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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

Aim : To estimate the cost-effectiveness of therapy and analyse the effect of therapy compliance in naive patients with chronic hepatitis C.

Methods : A decision analysis using the Markov model was performed for four different therapeutic strategies using peginterferon alfa-2b plus ribavirin or interferon alfa-2b plus ribavirin. Clinical data were obtained from available published reports and from the Spanish health system perspective.

Results : The incremental cost-effectiveness ratio of peginterferon alfa-2b plus ribavirin at a fixed dose, compared with interferon alfa-2b plus ribavirin, was 8478 euros per life year saved and 3737 euros per quality-adjusted life year gained. Good therapeutic compliance and weight-adjusted doses of ribavirin decreased the incremental cost-effectiveness ratio to 1636 euros per life year saved and 721 euros per quality-adjusted life year gained. In compliant genotype 1 patients, the incremental cost-effectiveness ratio decreased to 916 euros per life year saved and 404 euros per quality-adjusted life year gained, with an increase from 64 to 69 years in the threshold age at which therapy was cost-effective. The sensitivity analysis demonstrated that changes in the values of the most relevant parameters do not modify the study outcomes.

Conclusion : From the clinical and pharmaco-economics perspective, the use of decision therapeutic analysis models suggests that the most effective therapy for chronic hepatitis C is peginterferon alfa-2b plus ribavirin adjusted to patient body weight and with good compliance, particularly in genotyped patients.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

Therapy of chronic hepatitis C is based on a combination of interferon alfa and ribavirin. A sustained virological response, defined by viral loss 6 months after the end of therapy, is observed in approximately 40% of patients treated with interferon plus ribavirin for 48 weeks, in contrast with only 12% of patients treated with interferon monotherapy for the same period.1, 2

In 2001, a new type of interferon, pegylated interferon, was approved for chronic hepatitis C therapy. Peginterferon alfa-2b, created by attaching a polyethylene glycol molecule to interferon, has a longer half-life and is typically given at a dose of 1.5 µg/kg body weight once per week.3, 4

Treatment with peginterferon alfa-2b for 48 weeks results in a sustained response rate of 30%, which is double that of standard interferon. The combination of peginterferon alfa-2b and ribavirin increases the response rate to 61%, and this is especially important for patients infected with genotype 1.4

Different factors, such as viral genotype, viral load, liver fibrosis, ribavirin dosage and therapeutic compliance, can modify or increase the sustained virological response.5 Considering these factors, hepatitis C virus (HCV) therapy can be individually tailored to increase the sustained response for each patient. A recent National Institutes of Health consensus conference recommended the selection of therapy for chronic hepatitis C patients according to HCV genotype.6 For genotype 1 patients, peginterferon alfa-2b plus ribavirin (1000–1200 mg daily) for 48 weeks was recommended, whereas for genotype 2 and 3 patients, the same dose of peginterferon alfa-2b was recommended, but a lower dose of ribavirin, 800 mg daily, for 24 weeks. Therapy with peginterferon alfa-2b plus ribavirin is associated with an increase in treatment costs attributable to peginterferon alfa-2b. The increasing interest in the economic efficiency of new drugs has prompted health care authorities to assess the value of peginterferon alfa-2b plus ribavirin therapy in clinical practice.6

The long-term clinical course of HCV infection makes it necessary to use a decision analysis model to evaluate the improvement in survival or the increase in life years gained in patients treated with peginterferon alfa-2b plus ribavirin.7–13

The aims of this study were to evaluate the cost-utility and cost-effectiveness of peginterferon alfa-2b plus ribavirin for chronic hepatitis C in all patients, and in genotype 1 patients — those most difficult to treat. The results were compared with those obtained with previous standard therapy of interferon and ribavirin. The study also analysed the cost-utility and cost-effectiveness of peginterferon alfa-2b plus ribavirin when both drugs were adjusted for the patient's body weight and when there was therapeutic compliance.

