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Title: Identification and treatment of Medicaid recipients with Hepatitis C
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Title: Identification and treatment of Medicaid recipients with Hepatitis C
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Table of Contents
    Front Cover
        Page i
    Title Page
        Page ii
    Main
        Page 1
        Page 2
        Page 3
        Page 4
        Page 5
        Page 6
        Page 7
        Page 8
        Page 9
        Page 10
        Page 11
        Page 12
        Page 13
        Page 14
        Page 15
    Reference
        Page 16
        Page 17
        Page 18
        Page 19
    Appendix
        Page 20
        Page 21
        Page 22
        Page 23
Full Text




The Identification and Treatment of Medicaid Recipients with
Hepatitis C


Earlene Lipowski, PhD
Richard Segal, PhD

With technical assistance provided by:

Annesha White, PharmD, MS
Chris Mallison
Jianyi Zhang, PhD


Florida Center for Medicaid & the Uninsured
College of Public Health and Health Professions
University of Florida
352/273-5059

Sponsored by
The Agency for Health Care Administration













lorida Center for Medlcad and the Uninsured
^ .> . . 1'


M0416, Deliverable 10:3
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October, 2004









EXECUTIVE SUMMARY


The estimated prevalence of hepatitis C virus (HCV) in the U.S. is at least 1.8% of the
population, although high HCV prevalence rates (15-50%) occur in specific
subpopulations such as the homeless, incarcerated persons, and injection drug users.
Consequently it is thought that HCV is highly prevalent among the uninsured and
publicly funded programs. The prevalence of HCV infection and the feasibility of
management and treatment in these populations was designated as an important
area for research by the NIH.

According to the 2002 NIH Consensus Conference HCV is a leading cause of cirrhosis, a
common cause of hepatocellular cancer, and the leading cause of liver
transplantation in the United States. Because most persons with chronic HCV infection
have not yet been diagnosed, the number of adults with compromised liver function
may increase four-fold from 1990 to 2015.

The NIH treatment guidelines for HCV call for weekly injections of pegylated-interferon
in combination with daily ribavirin by mouth. Treatment for 24 weeks appears to
produce a sustained viral response in 73-78% of persons with genotypes 2 and 3,
whereas 48 weeks of treatment produce a sustained viral response in 51% of those with
genotype 1. Significant side effects often result in premature discontinuation of
treatment.

The aim of this study was to estimate the prevalence of HCV in the Florida Medicaid
program, examine patterns of treatment according to NIH guidelines and expenditures
incurred by Medicaid.


FINDINGS AND POLICY IMPLICATIONS

The prevalence of HCV documented among Florida Medicaid adult recipients
by this analysis was less than one percent. This is well below national estimates of
1.8% for the population in general, and far below the estimated prevalence in
sub-populations known to be at higher risk. This estimate suggests that there are
a significant number of persons in the Florida Medicaid program with HCV that is
not diagnosed or documented.

Among the 15,612 persons whose records included a diagnosis of HCV, one-third
had fibrosis or cirrhosis of the liver, 103 had cancer of the liver and 275 had
received a liver transplant. Conversely, among the 718 persons identified with a
liver transplant, 40% had a diagnosis of HCV.

From FY2000 through FY2003, there was a record of HCV treatment for
approximately 15% of persons whose records carried a diagnosis of HCV.

Out of 1,657 persons receiving a single course of treatment, about one-third
reached the recommended duration of 24 weeks therapy for genotype 2 or 3.

M0416, Deliverable 10:3
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Less than 10% received the full course of 48 weeks of treatment that is
recommended for genotype 1.

* An additional 438 persons received multiple episodes of treatment ranging from
2-7 episodes over the 4-year observation period. This group represents persons
on long term maintenance therapy or persons who terminated treatment
prematurely and subsequently were re-treated.

* Considering all patients treated for HCV with either single or multiple episodes of
therapy, 13% received at least one episode of treatment over a period of 48
weeks or longer.

* There was a group of 1,273 individuals without a diagnosis of HCV who were
treated with drug therapy indicated only for HCV. A utilization review is
recommended.

