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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

Summary

Background

Different peg-interferon alpha-2b plus ribavirin treatment strategies are more effective in treating hepatitis C. However, no cost-effectiveness data have been published using the clinical data from the peg-interferon alpha-2b and ribavirin in the treatment of patients with hepatitis C in Taiwan.

Aim

To estimate the cost-effectiveness of different treatments with peg-interferon alpha-2b plus ribavirin for the initial treatment of patients with different genotype chronic hepatitis C.

Methods

Individual patient level data from a randomized clinical trial with peg-interferon plus ribavirin were applied to a Markov model to project lifelong clinical outcomes. Economic estimates and quality of life were based on published data and Taiwan patient data. We used a societal perspective and applied a 3% annual discount rate.

Results

Compared with different combination therapy strategies, peg-interferon alpha-2b plus weight-based dosing of ribavirin in all patients for 24 weeks is the most cost-effective treatment strategy. If the sustained virological response of peg-interferon plus ribavirin treatment for 48 weeks therapy in genotype 1 patients was higher than 67.8%, the best strategy of treating patients will be the peg-interferon plus weight-based dosing of ribavirin therapy for 48 weeks in genotype 1 patients and for 24 weeks in non-genotype 1 patients.

Conclusions

Peg-interferon alpha-2b plus ribavirin combination for 24 weeks therapy in all genotype patients should reduce the incidence of liver complications, prolong life, improve quality of life and be cost-effective for the initial treatment of chronic hepatitis C.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

The global hepatitis C prevalence rate is estimated to be 3%.1 In the United States, Europe, Southeast Asia and most of Africa, the prevalence rate is under 2.5%. The prevalence rate for hepatitis C in the western Pacific region, however, is 2.5–4.9%2 and is 1–12% in the Middle East.1 There are nearly 170 million people infected with hepatitis C around the globe, with about four million in the United States3 and five million in western Europe.

Taiwan is one of the regions in the world where hepatitis is highly prevalent, with hepatitis B being the most common, followed by hepatitis C. According to the results published in the ‘Hepatitis C Study in Taiwan’, the prevalence rate of hepatitis C virus (HCV) antibody in adults is about 1–2% in Taiwan. Moreover, it can exceed 5% for those at or over 50 years of age. Based on a quarterly report published by the Taiwan Association for the Study of the Liver in January 2003, the prevalence rate in adults (18 years and above) reaches as high as 2–5%.4–7 An estimated 20–35% of patients with chronic hepatitis C (CHC) develop liver cirrhosis within 20 years and many of these patients ultimately require liver transplantation.

The combination of conventional interferon alpha plus ribavirin is more effective than interferon alpha alone to treat hepatitis C. Sustained virological responses (SVR) for combination therapy exceed 40%. Furthermore, according to the recent results of two large registration trials that mainly enrolled Caucasian patients, the SVR rate can be achieved in 54–56% of subjects.8,9 The overall side effect profiles were similar between patients receiving ribavirin with peg-interferon alpha or traditional interferon. The studied factors included younger age, female gender, HCV non-genotype 1, lower baseline viral levels, early clearance of virus during therapy, less fibrosis or inflammation on liver biopsy and lower body weight. When compared with interferon alpha-2b plus ribavirin, the beneficial effect of peg-interferon plus ribavirin on treatment response was apparent in Caucasian patients with genotype 1, but controversial in patients with non-genotype 1. Several studies have demonstrated the cost-effectiveness of combination therapy compared with monotherapy for the treatment of established CHC.10–12 For example, a recent paper employed clinical efficacy data from Manns et al.13 and German health care treatment patterns and costs, and concluded that peg-interferon alpha-2b plus ribavirin combination therapy was more cost-effective than interferon alpha-2b plus ribavirin. The rates of end-of-treatment and sustained responses were significantly lower in African-American populations when compared with Caucasians with the same genotype. In addition, two recent studies14 showed that host ethnicity does influence the clinical outcome, cytokine production, anti-viral CD4 T-cell response during HCV infection.