Decision analysis model

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

A Markov decision analysis model was used to estimate the future clinical course and economic costs and benefits of different treatment strategies in a hypothetical cohort of patients with chronic hepatitis C. The Markov model has been used in previous cost-effectiveness studies of chronic hepatitis C, and is considered to be the most appropriate method of studying the natural history of the disease to evaluate the costs and benefits of combination therapy.8–11 This model simulates the course of the disease from its initial stages until death due to liver-related or other causes, and the effects of combination therapy in the outcome of the disease. The model uses probabilities of progression from chronic hepatitis to cirrhosis, decompensated liver disease and finally death obtained from the results of several different published studies that have been validated previously.7–13

The time that patients remain in each clinical stage, the resources used and the treatment costs for the different strategies have been estimated from data published in a previous study.9

Patient population

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The demographics, biochemical and virological characteristics of the patients were obtained from a multi-centre study on peginterferon alfa-2b plus ribavirin.4 The base-case patient was a 43-year-old male with chronic hepatitis C, the mean age in the reference study.1–4 The percentages of patients with mild disease, moderate disease and cirrhosis (31.2% mild hepatitis, 64% moderate hepatitis, 4.8% cirrhosis) in the cohort of treated patients were considered to be the same as in multi-centre studies.1–3

Therapeutic strategies

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

Four therapeutic strategies were applied to a base-case patient cohort with untreated chronic hepatitis C. The strategies were based on different types of interferon alfa-2b, different doses of ribavirin and therapy compliance. The four strategies considered were: strategy 1, interferon alfa-2b (3 million units, three times per week) plus ribavirin (1000–1200 mg daily depending on the body weight) for 48 weeks (IFN + R); strategy 2, treatment with 1.5 µg/kg weekly of peginterferon alfa-2b plus 800 mg daily of ribavirin at a fixed dose (Peg + R800) for 48 weeks; strategy 3, treatment with 1.5 µg/kg weekly of peginterferon alfa-2b plus ribavirin adjusted according to body weight (Peg + RAB) for 48 weeks; the dose of ribavirin was adjusted according to body weight as follows: 800 mg for weight below 65 kg, 1000 mg for between 65 and 85 kg, and 1200 mg for 85 kg or more; strategy 4, treatment with 1.5 µg/kg weekly of peginterferon alfa-2b plus ribavirin adjusted for body weight for 48 weeks with patients compliant with their scheduled therapy regimen (i.e. patients who received at least 80% of both drugs for at least 80% of the treatment duration) (Peg + RAB + C).

Definition of response to therapy

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The sustained virological response was defined as HCV RNA negativity at the end of treatment and after 24 weeks of follow-up. Patients with detectable HCV RNA during and at the end of therapy were considered to be non-responders.4

The sustained virological response rates for all patients and for genotype 1 patients, and the rates of therapy discontinuation used in this analysis, were obtained from the study of Manns et al.4(Tables 1 and 2).

Table 1.  Results for all base-case patients
Strategy*SVR (%)CostsEffectivenessΔ EffectivenessRatios
CostLCΔLCLEQALEΔLYSΔQALYsICERICUR
  • Sustained virological response (SVR), cost of treatment (including visits, laboratory tests, HCV RNA determination, thyroid-stimulating hormone levels, liver biopsy, genotyping, pregnancy test, electrocardiogram and eye examination, when appropriate), lifetime costs (LC), incremental lifetime cost (ΔLC) (all costs in euros), life expectancy (LE) in years, quality-adjusted life expectancy (QALE) in quality-adjusted life years (QALYs), incremental effectiveness [life years saved (LYS) or QALYs gained], incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Costs and effectiveness were discounted at 3%. CS = cost saving. Incremental values were calculated by comparison with the next most costly or effective treatment alternative.

  • *

     Defined in the text.

