interferon-based therapies for hepatitis c: original ... · interferon alfacon-1). dual combination...

ABSTRACTBackground: Veterans using the Veterans Health Administration’s (VA's) services have a higher incidence of chronic hepatitis C virus (HCV) infection than the general population.

Objectives: To examine treatment patterns, direct costs associ-ated with interferon-based HCV therapy, and sustained virologic response (SVR) rates for genotypes 1 and 2.

Study Design: Retrospective review of utilization, cost, and outcome data for a cohort of 99 consecutive patients diagnosed with HCV receiving antiviral therapy beginning in January 2000 at a midwestern VA Medical Center.

Methods: Outpatient utilization and direct costs of clinical encounters and medications spanning calendar years 1997 to 2004 were extracted from VA administrative databases for 3 therapy combinations: interferon and ribavirin (IR); interferon, pegylated interferon, and ribavirin; and pegylated interferon and ribavirin (PR). Final costs were adjusted to 2010 prices. Identifying patients’ earliest diagnostic dates ensured analyses of treatment-naïve patients.

Results: Clinic visits and medications accounted for 20% and 80% of treatment costs respectively, regardless of genotype. Although genotype 1 patients’ treatment length and costs were substantially higher than those of non–genotype 1 patients, SVR rates were lower (31%) than those in non–genotype 1 patients (57%). Cost per SVR for genotype 1 patients ranged from $54,768 (IR) to $70,364 (PR). The overall cost per SVR for non–genotype 1 patients was $25,152.

Conclusions: Antiviral medications accounted for the majority of treatment costs. Cost per SVR was sensitive to genotype, effi cacy, and treatment duration. Utilization, costs, and outcomes associ-ated with interferon-based treatments serve as important baseline data for future comparative cost-effectiveness analyses.

(Am J Pharm Benefi ts. 2013;5(1):25-33)

Original Research

Since the hepatitis C virus (HCV) was fi rst identifi ed in

1989,1 it has become recognized as a common cause

of chronic liver disease around the world. Between

130 and 170 million people are chronically infected with

HCV worldwide and more than 350,000 die from HCV-relat-

ed liver disease annually.2 In the United States alone 1.6% of

the general population is seropositive for HCV antibodies,

and 1.3% (3.2 million individuals) have chronic hepatitis C.3

Currently, 36% of patients wait-listed for liver transplant in

the United States have chronic HCV infection.4 Over the next

decade, it is estimated that US direct medical care costs for

hepatitis C will range from $7 to $14 billion.5

Veterans have higher rates of HCV infection than the

general population.6 Patients with chronic hepatitis C in

the Veterans Health Administration (VA) system represent

a signifi cant number of patients; more than 147,000 active

patients with documented HCV viremia were in the VA HCV

Clinical Case Registry as of 2008.7 A 1999 national cross-

sectional study of more than 26,000 veterans receiving care

through the VA found a 6.6% point prevalence of HCV se-

ropositivity.8 A similar study conducted in 2001 reported

that 5.4% of VA users were seropositive for HCV antibod-

ies.9 Antiviral treatment for HCV is complex and has evolved

over time. In 1991, initial treatment consisted of interferon

alfa monotherapy (interferon alfa-2b, interferon alfa-2a, or

interferon alfacon-1). Dual combination therapy with inter-

feron alfa and ribavirin became available in 1998,10 and the

combination of pegylated interferon and ribavirin became

available beginning in 2001.11,12 Recently 2 new direct-acting

antiviral protease inhibitors, telaprevir and boceprevir, have

been approved for the treatment of patients with HCV geno-

type 1 infection in combination with pegylated interferon

and ribavirin.13-17

To date, treatment success is largely dependent on the

HCV genotype and duration of treatment. Six strains of

HCV have been identifi ed. Of these, genotype 1 is the most

At a GlancePractical Implications p 26

Author Information p 32

Full text and PDF www.ajpblive.com

Interferon-Based Therapies for Hepatitis C: Utilization, Costs, and Outcomes

Yvonne C. Jonk, PhD; Titilope Adeniyi, MS; Astrid Knott, PhD; Eric W. Dieperink, MD; and Samuel B. Ho, MD

www.ajpblive.com Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts 25 Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts

P R A C T I C A L I M P L I C A T I O N S

This study provides important baseline data for comparative cost-effectiveness analyses of therapeutic interventions to improve sus-tained virologic response (SVR) rates and reduce utilization and direct costs of clinical encounters and medications for hepatitis C patients.

