|The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal haemorrhage
|Targownik L E, Spiegel B M, Dulai G S, Karsan H A, Gralnek I M
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.
Three strategies for the prevention of recurrent variceal haemorrhage (RVH) were evaluated.
Option 1 was endoscopic band ligation (EBL).
Option 2 was combination medical therapy with nadolol and isosorbide-5-mononitrate, without hepatic venous pressure gradient (HVPG) monitoring to gauge therapeutic response. Nadolol was given at a dose of 20 mg/day immediately prior to hospital discharge. Afterwards, the dose was titrated to reduce systolic blood pressure by 25% or to reduce the resting heart rate to 55 beats/minute. Isosorbide-5-mononitrate was given initially at a dose of 20 mg/day. This dose was adjusted weekly until either systolic blood pressure dropped to less than 85 mmHg, any dose-limiting symptoms occurred, or the maximal dose of 40 mg twice daily was achieved.
Option 3 was combination medical therapy with nadolol and isosorbide-5-mononitrate (similar doses to those in option 2) with HVPG monitoring, with nonresponders receiving EBL.
Economic study type
The study population comprised a hypothetical cohort of cirrhotic patients following successful EBL for an index episode of oesophageal variceal haemorrhage.
The setting was secondary care. The economic study was carried out in the USA.
Dates to which data relate
The effectiveness data were obtained from studies published between 1981 and 2002. The price year was 2001.
Source of effectiveness data
The effectiveness evidence was derived from a review or synthesis of completed studies and authors' assumptions.
A Markov model was used to estimate the costs and benefits associated with each strategy. The model was created with 1-month transition intervals to simulate the natural history of patients with cirrhosis following an initial variceal haemorrhage over a 24-month time horizon. The model incorporated four states: alive, no re-bleed; alive, re-bleed; dead, re-bleed; dead, no re-bleed.
Outcomes assessed in the review
The outcomes assessed were:
the 2-year rate of RVH in patients receiving no prophylactic therapy;
the probability of developing an appropriate decline in HVPG in patient receiving combination nadolol-isosorbide therapy;
the 2-year rate of RVH in patients receiving EBL;
the probability of compliance with the EBL regimen;
the probability of compliance with combination nadolol-isosorbide therapy;
the compliance rate with HVPG monitoring;
the probability of complications with EBL; and
the probability of complications with HVPG measurement using an internal jugular approach.
Study designs and other criteria for inclusion in the review
Sources searched to identify primary studies
The authors stated that a systematic review of relevant English-language publications from January 1985 to January 2002 was undertaken using MEDLINE.
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 34 studies were included in the review.
Methods of combining primary studies
Where there was a range of data, the estimates that would tend to favour the EBL strategy were chosen.
Investigation of differences between primary studies
Results of the review
The 2-year rate of RVH in patients receiving no prophylactic therapy was 65% (range: 33 - 100).
The probability of developing an appropriate decline in HVPG in patient receiving nadolol-isosorbide therapy was 55% (range: 0 - 100).
The 2-year rate of RVH in patients receiving EBL was 35% (range: 17 - 52).
The probability of compliance with the EBL regimen was 85% (range: 0 - 100).
The probability of compliance with combination nadolol-isosorbide therapy was 75% (range: 0 - 100).
The compliance rate with HVPG monitoring in patients compliant with medical therapy was 90% (range: 0 - 100).
The compliance rate with HVPG monitoring in patients noncompliant with medical therapy was 30% (range: 0 - 100).
The probability of complications with EBL was 2% (range: 0 - 10).
The probability of complications with HVPG measurement using an internal jugular approach was 5% (range: 0 - 30).
Methods used to derive estimates of effectiveness
The authors also made assumptions to determine estimates of effectiveness.
Estimates of effectiveness and key assumptions
Only one episode of re-bleeding was considered in the model.
In the EBL strategy it was assumed that complete variceal obliteration would not occur before 1 month following the initial variceal bleed. During this month, it was assumed that patients would have the same rate of RVH as a person receiving no secondary prophylactic therapy. It was also assumed that patients who were not compliant with the entire ligation regimen had the same risk of recurrent haemorrhage as those receiving no specific treatment.
In the medical therapy with or without HVPG monitoring strategies, it was assumed that the onset of benefit of medical therapy did not occur until the appropriate dose was achieved. It was also assumed that the titration of the effective dose required 1 month. Therefore, patients were assumed to have a rate of recurrent variceal bleeding equivalent to patients receiving no specific secondary prophylactic therapy for that first month.
It was assumed that 75% of the recurrent bleeds occurred within the first year following the index haemorrhage.
It was assumed that any patient who failed to achieve an appropriate decline in HVPG subsequently bore the rate of recurrent haemorrhage equivalent to those receiving no therapy.
It was assumed that the risk of dying from pneumothorax was 20%.
It was assumed that 55% of patients who were compliant with combination medical therapy achieved a significant decline in their HVPG.
Measure of benefits used in the economic analysis
The measure of benefits used was the number of additional variceal bleeds prevented. This measure was obtained through the model. Discounting was not relevant given the time horizon considered in the model.
Discounting was not relevant since the costs were incurred during 2 years. The unit costs were reported separately. The costs considered in the analyses were for EBL sessions, combination medical therapy with isosorbide mononitrate and nadolol, HVPG measurement, HVPG measurement complications (after pneumothorax), inpatient admissions for RVH and for nonvariceal complications of cirrhosis, ongoing care of persons surviving an episode of recurrent variceal bleeding, and gastroenterologist visits. The costs for endoscopic procedures and physician services were obtained from the 2001 American Medical Association Current Procedural Terminology codebook and the 2001 Medicare Fee Schedule. The drug costs were obtained from the 2001 Blue Book of the average wholesale prices for pharmaceuticals. The price year was 2001.
