Evidence-based Synthesis Program Department of Veterans Affairs 

Health Services Research & Development Service 

March 2013 

Assessment of Alternative 

Treatment Strategies for Chronic 

Genotype 1 Hepatitis C 

Prepared for: 

Department of Veterans Affairs 

Veterans Health Administration 

Quality Enhancement Research Initiative 

Health Services Research & Development Service 

Washington, DC 20420 

Prepared by: 

Evidence-based Synthesis Program (ESP) Center 

West Los Angeles VA Medical Center 

Los Angeles, CA 

Paul G. Shekelle, MD, PhD, Director 

VA Health Economics Resource Center
 

Menlo Park, CA
 

Paul G. Barnett, PhD, Director
 

Investigators: 

Principal Investigator: 

Jeremy D. Goldhaber-Fiebert, PhD 

Investigators:
 

Paul G. Barnett, PhD
 

Sharon Dally, MS 


Steven M. Asch, MD, MPH
 

Shan Liu, SM
 

Lauren Cipriano, BSc, BA
 

Douglas K. Owens, MD, MS 


Research Associates:
 

Isomi M. Miake-Lye, BA
 

Jessica M. Beroes, BS
 
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Assessment of Alternative Treatment Strategies 

for Chronic Genotype 1 Hepatitis C Evidence-based Synthesis Program

PREFACE
 

Quality Enhancement Research Initiative’s (QUERI) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA. 

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help to: 

•		 develop clinical policies informed by evidence 

•		 guide the implementation of effective services to improve patient 

outcomes and to support VA clinical practice guidelines and 

performance measures, and 

•		 set the direction for future research to address gaps in clinical 

knowledge 

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov. 

Recommended citation: Goldhaber-Fiebert JD, Barnett PG, Dally S, Asch SM, Liu S, Cipriano 

L, Owens DK, Miake-Lye IM, Beroes JM, Shekelle PG. Assessment of Alternative Treatment 

Strategies for Chronic Genotype 1 Hepatitis C. VA ESP Project #05-226, 2013. 

This report is based on research conducted by the Evidence-based Synthesis 

Program (ESP) Center located at the West Los Angeles VA Medical Center, Los 

Angeles, CA funded by the Department of Veterans Affairs, Veterans Health 

Administration, Office of Research and Development, Quality Enhancement Research 

Initiative. The findings and conclusions in this document are those of the author(s) 

who are responsible for its contents; the findings and conclusions do not necessarily 

represent the views of the Department of Veterans Affairs or the United States 

government. Therefore, no statement in this article should be construed as an official 

position of the Department of Veterans Affairs. No investigators have any affiliations 

or financial involvement (e.g., employment, consultancies, honoraria, stock ownership 

or options, expert testimony, grants or patents received or pending, or royalties) that 

conflict with material presented in the report. 
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EXECUTIVE SUMMARY
 

BACkgROUNd 

There is great potential to improve health outcomes for Veterans and other patients with 

chronic genotype 1 (GT1) Hepatitis C (HCV) infections through the use of newly-available 

triple combination therapies that include directly acting antivirals (DAA) along with recently 

developed patient genotyping (IL-28B) which is predictive of HCV treatment response. Chronic 

GT1 HCV infections have been historically difficult to treat, with low cure rates on standard 

two drug therapy (Pegylated Interferon + Ribavirin), high rates of side-effects and treatment 

discontinuation, and low rates of uptake. Recently, FDA approved two DAAs (boceprevir and 

telaprevir). Used in combination with standard two drug therapy as triple therapy, these DAAs 

show higher rates of sustained viral response, though they are also more costly and have more 

severe side-effect profiles. IL-28B genotyping can help to identify patients least likely to respond 

to standard therapy and hence who stand to benefit the most from triple therapy and for whom, 

therefore, the increased risks of side-effects may be most justified. 

METhOdS 

We addressed four related questions: 

•	 Key Question #1: What are the current usage patterns of directly acting antivirals and 

of IL-28B patient genotyping in the VA health system? And how do these patterns 

differ by VISN? 

•	 Key Question #2: What will be the health impacts of using either of two available 

directly acting antivirals combined with pegylated interferon and ribavirin (triple 

therapy)? 

•	 Key Question #3: How will be the magnitudes of the health impacts measured in Key 

Question #2 change if IL-28B patient genotyping is used to offer triple therapy to those 

less likely to benefit from two-drug pegylated interferon + ribavirin? 

•	 Key Question #4: What will be the cost and resource use patterns when using either 

triple therapy or IL-28B-guided triple therapy? 