However, no cost-effectiveness data have been published using the clinical data from the peg-interferon alpha-2b and ribavirin development programme in Taiwan.15,16 The objective of the current study was to determine whether the gain in SVR achieved with different treatment strategies is worth the incremental cost in the context of the Bureau of National Health Insurance (BNHI) of Taiwan reimbursement scheme, and to determine which the best strategy is.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

Model structure

Hepatitis C is a chronic condition with a latent and non-linear pattern of disease progression. The median time to cirrhosis in an untreated population is about 20 years. Thus, evaluations of treatment cost-utility must rely on mathematical modelling techniques. In this study, we constructed a short-term decision model and a deterministic Markov state transition model of CHC disease progression that reflects various stages of HCV-associated liver disease.

The research applied a computerized economic modelling technique and performed a cost-effectiveness analysis targeting CHC patients who received peg-interferon alpha-2b plus ribavirin combination therapy 24 weeks, interferon alpha-2b plus ribavirin combination therapy 24 weeks or peg-interferon alpha-2b plus ribavirin combination therapy 48 weeks, depending on the infected genotype. The Markov model is programmed using TreeAgePro 2005 (TreeAge Software, Williamstown, MA, USA).

Study subjects

Subjects in this study were CHC patients who were assumed to be 45 years old and met the following criteria: (i) positive anti-HCV; (ii) positive serum HCV RNA; (iii) serum alanine aminotransferase value more than twice the upper limit of normal, twice in a year; (iv) liver tissue biopsy of hepatic portal and intraportal fibrosis, at or above the moderate stage in hepatic cell inflammation and necrosis; (v) no cirrhosis; (vi) no concurrent infection with hepatitis B or human immunodeficiency virus and (vii) never received interferon, peg-interferon or ribavirin treatments.

For CHC patients meeting the above criteria, the objective of this study was to determine which one of the three treatment strategies was most cost-effective for patients without differentiation of genotype or for patients with different viral genotypes. Therefore, based on the course of drug treatment requirement, and referring to the literature published by Younossi et al. in 1999 and Buti et al. in 2003, a short-term economic analysis model was constructed (Figure 1), and the lifelong model (Figure 2) was developed based on the major natural disease progression parameters of CHC (Figure 3). Patients who received 24 weeks of combination treatment and used the effectiveness data (% reached SVR) were found only in the domestic clinical trial. The model provides predictions of clinical outcomes and costs of a hypothetical cohort of treated patients followed over their expected lifetimes. In the lifelong model, subjects can make transitions between health states at annual intervals. The transition probabilities and health utility values were referenced from the literature.

image

Figure 1.    Structure of decision tree model, patients receiving different therapy and followed for 24 additional weeks (INF, interferon; PEG-INF, peg-interferon alpha-2b; ETVR, end-of-treatment virological response; SVR, sustained virological responses).

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image

Figure 2.  Structure of Markov model after no sustained virological responses or no end-of-treatment virological response.

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image

Figure 3.  Major natural disease progression of chronic hepatitis C.

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The treatment strategies in the model were

  • 1
     Combination treatment with peg-interferon alpha-2b (1.5 μg/kg), subcutaneously, one time a week, plus ribavirin >10.6 mg/kg/day, orally, for 24 weeks and follow-up of the therapeutic effect for another 24 weeks, no matter what genotype.
  • 2
    Combination treatment with interferon alpha-2b, 3 MU, subcutaneously, three times a week, plus ribavirin >10.6 mg/kg/day, orally, for 24 weeks and follow-up of the therapeutic effect for another 24 weeks in patient infected with non-genotype 1, and combination treatment with peg-interferon alpha-2b (1.5 μg/kg), subcutaneously, one time a week, plus ribavirin >10.6 mg/kg/day, orally, for 24 weeks and follow-up of the therapeutic effect for another 24 weeks in patients infected with genotype 1.
  • 3
    Combination treatment with peg-interferon alpha-2b (1.5 μg/kg), subcutaneously, one time a week, plus ribavirin >10.6 mg/kg/day, orally, for 48 weeks and follow-up of the therapeutic effect for another 24 weeks, in patients infected with genotype 1, and combination treatment with peg-interferon alpha-2b (1.5 μg/kg), subcutaneously, one time a week, plus ribavirin >10.6 mg/kg/day, orally, for 24 weeks and follow-up of the therapeutic effect for another 24 weeks in patients infected with non-genotype 1.