� From 1997 to 2004, we compared 3 therapy combinations: inter-feron and ribavirin (IR); interferon, pegylated interferon, and ribavi-rin; and pegylated interferon and ribavirin (PR).

� Antiviral medications accounted for the majority of treatment costs.

� Compared with non–genotype 1 patients, genotype 1 patients had higher overall costs per SVR: $54,768 (IR) to $70,364 (PR) versus $25,152 (2010 dollars).

26 The American Journal of Pharmacy Benefi ts • January/February 2013 www.ajpblive.com

� Jonk • Adeniyi • Knott • Dieperink • Ho

prevalent in the United States, followed by genotypes

2 and 3 (collectively referred to as non–genotype 1).18

Genotype 1 is the most diffi cult strain to treat and gener-

ally requires treatment duration of 48 weeks. The recom-

mended treatment duration for patients with genotype 2

or 3 is 24 weeks.19,20 With currently available pegylated

interferon and ribavirin therapies, the sustained virologic

response (SVR) rates from registration trials associated

with treatment of genotype 1 is 42% to 46%, and with

treatment of genotypes 2 and 3 it is 76% to 82%.11,12 In

contrast, the actual SVR rate achieved in US veteran pa-

tients with HCV genotype 1 is 20%, while the SVR rates

for genotypes 2 and 3 are 52% and 43%, respectively.21

The newly approved therapies telaprevir and boceprevir

will require 24 to 48 weeks of treatment and are expected

to increase SVR rates.

In response to the rising number of HCV diagnoses,

the VA initiated a directive for implementing broad clini-

cal care programs for HCV, including routine screening

of all VA patients.22,23 As VA medical centers are reim-

bursed for caring for complex patients treated for HCV,

the cost associated with screening, treatment, and follow-

up for HCV patients is important to VA administrators.

Identifying strategies aimed at improving the quality and

cost-effectiveness of care provided to HCV patients is an

important administrative goal.

A number of studies in general populations of HCV

patients have found that dual therapy with interferon

and ribavirin can be considered cost-effective.24-28 Very

few studies have reported the actual costs incurred while

treating patients diagnosed with HCV infection,29 and

no studies have focused on VA costs. The most accurate

method to determine cost components is a “top down”

approach directly following a cohort and collecting actual

longitudinal frequency and unit cost data.30 The purpose

of this study was to examine the treatment patterns, di-

rect costs, and health outcomes associated with HCV an-

tiviral therapy in an actual VA HCV treatment population.

These data can then be used as baseline data for future

cost-effectiveness studies comparing current treatment

strategies with newly approved therapies.

METHODSA consecutive cohort of patients with chronic hepa-

titis C receiving antiviral treatment between January 1,

2000, and December 31, 2001, were identifi ed. During

this time period, 681 VA patients had a positive HCV en-

zyme-linked immunoassay test at a midwestern Depart-

ment of VA Medical Center (Figure). Of these patients,

557 did not receive antiviral therapy and were excluded

from the analysis. Patients who received experimental or

alternative therapies such as gamma interferon (n = 5)

or peginterferon antiviral monotherapy (n = 1) were also

excluded. Finally, additional patients were excluded due

to a lack of cost data (n = 17) or the inability to deter-

mine their genotype (n = 2), resulting in a fi nal sample

size of 99 patients treated for HCV with interferon-based

therapies.

Because some patients had been diagnosed prior to 2000,

we identifi ed the earliest diagnostic date in the patients’ ad-

ministrative records going back to 1997, thus ensuring that

the analyses pertained to patients who were treatment na-

ïve. Treatment start date for antiviral therapy was based on

the date of the fi rst prescription and the treatment duration

of the last prescription written by the physician.

