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Low-dose or standard-dose proton pump inhibitors for maintenance therapy of gastro-oesophageal reflux disease: a cost-effectiveness analysis |
You J H, Lee A C, Wong S C, Chan F 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 The study compared standard-dose histamine-2 receptor antagonist (H2RA), low-dose proton-pump inhibitor (PPI) and standard-dose PPI as maintenance therapy in patients with gastrooesophageal reflux disease (GERD). The H2RAs studied were ranitidine (150 mg twice daily) and famotidine (20 mg/day). The low-dose PPIs were omeprazole (10 mg/day) and lanzoprazole (15 mg/day). The standard-dose PPIs were omeprazole (20 mg/day), lanzoprazole (30 mg/day), pantoprazole (40 mg/day) and rabeprazole (20 mg/day).
Study population The study population comprised a hypothetical cohort of patients with healed oesophagitis who were in remission. No further inclusion or exclusion criteria were reported.
Setting The setting was secondary care. The economic study was carried out in Hong Kong, China.
Dates to which data relate The effectiveness data were collected from studies published between 1991 and 2001. The quality-adjusted life-years (QALYs) were derived from a study published in 1998. The dates to which the costs related and the price year were not reported.
Source of effectiveness data The effectiveness data were derived from a review and synthesis of completed studies.
Modelling A Markov model was designed to simulate the clinical outcomes and health care resource use. The time horizon of the model was 12 months with monthly cycles. In each month, patients might remain in remission or experience symptomatic relapse of GERD. The patients who remained in remission on standard-dose H2RA or low-dose PPI were maintained on the same regimen. Patients who experienced symptomatic relapse on standard-dose H2RA or low-dose PPI were stepped up to standard-dose PPI. If GERD symptoms persisted, or symptomatic relapse occurred with standard-dose PPI, patients were stepped up to high-dose PPI. Patients who were non-responsive to high-dose PPI underwent oesophago- gastro-duodenoscopy, 24-hour pH monitoring and evaluation for surgery. Patients who experienced relapse when the therapy was stepped down were placed on the previous regimen, with remission for the remaining time.
Outcomes assessed in the review The outcomes used to derive input parameters for the model were:
for maintenance therapy, the monthly transition probabilities of symptomatic relapse during standard-dose H2RA, low-dose PPI and standard-dose PPI; and
for active therapy, the monthly transition probabilities of treatment success with standard-dose PPI and high-dose PPI.
Study designs and other criteria for inclusion in the review Clinical trials that involved symptom-free patients with healed oesophagitis were selected. For assessing monthly probabilities of treatment success with standard-dose PPI and high-dose PPI, clinical trials involving patient with Savary-Miller classification grade I-III oesophagitis were used.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Not reported. However, the authors appear to have selected studies appropriate to their study question, and selected information that would assist in their analysis.
Number of primary studies included Approximately 20 studies were used to derive data for the model.
Methods of combining primary studies Investigation of differences between primary studies Results of the review For maintenance therapy, the monthly transition probability of symptomatic relapse was:
0.053 (95% confidence interval, CI: 0.051 - 0.55) with standard-dose H2RA;
0.026 (95% CI: 0.024 - 0.031) with low-dose PPI; and
0.021 (95% CI: 0.018 - 0.023) with standard-dose PPI.
For active therapy, the monthly transition probability of response was:
0.49 (95% CI: 0.47 - 0.50) with standard-dose PPI; and
0.55 (95% CI: 0.44 - 0.66) with high-dose PPI.
Measure of benefits used in the economic analysis The measures of benefit used were the number of symptom-free patient-years gained and the number of QALYs gained. The symptom-free patients-years gained were calculated from the model. Utility scores for symptomatic GERD were derived from a published study using the time trade-off method and were used to estimate the QALYs. The utility score for the symptom-free states of GERD was assumed to be unity. The health states were not valued in this study.
Direct costs The costs were estimated from the perspective of a public health organisation. The quantities were estimated using actual data and they were retrieved retrospectively from the medical records of GERD patients treated in a public hospital in Hong Kong. The cost analysis focused on the cost of clinic visits, hospitalisation, drugs for the management of GERD, and diagnostic tests. The quantities and the costs were not reported separately. Charges were used to proxy prices for itemised health care services in public hospitals. These were retrieved from a published source (Hong Kong Gazette). The drug costs were based on the Hospital Authority-specific acquisition costs. The time horizon of the model was varied from 1 to 5 years in the sensitivity analysis. Discounting was not carried out but, as the time-horizon of the base-case model was only one year, it would not have been relevant. The dates to which the costs related and the price year were not reported.
Statistical analysis of costs There was no stochastic analysis of the costs.
Indirect Costs No indirect costs were reported.
Currency US dollars ($). No conversion rate was reported.
Sensitivity analysis A sensitivity analysis, with all the clinical probabilities and direct medical costs, was carried out to examine the robustness of the data. The ranges for the monthly transition probabilities and monthly direct medical costs of symptomatic and asymptomatic months were based on the 95% CIs. The ranges used for the other monthly costs were +/- 20% of the base-case value. The effect of generic pricing of omeprazole was also examined.
Estimated benefits used in the economic analysis Of the three maintenance strategies, standard-dose PPI was dominant, generating 0.954 symptom-free patient-years and 0.999 QALYs. This was followed by low-dose PPI (0.934 symptom-free patient-years and 0.998 QALYs) then standard-dose H2RA (0.887 symptom-free patient-years and 0.997 QALYs).