Clinical data

The SVR data used in the Markov model were drawn from literature review. In addition, the study used recent reported data of Taiwan15,17 and other clinical trials’ data.25–31 Patients were required to complete drug treatment, and receive virus examination (PCR) at the end of drug treatment. If the patient displayed a negative result for HCV RNA, this meant that the end-of-treatment virological response (ETVR) was attained. In contrast, for those who showed a positive result in HCV RNA, this indicated no ETVR. For patients reaching ETVR, another 24 weeks of therapeutic follow-up was initiated, and another virus examination (PCR) was requested at completion of follow-up. The SVR rates by HCV genotype are shown in Table 1.

Table 1.   Model parameters: treatment response
 Base case (%)Low (%)High (%)Source
  1. Base case model parameters for treatment response according to hepatitis C virus genotype are combined with Taiwan and international data (meta-analysis from Refs12, 13, 15, 17–24).

  2. ETVR, end-of-treatment virological response; SVR, sustained virological response.

Peg-interferon alpha-2b plus ribavirin 24 weeks
 ETVR
  Overall86.065.288.212, 13, 15
  Genotype 182.780.092.115,17, 22
  Non-genotype 189.275.794.115, 16, 20, 23
 SVR
  Overall64.15067.1 
  Genotype 151.648.965.8 
  Non-genotype 176.264.381.2 
Peg-interferon alpha-2b plus ribavirin 48 weeks for genotype 1 patients
 ETVR65.753.993.313, 24, 26
 SVR56.241.180.0 
Interferon alpha-2b plus ribavirin 24 weeks for non-genotype 1 patients
 ETVR68.052.097.427–29
 SVR61.150.086.8 

Disease progression data are reported in Table 2. Because well-designed, long-term prospective studies in patients with CHC are lacking, published estimates of progression to cirrhosis and hepatocellular carcinoma (HCC) were used based on projections. The study relied largely on a Siebert et al. study on patients with cirrhosis to estimate progression to cirrhosis. Additionally, expert opinion is an important estimate of progression. Progression of disease from liver transplantation to death was estimated from published data. In addition, the transition probabilities for patients varied from cure to CHC and compensated cirrhosis to death, and were determined with regard to the age-specific death profile of Taiwan, as released by the Department of Health in 2003.

Table 2.   Annual transition probability of each health status
Health stateTransition probability (%)Source
Base caseLower limitUpper limit
  1. Annual transition probability of each health status in natural disease progression of chronic hepatitis C.

Chronic hepatitis[RIGHTWARDS ARROW]cure0.200.519
Chronic hepatitis[RIGHTWARDS ARROW]compensated cirrhosis7.35.19.519
Chronic hepatitis[RIGHTWARDS ARROW]hepatocellular carcinoma0.100.219
Compensated cirrhosis[RIGHTWARDS ARROW]ascites2.51.83.219
Compensated cirrhosis[RIGHTWARDS ARROW]variceal bleeding1.10.61.619
Compensated cirrhosis[RIGHTWARDS ARROW]hepatic encephalopathy0.40.10.719
Compensated cirrhosis[RIGHTWARDS ARROW]hepatocellular carcinoma1.51.02.019
Ascites[RIGHTWARDS ARROW]liver transplantation3.12.93.3Expert opinion
Ascites[RIGHTWARDS ARROW]death (first year)117.714.319
Ascites[RIGHTWARDS ARROW]death (after first year)33283819
Variceal bleeding[RIGHTWARDS ARROW]liver transplantation3.12.93.3Expert opinion
Variceal bleeding[RIGHTWARDS ARROW]death (first year)4033.444.619
Variceal bleeding[RIGHTWARDS ARROW]death (after first year)138.517.519
Hepatic encephalopathy[RIGHTWARDS ARROW]liver transplantation3.12.93.3Expert opinion
Hepatic encephalopathy[RIGHTWARDS ARROW]death (first year)6865.970.119
Hepatic encephalopathy[RIGHTWARDS ARROW]death (after first year)4033.444.619
Hepatocellular carcinoma[RIGHTWARDS ARROW]death8683.788.319
Liver transplantation[RIGHTWARDS ARROW]death (first year)105.021.030
Liver transplantation[RIGHTWARDS ARROW]death (after first year)5.74.76.719

