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, 10 (11), e0141660

Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis C Genotype 1b Naïve Patients in Chile


Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis C Genotype 1b Naïve Patients in Chile

Constanza L Vargas et al. PLoS One.


Introduction: Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources.

Methods: A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed.

Results: PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$ 16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$ 6,375/QALY at a price of US$ 38,710; and US$ 1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$ 38,710 was 91.6% while there is a 21.43% probability that DCV/ASV dominates PR if the total treatment price was US$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita.

Conclusions: DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system.

Conflict of interest statement

Competing Interests: ME and AS have participated under the terms of their contract as academics of the University and they have not received specific payments related to the execution of this study. CV and AG have received fees from the university and not directly from the sponsor for the execution of this study. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.


Fig 1
Fig 1. Markov State-transition decision model for Hepatitis C and liver disease: The model consists of two phases: treatment and natural history.
If patients discontinue treatment due to adverse events or fail to respond and hence not achieve SVR, they enter the natural history component of the model, consisting of 15 health states: Fibrosis states (F0–F4); decompensated cirrhosis first (DC1) and subsequent years (DC2); hepatocellular carcinoma first (HCC1) and subsequent years (HCC2); liver transplant first (LT1) and subsequent years (LT2); disease specific mortality; mortality from all other causes (not shown); and SVR status states stratified by fibrosis stage (“SVR F0-F2”, “SVR-F3”, SVR-F4). For clarity, only liver transplant is stratified by state year. This figure is similar but not identical to the original image, and is therefore for illustrative purposes only.
Fig 2
Fig 2. Deterministic sensitivity analysis tornado graph: Tornado graph showing the variation of the ICER when parameters are varied independently.
The parameters with highest impact on the ICER are shown on the graph: transition probability from F4 to SVR when the treatment is DCV/ASV and PR, transition probability from F2-F3, transition probability from f4 to DC, QALY of the SVR-F4 and SVR-F3 states, QALY of the F2, F3 and F4 state, treatment discontinuation at week 4 for PR and DCV/ASV.
Fig 3
Fig 3. Cost-effectiveness plane for DCV/ASV versus PR: The cost-effectiveness plane represents the base case scenario assuming a DCV/ASV total treatment price of US$ 38,710.
Fig 4
Fig 4. Acceptability curves for DCV/ASV versus PR for different prices of DCV/ASV: The acceptability curve shows the probability of cost-effectiveness considering four different prices for DCV/ASV (total drug treatment cost): US$ 77,419—US$ 58,065- US$ 38,710- US$ 19,355.

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Bristol Meyers Squib provided the funding of this study to the Centre for Clinical Research, Pontificia Universidad Católica de Chile. The study was performed under strict clauses of independence of the authors regarding matters of study design, data collection, interpretation of data, analysis of the results and elaboration of the manuscript. This manuscript did not require the approval of BMS for its submission.