Cost results The costs were reported per patient. The total cost per patient was $904 with standard-dose PPI, $1,372 with low-dose PPI and $1,628 with standard-dose H2RA. The expected direct medical cost per patient in the standard-dose PPI group was $468 lower than in the low-dose PPI group and $724 lower than in the standard-dose H2RA group.
Synthesis of costs and benefits Standard-dose PPI was the dominant treatment strategy. It generated a cost per symptom-free patient-year gained of $948 and a cost per QALY gained of $905. Compared with standard-dose PPI, the incremental cost per symptom-free patient-year gained was $1,469 with low-dose PPI and $1,835 with standard-dose H2RA. The corresponding incremental costs per QALY gained were $1,374 (low-dose PPI) and $1,633 (standard-dose H2RA), respectively.
The sensitivity analysis showed that the results of the model were robust to the variation of all variables, and no threshold value was identified. Extending the time-horizon of the model from 1 to 5 years revealed that standard-dose PPI remained the dominant strategy over the 5-year period. In this case, although discounting would have been relevant, it was not carried out.
Authors' conclusions A standard-dose proton-pump inhibitor (PPI) would seem to be the most effective and least costly strategy for the maintenance management of patients with gastrooesophageal reflux disease (GERD) in Hong Kong.
CRD COMMENTARY - Selection of comparators The selection of the comparators was explicitly stated. H2RAs and PPIs are the mainstays of therapy in the authors' setting. Although standard-dose PPI has been shown to be superior to standard-dose H2RA, there is a lack of evidence as to the most cost-effective treatment. In addition, owing to the high drug acquisition costs of PPIs compared with H2RAs, physicians in the authors' setting tend to prescribe H2RA more often. The authors also chose to assess low-dose PPI, as it has been proven that it might be comparable with standard-dose PPI and superior to standard-dose H2RA. Again, there is a lack of evidence about the economic benefits of low-dose PPI compared with the other two treatment regimens. You should decide if these represent widely used technologies in your own setting.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature was carried out. It is therefore possible that the data from the available studies were used selectively. The authors did not note any differences between the efficacy estimates from the primary studies. There was little commentary on the quality of the retrieved studies, making it difficult to comment on the quality of the efficacy estimates. However, the authors carried out a number of sensitivity analyses relating to the efficacy estimates. These analyses improved both the internal validity and the generalisability of the study by demonstrating the robustness of the results to changes in the base-case estimates.
Validity of estimate of measure of benefit The number of symptom-free patient-years gained was derived from the model. The number of QALYs gained in each study arm was also estimated in the model, using utility scores for the symptomatic state and symptom-free state of GERD. The utility scores were derived from a published study using the time trade-off method. The efficacy and benefit measures were not reported separately. This makes it difficult for the reader to recreate the results and better understand the key factors impacting on the cost-effectiveness ratios.
Validity of estimate of costs The perspective adopted was that of a public health organisation in Hong Kong. Whilst relevant categories of cost were included, the use of summary costs means that it is impossible to determine what aspects of the costs were included within the categories. For instance, it was unclear whether the hospitalisation costs included overheads. The quantities and the costs were not reported separately. The authors mentioned that the charges listed in this source were assumed to represent only the cost components (including labour costs) with no addition for profits. Therefore, they approximated their costs using these charges. In the sensitivity analysis, where the time-horizon of the model was extended to 5 years, although discounting was relevant it was not carried out. The dates to which the costs related and the price year were not reported. The costs were reported in US dollars, but no adjustment for conversion or conversion rate was reported.
Other issues The authors made appropriate comparisons of their effectiveness results with those from other studies, reporting consistency in their results. They also addressed the issue of the generalisability to other settings by reporting that, in different countries and health care systems, there might be various practice patterns or treatment pathways for the management of GERD, which might result in differences in health care resource utilisation. The authors suggested that other health care systems in different countries could adopt their model using local average costs associated with symptomatic and symptom-free months. The authors mentioned that the percentage of patients undergoing surgical therapy, and the cost of surgery, were not simulated. This was because Chinese patients tend to suffer from mild to moderately severe GERD compared with the Caucasian population and, therefore, none of the local patients with GERD received surgery. They suggested that the model could be appropriately modified to suit specific patient populations by including surgery as a model outcome.
The authors reported a number of further limitations to their study. First, the clinical probabilities input to their model were derived from studies conducted on European and US populations, which might not reflect Asian rates. Second, the monthly direct medical cost for GERD was estimated from a small sample size (27 patients) but, despite the small sample size, the average duration of GERD was 3 years and resource use was documented for 946 patient-months.
The results were not reported selectively and the conclusions reflected the scope of the study.
Implications of the study Standard-dose PPI was the most effective treatment option with the lowest total direct medical cost. The authors did not make any explicit recommendations for policy change, nor did they propose any explicit areas for further research.
Source of funding Supported by the School of Pharmacy, Chinese University of Hong Kong, Hong Kong, China.
Bibliographic details You J H, Lee A C, Wong S C, Chan F K. Low-dose or standard-dose proton pump inhibitors for maintenance therapy of gastro-oesophageal reflux disease: a cost-effectiveness analysis. Alimentary Pharmacology and Therapeutics 2003; 17(6): 785-792 Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Dose-Response Relationship, Drug; Gastroesophageal Reflux /drug therapy /economics; Histamine H2 Antagonists /therapeutic use; Humans; Proton Pump Inhibitors; Proton Pumps /economics; Quality-Adjusted Life Years AccessionNumber 22003000607 Date bibliographic record published 31/01/2005 Date abstract record published 31/01/2005 |
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