Cost measurement and valuation

The study was analysed from BNHI's perspective; therefore, the cost items analysed were mainly based on reimbursed items. Calculation of treatment costs included the medical expenditure incurred during combination treatment, along with all medical expenditures associated with the treatment of hepatitis C from the end of combination treatment to patient death. The costs generated during combination treatment were cited from research results of short-term model analysis. For medical costs from the end of treatment until death, length of survival under different health status conditions was first determined with respect to transition probabilities, then multiplied by the annual medical costs of treating hepatitis C at each health status separately, and then all costs were summed. Annual medical costs of treating hepatitis C patients in each health status were taken from the analysis of database from the BNHI (Table 3).

Table 3.   Quality of life and cost estimate of each health status
Health statusQuality of life utility valuesSource
Base caseLower limitUpper limit
Cure1.0019, 31
During interferon + ribavirin treatment0.950.91 
During peg-interferon + ribavirin treatment0.900.860.94 
Chronic hepatitis0.920.890.95 
Compensated cirrhosis0.890.820.92 
Hepatic encephalopathy0.810.760.87 
Hepatocellular carcinoma0.810.760.87 
Liver transplantation (first year)0.860.730.99 
Liver transplantation (after first year)0.860.730.99 
Death0.0000 
Ascites0.81Expert opinion
Portal variceal bleeding0.81Expert opinion
Annual costsAverage direct medical cost (US$)Source
 Base caseLower limitUpper limit
Cure000BNHI data
Chronic hepatitis277.3184.9369.8 
Compensated cirrhosis1086.2724.11448.3 
Ascites2890.11926.73853.5 
Variceal bleeding4515.93010.66021.3 
Hepatic encephalopathy6843.44562.29124.5 
Hepatocellular carcinoma4286.92857.95715.8 
Liver transplantation (first year)17142.911428.622857.1 
Liver transplantation (after first year)8571.45714.311428.6 
Interferon + ribavirin treatment for 24 weeks2451.81634.53269.1 
Peg-interferon + ribavirin treatment for 24 weeks2446.91631.23262.5 
24 weeks follow-up cost236157.3314.6 
No anti-viral treatment 1 year229184.9369.8 
Price of peg-interferon129.248.8175.6 
Price of ribavirin21.42.3 

The BNHI database employed in this study was a randomly selected patient pool that consisted of 200 000 patients, released by BNHI. The database recorded the medical resources utilized during 1996–2001 by those 200 000 patients. There were three steps used in the analysis of the database: (i) identification of those patients with hepatitis C from the 200 000 patients using the International Classification of Diseases, Clinical Modification (ICD-9 CM) codes for hepatitis C: 070.41 and 070.51; (ii) all hepatitis C patients were classified into various health states, in accordance with ICD-9 CM codes: 571.4, 571.40, 571.41, 571.49, 571.5, 456.20, 789.5, 070.41, 572.2, 155.0, A095, 50.5, 50.51 and 50.59 and (iii) finally, all of the reimbursed medical resources consumed were aggregated and the average cost calculated for a patient with each of the health status conditions. Medical expenditure in each year was converted into the price level in 2003 at a 3% discount rate. Finally, direct medical costs for a case of liver transplantation were obtained by collating experts’ opinion by way of a questionnaire.

Outcome measurement

The outcome variables used in the lifelong Markov model were life expectancy and quality-adjusted life year (QALY), and both were calculated from the transition of each health state during their lifetime. The difference between QALY and life expectancy was that QALY took consideration of the utility values in each patient's health status. When computing QALY, a patient's length of life with a particular health status should be determined through his/her transition probability from that health status first. The quality of life represented by the utility value at that health state should then be multiplied by the length of life to obtain the QALY for that individual patient in that particular health status. Transition probabilities and the patient's quality of life (presented by the utility value) for each health status condition are necessary parameters in determining the effectiveness of the therapy (life expectancy and QALY). Using the Markov model, this study assumed the transition cycle to be 1 year. This means that transition from one health status to another health status is 1 year with a specific probability. For both the transition probability and the utility value denoted in this study, data were taken from the literature published by Siebert et al. in 2003,19 with the following assumptions made specifically for this study:

  • 1
     All transition probabilities from one health status to another are identical for CHC patients in Taiwan and those in foreign counties.
  • 2
    Quality of life utility values for each health status are identical for CHC patients in Taiwan and those in foreign counties.

