histamine H2 antagonists, and various PPIs. However, several studies showed that PPIs were significantly more effective in relieving symptoms and preventing recurrence than other strategies. The authors stated that a true continuous strategy was not included as a potential comparator, because it was not a licensed strategy and there were no comparative data available. Therefore, the choice of the comparators appears to have been appropriate. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The analysis of effectiveness used data derived from the literature. However, a formal review of the literature was conducted only to assess the probability of relapse in untreated patients. No information on the review was provided. Other key probability values were derived from studies that were selected individually. Details of the design were provided only for two primary studies, whose data were combined by pooling the final results as if they were a single study. The validity of the sources was ensured by the robust design of the studies. The authors also stated that the two studies were homogenous in terms of the methods and study protocol. These issues increase the validity of the effectiveness estimates, although the use of a more systematic review of the literature would have been helpful.
Validity of estimate of measure of benefit
The summary benefit measure was specific to the interventions under evaluation. Therefore, it would be difficult to compare it with the benefits of other health care interventions. It was obtained from the decision model, which appears to have been a valid tool for assessing the long-term effectiveness of the treatment strategies. The authors did not consider the impact of the intervention on quality of life, which, as they acknowledged, was an important dimension given the characteristics of the disease considered in the study.
Validity of estimate of costs
The authors explicitly stated which perspective was adopted in the study. It appears that all the relevant categories of costs have been included in the analysis. However, the adoption of a societal perspective and the inclusion of indirect costs would have been interesting, as GORD presumably has a substantial impact on productivity. The source of the data was reported for all items but the price year was not given, thereby limiting the possibility of carrying out reflation exercises in other settings. The unit costs were reported. Resource use was based on data derived from a survey of UK physicians, which represents a robust source of data. Several assumptions were also made to reflect treatment patterns in the UK. The costs were treated deterministically and were specific to the study setting. However, sensitivity analyses were conducted to assess the impact of variations in costs on the estimated cost-savings associated with ESO. This further enhanced the robustness of the cost analysis.
The authors did not compare their findings with those from other studies. They also did not address the issue of the generalisability of their results to other settings. Overall, the external validity of the analysis was low, although some sensitivity analyses were conducted. These showed that the dominance of ESO held across several scenarios. The study involved patients with GORD without oesophagitis and this was reflected in the conclusions of the study.
Implications of the study
The authors suggested that future studies should compare the cost-effectiveness of on-demand strategies with continuous treatments.
Source of funding
Supported by a grant from AstraZeneca, Molndal, Sweden.
Wahlqvist P, Junghard O, Higgins A, Green J. Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies. PharmacoEconomics 2002; 20(4): 267-277
Other publications of related interest
Carlsson R, Dent J, Watts R, et al. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. European Journal of Gastroenterology and Hepatology 1998;10;119-24.
Talley NJ, Lauritsen K, Tunturi-Hihnala H, et al. Esomeprazole 20mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months. Alimentary Pharmacology and Therapeutics 2001;15:347-54.
Subject indexing assigned by NLM
Adult; Cost-Benefit Analysis; Enzyme Inhibitors /economics /therapeutic use; Esomeprazole; Esophagitis /complications; Female; Gastroesophageal Reflux /drug therapy /economics; Great Britain; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Omeprazole /analogs & Proton Pump Inhibitors; derivatives /economics /therapeutic use
Date bibliographic record published
Date abstract record published