* The average annual cost to Florida Medicaid for each person with a diagnosis of
hepatitis C was $15,144 between FY 2000 and FY 2003. Additional studies using a
comparison population are warranted to estimate the marginal cost of HCV over
the frequently occurring co-morbid conditions.
































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BACKGROUND


The estimated prevalence of hepatitis C virus (HCV) in the U.S. is at least 1.8% of the
population, making HCV the most common chronic blood-borne infection nationally.
High HCV prevalence rates (15-50%) occur in specific subpopulations, such as the
homeless, incarcerated persons, injection drug users, and persons with hemophilia who
were treated with clotting factors before 1992. The 2002 NIH Consensus Conference on
Hepatitis C noted that HCV is highly prevalent in patient populations without health
insurance or with publicly funded healthcare payers, although there are no data to
support this assumption. The prevalence of HCV infection and the feasibility of
management and treatment in these populations was designated as an important
area for research by the conferees.

According to the NIH Consensus Conference Hepatitis C is a leading cause of cirrhosis,
a common cause of hepatocellular cancer, and the leading cause of liver
transplantation in the United States. Prospective studies show that 60-85% of HCV-
infected persons develop chronic infections. An estimated 10-15% of those chronically
infected will develop cirrhosis 20 years after initial infection. Deaths associated with
chronic hepatitis C are most likely to be the result of decompensated cirrhosis, and the
only treatment option for persons with decompensated cirrhosis is liver transplantation.
Also, it is estimated that HCV accounts for one-third of hepatocellular cancer in the U.S.

The NIH treatment guidelines for hepatitis C call for weekly injections of pegylated-
interferon in combination with daily ribavirin by mouth. Treatment for 24 weeks appears
to produce a sustained viral response in 73-78% of persons with genotypes 2 and 3
whereas patients with genotype 1 need 48 weeks of treatment with higher doses of
ribavirin to achieve a sustained viral response in 51% of those treated. However,
significant side effects often result in premature discontinuation of treatment.

Risk factors for hepatitis C are well known and there has been a dramatic decrease in
the incidence of new HCV infections in recent years (Davis et al. 2003). Because most
persons with chronic HCV infection have not yet been diagnosed, the number of adults
diagnosed with compromised liver function is projected to increase four-fold from 1990-
2015.

The goals of this study are to estimate (1) the prevalence of a diagnosis for hepatitis C
within the Florida Medicaid program, (2) the number of persons who have undergone
treatment for this condition in accordance with NIH guidelines, and (3) total Medicaid
expenditures for those who received treatment and those who did not receive
treatment.


METHODS

Data for the study were obtained from Florida Medicaid for paid claims covering
services rendered in fiscal years (FY) 2000 through 2003, that is, for four years beginning
July 1, 1999 and ending June 30, 2003 inclusive. Personnel at the Agency for Health
Care Administration created a list of study subjects who had a claim with diagnostic
code for HCV and/or drug treatment unique to HCV based upon our specifications. All
M0416, Deliverable 10:3
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persons with a history of liver transplant were added to the list. Medicaid eligibility files
provided demographic data for each subject. Specifications for the data extraction
and the analyses are given in the appendices.

All claims for services rendered to the subjects during the observation period were
retrieved. Patient identifiers were scrambled and encrypted files transferred to
researchers at the University of Florida in Gainesville for analysis.

There is a lag time between date of service and claims adjudication (primarily physician
and hospital claims). Approximately 90-95% of Florida Medicaid claims are recorded
within 6 months of the date of service. There may be some claims that were not
recorded at the time the data were extracted in November 2003. However, the
observation period through July 1, 2003 was selected to capture the use of
peginterferon alfa-2a, which was newly approved by the FDA in October 2002 for
treatment of hepatitis C. The availability of the newer product reduces the number of
injections from three per week for interferon to one injection per week for the
pegylated form, and purportedly increases the likelihood of patients experiencing a
sustained viral response.

The total expenditures for each subject were computed for all services rendered rather
than limiting the analysis to claims where HCV was listed as the primary diagnosis. This
decision was made because complications of HCV and services needed to monitor the
disease may be submitted with general codes associated with diseases of the liver or
for symptoms. In addition, it is known that the presence of HCV increases the cost of
care for other health care services due to the presence and potential for liver damage.