Hepatitis C virus–related outpatient encounters, labs,

and biopsies were identifi ed using VA clinic stop code

307 for gastroenterology and the Current Procedural Ter-

minology (CPT) codes listed in Table 1. Each patient’s

HCV antiviral genotype, therapy combination, and treat-

ment length were examined. Patients were classifi ed as

either genotype 1 or non–genotype 1 patients. Three

therapy combinations were identifi ed: interferon and

ribavirin (IR); interferon, pegylated interferon, and riba-

virin (IPR); and pegylated interferon and ribavirin (PR).

These included the following medications: interferon

alfa-2b, ribavirin, combination of interferon alfa-2b and

ribavirin, pegylated interferon alfa-2a, and pegylated in-

terferon alfa-2b.

Using the VA’s clinic stop code 307 for gastroenterol-

ogy, the timeline used to identify associated HCV clinic

visits was defi ned as occurring 7 days prior to initiation of

antiviral therapy and 1.5 years after the prescription treat-

ment end date. The 1.5-year follow-up period was based

on the following clinical treatment regimen: HCV patients

The American Journal of Pharmacy Benefi ts • January/February 2013

www.ajpblive.com Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts 27

Interferon-Based Therapies for Hepatitis C

returned for a follow-up visit 6

months after completion of an-

tiviral therapy. Negative results

indicated SVR achievement,

and patients came in for a sec-

ond follow-up visit 1 year after

the initial 6-month follow-up

visit. If the 6-month HCV test

was positive, patients were re-

evaluated. Decisions regarding

a subsequent round of antiviral

treatment depended on the pa-

tients’ prior response and their

ability to tolerate side effects.

Physician recommendations

regarding other behavioral and

medical changes that would re-

duce fi brosis progression were

provided.

In order to accommodate

the range of therapeutic dura-

tion, treatment lengths of 1.5

times the expected number of weeks of medication therapy

were used to distinguish between patients undergoing 1

versus more than 1 course of treatment. Thus, genotype

1 patients were classifi ed as having either “greater than or

equal to” or “less than” 48 � 1.5 = 72 weeks of treatment.

Non–genotype 1 patients were classifi ed as having either

greater than or equal to or less than 24 � 1.5 = 36 weeks

of treatment.

Finally, regression analyses were used to address

factors predictive of differences in costs across the 3

Figure. Inclusion and Exclusion Criteria for Sample of VA Patients With Hepatitis C

681 HCV-positive patients

124 patients received AVT 557 patients did not receive AVT

118 received standard of care therapy 6 received experimental therapy(gamma interferon or PEG monotherapy)

101 had HERC outpatient cost data 17 had no HERC outpatient costs

99 patients—final sample 2 lacked information on genotype

AVT indicates antiviral therapy; HCV, hepatitis C virus; HERC, Health Economics Resource Center; PEG, pegylated interferon; VA, Veterans Health Administration.

Table 1. Laboratory CPT Codes Corresponding to HCV Clinic Visitsa

Lab or Biopsy CPT Code

Biopsy identifi cation 47000

Complete blood count 85027

Alanine aminotransferase 84460

Aspartate aminotransferase 84450

Alkaline phosphate 84075

Total bilirubin 82247

Creatinine 82565

Sodium potassium 84295, 84132

Albumin 82040

Glucose 82947

Thyroid-stimulating hormone 84443

Hepatitis C antibody 86803

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, amplifi ed probe technique

87521 (qualitative)

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, quantifi cation

87522 (quantitative)

CPT indicates Current Procedural Terminology; HCV, hepatitis C virus.aHCV clinic visits were identifi ed using Veterans Health Administration stop code 307 for gastroenterology.



treatment groups. Because cost data are typically skewed

and not normally distributed, we estimated log expendi-

ture models that included indicator variables for the IPR

and PR groups. The largest group of IR patients served as

our reference category. Demographic data included age,

sex, marital status, service-connected status, genotype,

and treatment group. Service connection is determined

by the VA as an injury or disease incurred while serving

on active duty. Service-connected ratings vary from 0% to

100%, with higher ratings generally indicative of increas-

ing disease severity.