IFN + R4712154.4118410.13018.9116.290000
Peg + R8005414936.4220365.361955.2319.1416.810.230.528501.003760.06
Peg + RAB6116455.0121057.16691.8019.3717.330.230.523007.831330.38
Peg + RAB + C7216455.0119757.92− 1299.2419.7318.160.360.83CSCS
Table 2.  Results for genotype 1 base-case patients
Strategy*SVR (%)CostsEffectivenessΔ EffectivenessRatios
CostLCΔLCLEQALEΔLYSΔQALYsICERICUR
  • Sustained virological response (SVR), cost of treatment (including visits, laboratory tests, HCV RNA determination, thyroid-stimulating hormone levels, liver biopsy, genotyping, pregnancy test, electrocardiogram and eye examination, when appropriate), lifetime costs (LC), incremental lifetime cost (ΔLC) (all costs in euros), life expectancy (LE) in years, quality-adjusted life expectancy (QALE) in quality-adjusted life years (QALYs), incremental effectiveness [life years saved (LYS) or QALYs gained], incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Costs and effectiveness were discounted at 3%. CS = cost saving. Incremental values were calculated by comparison with the next most costly or effective treatment alternative.

  • *

     Defined in the text.

  •  33% IFN + R vs. Peg + R800; 34% IFN + R vs. Peg + RAB.

IFN + R3312154.4120063.71018.4515.240000
Peg + R8004214936.4221782.711719.0018.7515.910.300.675730.002565.67
Peg + RAB4816455.0122592.62809.9118.9416.360.190.454262.681799.80
Peg + RAB + C6316455.0120820.93− 1771.6919.4417.480.501.12CSCS

Quality of life adjustments

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

Quality of life analysis was performed with assigned estimates of utility for each health state determined by a panel of hepatologists. These utility assignments were based on those published by Bennett et al.10 and Wong et al.12 and ranged from ‘1’ (viral negativity or perfect health) to ‘0’ (death). To calculate the quality-adjusted life years, the time spent in each health state according to the projected model was multiplied by each utility value.

Cost data, discount rate and perspective

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The cost analysis included all costs associated with direct health care, i.e. those related to the screening of patients for therapy, diagnostic and laboratory testing, drugs, monitoring during therapy and follow-up and hospital stays for each specific health care state that might require hospitalization.14 All costs were adjusted for inflation to year 2000 values and converted to euros. Costs were built up from a database of health care cost elements and from the currently applicable pharmaceutical prices from the Catalogue of Medicinal Products 2000 in Spain. The relevant procedures and their costs have been published in another study.9, 14, 15

No indirect costs, such as lost work days, loss of productivity or intangible costs related to patient suffering, were included in this model. The perspective adopted was that of the Spanish national health system, which is the final payer of direct treatment costs over the patients' lifetimes. To convert future costs (beyond the first year) into today's values, a discount rate of 3% was applied to costs and health benefits based on international recommendations.16

Assumptions

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The natural history model assumes a constant rate of disease progression at each histological or clinical stage over time, as in other published cost-effectiveness studies.8–12 The model assumes that a sustained response (normal serum alanine aminotransferase levels and HCV RNA negativity) at 6 months of follow-up is equivalent to a prolonged response and therefore a ‘cure’.17–20 Furthermore, a cure is considered to restore population-specific life expectancy.

The weight distribution considered in this cohort for the Spanish population was 25% below 60 kg, 25% between 61 and 75 kg, 25% between 76 and 85 kg and 25% more than 85 kg.

In this comparison, the assumption of equality has been applied; in other words, it is considered that all years of life saved are equal, regardless of age, presence of other diseases or other circumstances. This means that 1 year of life saved has the same value whoever the beneficiary is and however such improvement in life expectancy is obtained. To determine which treatment should be implemented in clinical practice, a decision rule must be introduced comparing the information on cost per life year saved or quality-adjusted life year gained vs. other therapeutic procedures. Although it is very difficult to establish a precise limit defining whether a process should be considered to be cost-effective or not, it is generally considered that therapies costing less than 26 600 euros per life year saved are cost-effective.8

