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.

Different interferon-based treatment strategies were compared for the management of chronic hepatitis C virus (HCV) infection in children.

Treatment.

Cost-effectiveness analysis.

The study population comprised a cohort of 1,000 healthy 10-year old children with a chronic HCV infection. The timeframe of the analysis was based on the average life expectancy of a healthy 10-year old child, which is 66 years.

The setting was secondary care. The economic study was carried out in the USA.

The effectiveness data were gathered from studies published between 1987 and 1998. The cost data were gathered from studies published between 1997 and 1998. The price year was not reported.

The effectiveness data were obtained from a synthesis of published studies.

A Markov model was used to determine the cost-effectiveness of different interferon-based strategies for the management of chronic HCV in children. The timeframe of the model was 66 years.

The outcomes in the model were the probabilities of compensated cirrhosis, decompensated cirrhosis, chronic hepatitis, hepatocellular carcinoma, orthoptic liver transplantation (OLT) and death.

The designs of the included studies were not reported. No inclusion or exclusion criteria were stated.

The authors did not report the sources searched or the search strategy used to identify the studies for the data synthesis.

The authors did not report the criteria used to ensure the validity of the studies used in the data synthesis.

The methods used to judge the relevance and validity of the studies, and to extract the data, were not reported.

Twenty-four primary studies were included in the review.

The authors did not report the methods used to combine the data from primary sources.

The differences between the primary studies were reported with respect to the number of patients, the drug doses administered, and the duration of the studies. No explanation for these differences was provided. There was no investigation of the impact of these differences on the estimate of effectiveness.

The transitional probabilities were:

4% (range: 3 - 5) for moving from compensated cirrhosis to decompensated cirrhosis,

0.1% (range: 0.05 - 0.2) for moving from chronic hepatitis to hepatocellular carcinoma,

1.5% (range: 1 - 3) for moving from compensated cirrhosis to hepatocellular carcinoma,

3% (range: 1.5 - 5) for moving from decompensated cirrhosis to hepatocellular carcinoma,

3% (range: 1 - 10) for moving from decompensated cirrhosis to OLT,

2% (range: 1 - 3) for moving from compensated cirrhosis to death,

10% (range: 5 - 15) for moving from decompensated cirrhosis to death,

15% (range: 6 - 25) for moving from OLT to death in the first year,

and 6% (range: 5 - 10) for moving from OLT to death in the subsequent years.

The quality of life-adjusted utility values were:

0.9 (range: 0.82 - 1.0) for chronic hepatitis,

0.85 (range: 0.8 - 1.0) for compensated cirrhosis,

0.7 (range: 0.5 - 1.0) for decompensated cirrhosis,

0.5 (range: 0.15 - 0.95) for hepatocellular carcinoma,

0.8 (range: 0.7 - 1.0) for the first post-OLT year, and

0.9 (range: 0.8 - 1.0) for the subsequent post-OLT year.

The measure of benefits was quality-adjusted life-years (QALYs). The quality of life utility values were estimated for chronic hepatitis, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, the first post-OLT year, and the subsequent post-OLT years. The utility values were taken from two published studies. The authors did not report the method used to derive the values. The values were estimated for adults not children.

The model included the cost of treating the various disease states and the cost of antiviral therapy.

The cost per year for treating the various disease states was $100 for chronic hepatitis, $150 for compensated cirrhosis, $20,000 for decompensated cirrhosis, $25,000 for hepatocellular carcinoma, $100,000 for transplantation and care in the first post-OLT year, and $20,000 for care in the subsequent post-OLT years.

The costs of antiviral therapy for three different age cohorts aged 5, 10 and 15 years were:

$1,800 (5 years), $2,160 (10 years) and $2,160 (15 years) for 6 months' interferon treatment;

$3,600 (5 years), $4,320 (10 years) and $4,320 (15 years) for 12 months' interferon treatment; and

$2,808 (5 years), $3,840 (10 years) and $5,184 (15 years) for 6 months' combined treatment with interferon and ribavirin.

The costs were both estimated on the basis of the actual charge data and derived using modelling techniques. The cost-to-charge ratios were used to adjust the charge data to approximate true costs. The price year used to estimate costs was not reported. All future costs were discounted at a rate of 3%.

There was no statistical analysis of costs.

No indirect costs were included in the analysis.

US dollars ($). No currency conversions were reported.