Data SourcesFor calendar years 1997 to 2004, clinical encounters

and laboratory tests were extracted from the VA’s Patient

Treatment and Outpatient Care fi les using VA clinic stop

codes and CPT codes. Patients’ demographic character-

istics, SVR status, genotype, and whether veterans were

service connected for injuries or disease incurred or ag-

gravated in military service were obtained by reviewing

patient medical records.

Outpatient costs were extracted from the Health Eco-

nomics Resource Center’s (HERC) Average Outpatient Cost

database. Because the HERC’s data sets are available only

from VA fi scal year 1999 onward (ie, October 1998 onward),

costs for outpatient encounters occurring prior to October

1998 were estimated using similar outpatient costs for en-

counters occurring after October 1998. Because the HERC’s

outpatient cost data are based on Medicare reimbursement

rates, the relative costs of clinic visits experienced by vet-

erans in each treatment regimen are comparable to those

in Medicare. Because VA costs are adjusted to refl ect the

VA’s overall annual budget, the actual dollar amounts for

specifi c healthcare events differ from those of Medicare.

Prescription medications and costs were derived from

the Veterans Health Information Systems and Technology

Architecture database. The costs for individual prescrip-

tions were calculated by multiplying the medication’s

unit price by the quantity supplied for that particular

prescription. All costs (medication and clinic visit) were

converted to 2010 prices using the Consumer Price Index

for medical care.31

This project was approved by an institutional review

board. The analyses were performed using SAS version

9.2 (SAS Institute Inc, Cary, North Carolina).

RESULTSDemographic Characteristics

The percentage of the study population who were

white (81%) and male (96%) closely resembles the gen-

eral VA patient population (Table 2); the study sample

of HCV patients was signifi cantly younger (49 years)

than the national 2001 VA average of 58 years, and more

likely to be divorced.32 As is characteristic of the general

US population of HCV patients,33 most veteran patients

(71/99, or 72%) were infected with the genotype 1 strain

of HCV.

Antiviral Medications and Costs Genotype 1 patients receiving IR therapy (n = 28) had

the lowest total medication cost ($12,188 per person),

with an overall duration of antiviral therapy of 63 weeks

(Table 3). Although patients receiving PR therapy (n =

24) had higher medication costs ($14,716) but shorter an-

tiviral treatment duration (32 weeks) compared with the

IR group, this difference was not signifi cant. On average,

genotype 1 patients requiring multiple treatments in the

IPR group (n = 19) had the longest antiviral treatment du-

ration (114 weeks) as well as the highest medication cost

of all 3 treatment groups ($23,517 per person) (P <.01). Concurrent with treatment guidelines, the treatment

regimen for non–genotype 1 patients was generally half

as long as that for genotype 1 patients. Subsequently,

medication costs for non–genotype 1 patients were 15%

to 24% lower than those of genotype 1 patients.


Table 2. Demographic Characteristics of HCV Patients Receiving Antiviral TherapyCharacteristic HCV Patients

Sample size 99

Sex, %

Male 96

Race/ethnicity, %

Caucasian 81

African American 10

American Indian/Alaskan Native 1

Unknown 7

Age, y

Range 39-70

Mean 49

Median 49

Marital status, %

Divorced 41

Married 32

Single 16

Separated 6

Widowed 4

HCV indicates hepatitis C virus.



Across both genotypes, while 1 course of IR therapy

was typically longer than 1 course of PR therapy, IR

medication costs were 24% to 47% less expensive than

PR therapy (for genotype 1 patients, IR medications

cost $11,249 and PR medications cost $14,716; for non–

genotype 1 patients, IR medications cost $6681 and PR

medications cost $12,509). The extended duration of IR

therapy refl ects the attempt to increase SVR rates, as well

as the need for some patients with interrupted treatment

regimens to repeat the course of treatment. Independent

of genotype, patients experiencing more than 1 course

of IR therapy had higher costs than patients experienc-

ing PR therapy. Considering the additional medication

and clinical costs, multiple courses of IR therapy were

the second-most expensive treatment regimen overall

($22,439 for genotype 1; $21,642 for non–genotype 1).

