Antiviral Combination Therapy with Interferon/Peginterferon Plus Ribavirin for Patients with Chronic Hepatitis C in Germany: A Health Technology Assessment Commissioned by the German Agency for Health Technology Assessment

Objective: The purpose of this health technology assessment (HTA), commissioned by the German Agency for HTA at the German Federal Ministry of Health and Social Security, was to systematically review the evidence on effectiveness and cost-effectiveness of antiviral treatment (AVT) for initial chronic hepatitis C (CHC) and to apply these data in the context of the German health care system. Methods: A systematic literature search was conducted to identify randomised controlled trials (RCTs), meta-analyses, and HTAs that evaluated initial AVT for CHC. A modified version of the German Hepatitis C Model (GEHMO) -- a decision-analytic Markov model -- was used to determine long-term morbidity, life expectancy, quality of life, costs and cost-effectiveness of different treatment strategies. Model parameters were derived from German databases, international RCTs, and a Cochrane Review. Results: Overall, 9 RCTs, 2 HTA reports, 1 Cochrane review, and 2 meta-analyses examining medical effectiveness of antiviral combination therapy, as well as 7 economic evaluations, met the inclusion criteria. These studies indicate that combination therapy with peginterferon plus ribavirin produced the highest sustained virological response rates (54-61%), followed by interferon plus ribavirin with 38-54%, and interferon monotherapy with 11-21%. Based on international cost-effectiveness studies, interferon plus ribavirin is cost-effective compared to interferon monotherapy. No published articles were available regarding cost-effectiveness of peginterferon plus ribavirin. In our decision analysis, these findings were confirmed and the discounted incremental cost-effectiveness ratio for peginterferon plus ribavirin was € 9,800 per quality-adjusted life-year gained compared to interferon monotherapy (as the next best non-dominated strategy). Sensitivity analyses showed robust results across a wide range of model parameters. Conclusions: This HTA suggests that initial combination therapy prolongs life, improves quality of life, and is cost-effective in patients with CHC. Combination of peginterferon and ribavirin is the most effective and efficient treatment strategy among the examined options

ein Health Technology Assessment im Auftrag der Deutschen Agentur für Health Technology Assessment

