Health technology The use of four different combined treatments for Helicobacter pylori (H. pylori) infection. These were:

Transcription

1 Tratamiento de la infeccion por Helicobacter pylori en pacientes con ulcera duodenal: estudio de costo-beneficio [Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a cost-benefit study] Rollan A, Giancaspero R, Acevedo C, Fuster F, Hola K 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 use of four different combined treatments for Helicobacter pylori (H. pylori) infection. These were: FAM, i.e. famotidine (40 mg, once daily), amoxycillin (750 mg, three times daily) and metronidazole (500 mg, three times daily); OAT, i.e. omeprazole (20 mg, twice daily), amoxycillin (750 mg, twice daily) and tinidazole (500 mg, twice daily); LAC1, i.e. lansoprazole (30 mg, once daily), amoxycillin (750 mg, three times daily) and clarithromycin (500 mg, three times daily); and LAC2, i.e. lansoprazole (30 mg, once daily), amoxycillin (1,000 mg, twice daily) and clarithromycin (500 mg, twice daily). All treatments were generally carried out for 14 days. There were two exceptions. First, in the FAM group, famotidine was continued for 4 weeks after antibiotics. Second, in the OAT group, omeprazole was administered for 4 weeks, starting 2 weeks earlier than the other drugs. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The study population comprised patients presenting with active duodenal ulcer, as diagnosed by endoscopy, and H. pylori infection. Patients were excluded if they had undergone previous gastric surgery, presented with concomitant gastric ulcer, or had known coagulopathy. They were also excluded if they were allergic to penicillin, were younger than 16 years or older than 75 years, or were receiving oral anticoagulants. Setting The setting of the study was unclear. The economic study was carried out in Chile. Dates to which data relate The dates during which the effectiveness and resource use data were gathered were not reported. The studies obtained from the literature were published in No price year was reported. Page: 1 / 6

2 Source of effectiveness data The effectiveness data were derived from a single study and some studies from the literature. Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the single study of effectiveness. Study sample Power calculations were not performed to determine the sample size. In addition, the method used to select the study sample was unclear. Overall, 201 patients were enrolled, but 34 (16.9%) were excluded. Of these, 20 patients were lost to follow-up, 9 changed treatment schedule, 4 did not comply with regimen indications, and 1 suspended the treatment. A final sample of 167 patients was included in the study. There were: 67 patients (17 were men) with a mean age of 38.1 (+/-11.9) years in the FAM group; 48 patients (15 were men) with a mean age of 38 (+/-11.1) years in the OAT group; 28 patients (11 were men) with a mean age of 41.6 (+/-13.4) years in the LAC1 group; and 24 patients (10 were men) with a mean age of 36.5 (+/-10) years in the LAC2 group. All patients were proven to be positive for infection using a rapid urease test. Study design The study was a prospective case-control study. The number of centres involved was not reported. The patients were followed for 1 year. The eradication of infection was tested for at the end of the treatment. The persistence of eradication was confirmed every 4 months using one or more direct methods such as the rapid urease test and histology or carbon-14 UBT. Analysis of effectiveness Only patients who completed the treatment were included in the effectiveness analysis. The primary health outcomes were the eradication rate, adverse effects, and the eradication rate at one year. Statistical analyses were conducted to show the comparability of the study groups in terms of their demographics and medical conditions. Effectiveness results The overall eradication rate was 80.2%, since the infection was successfully eradicated in 134 of the 167 patients after the course of the therapies. The authors reported that the patients in whom the eradication was not completely successful did not differ significantly from those for whom it was successful. The eradication rates were 74.6% (95% confidence interval, CI: ) with FAM, 72.9% (95% CI: ) with OAT, 96.4% (95% CI: ) with LAC1, and 91.7% (95% CI: ) with LAC2. There were statistically significant differences between LAC1 and both FAM, (p=0.02) and OAT, (p=0.01). Adverse effects were reported in 20 patients (29.9%) in the FAM group, 17 patients (35.4%) in the OAT group, 10 patients (35.7%) in the LAC1 group, and 16 patients (66.7%) in the LAC2 group. The difference between LAC2 and the remaining therapies was statistically significant. Eradication at one year was confirmed in 124 of the 134 patients (92.5%). The risk of infection recurrence was similar in the study groups. Page: 2 / 6

3 Clinical conclusions LAC1 and LAC2 proved to be highly effective therapies for the eradication of H. pylori infection, but adverse effects were particularly frequent for LAC2. Modelling A decision analytic model was constructed to describe the cost and clinical outcomes of the four treatment options. The time horizon of the model was one year. The data to populate the decision model were derived from the literature and from the single study. The model simulated patients with persistent infection treated with a second-line therapy. The second-line therapy was LAC1 when the initial therapy was FAM or OAT, or a quadruple therapy when the initial therapy was LAC1 or LAC2. The quadruple therapy (OBTM) comprised omeprazole (40 mg daily), subcitrate of bismuth (240 mg, four times daily), tetracycline (500 mg, four times daily) and metronidazole (500 mg, 3 times daily). It was assumed that patients with persistent infection after the second-line therapy were administered famotidine (40 mg daily). Outcomes assessed in the review The outcomes assessed in the review were data regarding the eradication rates of LAC1 and OBTM as second-line therapies for H. pylori infection. Study designs and other criteria for inclusion in the review 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 Number of primary studies included Two primary studies were used to derive the effectiveness evidence that was not obtained from the single study. Methods of combining primary studies The primary studies were not combined. Investigation of differences between primary studies Not carried out. Results of the review The eradication rates of LAC1 and OBTM, when used as second-line therapies, were 85% (LAC1) and 75% (OBTM). Measure of benefits used in the economic analysis No benefit measure was used in the economic analysis. This was because the outcome measures assessed in the Page: 3 / 6