The data include every patient with a diagnostic code associated with HCV. This
population may include some individuals just undergoing testing for the condition. A
closer examination of the services and pattern of treatment associated with a HCV-
related diagnostic code, and possibly a medical record review, would be needed to
define the affected population more precisely.


FINDINGS

Research question 1. What percentage of Florida Medicaid patients have a diagnosis
HCV recorded and/or are taking drug therapy specific to HCV?


Table 1. HCV Diagnosis and Treatment in Florida Medicaid
Population, FY 00-03
Recipients with ICD-9 Diagnosis of HCV
HCV Diagnosis without drug 13,049 (83.6%)
therapy
HCV Diagnosis with drug therapy 2,288 (14.6%)
HCV Diagnosis and liver transplant 275 (1.8%)
Total 15,612 (100.0%)


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Enrollment history data for Florida Medicaid is shown in Appendix III. The number of
unique recipients served through fee-for service and Medipass in FY2003 provides a
conservative estimate of the number of individuals with claims for service during the 4-
year observation period covered by this study. HMO members were not included in the
estimate because no claims for individual services are in the database. Thus, the 15,612
cases of HCV among 2,732,056 recipients represents about 0.5% of the FY2003 Medicaid
population. The CDC estimates that 2 percent of the U.S. population is infected with
HCV and the NIH Consensus Conference concluded that it is likely that the percentage
is higher among persons covered by publicly funded insurance. This estimate suggests
that there are a significant number of persons in the Florida Medicaid program with
HCV that is not diagnosed or documented.

The age distribution is consistent with the prevalence of hepatitic C from national
estimates (Alter et al. 1999).

As seen in Table 1, a large majority (83.6%) of patients with a diagnosis of HCV did not
receive treatment with medication or liver transplant during the observation period.
Factors to be considered in recommending treatment include favorable genotype,
presence of hepatic fibrosis, patient motivation, symptoms, severity of co-morbid illness,
and patient age (Muir and Provenzale 2002, Zeuzem 2004).

Table 2. Demographic Composition of Persons with HCV Diagnosis by History of Liver
Transplant and Drug Treatment
Percentage of No HCV Rx HCV Rx Transplant Transplant
all Persons No Transplant No No HCV Rx HCV Rx
with HCV Transplant
Diagnosis
Total 15,612 (100%) 13,049 (83.6%) 2,288 (14.6%) 183 (1.2%) 92(0.6%)

Age
<21 490 (3.1%) 459 (93.7%) 13 (2.7%) 16(0.1%) 2(0.0%)
22-44 5,483 (35.1%) 4,636 (84.5%) 804 (14.7%) 29 (0.2%) 14(0.1%)
45-54 6,593 (42.2%) 5,375 (81.5%) 1,078 (16.4%) 84 (0.5%) 56 (0.4%)
55-64 2,303 (14.8%) 1,921 (83.4%) 320 (13.9%) 45 (0.3%) 1 7 (0.1%)
>65 743 (4.8%) 658 (88.6%) 73 (9.8%) 9 (0.1%) 3 (0.0%)

Gender
Male 7,735 (49.5%) 6,544 (84.6%) 1,090 (14.1%) 70(0.5%) 31 (0.2%)
Female 7,877 (50.5%) 6,505 (82.6%) 1,198 (15.2%) 113 (0.7%) 61(0.4%)

Race
White 9,068 (58.1%) 7,556 (83.3%) 1,365 (15.1%) 106 (0.7%) 42(0.3%)
Black 3,089 (19.8%) 2,643 (85.5%) 422 (13.7%) 20(0.1%) 4(0.0%)
Native
American 7 (0.0%) 4 (57.1%) 3 (42.9%) 0(0.0%) 0(0.0%)
Oriental 53 (0.3%) 44 (83.0%) 7 (13.2%) 2 (0.0%) 0 (0.0%)
Hispanic 1,019 (6.5%) 826 (81.0%) 168 (16.5%) 13(0.1%) 12(0.1%)
Other 2,376 (15.2%) 1,977 (83.2%) 323 (13.6%) 42 (0.3%) 34 (0.2%)
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Table 2 shows that there is a relatively small number of children under 21 with HCV who
received any form of treatment, likely because serious liver damage did not have time
to emerge. Those who are age 65 and older, who are more likely to have advanced
liver disease, are less likely to receive drug treatment for their HCV. The age group
between 45 and 54 years old receives the greatest proportion of treatment overall.