Objective: The purpose of this health technology assessment (HTA), commissioned by the German Agency for HTA at the German Federal Ministry of Health and Social Security, was to systematically review the evidence on effectiveness and cost-effectiveness of antiviral treatment (AVT) for initial chronic hepatitis C (CHC) and to apply these data in the context of the German health care system.Methods: A systematic literature search was conducted to identify randomised controlled trials (RCTs), meta-analyses, and HTAs that evaluated initial AVT for CHC. A modified version of the German Hepatitis C Model (GEHMO) -- a decision-analytic Markov model -- was used to determine long-term morbidity, life expectancy, quality of life, costs and cost-effectiveness of different treatment strategies. Model parameters were derived from German databases, international RCTs, and a Cochrane Review.Results: Overall, 9 RCTs, 2 HTA reports, 1 Cochrane review, and 2 meta-analyses examining medical effectiveness of antiviral combination therapy, as well as 7 economic evaluations, met the inclusion criteria. These studies indicate that combination therapy with peginterferon plus ribavirin produced the highest sustained virological response rates (54-61%), followed by interferon plus ribavirin with 38-54%, and interferon monotherapy with 11-21%. Based on international cost-effectiveness studies, interferon plus ribavirin is cost-effective compared to interferon monotherapy. No published articles were available regarding cost-effectiveness of peginterferon plus ribavirin. In our decision analysis, these findings were confirmed and the discounted incremental cost-effectiveness ratio for peginterferon plus ribavirin was Euro 9,800 per quality-adjusted life-year gained compared to interferon monotherapy (as the next best non-dominated strategy). Sensitivity analyses showed robust results across a wide range of model parameters.Conclusions: This HTA suggests that initial combination therapy prolongs life, improves quality of life, and is cost-effective in patients with CHC. Combination of peginterferon and ribavirin is the most effective and efficient treatment strategy among the examined options.Ziel: Gegenstand dieses Health Technology Assessments (HTA), welches im Auftrag der Deutschen Agentur für HTA (DIMDI/Bundesministerium für Gesundheit und Soziale Sicherung) durchgeführt wurde, war die systematische Bewertung der medizinischen Effektivität und der Kosteneffektivität antiviraler Therapien bei therapienaiven Patienten mit chronischer Hepatitis C im Kontext des deutschen Gesundheitswesens.Methoden: Es wurde eine systematische Literaturrecherche zur Identifikation von randomisierten klinischen Studien (RCT), Metaanalysen und HTAs zur initialen antiviralen Therapie bei chronischer Hepatitis C durchgeführt. Mit einer modifizierten Version des German Hepatitis C Model (GEHMO), einem entscheidungsanalytischen Markov-Modell, wurden Langzeitmorbidität, Lebenserwartung, qualitätskorrigierte Lebensjahre (QALY), Lebenszeitkosten und das inkrementelle Kosten-Nutzwert-Verhältnis (IKNV) für verschiedene Therapiestrategien ermittelt. Die Modellparameter wurden deutschen Datenbanken, internationalen RCTs und einem Cochrane-Review entnommen.Ergebnisse: Insgesamt erfüllten 9 RCTs, 2 HTA-Berichte, 1 Cochrane Review und 2 Metaanalysen zur medizinischen Effektivität sowie 7 ökonomische Evaluationen die Einschlusskriterien dieses HTA. Die Sustained Virological Response Raten (SVR) waren am höchsten für Peginterferon plus Ribavirin mit 54-61%, gefolgt von Interferon plus Ribavirin mit 38-54% und der Interferon-Monotherapie mit 11-21%. In internationalen Kosten-Effektivitäts-Studien wurde die Kombinationstherapie mit Interferon und Ribavirin im Vergleich zur Interferon-Monotherapie als kosteneffektiv eingeschätzt. Publizierte Studien zur Kosteneffektivität der Kombinationstherapie mit Peginterferon und Ribavirin wurden im Recherchezeitraum nicht identifiziert. Die Ergebnisse dieses Reviews wurden in unserer entscheidungsanalytischen Modellierung bestätigt. Die Kombinationstherapie mit Peginterferon und Ribavirin erzielte im Vergleich zur Interferon-Monotherapie ein IKNV von 9.800 Euro/QALY. In Sensitivitätsanalysen zeigten sich robuste Ergebnisse über weite Bereiche der relevanten Modellparameter.Schlussfolgerung: Basierend auf den Ergebnissen dieses HTAs ist davon auszugehen, dass antivirale Kombinationstherapien bei therapienaiven Patienten die Lebenserwartung erhöhen, die Langzeit-Lebensqualität verbessern und als kosteneffektiv einzustufen sind. Die Kombinationstherapie mit Peginterferon und Ribavirin besitzt unter den untersuchten Therapien die höchste Effektivität und ist im Vergleich zu anderen im deutschen Gesundheitswesen akzeptierten medizinischen Verfahren als kosteneffektiv zu bewerten

Antiviral combination therapy with interferon/peginterferon plus ribavirin for patients with chronic hepatitis C in Germany: a health technology assessment commissioned by the German Agency for Health Technology Assessment

Objective: The purpose of this health technology assessment (HTA), commissioned by the German Agency for HTA at the German Federal Ministry of Health and Social Security, was to systematically review the evidence on effectiveness and cost-effectiveness of antiviral treatment (AVT) for initial chronic hepatitis C (CHC) and to apply these data in the context of the German health care system. Methods: A systematic literature search was conducted to identify randomised controlled trials (RCTs), meta-analyses, and HTAs that evaluated initial AVT for CHC. A modified version of the German Hepatitis C Model (GEHMO) -- a decision-analytic Markov model -- was used to determine long-term morbidity, life expectancy, quality of life, costs and cost-effectiveness of different treatment strategies. Model parameters were derived from German databases, international RCTs, and a Cochrane Review. Results: Overall, 9 RCTs, 2 HTA reports, 1 Cochrane review, and 2 meta-analyses examining medical effectiveness of antiviral combination therapy, as well as 7 economic evaluations, met the inclusion criteria. These studies indicate that combination therapy with peginterferon plus ribavirin produced the highest sustained virological response rates (54-61%), followed by interferon plus ribavirin with 38-54%, and interferon monotherapy with 11-21%. Based on international cost-effectiveness studies, interferon plus ribavirin is cost-effective compared to interferon monotherapy. No published articles were available regarding cost-effectiveness of peginterferon plus ribavirin. In our decision analysis, these findings were confirmed and the discounted incremental cost-effectiveness ratio for peginterferon plus ribavirin was € 9,800 per quality-adjusted life-year gained compared to interferon monotherapy (as the next best non-dominated strategy). Sensitivity analyses showed robust results across a wide range of model parameters. Conclusions: This HTA suggests that initial combination therapy prolongs life, improves quality of life, and is cost-effective in patients with CHC. Combination of peginterferon and ribavirin is the most effective and efficient treatment strategy among the examined options