Cost-effectiveness ratios

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

In order to maximize the effectiveness of a given amount of resources, incremental cost-effectiveness ratios and incremental cost-utility ratios were calculated by dividing the incremental cost by the incremental effectiveness (life year saved or quality-adjusted life year gained) for each strategy, using the following formula: C/E or C/U = (CA − CB)/(EA − EB), where C is the cost, E is the effectiveness in terms of life expectancy (C/E) or quality-adjusted life expectancy (C/U), A is the most effective strategy and B is the least effective strategy.21

Sensitivity analysis

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

In order to evaluate the robustness of the model, uncertainties associated with the various assumptions must be managed by means of a sensitivity analysis to identify the impact of changes in the most significant variables on the study conclusions.12 The effect of therapy discontinuation was introduced. In the base-case results, we considered that all patients completed 48 weeks of treatment, but, in the sensitivity analysis, we introduced the effect of treatment duration according to the number of subjects treated every week. In the study, patients' body weights were changed to reflect average Spanish body weight distribution, but, in the sensitivity analysis, we considered the body weights of subjects participating in the clinical trial.4 The key probability rates of disease progression were halved or doubled and different discount rates for costs and health benefits (0 and 5%) were applied according to international recommendations. We also modified the sustained virological response of the strategies with peginterferon alfa-2b (maintaining the sustained virological response of interferon alfa-2b plus ribavirin at 47%).

Base-case analysis

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The results of the Markov model, projecting the effects of a sustained virological response on the clinical outcomes relative to the type of therapy, are shown in Table 3 for all patients. The model shows that, after 30 years of therapy for chronic hepatitis C, there is a reduction in the proportion of patients with decompensated cirrhosis and other related liver complications, and this reduction is higher using Peg + RAB, especially with therapeutic compliance for 48 weeks (Peg + RAB + C). The average cost of each strategy per patient (including visits, laboratory tests, HCV RNA determination, thyroid-stimulating hormone levels, liver biopsy, genotyping, pregnancy test, electrocardiogram and eye examination, when appropriate) and the lifetime costs are shown in Table 1 for all patients and in Table 2 for genotype 1 patients. All costs were calculated for 48 weeks of therapy. No stopping rules (stoppage for the absence of viral response during treatment) were applied in the base case, but dose reduction and discontinuations were considered in the sensitivity analysis.

Table 3.  Clinical outcomes of the four treatment strategies (defined in the text) in all patients (percentage of patients in each clinical stage at 20 and 30 years after the start of treatment)
 IFN + RPeg + R800Peg + RABPeg + RAB + C
20 years30 years20 years30 years20 years30 years20 years30 years
Cirrhosis17.812.516.011.314.210.011.38.1
Decompensated cirrhosis2.92.32.52.02.21.71.51.2
Liver transplantation0.60.80.50.70.40.60.30.4
Hepatocellular carcinoma0.30.20.30.20.20.10.20.1
Liver-related death9.917.38.615.07.312.75.39.1
Non-liver-related death12.127.312.227.712.328.212.428.9

To estimate the incremental cost-effectiveness ratios or incremental cost-utility ratios, treatment alternatives were ranked according to effectiveness (in terms of the number of life years saved (LYS) or number of quality-adjusted life years gained [QALYs]), and the incremental values were estimated by dividing the incremental lifetime costs by the incremental effect for each successively more effective strategy. In Table 1, the incremental lifetime cost (ΔLC), incremental effectiveness (ΔLYS or ΔQALYs) and incremental cost-effectiveness and incremental cost-utility ratios are calculated for all patients and treatments. Life expectancy is between 18.91 and 19.73 years and between 16.29 and 18.16 quality-adjusted life years for IFN + R and Peg + RAB + C, respectively, with an increase in life expectancy of 0.23–0.36 years and 0.52–0.83 quality-adjusted life years compared with the previous less effective therapy. The incremental cost-effectiveness ratio is the incremental cost divided by the incremental benefit of the more expensive treatment compared with the next less expensive option, and ranged from 8501 euros per life year saved to cost saving.