The IPR subgroup primarily represents patients with IR

treatment relapses or failures who were transitioned to PR

therapy. Approximately 75% of patients (74% [14/19] of

genotype 1 patients; 80% [4/5] of non–genotype 1 patients)

experienced a signifi cant lapse in their treatment regimen

before transitioning to PR, while the remaining 25% did

not experience treatment delays while transitioning. The

extended treatment duration along with higher medica-

tion costs and more intensive clinical encounters resulted

in IPR patients comprising the most expensive treatment

group (P <.01).

Average Total Costs of Prescriptions and Outpatient Clinical Encounters

Over all treatment regimens, the average total cost

of antiviral therapy and HCV-related clinical encounters

was higher for genotype 1 patients ($19,660 per person)

than for non–genotype 1 patients ($14,373 per person)

(not shown). For each treatment regimen, the average

total cost of genotype 1 patients treated with IR, IPR, or

PR therapy was $15,647, $28,187, and $17,591 per per-

son, respectively, compared with $12,713, $20,856, and

$14,626 per person, respectively, for non–genotype 1 pa-

tients. Differences in cost were signifi cant between the

IPR and IR groups as well as between the IPR and PR

groups (P <.01 for both comparisons).

Cost per Sustained Virologic Response The overall HCV study population achieved an SVR rate

of 38% (38/99) (Table 4), resulting in an overall cost per

SVR of $47,324. Concurrent with the literature, non–geno-

type 1 patients achieved a higher SVR rate than the geno-

type 1 patients (57% [16/28] vs 31% [22/71], respectively).

Combined with lower treatment costs, it was generally

Table 3. Treatment Patterns and Cost for HCV Patients by Genotype and Therapy, 1997 to 2003a

Therapy Type

Average Length of Antiviral Therapy

(wk) (SD)

Average Cost of Antiviral Medication

per Person (SD)

Average Number of Clinic Visits

per Person (SD)

Average Cost of Visits

per Person (SD)Average Total Cost

per Person (SD)

Genotype 1

IR (n = 28) 63 (67) 12,188 (5059)b 35 (15) 3459 (1844)b 15,647 (5945)b

IR <72 wk (n = 24) 36 (14) 11,249 (4454) 33 (12) 3267 (1798) 14,516 (5099)

IR >72 wk (n = 4) 220 (19) 17,825 (5368) 52 (22) 4614 (1940) 22,439 (6860)

IPR (n = 19) 114 (68) 23,517 (10,488)b,c 46 (20) 4670 (2084)b,c 28,187 (11,575)b,c

IPR <72 wk (n = 5) 51 (12) 16,294 (5972) 28 (11) 2777 (608) 19,071 (5560)

IPR >72 wk (n = 14) 136 (65) 26,096 (10,681) 52 (19) 5346 (2007) 31,442 (11,516)

PR (n = 24) 32 (16) 14,716 (7233)c 26 (17) 2875 (1580)c 17,591 (7889)c

Non–genotype 1

IR (n = 20) 32 (22) 9964 (5859) 27 (15) 2751 (1232) 12,713 (6941)

IR <36 wk (n = 14) 22 (9) 6681 (2885) 20 (10) 2207 (978) 8888 (3628)

IR >36 wk (n = 6) 58 (21) 17,621 (2879) 45 (11) 4020 (721) 21,642 (3498)

IPR (n = 5) 99 (48) 17,866 (12,303) 23 (29) 2990 (2122) 20,856 (13,442)

IPR <36 wk (n = 1) 15 (NA) 3283 (NA) 12 (NA) 2493 (NA) 5776 (NA)

IPR >36 wk (n = 4) 120 (10) 21,512 (10,640) 26 (32) 3114 (2429) 24,627 (12,089)

PR (n = 3) 20 (20) 12,509 (13,157) 20 (21) 2118 (2315) 14,626 (15,438)

HCV indicates hepatitis C virus; IPR, interferon, pegylated interferon, and ribavirin; IR, interferon and ribavirin; NA, not applicable; PR, pegylated interferon and ribavirin.aCosts were adjusted for infl ation using the Consumer Price Index for medical care and represent 2010 dollars.bCosts for the IR group differ signifi cantly from those for the IPR group, P = .01.cCosts for the IPR group differ signifi cantly from those for the PR group, P = .01.



more cost-effective to treat non–genotype 1 patients, with

an overall cost per SVR of $25,152. By contrast, the overall

cost per SVR for genotype 1 patients was $63,448.

