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'Proton-pump inhibitor-first' strategy versus 'step-up' strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan |
Habu Y, Maeda K, Kusuda T, Yoshino T, Shio S, Yamazaki M, Hayakumo T, Hayashi K, Watanabe Y, Kawai K |
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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 Two strategies for the treatment of patients with gastro-oesophageal reflux disease (GORD) were examined. One was an approach based on a first-line proton-pump inhibitor (PPI), lansoprazole 30 mg/day (LAN), for 8 weeks (plus a further 12 weeks for unhealed patients). The other was a step-up approach in which patients started with a histamine H2-receptor antagonist (H2RA), ranitidine 300 mg/day (RAN), for 8 weeks and then switched to LAN in case of failure.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of patients with endoscopically verified uncomplicated GORD.
Setting The setting was primary care. The economic study was carried out in Japan.
Dates to which data relate The effectiveness data were derived from studies published between 1982 and 1997. No dates for resource consumption were explicitly stated. The price year was 2005.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies.
Modelling A Markov model with a 5-month time horizon and a 4-week cycle length was used to assess the clinical and economic impact of the two treatments for GORD. A schematic representation of the model was presented. In the PPI-first strategy, patients received LAN for 8 weeks. Healed patients did not require further treatment and office visits, while unhealed patients received LAN for the rest of the study period. In case of relapse, the patients restarted LAN therapy for a further 12 weeks. In the step-up approach, patients received RAN for 8 weeks. Healed patients did not undergo further treatment or physician visits. Unhealed patients were switched to LAN for 8 weeks. If patients were still unhealed, they continued with LAN until the end of the follow-up period (further 4 weeks). In case of recurrence after initial healing, the patient started again with the step-up approach.
Outcomes assessed in the review The outcomes estimated from the literature were the healing rates and the relapse rates after successful healing.
Study designs and other criteria for inclusion in the review A comprehensive systematic review of the literature was undertaken to identify relevant studies on healing rates and relapse rates. All studies were open clinical trials performed in Japan with no random allocation of the patients to the treatment groups.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies All primary studies had to be performed in Japan to reflect the authors' setting.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included Eight primary studies provided clinical evidence.
Methods of combining primary studies Weighted mean values were calculated for healing rates. Median values were used for relapse rates.
Investigation of differences between primary studies Results of the review The mean healing rates with LAN were 0.87 after 4 weeks and 0.94 after 8 weeks.
The mean healing rates with RAN were 0.54 after 4 weeks and 0.63 after 8 weeks.
The median relapse rate after successful healing was 0.14 per month (95% confidence interval, CI: 0.075 to 0.24).
Measure of benefits used in the economic analysis The summary benefit measure was the number of disease-free days (DFDs). These were estimated using the decision model. No discounting was performed because of the short time horizon (5 months).
Direct costs The analysis of the costs was carried out from the perspective of the health care system. It included the costs of medications (including prescription and dispensing), visits and physical examination, routine blood tests, and endoscopic examination. Although the unit costs were presented, there were few details on the quantities of resources used. The costs were estimated from official charges specified by the Japanese health insurance system. Resource consumption was presumed to have been based on authors' assumptions, which reflected Japanese treatment patterns. In particular, it was assumed that endoscopies to confirm healing or recurrence of symptoms were performed in 29.5% of the patients. Given the short timeframe of the analysis, discounting was not relevant. The price year was 2005.
Statistical analysis of costs No statistical analyses of the costs were performed.
Indirect Costs The indirect costs were not included in the economic analysis.
Currency Japanese yen (JPY). The authors stated that one US dollar was equivalent to approximately JPY 110.
Sensitivity analysis A deterministic sensitivity analysis was performed to assess the impact of changes in clinical inputs on the cost-effectiveness ratios. Alternative values of healing rates were based on pooled data derived from five randomised clinical trials carried out in Western countries. Published CIs were used. Both one- and two-way sensitivity analyses were carried out.
Estimated benefits used in the economic analysis The number of DFDs was 140 with the PPI-first strategy and 123 with the step-up approach.
Cost results The direct medical costs per patient were JPY 29,558 with the PPI-first strategy and JPY 26,573 with the step-up approach.
Synthesis of costs and benefits Average cost-effectiveness ratios were calculated to combine the costs and benefits of the alternative strategies. The average cost per DFD was JPY 211 with the PPI-first strategy and JPY 217 with the step-up approach.
The results of the sensitivity analysis confirmed the robustness of the base-case results, since only in an extreme scenario (where the lowest healing rate with LAN and the highest healing rate with RAN were used) did the step-up approach have a lower average cost-effective ratio compared with the PPI-first strategy.