The incremental cost-effectiveness and incremental cost-utility ratios for all patients and for genotype 1 patients are shown in Figures 1–3. Figures 2 and 3 show the total costs and total effectiveness for the cohort of 1000 patients in each treatment alternative. For example, if all patients receive IFN + R, the total effectiveness is 18 910 life years saved and the total cost is 18 410 132 euros. The incremental cost-effectiveness ratio (incremental cost to gain 1 year of life) is the slope of the line between the two treatments; for example, the slope of the line between IFN + R and Peg + RAB + C is 1636 euros per life year saved, which is the incremental cost-effectiveness ratio of Peg + RAB + C vs. IFN + R.

image

Figure 1. Incremental cost-effectiveness ratios (ICER) in euros per life year saved (LYS) and incremental cost-utility ratios (ICUR) in euros per quality-adjusted life year gained (QALY) of different strategies (defined in the text) with peginterferon alfa-2b plus ribavirin vs. interferon alfa-2b plus ribavirin in all patients and in genotype 1 patients.

Download figure to PowerPoint

image

Figure 2. Hypothetical total costs and effectiveness of the four strategies (defined in the text) for the cohort of all base-case patients. The numbers in the boxes are the incremental cost-effectiveness ratios [euros per life year saved (LYS)] of different strategies with peginterferon alfa-2b plus ribavirin vs. interferon alfa-2b plus ribavirin.

Download figure to PowerPoint

image

Figure 3. Hypothetical total costs and effectiveness of the four strategies (defined in the text) for the cohort of all genotype 1 patients. Numbers in the boxes are the incremental cost-effectiveness ratios [euros per life year saved (LYS)] of different strategies with peginterferon alfa-2b plus ribavirin vs. interferon alfa-2b plus ribavirin.

Download figure to PowerPoint

Because hepatitis C usually progresses slowly, the age at the time of initiation of therapy modifies the cost-effectiveness ratio. Thus, Table 4 shows that the incremental cost-effectiveness ratio increases as the age at the start of treatment increases. The threshold age, that is the maximum age at which the treatment remains cost-effective, was calculated for each type of therapy and ranged from 61 years with Peg + R800 to 71 years with Peg + RAB + C. A similar increase in the threshold age was observed for genotype 1 patients.

Table 4.  Incremental cost-effectiveness ratio (ICER) and threshold age (TA) of different strategies * (peginterferon alfa-2b plus ribavirin vs. interferon alfa-2b plus ribavirin) according to the age at the time of initiation of treatment
 Age (years)ICER (euros per life year saved)
Peg + R800 vs. IFN + RPeg + RAB vs. IFN + RPeg + RAB + C vs. IFN + R
  • *

     Defined in the text.

All patients304987.893212.39553.17
459386.086405.381941.10
6024 579.3517 742.887503.72
TA616471
Genotype 1303250.293212.3986.34
456469.026405.381157.40
6017 888.8417 742.885706.25
TA636473

Sensitivity analysis

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

The results of the sensitivity analysis are shown in Table 5. In all cases, Peg + RAB + C is the most cost-effective therapy. The incremental cost-effectiveness ratio in all cases is below the benchmark of 26 600 euros per life year saved and, even when no discount rate is applied, Peg + RAB + C is a cost-saving strategy compared with IFN + R.

Table 5.  Sensitivity analysis for all patients showing the changes in the incremental cost-effectiveness ratio (ICER) as a function of the modification of key variables using the four different therapeutic strategies *
 ICER (euros per life year saved)
Peg + R800 vs. IFN + RPeg + RAB vs. IFN + RPeg + RAB + C vs. IFN + R
  • *

    Defined in the text.

  •  7.3% to 3.7%.

  •  7.3% to 14.6%.

  • §

     3.1% to 1.5%.

  •  3.1% to 6.2%.