Women are more likely than men to receive drug treatment and more likely to receive
a liver transplant. Conclusions regarding race are drawn with caution because there is
a large number of recipients where race is not known and the number of liver
transplant cases is relatively few. It appears that there is a disproportionately higher
frequency of drug treatment and liver transplant among Hispanics and a
disproportionately lower frequency of both treatment modalities among Blacks.
Whereas the percentage of white persons treated with drug therapy is proportionally
higher, there are proportionately fewer recipients of a liver transplant in this group. The
number of those identified as Native American or Oriental is quite small and it is difficult
to draw conclusions about treatment patterns in these groups, although the proportion
of Oriental persons who receive treatment appears to be higher than any other racial
group.

In clinical trials with pegylated interferon and ribavirin, researchers found significant side
effects that resulted in discontinuation of treatment in approximately 10-14% of patients.
Major side effects of combination therapy include influenza-like symptoms,
hematologic abnormalities and neuropsychiatric symptoms. Psychological conditions,
particularly depression, are common among persons with HCV and are frequent side
effects of interferon (Jensen et al. 2004). However, there are very little data outside the
clinical trials about side effects and important co-morbidities among patients who
present for treatment.

Due to the likelihood that treatment would not be tolerated or successful in certain
individuals, the Durham Veterans Affairs Medical Center set eligibility criteria for HCV
treatment (Muir and Provenzale 2002). Patients considered ineligible for treatment were
those with severe mental illness, hazardous alcohol consumption, current drug abuse,
decompensated cirrhosis, dementia, terminal illness, diabetic ketoacidoses, severe
cardiac or pulmonary disease, or were homeless. HIV infection was also considered a
factor complicating treatment but these patients remained eligible for treatment.

Subsequent to the adoption of these eligibility criteria, clinicians at the Durham VA
Medical Center found that only 32 out of 100 consecutively diagnosed veterans met
the criteria for treatment. Excessive alcohol consumption eliminated 44 percent and
major depressive symptoms accounted for an additional 12 percent being removed
from the treatment pool. Ineligible patients were referred for psychiatric and substance
abuse treatment. Thirteen percent remained eligible but were infected with the HIV
virus.

We examined the data for the presence of similar factors that could influence the
decision to treat individual patients with HCV or that could affect their adherence to
therapy. The pool of subjects was divided by the presence or absence of drug
treatment, irrespective of the receipt of a liver transplant. The number receiving any
M0416, Deliverable 10:3
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form of drug therapy was 2,380. There were 13,232 persons having no claim for
interferon, ribavirin or a combination of the two. An analysis of co-morbidities and a
comparison between the two groups is displayed in Table 3.


Table 3. Co-Morbidities Among Persons with a Diagnosis of HCV, Treated and Not Treated
Persons with HCV and
Co-Morbidity as No HCV Rx HCV Rx Treatment
Percentage of Total Treatment
(N=15,612) (N = 13,232; 84.8%) (N = 2,380; 15.2%)
Alcohol Abuse 3,734 (23.9%) 3,401 (91.1%) 333 (8.9%)
Drug Dependence 2,080 (13.3%) 1,785 (85.8%) 295 (14.2%)
Alcohol Abuse and
Drug Dependence 887 (5.4%) 790 (89.1%) 97 (10.9%)

Psychosis 1,681 (10.5%) 1,466 (87.2%) 215(12.8%)
Depression 920 (5.9%) 767 (83.4%) 153 (16.6%)
Psychosis and
Depression 171 (1.1%) 151 (88.3%) 20 (11.7%)

All of the Above 58 (0.4%) 54(93.1%) 4 (6.9%)
One of the Above 6,158 (39.4%) 5,418 (88.0%) 740 (12.0%)
None of the above 9,454 (60.5%) 7,814 (82.7%) 1,640 (17.3%)

Advanced Liver
Disease 3,446 (22.1%) 2,952 (22.3%) 494 (20.8%)

HIV/AIDS 2,783 (17.8%) 2,332 (83.8%) 451 (16.2%)
Note: Appendix gives ICD-9 codes used to identify co-morbidities.