Authors' conclusions In Japan, the proton-pump inhibitor (PPI)-first strategy based on lansoprazole (LAN) for the treatment of gastro-oesophageal reflux disease (GORD) was more cost-effective than the step-up approach based on ranitidine (RAN). The PPI approach also led to fewer days of medications and endoscopic examinations, which might strongly affect quality of life.
CRD COMMENTARY - Selection of comparators The choice of the comparators appears to have been appropriate since the authors stated that PPIs and H2RAs were the two most commonly used antacid agents used for patients with GORD. Standard dosages were considered. RAN and LAN were considered as representative of their respective drug classes because they were widely used in Japan. The authors did not investigate the cost-effectiveness of alternative PPIs or H2RAs. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The primary studies used to estimate the clinical data used in the model were identified by performing an extensive review of the literature. Since Japanese data were required, only non-randomised studies were found and used in the analysis. Alternative data derived from Western clinical trials were used in the sensitivity analysis. The approach used to combine the primary estimates was reported, but the issue of homogeneity among the primary studies was not explicitly addressed. No information on the characteristics of the patients included in the studies was provided.
Validity of estimate of measure of benefit The summary benefit measure was specific to the disease considered in the study. It would not comparable with the benefits of other health care interventions. The impact of the treatments on quality of life was not considered although, as the authors noted, it might have been relevant given the characteristics of the disease.
Validity of estimate of costs The analysis of the costs was restricted to those medical costs relevant to the perspective of the health care system. The impact of other costs (e.g. productivity losses) was not considered, although the authors stated that the indirect costs would presumably be higher in the step-up approach, which was characterised by fewer DFDs and more office visits than the PPI strategy. A detailed breakdown of the cost items was reported and the unit costs were provided. This enhances the possibility of replicating the analysis in other settings. The estimation of resource consumption reflected Japanese treatment patterns, although this was not explicitly stated. The cost estimates were specific to the study setting, and the impact of variations in the costs or quantities of resource used was not tested. The price year was reported, which means that reflation exercises in other time periods should be possible.
Other issues The authors did not compare their findings with those from other studies. They also did not address the issue of the generalisability of the study results to other settings. The authors showed that the clinical results of Western studies were similar to those used in this study for the Japanese setting. It was highlighted that healing rates were slightly higher in Japan than in other countries, owing to a higher incidence of Helicobacter pylori, but the difference between healing rates with PPIs or H2RAs was consistent with Western countries. Limited sensitivity analyses were carried out on the costs, and the external validity of the study appears low. The issue of uncertainty around key model parameters was only partially addressed, given that cost values were not varied. Average cost-effectiveness ratios were calculated but an incremental analysis was not performed, although it would have been helpful. The study referred to patients with GORD and this was reflected in the authors' conclusions.
Implications of the study The study results support the use of PPIs as the first-line treatment for patients with GORD. An incremental analysis would be needed to confirm the results of this analysis which was based only on average values.
Bibliographic details Habu Y, Maeda K, Kusuda T, Yoshino T, Shio S, Yamazaki M, Hayakumo T, Hayashi K, Watanabe Y, Kawai K. 'Proton-pump inhibitor-first' strategy versus 'step-up' strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan. Journal of Gastroenterology 2005; 40(11): 1029-1035 Other publications of related interest Bate CM, Richardson PD. A 1 year model for cost-effectiveness of treating reflux esophagitis. Br J Med Econ 1992;2:5-11.
Hillman AL, Bloom BS, Fendrik AM, Schwartz JS. Cost and quality effects of alternative treatment for persistent gastroesophageal reflux disease. Arch Intern Med 1992;152:1467-72.
Stal JM, Gregor JC, Preiksaitis HG, Reynolds RP. A cost-utility analysis comparing omeprazole with ranitidine in the maintenance therapy of peptic esophageal stricture. Can J Gastroenterol 1998;12:43-9.
Indexing Status Subject indexing assigned by NLM MeSH 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents /economics /therapeutic use; Cost-Benefit Analysis; Decision Support Techniques; Esophagitis, Peptic /drug therapy /economics; Histamine H2 Antagonists /economics /therapeutic use; Humans; Japan; Lansoprazole; Models, Statistical; Omeprazole /analogs & Proton Pump Inhibitors; Ranitidine /economics /therapeutic use; derivatives /economics /therapeutic use AccessionNumber 22006000150 Date bibliographic record published 30/09/2006 Date abstract record published 30/09/2006 |
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