The SVR rates for genotype 1 patients were similar for

IR and PR treatment groups. Interestingly, the SVR rate

for the IPR group was higher, possibly due to the longer

duration of therapy received; however, defi nite compari-

sons cannot be made due to the relatively small num-

bers of patients in each group. Across treatment groups,

costs per SVR for genotype 1 patients were $70,364 (PR),

$68,250 (IPR), and $54,768 (IR).

Costs per SVR for non–genotype 1 patients were

$34,761 (IPR) and $19,559 (IR). Note that there were too

few non–genotype 1 patients treated with PR to defi ni-

tively evaluate SVR rates.

Regression AnalysesAdjusting for differences in patient characteristics,

Table 5 lists the results for estimating the log expenditure

models. In the adjusted analyses, the IPR (P = .07) and

the PR (P = .03) groups incurred a signifi cantly higher

level of medication costs than the IR group. While the

costs associated with outpatient visits were not found

to signifi cantly differ across the 3 treatment groups, the

higher level of medication costs contributed to higher

total (outpatient and medication) costs for the IPR (P =

.06) and the PR (P = .07) groups relative to the IR group.

However, these differences were not signifi cant at the

P = .05 level. Generally speaking, across all treatment

groups, longer treatment duration was associated with

higher medication, outpatient, and total costs (P <.01).

DISCUSSIONAntiviral treatment of patients with HCV is intense and

complex, requiring many visits over the initial treatment

period of 24 to 48 weeks, as well as subsequent follow-up

visits and/or re-evaluation. Our data indicate that the total

overall costs related to treatment of patients with HCV

are highly dependent on genotype, medication costs, and

duration of therapy. Patients treated during periods that

include conversion of actively treated or previous treat-

ment failures to newer therapies, as represented by the

IPR group, have the longest duration and highest costs.

Despite these higher costs, the HCV genotype 1 patients

in this group demonstrated relatively high SVR rates, in-

dicating that there is a benefi t from more intensive care

during a period of changing protocols.

The greater number of visits (n = 33 visits) observed

with IR patients undergoing 1 course of therapy (<72

weeks) may be due to more favorable tolerability of

this regimen compared with PR (n = 26 visits) and an

attempt at a longer duration of treatment. Overall SVR

rates of 29% and 25% for IR and PR genotype 1 patients,

respectively, were comparable and better than national

estimates of 20% reported elsewhere.21

Largely due to the longer duration of the antiviral ther-

apy, it is more expensive to treat genotype 1 patients than

non–genotype 1 patients. Additionally, the higher SVR rate

in the non–genotype 1 group resulted in a lower cost per

cure ($25,152 per SVR) than that in the genotype 1 group

($63,448 per SVR). These results are comparable to those

reported by Malone et al.34 Comparing the outcomes of pa-

tients treated with pegylated interferon alfa-2b plus ribavirin

with the outcomes of patients treated with pegylated inter-

feron alfa-2a plus ribavirin, Malone et al estimated the cost

per SVR for treatment-naïve patients, 75% of whom were

genotype 1 patients, as $37,638 and $46,717, respectively

(ie, $47,146 and $58,518, respectively, in 2010 dollars).34

Finally, given that the annual cost of HIV treatment

in 1999 was $20,280 per patient (ie, $31,434 in 2010

dollars)35 and the 1-year event and angina-free cost of

coronary artery bypass grafting in 2001 was $14,095 (ie,

$20,070 in 2010 dollars),36 these results support the pri-

mary hypothesis that the direct cost of medical care asso-

ciated with the treatment and follow-up of HCV patients

is comparable to that of other chronic disorders.