If treatment had been restricted to persons with no evidence of alcohol abuse, drug
abuse or serious mental illness, then 6,158 (39.4%) of the individuals in the pool would be
considered ineligible for treatment. It appears that alcohol abuse reduced the
likelihood of drug therapy for HCV more than evidence of drug abuse and serious
mental illness. In the case of a diagnosis of depression, it is difficult to know if treatment
was more likely- a counter-intuitive finding- or if there is a greater likelihood of
depression as the result of the disease or treatment itself. Up to 20% of patients with
HCV infection are thought to have psychological disorders including depression (NIH
Consensus Statement 2002).

Collectively, however, those with at least one of the risk factors were somewhat less
likely to receive treatment (12.0%) than those with none of the risk factors (17.3%). Drug
therapy was given to a greater proportion of those whose liver deterioration had
advanced. The presence of HIV/AIDS was not a factor in deferring drug therapy.



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Research question 2. What percentage of persons with a diagnosis for HCV also have a
diagnosis of fibrosis, cirrhosis, cancer of the liver, or a liver transplant?

Cirrhosis, cancer of the liver, and liver transplant are markers for persons with HCV in the
terminal stages.


Table 4. Florida Medicaid Recipients with HCV Diagnosis (N=15612) with Advanced
Liver Disease,* FY 00-03
Advanced Liver Disease 3446 (22.1%)
Cancer of the liver 103 (0.7%)
Liver Transplant 275 (1.8%)
categories are not mutually exclusive


Research question 3. Of those who have had a liver transplant, what percentage had
a diagnosis of hepatitis C and/or a record of drug treatment for HCV?

It is expected that HCV infection will recur after liver transplantation in nearly all persons
who are HCV-positive prior to the transplant procedure. Immunosupppresive therapy
used to prevent organ rejection contributes to the risk of HCV recurrence. Up to 30% of
HCV patients will develop severe graft hepatitis and cirrhosis within 10 years after the
transplant procedure, most within the first year (Neumann et al., 2004).

The 5 and 10 year survival rate among HCV patients with liver transplants has been
estimated at 76% and 69%, respectively (Neumann et al., 2004). A recent study
following 209 HCV patients who received a liver transplant found that 18 died because
of HCV recurrence within ten years after the transplant procedure. That is, the cause
of death was attributed to HCV recurrence for approximately one in three of those who
died over the 10-year observation period.


Table 5. Florida Medicaid Recipients with Liver Transplant, FY 00-03
Liver transplant without diagnosis of HCV
No drug therapy for HCV 430 (60%)
With drug therapy for HCV 13 (2%)

Liver transplant and diagnosis of HCV
No drug therapy for HCV 183 (25%)
With drug therapy for HCV 92(13%)

Total 718(100%)


Among 275 Florida Medicaid recipients who had a liver transplant and a diagnosis of
HCV, about one-third have received drug therapy for HCV. However, additional
analyses are needed to determine whether the diagnosis and drug therapy occurred
before or after the liver transplant procedure.
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Research question 4. Of those receiving treatment with pegylated interferon and
ribavirin, what is the therapeutic possession ratio for each drug?

Effective treatment for HCV requires the use of both ribavirin administered orally and
interferon administered by injection. Among 2,380 persons receiving drug therapy,
there were 255 who received the injection but had no claim for the oral agent. One
reason that may account for this observation is that oral ribavirin is contraindicated in
persons with end stage renal failure (ESRD). Alternative explanations are that there are
some individuals who obtain the medication from another source or are not compliant
with the oral component of the treatment.