We used analysis of observational data and decision analysis to answer these questions over a 5 

year time horizon, all in comparison to health outcomes and costs if standard two-drug treatment 

were continued without adoption of either of the new technologies. Importantly, these results 

are appropriate for short-term budgeting and planning considerations but are not appropriate for 

formal cost-effectiveness analyses as they do not represent the full costs and benefits experienced 

over a life time. 
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PEER REVIEw 

A draft version of this report was reviewed by six technical experts, as well as clinical leadership. 

Reviewer comments were addressed and our responses were incorporated in the final report 

(Appendix A) 

RESULTS 

key Question #1: what are the current usage patterns of directly acting antivirals 

and of IL-28B patient genotyping in the VA health system? And how do these 

patterns differ by VISN? 

Between July 2011 and June 2012 nearly 3,000 people initiated DAA treatment, with 

approximately 80% using on-formulary boceprevir (Boceprevir N=2,366, Telaprevir N=501). 

During this same period, 2,171 individuals had an IL-28B test. There was heterogeneity in the 

number of people taking up DAA therapies and IL-28B testing across VISNs. 

VISNs differed in their rate of use of IL-28B testing in patients receiving DAAs, with a national 

average just above 10 percent. VISN 22 had the greatest number of IL-28B tests, while VISNs 

8, 16, and 21 had the greatest number of patients initiating DAA therapy. In some VISNs there 

are more patients initiating DAA therapy than getting IL-28B tests, while in other VISNs the 

reverse was true. Seven VISNs used testing in five percent or less of patients receiving DAA 

medications, whereas three VISNs tested 30 percent or more of their patients. 

The median length of boceprevir treatments was just under 28 weeks. Of those who initiated 

boceprevir, 89% continued to 8 weeks, 81% to 12 weeks, 76% to 16 weeks, and 29% to 32 

weeks. Telaprevir treatment episodes were much shorter per its therapeutic protocol. The median 

length of telaprevir treatment was between 12 and 16 weeks. None lasted beyond 28 weeks. 

key Question #2: what will be the health impacts of using either of two available 

directly acting antivirals combined with pegylated interferon and ribavirin (triple 

therapy)? 

We used simulation modeling analysis over five years to project the likely effect of universal 

triple therapy compared to standard therapy. Universal triple therapy was likely to reduce the 

annual number of cases of decompensated cirrhosis by 10-29 (current uptake: 10; doubled 

uptake: 29; quadrupled uptake: 50), the annual number of cases of hepatocellular carcinoma by 

5-16 (current: 5; doubled: 16; quadrupled: 27) and the annual number of liver transplants by 0-1 

(current: 0; doubled: 1; quadrupled: 2). Compared to standard therapy, adoption of universal 

triple therapy is likely to increase the annual number of quality adjusted life years (QALYs) by 

148-213 (current: 148; doubled: 213; quadrupled: 322). 

key Question #3: how will the magnitudes of the health impacts measured in key 

Question #2 change if IL-28B patient genotyping is used to offer triple therapy to 

those less likely to benefit from two-drug pegylated interferon + ribavirin? 

We used simulation modeling analysis over 5 years to compare IL-28B guided triple therapy 

to standard two-drug therapy. IL-28B guide triple therapy was likely to reduce the annual 
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Assessment of Alternative Treatment Strategies 

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number of cases of decompensated cirrhosis by 8-26 (current uptake: 8; doubled uptake: 26; 

quadrupled uptake: 45), annual cases of hepatocellular carcinoma by 4-14 (current: 4; doubled: 

14; quadrupled: 25), and annual numbers of liver transplants by 0-1 (current: 0; doubled: 1; 

quadrupled: 2). Compared to standard therapy, IB-28B guided triple therapy is likely to result in 

an annual increase in QALYs of 110-145 (current: 110; doubled: 145; quadrupled: 225). 

key Question #4: what will be the cost and resource use patterns when using 

either triple therapy or IL-28B-guided triple therapy? 

Based on our simulation modeling analysis, replacement of standard two-drug therapy with triple 

therapy was likely to increase total expenditures for HCV treatment and care for individuals with 

GT1 HCV by $32-$100 million annually, depending on treatment strategy and uptake patterns. 

At the current uptake rate of 2 percent per year, universal triple drug therapy would be expected 

to cost $43 million more than standard two-drug therapy. IL-28B guided therapy would cost $32 

million more. 

ABBREVIATIONS TABLE 

abbreviation meaning 

DAA Directly Acting Antiviral 

DSS Decision Support System 

FDA U.S. Food and Drug Administration 

FY Fiscal Year 

GT1 Genotype 1 

HCV Hepatitis C Virus 

IEN Internal Entry Number 

IL-28B Interleukin 28-B 

NDC National Drug Code 

PEG Pegylated Interferon 

QALY Quality Adjusted Life Year 

RIB Ribavirin 

SVR Sustained Viral Response 

VISN Veterans Integrated Service Network