Study LimitationsBecause our analysis of utilization and costs relied on


Table 4. Average Total Cost per Sustained Virologic Responsea

Therapy Type SVR Cost per SVR, $

Genotype 1

IR 8/28 (29%) 54,768

IPR 8/19 (42%) 68,250

PR 6/24 (25%) 70,364

Overall 22/71 (31%) 63,448

Non–genotype 1

IR 13/20 (65%) 19,559

IPR 3/5 (60%) 34,761

PR 0/3 (0%) NA

Overall 16/28 (57%) 25,152

Entire cohort 38/99 (38%) 47,324

IPR indicates interferon, pegylated interferon, and ribavirin; IR, interferon and ribavirin; PR, pegylated interferon and ribavirin; NA, not applicable; SVR, sustained virologic response.aCosts include medication and outpatient clinical encounters. Costs were adjusted for infl ation using the Consumer Price Index for medical care and represent 2010 dollars.



the use of secondary administrative data sets, assump-

tions were made regarding the acceptability of time

lapses between multiple antiviral treatments and the time

frame for applicable clinic visits. In addition, we made

the assumption that all visits to the gastroenterology

clinic were related to HCV care, whereas some of these

encounters may have only been marginally related. Thus,

the cost per cure for the treatment regimens considered

in our analyses may be overstated. The costs per cure

could have been lower if some of the visits had been

determined not to be HCV related and were excluded

from our analyses. We also made the assumption that our

study population received care only at the VA. Because

the medications prescribed for patients diagnosed with

HCV are expensive, the treatment regimen is intense and

complex, and the patients tracked in this study received

care at the VA Medical Center throughout the duration of

the study, we believe that the likelihood of patients re-

ceiving care related to HCV outside the VA was minimal.

Thus, any bias associated with the use of non-VA care

was negligible. Because clinical encounters accounted

for only approximately 20% of the total cost of the care

provided, we believe that whatever bias was introduced

by the above limitations was minimal and did not af-

fect our conclusions. Moreover, our results appear to be

within the range of that estimated by other studies.

Our data are limited to inclusion of patients with HCV

who are patients at 1 VA Medical Center and may not

be generalizable to the nonveteran population. The VA

serves a fairly unique sector of the general population in

that veterans are largely white and male, and veterans

eligible to use VA services have open access to care with

no restrictions placed on referrals, specialists, or number

of visits.37 In addition, the VA receives larger pharmaceu-

tical discounts than the private market.38 Thus, medica-

tion costs will likely be higher in the private sector. To

illustrate this point, Yeh et al used data from a VA national

pharmacy database and from indirect expert opinion re-

garding the number of visits needed, and estimated that

the weekly costs of pegylated interferon plus ribavirin

in the VA system in 2005 ranged from $227 to $247 (ie,

$273-$297 in 2010 dollars), which was less than costs of

this regimen used in non-VA cost utility analyses ($433-

$817) (ie, $520-$982 in 2010 dollars).39 Because medica-

tion costs comprise approximately 80% of the cost of HCV

therapy, the relative cost-effectiveness of these therapies

may differ in the VA compared with the private sector.

Given these limitations, the results of this study may be

more applicable to patients in other large managed care

organizations receiving similar medication cost discounts.

Finally, inherently problematic in all observational stud-

ies is the issue of self-selection bias. Differences in costs and

SVR could be due to latent differences among the respective

patient groups themselves rather than to the treatment op-

tions. Although our study’s sample size limitations do not

lend themselves well to the traditional modes of correcting

for selection bias, at a minimum we conducted regression

analyses to account for measurable (observed) differences

using the data that we have on patient demographics, geno-

type, duration of treatment, and treatment type. Although

these analyses did not attempt to adjust for unobserved dif-

ferences in patient treatment groups, we believe that the

Table 5. Log Expenditure Models for Hepatitis C Patients (n = 99)a

Log (Medication Costs) Log (Outpatient Costs)Log (Total Outpatient and

Medication Costs)

Variable Parameter Estimate Pr >|t| Parameter Estimate Pr >|t| Parameter Estimate Pr >|t|