There were an additional 30 persons who had claims for the oral component, but no
claims recorded for the injection. This could be attributed to the injection being
covered by other insurance or administered in a clinic or physician office and not being
billed on a Medicaid pharmacy claim. A preliminary examination of the data found at
least one non-pharmacy claim for 11 patients where injection treatment was billed
using the CMS billing code J9212.

This leaves 2,095 persons who received both oral and injectable therapy. We examined
the data for continuity of treatment as indicated by monthly billing. When ever there
was a lapse in claims for 90 days or more, we assumed the individual had stopped drug
therapy for some reason and were re-started on therapy at the later date. There were
438 persons who had multiple episodes of drug therapy for HCV by this definition. This
group was analyzed separately under Research question 6 (page 11).

For the remaining 1,658 patients we estimated the number who received both oral and
injectable components in adequate quantities for effective treatment. We did this by
estimating a therapeutic possession ratio that divides the days supply of oral ribavirin
therapy by the days supply of injectable interferon therapy. If the patient received
both components in appropriate quantities, the ratio will be 1.0. A ratio less than one
than one would suggest under-treatment with the oral component and a ratio greater
than one implies under-treatment with the injectable.

The median and modal possession ratio was 1.0. In fact, the possession ratio was equal
to 1.0 for 903 (54.5%) of the group and there were a substantial number of persons with
a possession ratio close to 1.0 that would be considered clinically sufficient.


Table 6. Therapeutic Possession Ratio for Persons Undergoing Oral Treatment with
Ribavirin and Injection Treatment with Interferon alfa (N=1657)
Possession Ratio Possession Ratio Possession Ratio
1.00 903 (54.5%) 0.99-1.01 972 (58.6%) 0.90-1.10 1237 (74.6%)
<1.00 435 (26.3%) <0.99 422 (25.5%) <0.90 322 (19.5%)
>1.00 319 (19.2%) >1.01 263 (15.9%) >1.10 98 (5.9%)



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There were more patients with a possession ratio below 1.0 than over 1.0. The
interpretation is that patients are less likely to obtain a sufficient quantity of the oral
ribavirin relative to the injection. Overall, however, three out of four patients received
both drugs in the appropriate ratio. The next question was to determine if the
treatment was sustained over an adequate period consistent with current practice
guidelines.

Research question 5. Of those with continuous Medicaid eligibility who received
treatment with pegylated interferon and ribavirin, what proportion receive quantities
sufficient for continuous treatment for less than 12 weeks; for 12 weeks; more than 12
weeks but less than 24 weeks; more than 24 weeks but less than 48 weeks; more than 48
weeks?

The NIH Consensus Conference concluded that patients who fail to achieve an early
viral response by week 12 have only a small chance of achieving a sustained viral
response, even if therapy is continued for a full year. Treatment need not be extended
beyond 12 weeks in these patients. Individuals with HCV genotype 2 or 3 who show a
positive response to treatment should continue treatment for a total of 24 weeks;
individuals with genotype 1, the form that is most prevalent in the U.S., should maintain
therapy for 48 weeks.

An examination of the length of therapy among those who were treated for HCV found
that about one-third (N=537) did not have claims sufficient for 12 weeks of treatment.
These patients may be those who did not tolerate the side effects of treatment or
otherwise did not adhere to the treatment regimen that requires weekly injections. In
clinical trials 10% to 14% of subjects withdrew due to adverse effects of treatment (NIH
Consensus Conference 2002). Presumably, those who stopped therapy after 12 weeks
(N=156) and at least some who stopped before 24 weeks (N=274), were individuals who
did not experience a significant response to the therapy.


Table 7. Length of HCV Treatment for Persons with a Single Episode of Treatment
Length of HCV Therapy Number of Patients
Less than 12 weeks 537 (32.4%)
12 weeks 156 (9.4%)
More than 12 weeks but less than 24 weeks 274 (16.5%)
24 weeks 155 (9.3%)
More than 24 weeks but less than 48 weeks 380 (22.9%)
48 weeks 81 (4.9%)
More than 48 weeks 74 (4.5%)
Total Number of Persons Treated 1657 (100%)
Note: treatment duration was estimated from days supply of medication + 10%.