Regarding the data on liver transplantation in Taiwan, the percentage of patients receiving transplantation surgery and the post-operative mortality rate were different from that of foreign countries,30 because of differences in medical practice backgrounds. Therefore, transition probabilities from each health status condition to liver transplantation and post-operative mortality rates were obtained by collecting experts’ opinion using a questionnaire. These data are shown in Table 3.

When the incremental cost-effectiveness ratio (ICER) was lower than US$14 000 per QALY gained, which means it costs an additional US$14 000 (equivalent to NT$448 000, exchange rate between US$ and NT$ was 1:32) for one QALY, which was considered cost-effective.

Sensitivity analysis

Using one-way sensitivity analyses, the study varied treatment effectiveness, relevant progression probabilities, discount rates, medical care costs and the price of peg-interferon alpha-2b plus ribavirin to evaluate uncertainty in the model parameters. The disease progression probabilities were varied around the base case estimates in both directions in sensitivity analyses. This also modified the SVR of the strategies with peg-interferon alpha-2b. The discount rate was calculated to be 3%, with an acceptable range of 3–5%, and the price for each ampoule of peg-interferon alpha-2b 100 μg was seven times that of the interferon alpha-2b 3 MU, with an acceptable range of 2.5–9 times.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

Base case analysis

The base case analysis used the combined data. The price of peg-interferon alpha-2b used in this study was US$136.6, and the price of ribavrin $2/cap. The discount rate was 3%. The annual stated cost is the average cost.

Short-term model

As shown in Table 4, if all patients with CHC were tested to differentiate the genotypes, strategy 2 is most cost saving; it is also the most cost-effective strategy. Average cost of per SVR achieved is $5562.5. The strategy 1 average cost is $6000.5, the strategy 3 average cost is $9591.0. The SVR in these two treatment strategies are more than strategy 2, but the ICERs of these two strategies compared with strategy 2 are too high. Does higher SVR worth it? This study did lifelong mode to solve the problem.

Table 4.   The short-term base case result of analysis in different genotypes
StrategyAverage cost (US$)SVR ratioCost-effective ratioICER (US$ per SVR)
16000.50.6419361.11141565.7
25562.50.54210262.92 
39591.00.62215419.611611400.0

Lifelong model

The result of lifelong model is different from short-term model (Table 5). Using genotype frequency distribution estimates from the clinical trial programme, if all patients with CHC were tested to differentiate the genotypes, the strategy 1 is the most cost-effective. Taking the lifetime cost into consideration, the lifetime total direct medical cost would be $10 647.69 on average, the strategy 2 is $11 463.31, the strategy 3 is $14 578.63 and the strategy 1 is less cost. As for the effectiveness variable, a 45-year-old CHC patient would have an average 29.2 QALY when receiving peg-interferon alpha-2b combination therapy in all patients, no matter what genotype infected. This is the most effective treatment strategy in contrast with 28.3 QALY and 29.1 QALY, for treatment strategy 2 or strategy 3, respectively.

Table 5.   The lifelong model base case result of analysis in different strategies
Strategy Cost (US$)Effectiveness (QALY)Cost- effective ratioICER cost per QALY
  1. * Compare strategy 3 with strategy 2.

110647.6929.2364.65 
211463.3128.3405.06 
314578.6329.1500.983894.15*

To estimate the ICERs or incremental cost–utility ratios, treatment alternatives were ranked according to effectiveness (in terms of the number of QALYs gained), and the incremental values were estimated by dividing the incremental lifetime costs by the incremental effect for each successively more effective strategy. In this study, the ICER between strategies 2 and 3 was calculated. The ICER is $3894.15 per QALY gained. It is more favourable than the benchmark of $14 000 per QALY gained.