Intercept 4.02 <.0001b 3.51 <.0001b 4.09 <.0001b

Age −0.01 .32 −0.01 .33 −0.004 .37

Female −0.01 .97 0.03 .83 0.004 .98

Married 0.12 .04b 0.01 .82 0.09 .10

SC 50%-100% −0.08 .15 −0.06 .31 −0.07 .18

SC <50% −0.02 .75 0.09 .20 0.01 .86

Non–genotype 1 −0.09 .15 −0.10 .11 −0.09 .11

IPR 0.13 .07c 0.04 .58 0.12 .06c

PR 0.14 .03b −0.07 .29 0.10 .07c

Treatment duration (wk) 0.003 <.0001b 0.002 .001b 0.002 <.0001b

IPR indicates interferon, pegylated interferon, and ribavirin; PR, pegylated interferon and ribavirin; Pr >|t|, P value for a 2-tail test; SC, service connected.aIR (interferon and ribavirin) is the reference category for treatment group. Boldfacing indicates signifi cant results. bSignifi cant at the P = .05 level.cSignifi cant at the P = .10 level.



analyses refl ect what the consulting provider considered an

appropriate treatment regimen given the patient’s history

and diagnosis. In the absence of a randomized controlled

trial, we believe that this analysis is useful in that it assesses

the observed cost of caring for HCV patients in one of the

largest managed care organizations in the United States.

Policy Implications In 2011, telaprevir and boceprevir became available

for treatment in combination with the standard of care,

PR, for treatment of patients with HCV genotype 1. Cur-

rent phase III clinical trials indicate an up to 2-fold im-

provement in SVR rates to 68% to 75% for genotype 1

HCV patients, and a 2- to 5-fold increase in SVR rates to

53% for genotype 1 nonresponders to standard PR treat-

ment.13-17 The timing of visits and laboratory monitoring

for these regimens are equivalent to visits required for

current interferon-based treatments, and the majority of

patients treated will require 24 weeks of treatment rather

than 48 weeks.13-17 New cost-effectiveness analyses will

be needed to take into account the improved effi cacy and

the increased costs associated with these novel drugs. The

current data regarding the actual treatment-related costs

of resource use for patients receiving 24 to 48 weeks of

interferon-based treatments are relevant to future cost-

effectiveness analyses using these new combinations.

Author Affi liations: From Rural Health Research Center (YCJ), Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN; Division of Health Policy and Management (YCJ, TA), School of Public Health, University of Minnesota, Minneapolis, MN; Hepatitis C Resource Center (AK, EWD), Minneapolis VA Health Care System, Minneapolis, MN; San Diego VA Healthcare Sys-tem (SBH), San Diego, CA.

Author Disclosures: Dr Ho reports receiving grants from Veterans Affairs, Genentech, Vital Therapies, and Aspire Bariatrics. The other au-thors (YCJ, TA, AK, EWD) report no relationship or fi nancial interest with any entity that would pose a confl ict of interest with the subject matter of this article.

Authorship Information: Concept and design (YCJ, TA, EWD, SBH); acquisition of data (YCJ, TA, SBH); analysis and interpretation of data (YCJ, TA, EWD); drafting of the manuscript (YCJ, TA, AK); critical re-vision of the manuscript for important intellectual content (YCJ, TA, AK, EWD, SBH); statistical analysis (YCJ, TA); provision of study materials or patients (EWD); obtaining funding (YCJ, EWD, SBH); administrative, technical, or logistic support (AK, EWD); and supervision (YCJ, SBH).

Funding Source: This study was funded in part through the Harold Hartman Hepatitis C Award from the Minnesota Veterans Research Insti-tute, Minneapolis, MN, and the Hepatitis C Resource Centers of the Pub-lic Health Strategic Health Care Group, Department of Veterans Affairs.

Address correspondence to: Yvonne C. Jonk, PhD, Senior Re-search Associate, Rural Health Research Center, University of Minne-sota, 2520 University Ave SE, Ste 201, Minneapolis, MN 55414. E-mail: [email protected].

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