About one-third of those undergoing treatment had claims for a duration of at least 24
weeks but less than 48 weeks. Less than 10% of those who started therapy had
treatment claims for the full 48 weeks recommended by the NIH Guidelines for
genotype 1. Given that approximately two-thirds of HCV cases in the U.S. are genotype
M0416, Deliverable 10:3
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1, it would be expected that two-thirds of those treated would require 48 weeks of
treatment.

Davis et al (2003) used a previously published natural history model of HCV to project
the number of cases of HCV infection, cirrhosis, and liver failure that will occur over the
next four decades. By assuming a positive treatment response rate of 50%, they
examined the impact of treating various proportions of patients. As shown in Figure 2
from Davis et al., with 10% successfully treated, one could expect a 4.9% reduction in
cases of liver decompensation over a 20 year period.


Figure 2. Projectd impact
on caes of hepatic deAompen-
sation by treating different
proportions of HCV-infcted
patients with interfeion-ribsvi-
rin combination therapy.


2000


2010 2020 2030 2040 2050


Source: Liver Transplantation 2003; 9: 335.

Furthermore, as shown in the following table from Davis et al., any reduction in morbidity
and mortality will occur over several decades depending upon the stage of hepatic
decompensation at the time that therapy is initiated. For persons with cirrhosis, a
response to treatment is expected to reduce disease complications by an average of
88% during the first five years following treatment. On the other hand, treating patients
with mild chronic hepatitis would account for an 11% reduction in complication after 10
years, nearly 32% reduction after 20 years and a 58.5% decrease after 40 years.
Treatment of patients with liver function in normal range would have relatively little
impact on disease complications in this population.


















M0416, Deliverable 10:3
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Source: Liver Transplantation 2003; 9: 335.

Research question 6. Of those with continuous Medicaid eligibility who initiated
treatment with either interferon and ribavirin, or pegylated interferon and ribavirin, what
proportion received a second course of therapy? (Re-treatment is defined as lapse in
any prescription claim for interferon, pegylated interferon, or ribavirin of 90 days or
more.)

Selected patients who fail to achieve a sustained viral response may benefit from re-
treatment according to the NIH Consensus Conference. Individuals who were initially
treated with interferon alfa, may have attempted a second course of treatment with
the pegylated interferon when it was introduced as a new alternative. Preliminary
research data suggest that 15-20% of those who did not respond to treatment with a
standard interferon-ribavirin combination will achieve a sustained viral response on re-
treatment with pegylated interferon-ribavirin (Zeuzem 2004).

The expected outcome of a complete second course of treatment for persons who
stopped therapy prematurely in earlier treatment attempts is unknown. Likewise, it is
not possible to predict the expected outcome for those who undertake multiple, short
courses of treatment.

In addition to the 1,657 persons with a single course of treatment with ribavirin and
interferon described previously, there were 438 (20.9%) who underwent multiple
episodes of treatment ranging from 2 to 7 episodes as shown in Table 8. Assuming that
at least one course of therapy must meet NIH guidelines for length of treatment, we
examined the records to determine the number of persons having one or more
sustained periods of treatment. There were similar proportions of persons with a


M0416, Deliverable 10:3
Page 12


Table 2. Propoi non of Treatment-Related Reduction in
Heparic Decompensation Accounted for by Ditffeient
Subgioups of Patients


Treated Group 2010 2020 2.030 20-14

Cirrhosis (excluding cases
with complications) 54.500 26.8% 14.9".0 9.1%
Moderate chronic hepatit is 33.5% 37.7% 32.1% 25.7%
Minimal-to-mild chronic
hepatitis 11.0% 31.900 48.0**' 58.5%
Persistently normal serum
ALT levels 2.0% 3.5% 5.0%' 6.7%
NOTE. Data shown at decade intervals.









sustained course of therapy irrespective of the number of attempts. Table 9 summarizes
the findings and compares the groups with single and multiple courses.