Statistical analysis of costs
The costs were treated deterministically.
The indirect costs were not included in the analysis.
Sensitivity analyses were performed to assess the robustness of the results. The variables evaluated were:
the 2-year rate of RVH in a patient receiving EBL;
the 2-year rate of RVH in a patient receiving nadolol-isosorbide who achieves an appropriate HVPG decline;
the probability of achieving a significant response in HVPG in patients receiving nadolol-isosorbide;
the probability of serious complication with HVPG monitoring;
the probability of serious complications with EBL;
the cost per month of medical therapy with nadolol and isosorbide;
the cost of EBL;
the compliance with nadolol-isosorbide therapy; and
the compliance with EBL.
The threshold value for each variable at which the most effective strategy became dominant over the next most effective strategy was assessed. Also assessed were the thresholds at which the incremental cost-effectiveness ratio was $20,000 or $50,000 per bleed prevented. An additional analysis was performed in which 100% compliance with all interventions was assumed.
Estimated benefits used in the economic analysis
The proportion of patients who developed an RVH at the end of the 2-year study period was 33% with option 3, 38% with option 1 and 39% with option 2.
The cost per patient was $11,744 with option 2, $12,525 with option 1 and $12,818 with option 3.
Synthesis of costs and benefits
An incremental cost-effectiveness analysis was carried out. The incremental cost per year to avoid one additional recurrent haemorrhage when using option 3 instead of option 1 was $5,974. The incremental cost per year to avoid one additional recurrent haemorrhage when using option 3 instead of option 2 was $16,984.
These results were sensitive to the cost of EBL, the cost of HVPG monitoring, the probability of medical therapy producing an adequate HVPG decline, and the rate of compliance.
The use of hepatic venous pressure gradient (HVPG) monitoring is more effective than the practice of endoscopic band ligation (EBL). It may be cost-effective in the secondary prophylaxis of variceal haemorrhage in patients with cirrhosis.
CRD COMMENTARY - Selection of comparators
The use of HVPG monitoring was compared with EBL because this was the standard practice in the study setting. The authors stated that other technologies are available for preventing RVH, such as endoscopic sclerotherapy, combination endoscopic modalities and transhepatic-intravenous portosystemic shunt. The authors stated that they limited their analysis to the strategies with proven effectiveness and limited risk of adverse outcomes. You should decide if the strategies evaluated in this study are relevant to your own setting.
Validity of estimate of measure of effectiveness
A systematic review of the literature was undertaken. The search methods were described, as was the method used to combine the primary studies. However, the authors made some assumptions to estimate some of the parameters of the model. Nevertheless, the uncertainty in the estimates was investigated in the sensitivity analysis.
Validity of estimate of measure of benefit
The benefit measure used in the economic analysis was the cases of RVH avoided. This represents a disease-specific end point, thus limiting the possibilities of comparison with other studies. The authors stated that a further limitation of the study was that they did not incorporate quality-adjusted life-years as a measure of benefits, although they provided several justifications for their exclusion from the present study. The health benefits were obtained using a Markov model, which was appropriately described in the article.
Validity of estimate of costs
The perspective adopted in the study was reported. It appears that all the relevant categories of costs have been included in the economic evaluation. The source of the cost data was reported. The price year was stated, which improves the reproducibility of the results. The source of resource consumption was not stated, but it was presumably derived from the probability values used in the model and authors' assumptions. Discounting was not applied, which was appropriate given the time horizon considered. The cost parameters were included in the sensitivity analyses so as to test variability in the data used.
The authors compared their results with those of another study, which showed their findings were concordant when considering the assumptions made in the model. The authors stated that the generalisability of their base-case estimates might be limited and further studies in diverse populations are warranted. The sensitivity analyses performed were very extensive and used reasonable ranges. The authors' conclusions reflected the scope of the analysis since their objective was to measure the cost-effectiveness of medical therapy, with or without HVPG monitoring, versus the standard practice of EBL for the secondary prophylaxis of variceal bleeding in patients with cirrhosis.
Implications of the study
This analysis showed that the adjunctive use of HVPG monitoring might be cost-effective in the secondary prophylaxis of variceal haemorrhage in patients with cirrhosis. The results obtained suggested that the more appropriate candidates for this strategy may be those patients listed for liver transplantation (given their high compliance rate). Further prospective trials comparing the effectiveness and costs of these strategies are needed.
Source of funding
Supported by an NIH Training Grant, an NIH K23 Award, and a VA HSR&D Advanced Research Career Development Award.
Targownik L E, Spiegel B M, Dulai G S, Karsan H A, Gralnek I M. The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal haemorrhage. American Journal of Gastroenterology 2004; 99(7): 1306-1315
Other publications of related interest
Hicken BL, Sharara AI, Abrams GA, et al. Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study. Alimentary Pharmacology and Therapeutics 2003;17:145-53.
Subject indexing assigned by NLM
Adrenergic beta-Antagonists /economics /therapeutic use; Blood Pressure Determination /economics; Cost-Benefit Analysis; Endoscopy, Digestive System /economics; Environmental Monitoring /economics; Esophageal and Gastric Varices /complications; Gastrointestinal Hemorrhage /economics /prevention & control /therapy; Hepatic Veins /physiopathology; Humans; Ligation /economics; Markov Chains; Nitrates /economics /therapeutic use; Recurrence; Sensitivity and Specificity; Treatment Outcome
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Date abstract record published