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A cost-utility analysis of secondary prophylaxis for variceal haemorrhage |
Rubenstein J H, Eisen G M, Inadomi J M |
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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 Five strategies for the secondary prophylaxis of oesophageal variceal haemorrhages (VH) in patients with cirrhosis were examined. The strategies were:
observation alone (OBS);
medications (MED), which consisted of treatment with nonselective beta-adrenergic receptor antagonists;
endoscopic band ligation (EBL), in which patients underwent the outpatient procedure every 2 weeks until eradication of the varices, or until they were too small to be ligated, with endoscopic surveillance scheduled every 6 months after the completion of the EBL series;
EBL plus MED (EBL+MED); and
transjugular intrahepatic portasystemic shunt (TIPS), in which patients underwent placement of the TIPS immediately upon enrolment, received a postprocedural Doppler ultrasound the next day and, if acute occlusion was found, underwent revision of the TIPS.
Study population The study population comprised a hypothetical cohort of men with Child's Class B cirrhosis and an average age of 50 years, with a history of controlled, bleeding oesophageal varices at the time of enrolment. Patients were excluded if they were intolerant of medications, or if they had persistent hepatic encephalopathy (HE) at the time of enrolment.
Setting Although not explicitly stated, the setting was most probably secondary care (a hospital). The economic study was carried out in the USA.
Dates to which data relate The effectiveness data and some resources use data were obtained from studies published between 1975 and 2003. The price year was 2001.
Source of effectiveness data The effectiveness evidence was derived from a review of completed studies and authors' assumptions.
Modelling A Markov model was developed to estimate the cost and benefits associated with each strategy. The model contained more than 1,300 branches. The main health states considered in the model were "no haemorrhage, no HE", "no haemorrhage + HE", "VH", "complication", "dead, VH", "dead, complication", "dead, HE" and "dead, other". The time horizon was 3 years and the cycle length was 2 weeks.
Outcomes assessed in the review The clinical outcomes assessed were the rates and odds ratios (ORs) of VH, HE, mortality, technical failure and complications.
Study designs and other criteria for inclusion in the review Data on effectiveness were gathered primarily from three randomised clinical trials and a meta-analysis. Follow-up studies and meta-analyses were also used to estimate the transition probabilities of the model.
Sources searched to identify primary studies MEDLINE and EMBASE were searched from 1966 and 1988, respectively, to 2002. Additional articles were found by cross-referencing those identified by the database search.
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 At least 74 studies were included in the review.
Methods of combining primary studies Generally, the mean values of the data reported in the literature were used in the base-case scenario. However, the results of the three clinical trials that compared medication with band ligation were not combined.
Investigation of differences between primary studies Results of the review The model parameters were too numerous to report here.
Methods used to derive estimates of effectiveness The authors made assumptions to derive some of the transitions probabilities used in the model.
Estimates of effectiveness and key assumptions It was assumed that there was no crossover for failed strategies.
It was assumed that the risk of VH stayed constant with time.
The rates of adherence with all strategies were taken to be 100% in the base-case scenario. This assumption was examined in the sensitivity analysis (range: 0% - 100%). The analysis assumed perfect knowledge of the patients' adherence. If patients become nonadherent they reverted to the same risk and costs as in the OBS arm. During the few weeks of the EBL series, patients were assumed to be adherent with MED if they were adherent with EBL. All patients were assumed to be adherent with initial TIPS placement.
Measure of benefits used in the economic analysis The summary measure of health benefits used was the quality-adjusted life-years (QALYs). The number of QALYs gained with each strategy was estimated using the model, according to the health utilities found in the literature. The authors assumed utilities tolls in different health states. These tolls were included in the sensitivity analysis. A discount rate of 3% was applied.
Direct costs The direct costs of the hospital were included in the analysis. Discounting was applied at a rate of 3%. The quantities of resources were reported separately from the costs. The median national reimbursement rates from the Health Care Financing Administration were used. Hypothetical pseudo-bills were created to estimate resource use. The price year was 2001.
