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Economic analysis of on-demand maintenance therapy with proton pump inhibitors in patients with non-erosive reflux disease |
Hughes D, Bodger K, Bytzer P, De Herdt D, Dubois D |
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Record Status 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. Health technology The study examined several on-demand maintenance therapies with oral proton-pump inhibitors (PPIs) in patients with endoscopy-confirmed non-erosive reflux disease (NERD). The PPIs studied were esomeprazole 20 mg, lansoprazole 15 mg, omeprazole 10 and 20 mg, pantoprazole 20 mg and rabeprazole 10 mg.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of symptomatic, endoscopy-confirmed NERD patients, who were treated for 4 weeks with continuous PPI treatment until complete resolution of heartburn. They received on-demand PPI treatment, with antacids if required, for at least 6 months.
Setting The setting was primary care. The economic study was carried out in the UK.
Dates to which data relate The clinical data came from studies published between 1999 and 2004, while the resource use data were estimated from a study published in 2000. The price year was 2003.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of completed studies and authors' opinions.
Modelling Owing to the lack of head-to-head trials, an analytic model was used to enable a direct comparison of the different PPIs. Weibull functions were used to model persistence with on-demand therapy. The model extrapolated beyond the 6-month horizon of the trials to 1 year in order to reflect symptom chronicity. Indirect comparisons were performed using placebo as the common comparator (placebo in esomeprazole trials for the base-case). The patients represented in the analysis were typically 50-year-old adults with endoscopy-confirmed NERD, with no significant co-morbidities or history of erosive reflux disease, ulceration or other severe gastrointestinal disease.
Outcomes assessed in the review The outcomes estimated from the literature were drug efficacy (time to discontinuation because of insufficient symptom control) and utility values.
Study designs and other criteria for inclusion in the review A systematic review of the literature was undertaken to identify clinical trials reporting information on drug efficacy. Only trials reporting the proportion of patients who discontinued as an end point, and with a study population comparable to that considered in the current pharmacoeconomic study, were included. The sample size, patients' demographics and other clinical characteristics were provided in detail for each selected trial. The utility values were derived from a survey of 1,011 Swedish and German patients with a diagnosis of reflux disease, with heartburn as the predominant symptom, and a history of heartburn with or without erosive changes for at least 1 year. The patients were administered the EuroQoL Five-Dimension Questionnaire (EQ-5D).
Sources searched to identify primary studies MEDLINE (from 1966) and EMBASE (from 1988) were searched for studies on drug efficacy. In addition, journal supplements of recent gastroenterology conference proceedings were scanned and the authors of unpublished studies were contacted for further details.
Criteria used to ensure the validity of primary studies The validity of the primary studies was ensured by the inclusion of clinical trials.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included There were eight primary studies in total. Seven clinical trials were used for efficacy data, while another study provided the utility data.
Methods of combining primary studies The results of the trials were pooled, weighted according to the number of patients in each trial.
Investigation of differences between primary studies Although the seven clinical trials were quite comparable with respect to baseline characteristics, the authors noted that were some differences among the trials in how "on demand" was defined.
Results of the review The median time to discontinuation was:
33 months with esomeprazole 20 mg;
19.1 months with lansoprazole 15 mg;
10.1 months with omeprazole 10 mg and 15.3 months with omeprazole 20 mg;
25.4 months with pantoprazole 20 mg; and
55.8 months with rabeprazole 10 mg.
The estimates of health-state utilities that had been derived directly from the survey were not reported.
Methods used to derive estimates of effectiveness The authors made some assumptions that were used in the analytic model.
Estimates of effectiveness and key assumptions In the model, patients who discontinued on-demand treatment received continuous PPI treatment and symptoms were fully resolved.
In mild, moderate or severe symptom states for each drug, the proportion, but not the duration, was the same as that for rabeprazole, as not all trials reported the proportions of patients in each state.
Measure of benefits used in the economic analysis The summary benefit measure used was the utility value associated with 1 year of PPI treatment. This was assessed using the analytic model. The utility values were taken from the literature using the EQ-5D.
Direct costs The analysis of the costs was carried out from the perspective of the NHS. The health services included in the economic evaluation were PPIs, patient prescription co-payment (only for 15% of the patients), antacid, pharmacy dispensing fee, general practitioner consultation, gastroenterologist consultation and upper gastrointestinal endoscopy. The unit costs were presented separately from the quantities of resources used for the majority of items. Resource use was based on a UK-based database that reported data at two urban general practices covering over 1,100 consultations for all-cause dyspepsia over a 1-year period. The costs and pharmacy dispensing fees were calculated from the Drug Tariff, while the other costs were obtained from Personal Social Service Research Units and a published study. Discounting was not relevant as the costs were incurred during one year. The price year was 2003.
Statistical analysis of costs The costs were presented as median values with percentiles (5th, 95th). A Kruskal-Wallis one-way analysis of variance with Dwass-Steel-Chritchlow-Fligner pair-wise comparisons was used to compare the costs.
Indirect Costs The indirect costs were not considered.
Currency Euros (Euro). The costs were estimated in UK pounds sterling () and then converted into Euros. The exchange rate was Euro 1 = 0.70.
Sensitivity analysis A Monte Carlo simulation with 1,000 replications was performed to address uncertainty in random variables. The probability distribution assigned to each model input was reported. An extensive univariate sensitivity analysis was also carried out to test the assumptions of the model. In particular, the choice of placebo group used for normalising data across the trials; the proportion of patients in the asymptomatic, mild, moderate or severe symptom states; the recording of the costs and benefits at 6 months; and the impact of changing sociodemographic characteristics.