4 effectiveness analysis (eradication rates) were used as probability rates in the decision model, in order to estimate the total costs of each treatment strategy (including first- and second-line therapies). As such, a cost-consequences analysis was conducted. Direct costs No discounting was conducted since the time horizon of the study was 1 year. The unit costs were only reported for some services, whilst the quantities of resources were not reported. The cost/quantity boundary adopted was unclear. The costs included in the analysis were for visits, endoscopy, drugs, urease test, and maintenance therapy (famotidine). The drug acquisition costs were estimated from retail prices, whilst other cost items were derived from the price list of Fonasa (Fondo Nacional de Salud). Both represented actual data. The quantities were estimated from the decision model. The period during which the resources used in the study were collected was not reported. No price year was used. Statistical analysis of costs No statistical analysis of the costs was carried out. Indirect Costs The indirect costs were not included. Currency Chilean pesos (Ch$). Sensitivity analysis One-way sensitivity analyses were conducted to assess the robustness of the estimated average costs to variations in several model inputs. These included the cost of LAC1 and LAC2, the effectiveness of the therapies, and the cost of famotidine (maintenance therapy). Estimated benefits used in the economic analysis See the 'Effectiveness Results' section. Cost results The costs of each first-line treatment (including all medications) were Ch$24,789 for FAM, Ch$45,512 for OAT, Ch$110,422 for LAC1, and Ch$65,943 for LAC2. The authors stated that the lowest average cost per patient assessed through the decision model was estimated for FAM (Ch$153,000 +/- 74,000). However, although the average cost of LAC2 was slightly higher (Ch$160,000 +/- 29,000), LAC therapy might be preferred for the smaller standard deviation. Sensitivity analyses showed that the costs of LAC1 and LAC2 should fall to Ch$63,000 and Ch$58,000, if they are to be as convenient as FAM. In addition, only if the eradication rate of FAM fell to 69% would LAC2 become the less costly therapy. The average costs were also sensitive to the cost of the maintenance therapy. Synthesis of costs and benefits Not relevant. Authors' conclusions Therapy using FAM (famotidine, amoxycillin and metronidazole) appears to have been the most cost-effective strategy Page: 4 / 6

5 for the treatment of patients with duodenal ulcer and Helicobacter pylori (H. pylori) infection. However, LAC2 (lansoprazole, clarithromycin and two daily doses of amoxycillin) was a feasible alternative due to a slightly greater cost and a better eradication rate than FAM. CRD COMMENTARY - Selection of comparators The rationale for the selection of the comparators was not explicitly stated. However, the four treatments represented widely used therapies for the treatment of H. pylori in patients with duodenal ulcer. You should assess whether these therapies represent routine interventions in your own setting. Validity of estimate of measure of effectiveness The effectiveness evidence was mainly derived from a case-control study, which appears to have been appropriate to the general objective of the analysis. However, power calculations were not performed to determine the sample size and, for some therapies, the sample size was quite small. This could have led, as the authors noted, to the lack of statistically significant differences among some study groups in terms of the health outcomes. However, statistical analyses were conducted to show the overall comparability of the groups. The setting of the study was unclear. Some of the data were unavailable from the study sample, and were derived from published studies. However, a review of the literature was not undertaken and the criteria for selecting the two primary studies were not reported. Validity of estimate of measure of benefit No summary benefit measure was used in the economic analysis. It would have been helpful to have derived a summary benefit measure, taking into account the patients' preferences. Validity of estimate of costs The perspective of the study was unclear. Only the direct costs of the treatment were included in the analysis. It could have been interesting had the potential impact of the indirect costs been assessed. The costs were treated deterministically and no statistical analyses were conducted. However, sensitivity analyses were carried out on some crucial cost items. No price year was reported. In addition, the period during which the resource use data were collected was not indicated. Other issues The authors compared their findings with those from other studies. Several sensitivity analyses were carried out to take into account the uncertainty around some estimates derived from the different sources. There were conducted appropriately. However, no incremental cost-effectiveness analysis was conducted, although this would have been of better use in comparing the four strategies. Implications of the study The analysis showed that treatments based on FAM and LAC2 as first-line therapies for the treatment of H. pylori infection should be recommended. However, the authors noted that these results should be confirmed in ordinary clinical practice. Source of funding None stated. Bibliographic details Rollan A, Giancaspero R, Acevedo C, Fuster F, Hola K. Tratamiento de la infeccion por Helicobacter pylori en pacientes con ulcera duodenal: estudio de costo-beneficio. [Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a cost-benefit study] Revista Medica de Chile 2000; 128(4): Page: 5 / 6

6 Powered by TCPDF ( PubMedID Indexing Status Subject indexing assigned by NLM MeSH Adult; Anti-Bacterial Agents /therapeutic use; Anti-Ulcer Agents /therapeutic use; Cost-Benefit Analysis; Drug Therapy, Combination; Duodenal Ulcer /drug therapy /microbiology; Female; Helicobacter Infections /drug therapy; Helicobacter pylori /drug effects; Humans; Male; Proton Pumps /therapeutic use; Treatment Outcome AccessionNumber Date bibliographic record published 30/09/2002 Date abstract record published 30/09/2002 Page: 6 / 6