The variability in the point estimates was explored using first-order Monte Carlo simulation, and one-way and two-way sensitivity analyses. The one-way sensitivity analysis assessed the parameters of cost, outcome and probability (ranges provided). The two-way sensitivity analysis simultaneously varied the probabilities of end of treatment response and sustained response, in order to determine the dominant treatment strategy.

The strategy of treating children with chronic HCV infection with interferon for 6 months resulted in 24.5987 QALYs. The 12-month interferon treatment generated 25.1097 QALYs, whilst the 'no treatment' strategy generated 22.3301 QALYs. The QALYs were estimated over the expected lifetime of a healthy 10-year old, i.e. 66 years.

The baseline costs of the different treatment strategies were $49,588 for 6 months' interferon, $44,508 for 12 months' interferon, and $76,735 for no treatment. This included the costs of treating the various disease states. The costs of treating complications were not included. The costs were discounted at a rate of 3%.

Strategies I (6 months' interferon) and III (no treatment) were associated with a higher expected cost and lower expected QALYs than strategy II (12 months' interferon). Strategy II therefore dominated and was the more cost-effective treatment. The sensitivity analysis indicated that the results of the analysis were not sensitive to variation in the parameters tested. The authors reported that when the annual rate of transition from chronic HCV was varied from 0.1 to 10%, strategy II remained the most cost-effective until the transition rate dropped below 0.3%, at which point strategy I was found to be the most cost-effective. In addition, when the end of treatment response to interferon therapy fell to less than 2%, and the sustained response rate to less than 3%, no treatment became the favoured strategy. The two-way sensitivity analysis showed that strategy I became the dominant strategy if the end of treatment and sustained response rates were set to unrealistically high values.

The authors concluded that interferon-based treatment strategies were cheaper, more effective in terms of QALYs saved, and overall more cost-effective when compared with the strategy of no treatment. However, it was also stated that combination therapy may be more cost-effective than interferon monotherapy. Clinical trials are needed to evaluate the use of combination therapy for the treatment of paediatric patients with chronic hepatitis C virus (HCV) infection.

The choice of 'no treatment' as the comparator was justified since it was the traditional practice in the USA at the time of the study. The authors reported that there was no economic evidence to support the interferon-based strategies. You should decide if these strategies are relevant or widely used health technologies in your own setting.

The measure of effectiveness used in the economic model was estimated using probability data derived from several sources. The authors did not state whether a systematic review of the literature had been undertaken. No information was provided on how the studies were identified and the criteria on which they were selected and assessed. The effectiveness estimates from the primary studies were combined, although the method used was not reported. The authors did not consider the impact of differences between the primary studies when estimating the effectiveness of the treatment strategies.

The benefits were estimated directly from the effectiveness analysis. The choice of QALYs as the outcome measure appeared appropriate, and an extensive sensitivity analysis was undertaken to test for variation in the data. When assigning the utility values, the authors assumed that the quality of life associated with the healthy state was unity, even though the absence of a particular disease may not be synonymous with perfect health. Thus, the effectiveness of the treatment strategies may have been overestimated. It was also assumed that there was no decrease in the quality of life associated with interferon therapy, and consequently any complications resulting from the treatment were not taken into consideration. The authors did not report the methods used to estimate the utility weights used, but did note that they were derived for adults, not children. They also did not report the utility values used in the model.

The costs were estimated from the societal perspective, although only the direct costs were estimated and the indirect costs were not included in the study. The authors reported that since only the direct costs of chronic HCV infection were considered, this may have biased the analysis against treatment strategies by reducing the saving associated with successful treatment. However, since the costs of treatment complications were excluded, this may have biased the analysis in favour of interferon-based therapy. All future costs were discounted at a rate of 3%, and a sensitivity analysis was performed using discount rates ranging from 0 to 7%. The quantities and costs were not reported separately. The price year was not stated.

The authors reported that the decision analysis used in the model only related to those patients with chronic HCV infection and without systematic disease. Also, the choice of therapy depended on the HCV genotype and other characteristics of the disease. Consequently, it may not be possible to extrapolate the results to other settings or to children with co-morbid ailments. In addition, the trials of interferon therapy in children were heterogeneous, which may have introduced bias. This was tested using sensitivity analyses.

The authors concluded that interferon-based treatment strategies were most effective in terms of QALYs saved and overall cost-effectiveness, when compared with a no treatment strategy. It was also postulated that combination therapy with interferon and ribavirin may be more cost-effective than interferon monotherapy. Clinical trials are urgently required to establish the effectiveness and safety of combination therapy for the treatment of chronic HCV infection in paediatric patients.

None stated.