Base case8477.525738.531636.28
Discontinuation7200.594720.08254.78
Disease progression
 Reduce moderate hepatitis to cirrhosis by 100%13 037.379154.223338.31
 Increase moderate hepatitis to cirrhosis by 100%5956.383865.26733.34
 Reduce decompensated cirrhosis to transplant by 100%§9023.006307.252239.79
 Increase decompensated cirrhosis to transplant by 100%7578.294800.54640.22
Patients' weight distribution
 50% (< 75 kg), 50% (> 75 kg)8477.685387.051439.43
 25% (< 65 kg), 25% (66–85 kg)
 25% (86–105 kg), 25% (> 105 kg)14 136.028567.813220.62
Discount rate
 5%15 681.3511 168.374409.15
 0%2348.881171.39Cost-saving

In all patients, the threshold sustained virological response at which the pegylated strategies are cost-effective (if we maintain the sustained virological response of IFN + R at 47% as in the original clinical trial) were calculated for each type of therapy. The following results were obtained: 50% for Peg + R800 and 52% for Peg + RAB and Peg + RAB + C.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References

This study compared different therapeutic strategies for chronic hepatitis C patients (peginterferon alfa-2b plus ribavirin and interferon alfa-2b plus ribavirin) in order to determine which strategy was the most cost-effective and should be recommended from a societal point of view. In the study, the optimal strategy is a combination of peginterferon alfa-2b and ribavirin adjusted to the patients' body weight for 48 weeks with good therapeutic compliance. This strategy is particularly cost-effective for genotype 1 patients, and is cost-saving compared with the previous less effective strategy.

In patients with a sustained virological response, this strategy decreases future liver complications, such as decompensated cirrhosis, hepatocellular carcinoma and liver-related death, prolongs life expectancy by over 4 years compared with no anti-viral therapy,7 and has a better cost-effectiveness than many other well-accepted medical interventions.

Several cost-effectiveness studies on the therapy of chronic hepatitis C have been published, analysing the effect of different drugs (interferon, pegylated interferon and ribavirin) and different drug dosages in ‘naive’ patients.8–14, 22 However, these studies have not evaluated the effect of therapeutic compliance. According to the base-case analysis, therapeutic compliance increases the threshold age below which pegylated interferon and ribavirin remain cost-effective from 61 to 71 years in all patients. The sensitivity analysis also confirmed these results. Therapeutic compliance is a key parameter, which not only increases the sustained response rate, but also reduces the future cost of disease because of the higher sustained virological response rate.4 Therefore, to ensure good therapeutic compliance and hence optimal outcomes, it is essential to maintain the involvement of doctors, the complete collaboration of patients and the support and counselling by nursing staff. This is especially important for patients who achieve a 2-log decrease in HCV RNA levels after 12 weeks of therapy, i.e. patients with a higher probability of achieving a sustained virological response.6 In the last few years, the most successful treatment outcomes have been obtained in previously untreated young patients with moderate to severe disease. Currently, there is a pool of older untreated patients and non-responders to interferon monotherapy or combination therapy;23 our study shows that, with full therapeutic compliance, there is still a strong possibility of a cost-effective ‘cure’ for patients between the ages of 61 and 71 years using peginterferon alfa-2b plus body weight-adjusted doses of ribavirin. Therefore, therapy should be recommended for naive patients aged more than 60 years from a societal point of view.24, 25

An important limitation to this study is that patients infected with genotype 1 who are HCV RNA positive at week 24, or who have less than a 2-log decrease in HCV RNA levels at week 12, normally stop therapy at these time points. This aspect has not been included in the study. If it had, it would have considerably reduced the drug costs of treatment and would have improved the cost-effectiveness of hepatitis C therapy. In addition, in clinical practice, the recommended duration of therapy for genotype 2 and 3 patients is 24 weeks and, again, this reduces the costs of therapy. These rules were not considered in this cost-effectiveness study, but, if applied in clinical practice, would make chronic hepatitis C therapy even more cost-effective.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Decision analysis model
  6. Patient population
  7. Therapeutic strategies
  8. Definition of response to therapy
  9. Quality of life adjustments
  10. Cost data, discount rate and perspective
  11. Assumptions
  12. Cost-effectiveness ratios
  13. Sensitivity analysis
  14. Results
  15. Base-case analysis
  16. Sensitivity analysis
  17. Discussion
  18. Acknowledgement
  19. References
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