Statistical analysis of costs No statistical analysis of the costs was performed.
Indirect Costs The indirect costs were not included in the analysis.
Sensitivity analysis One-way sensitivity analyses were performed on each of the model variables. Two-way sensitivity analyses were performed on the important variables found in the one-way sensitivity analysis. Specifically, the ORs of VH with EBL compared with MED and with EBL+MED compared with EBL alone were examined. Finally, a multi-way sensitivity analysis (Monte Carlo simulation) was performed. The utility tolls and the adherence rates were kept constant at the base-case values. A total of 10,000 combinations of randomly chosen values for the remaining variables were analysed.
Estimated benefits used in the economic analysis The QALYs gained with each strategy were as follows:
EBL+MED, 1.68;
MED, 1.57;
EBL, 1.67;
OBS, 1.44; and
TIPS, 1.63.
Cost results The direct costs over a time horizon of 3 years were:
$15,100 with EBL+MED,
$15,700 with MED,
$16,600 with EBL,
$21,100 with OBS, and
$30,900 with TIPS.
Synthesis of costs and benefits The strategy of EBL+MED dominated all other strategies in the base-case scenario. However, the Monte Carlo analysis found EBL+MED to be the optimal strategy in only 61% of cases. Therefore, there is significant uncertainty about which of the strategies is optimal.
Authors' conclusions The results of the base-case analysis were not robust enough to recommend endoscopic band ligation plus medication (EBL+MED) to all patients. The authors argued that further empirical studies are needed to improve the robustness of the model.
CRD COMMENTARY - Selection of comparators The preventive strategies compared were appropriate. However, not all possible combinations of strategies were considered, and it was assumed that there was no crossover for failed strategies. You should consider whether these strategies are widely used health technologies in your own setting.
Validity of estimate of measure of effectiveness The effectiveness results are likely to be valid since a systematic and comprehensive review of the literature was performed. Moreover, uncertainties were assessed in extensive sensitivity analyses. However, the criteria used to judge the relevance and the validity of the primary studies were not reported.
Validity of estimate of measure of benefit The Markov model used to estimate the QALYs appears to have been appropriate. The utility values were derived from the literature and the authors made some assumptions. The authors conducted a sensitivity analysis to account for these.
Validity of estimate of costs It would appear that, given the third-party payer perspective, the important cost categories have been included in the analysis. The price year was stated, and discounting was applied. The resource quantities were reported separately from the costs. Cost variables were considered in the sensitivity analyses. The authors reported the costing well.
Other issues The issue of the generalisability of the results was not assessed. The authors compared their findings with those of other economic analysis and discussed the limitations of the study. The authors' conclusions reflected the scope of the analysis.
Implications of the study The results of this study were not robust enough to recommend a preventive strategy for all patients. The authors highlighted the need to perform further studies to determine the relative efficacies of medication, band ligation, and their combination in preventing VH. Moreover, the authors argued that the effects of medication on health state utilities and the rate of adherence with the strategies in actual practice have yet to be determined.
Source of funding Supported by grants from the National Institutes of Health, an American College of Gastroenterology Faculty Development Award, and a grant from the Department of Veterans Affairs.
Bibliographic details Rubenstein J H, Eisen G M, Inadomi J M. A cost-utility analysis of secondary prophylaxis for variceal haemorrhage. American Journal of Gastroenterology 2004; 99(7): 1274-1288 Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Endoscopy, Gastrointestinal /economics; Esophageal and Gastric Varices /complications; Gastrointestinal Hemorrhage /economics /prevention & Humans; Markov Chains; Middle Aged; Odds Ratio; Patient Acceptance of Health Care; Patient Compliance; Portasystemic Shunt, Transjugular Intrahepatic /economics; Sensitivity and Specificity; Treatment Outcome; control AccessionNumber 22004001009 Date bibliographic record published 31/12/2005 Date abstract record published 31/12/2005 |
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