Sensitivity analysis

From the results of the sensitivity analyses (Table 6), it was found that when costs were within a certain reasonable range, none of the items listed above would cause a major variation in the overall cost, with the exception of changes in the medication costs of ribavirin and peg-interferon alpha-2b. The main reason for this is because the medication costs of peg-interferon alpha-2b or interferon alpha-2b plus ribavirin comprised three fourth of the total cost in the short-term model. The level of anti-viral drug cost, including peg-interferon alpha-2b, interferon alpha-2b and ribavirin, played the leading role in varying the overall direct medical cost over 2 years, while cost items other than the anti-viral drugs were not key cost drivers of direct medical cost. In the lifelong model, although the price of peg-interferon alpha-2b is 14 times that of interferon alpha-2b, on overall genotypes, compared with the strategy 2, the ICER is $265.16 per QALY, still within an acceptable range.

Table 6.   Sensitivity analysis of lifelong model of the incremental cost-effectiveness ratio (ICER) for strategies to uncertainty in parameter values in patients infected with hepatitis C virus
ItemSensitivity analysisICER of sensitive analysis (US$ per QALY)Statement
SVR of interferon + ribavirin treatment for 24 weeks therapy with non-genotype 1 patients50%Strategy 1 dominance
86.8%Strategy 1 dominance
SVR of peg-interferon + ribavirin treatment for 48 weeks therapy with genotype 1 patients41.1%Strategy 1 dominance
63.3%12537.25Strategy 3:strategy 1
93.3%1735.25Strategy 3:strategy 1
SVR of peg-interferon + ribavirin treatment for 24 weeks therapy with all genotyping50%4777.13Strategy 3:strategy 2
55%2139.84Strategy 1:strategy 2
56.6%5610.31Strategy 3:strategy 1
62.6%Strategy 1 dominance
SVR of peg-interferon + ribavirin treatment for 24 weeks therapy with non-genotype 1 patients80%Strategy 1 dominance
92.1%Strategy 1 dominance
Price of peg-interferon−50%Strategy 1 dominance
+100%265.16Strategy 1:strategy 2
Transient probability of liver transplantation to death (first year)5%Strategy 1 dominance
21%Strategy 1 dominance
Transient probability of hepatocellular carcinoma to death42.7%Strategy 1 dominance
86%Strategy 1 dominance

If the study changed the discount rate from 3% to 5%, it did not impact the result of the analysis. Changing the transient probability of HCC to death32 from 86% to 42.7%, again had no significant effect. Changing the transient probability of chronic hepatitis to compensated cirrhosis from 0.3% to 10%, also did not impact the results.

The important change is the SVR of peg-interferon plus ribavirin given for 24 weeks in non-genotype 1 patients, where the results show that if the SVR was lower than 63.6%, we should take strategy 3, it means that genotype 1 patients should receive peg-interferon plus ribavirin for their 48 weeks of treatment and non-genotype 1 patients should receive peg-interferon plus ribavirin for their 24 weeks of treatment. The result of sensitivity analysis also shows that when the SVR of peg-interferon plus ribavirin given for 24 weeks in all genotype patients is lower than 0.6, we should take strategy 3.

The other one is the SVR of peg-interferon plus ribavirin treatment for 48 weeks therapy with genotype 1 patients, where the results show that if the SVR was higher than 62.8%, we should take strategy 3.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

Because of the high prevalence of hepatitis C and its indolently progressive natural course, some studies have suggested that future population morbidity and mortality from hepatitis C may double over the next 10–20 years.33, 34 How to treat hepatitis C patients more effectively and at a lesser cost has therefore become a question of considerable urgency.

There are many studies which indicate that combination therapy in the treatment of naïve hepatitis C patients is cost-effective,12, 21, 35 but none provide data on the most cost-effective way to treat Chinese patients. This study sought to estimate the long-term cost-effectiveness outcome using clinical trial results and local cost data. The results show that combination therapy using peg-interferon alpha-2b plus ribavirin for 24 weeks in all genotypes is the most cost-effective and people live longer and better, also the therapy costs less.