Estimated benefits used in the economic analysis The median (5th, 95th percentile) utility values were:
0.89 (0.67, 0.99) for esomeprazole 20 mg;
0.91 (0.67, 1.00) for lansoprazole 15 mg;
0.91 (0.66, 1.00) for omeprazole 10 mg and 0.90 (0.68, 0.99) for omeprazole 20 mg;
0.90 (0.69, 0.99) for pantoprazole 20 mg; and
0.89 (0.69, 0.98) for rabeprazole 10 mg.
Differences in the utility values were not statically significant for any comparison.
Cost results The median (5th, 95th percentile) costs were:
Euro 190 (143, 384) for esomeprazole 20 mg;
Euro 195 (126, 364) for lansoprazole 15 mg;
Euro 210 (130, 351) for omeprazole 10 mg and Euro 201 (140, 367) for omeprazole 20 mg;
Euro 176 (111, 343) for pantoprazole 20 mg; and
Euro 123 (96, 324) for rabeprazole 10 mg.
Rabeprazole was statistically less expensive than the other strategies. The sensitivity analysis confirmed the robustness of the model results since none of the variations considered in the sensitivity analysis altered the rank ordering of the drugs.
Synthesis of costs and benefits A synthesis of the costs and benefits was not relevant as, owing to the lack of statistically significant differences in the benefit measure between the groups, a cost-minimisation analysis was performed.
Authors' conclusions The on-demand use of rabeprazole for the treatment of non-erosive reflux disease (NERD) incurred the least costs in comparison with the other proton-pump inhibitors (PPIs). Such cost-savings were mainly attributable to the reduced annual number of prescriptions.
CRD COMMENTARY - Selection of comparators The selection of the comparators was appropriate as all relevant PPIs were considered in the analysis. To reflect all possible treatment patterns, two dosages of omeprazole were considered. Other treatment strategies, such as over-the-counter medications or continuous or intermittent PPI, were not considered as comparators because the analysis focused on on-demand PPI. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The evidence on treatment efficacy came from a review of the literature, the methods and conduct of which were reported. Inclusion criteria were stated and the method used to pool the primary estimates was provided. The use of clinical trials ensured a high internal validity. The authors noted some differences in the definition of the clinical end point, but the primary studies were quite comparable. The baseline characteristics of the patients enrolled in each trial were reported. The utility weights were obtained from a published study, which was selectively identified. Extensive information on the source of the utility weights was provided. Some assumptions were also made and were tested in the sensitivity analysis.
Validity of estimate of measure of benefit The authors justified the choice of the benefit measure, and explained their reasons for not using quality-adjusted life-years since the differences in utility values between groups did not reach statistical significance. Further, it appears that the impact of treatment on survival is not an issue in the case of PPI. The authors noted that the use of utility weights extracted from German and Swedish patients might represent a limitation of the analysis since such data could not be generalised to UK patients. However, the German/Swedish study represented the most reliable source available. It should be noted that utility values estimated using a specific approach are not easily compared with the benefits of other health care interventions.
Validity of estimate of costs The costs included were consistent with the perspective adopted in the study. Typical NHS sources were used to derive the unit costs, which were reported. The resource use data came from a survey carried out at two general practices and information on resource consumption was reported for many items. In general, the study will be replicable in other settings since extensive information on the methods of calculating the costs was provided. Statistical analyses were performed and the types of tests used were described. Some key cost estimates were varied in the sensitivity analysis. The price year was reported, which will facilitate reflation exercises in other time periods.
Other issues The authors stated that comparisons with the results from other studies were not feasible because of the choice of using different benefit measures. The issue of the generalisability of the study results to other settings was addressed in the sensitivity analysis, in which alternative values were considered. The study referred to patients diagnosed negative for erosive mucosal injury by endoscopy and who responded fully to acute PPI therapy, and this was reflected in the authors' conclusions. The study results were clearly presented.
Implications of the study The results of the analysis support the use of rabeprazole as on-demand therapy for the treatment of endoscopy-confirmed NERD.
Source of funding Funded by Janssen Pharmaceutica N.V., Belgium.
Bibliographic details Hughes D, Bodger K, Bytzer P, De Herdt D, Dubois D. Economic analysis of on-demand maintenance therapy with proton pump inhibitors in patients with non-erosive reflux disease. PharmacoEconomics 2005; 23(10): 1031-1041 Other publications of related interest Inadomi JM. On-demand and intermittent therapy for gastrooesophageal reflux disease: economic considerations. Pharmacoeconomics 2002;20:565-76.
Wahlqvist P, Junghard O, Higgins A, et al. Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies. Pharmacoeconomics 2002;20:267-77.
Goeree R, O'Brien B, Hunt R, et al. Economic evaluation of long term management strategies for erosive oesophagitis. Pharmacoeconomics 1999;16:679-97.
Gerson L B, Robbins A S, Garber A, et al. A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Am J Gastroenterol 2000;95:395-407.
Indexing Status Subject indexing assigned by NLM MeSH Anti-Ulcer Agents /economics /therapeutic use; Clinical Trials as Topic; Cost-Benefit Analysis; Female; Gastroesophageal Reflux /drug therapy /economics; Heartburn /drug therapy /economics; Humans; Linear Models; Male; Middle Aged; Proton Pump Inhibitors AccessionNumber 22005008466 Date bibliographic record published 31/03/2006 Date abstract record published 31/03/2006 |
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