From the efficacy data of the clinical trial performed in Taiwan, the therapeutic effect of peg-interferon combination therapy was confirmed and exhibited a better outcome than other countries.18, 36 Therefore, the economic evaluation used combined efficacy data from both domestic and international results, and the domestic data were used to reflect treatment outcomes. This study found that when using Taiwan's clinical trial efficacy data, the best treatment strategy is strategy 3, 48 weeks peg-interferon alpha-2b plus ribavirin for genotype-1-infected patients and 24 weeks for non-genotype-1-infected patients.

According to the outcome of the clinical trial in Taiwan, the response of Chinese patients to peg-interferon alpha-2b plus ribavirin treatment is better than that of Caucasians.7, 37–39 While contrasting the outcome data from domestic and international clinical trial studies, it was clear that both interferon alpha-2b plus ribavirin and peg-interferon alpha-2b combination therapies resulted in a considerably higher SVR percentage in patients receiving the treatment in Taiwan than in other countries. This might be due to the small sample size used in Taiwan, or to the fact that the subjects sampled were different from those in other countries; in any event it created a systematic difference in overall therapeutic effect favouring a better effect than those in international studies. If the patients in the domestic clinical trial indeed represent all the CHC patients in Taiwan, then the major factors leading to the dissimilarity in domestic and international clinical study results could be the difference of virus species in Taiwan compared with other countries, or variations in drug adverse reaction tolerance. The other reason is that the dose of peg-interferon alpha-2b in Taiwan's clinical trial is higher than other trial. The patients’ compliance of Taiwan is also higher than other trial. These reasons may influence the efficacy data of Taiwan. 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 SVR rate. 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 pharmacist or nursing staff.

When performing sensitivity analyses for uncertain cost variables, none of the cost variables influence the conclusions. In terms of overall genotypes, 24 weeks of peg-interferon alpha-2b plus ribavirin was the most cost-effective treatment method. The strategy 2 is the treatment method in Taiwan now. When combination therapies were applied in treatment of genotype 1 patients,17 the outcome from sensitivity analysis proved that combination therapies for 48 weeks were more cost-effective than 24 weeks treatment. For genotype 2/3 patients, combination therapies were more cost-effective than no anti-viral drug treatment; however, in this group, 24 weeks of the interferon alpha-2b plus ribavirin combination therapy was more cost-effective than 24 weeks of the peg-interferon alpha-2b plus ribavirin combination therapy when using domestic data, and the result reversed when using combined data. Therefore, changes in all cost items exert no effect on the conclusions of this research.

This study has several limitations. First, there are no study data on the Chinese hepatitis C patient condition, probability of progression or quality of life. The data used here are from published papers, and when applied to estimate the outcome of the Chinese patient, it may not reflect the real conditions. Secondly, the study assumed that the patients have good compliance, but in the real world, the compliance may not be as good as the model assumes, and the outcome may not be as good as the study estimates. Thirdly, some transient probabilities used here are expert opinions, which probably have low power, and need more studies in order to be confirmed.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

Peg-interferon alpha-2b plus ribavirin is cost-effective compared with conventional interferon alpha-2b plus ribavirin for treatment of naïve adults with CHC, regardless of HCV genotype. The cost-effectiveness ratio of peg-interferon alpha-2b plus ribavirin for treatment of CHC is comparable to that of many well-accepted clinical interventions.35, 36, 40–44

This cost-effectiveness evaluation suggests, for patients without genotyping, 24 weeks of peg-interferon alpha-2b plus ribavirin combination therapy, using combined efficacy data, is the most cost-effective in Taiwan. For different genotype Chinese patients, using Taiwan clinical trial data, 48 weeks of peg-interferon alpha-2b plus ribavirin combination therapy for genotype 1 and 24 weeks peg-interferon alpha-2b plus ribavirin combination therapy for non-genotype 1 are the more desirable treatment methods in Taiwan.

Acknowledgement

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References

No external funding was received for this study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgement
  9. References
  • 1
    Hepatitis C: global prevalence. Wkly Epidemiol Rec 1997; 72: 3414.
  • 2
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