Table 8. Episodes of HCV therapy Number of patients
1 1657 (79.0%)
2 63 (3.0%)
3 251 (12.0%)
4 87 (4.2%)
5 30 (1.4%)
6 4 (0.2%)
7 3 (0.1%)


It appears that the proportion of patients who undergo a sustained course of therapy
over 48 weeks to meet the NIH guidelines for the most common genotype increased by
allowing them to undertake multiple treatment episodes. Nonetheless, only 12.9% of
the entire group met this goal.

It must be acknowledged that some persons with multiple episodes of therapy might
undergo retreatment because they were re-infected. More likely, retreatment occurs
among those who relapse or are treated to slow liver deterioration. Among the 438
patients with multiple episodes there were 31 persons who completed 2 year-long
episodes of treatment and 3 people who had 3 year-long episodes over the four-year
observation period.


Table 9. Length of Sustained HCV Treatment Period for Persons with Single and Multiple
Treatment Episodes
Length of HCV Therapy Single Episode Multiple Total
Episodes
Less than 12 wks 537 (32.4%) 48 (11.0%) 585 (27.9%)
12 wks or more but less than 24 430 (25.9%) 107 (24.4%) 537 (25.6%)
wks
24 wks or more but less than 48 535 (32.3%) 168 (38.3%) 703 (33.6%)
wks_
48 wks or more 155 (9.4%) 115(25.2%) 270 (12.9%)
Total Number of Persons Treated 1657 (100%) 438 (100%) 2095 (100%)
Note: treatment duration was estimated from days supply of medication + 10%.


Research question 7. What were the total Medicaid expenditures per member per
month (PMPM) for the population with hepatitis C and its sub-groups?

Hepatitis C is a chronic condition that may be present for decades before the disease
progression requires extensive medical intervention. We examined medical
expenditures for all persons identified in the study, although the observation period may
be too short to capture trends in the care and treatment of HCV in the program.
M0416, Deliverable 10:3
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Likewise it was not possible to track expenditures for individuals because the disease
progresses so slowly.


Table 10. Total Florida Medicaid Expenditures for Persons with HCV, FY 00-03
HCV HCV with Liver Cost PMPM
Diagnosis Transplant TOTAL
Pharmacy $256,260,518 $4,220,049 $260,480,566 $548
services (43.4%)
Inpatient 175,155,561 7,557,490 182,713,051 $384
services (30.4%)
Physician 121,728,667 2,158,311 123,886,978 $260
services (20.6%)
Outpatient 32,316,556 646,727 32,963,283 $69
services (5.6%)
Total Medicaid $585,461,301 $14,582,576 $ 600,043,878 $1262
(100%)


The total Florida Medicaid expenditures for 15,612 patients with a diagnosis of HCV over
the four-year observation period was $600,043,878. A breakdown of expenditures by
category shows the greatest proportion of charges were for pharmacy services.


POLICY IMPLICATIONS

Experts believe that hepatitis C is under-diagnosed, even among patients at high
risk of infection. Knowing the prevalence of diagnosed and treated cases allows
planners to estimate the additional demand for services among current cases
and those yet to be identified. The prevalence of hepatitis C documented
among Florida Medicaid recipients by this analysis was less than 0.5 percent. This
is far below national estimates of 1.8% for the population in general, and far
below the estimated prevalence in sub-populations known to be at higher risk for
contracting the infection.

Treatment response estimates are based upon controlled trials with patients who
are informed and consent to participation in the trials, and are closely monitored
by researchers, often in academic medical centers. There are few data from
clinical practice outside these trials (Jensen et al. 2004). There is considerable
variability in patients' willingness to undergo treatment, their tolerance for side
effects and the therapeutic response. Baseline data from this study illustrate the
variance in treatment patterns and adherence to treatment guidelines for HCV
among those patients who receive services from Florida Medicaid.

Two-thirds of the patients who initiated a single episode of drug therapy for HCV
maintained the treatment for 12 weeks or longer. It is not necessary to continue
treatment beyond this point for persons who fail to demonstrate an adequate
response to therapy. About one-third of those who initiated therapy remained
M0416, Deliverable 10:3
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on treatment for 24 weeks but less than 48 weeks, the recommended duration of
therapy for those with genotypes 2 or 3.

* The recommended duration of treatment for genotype 1, the most common
form, is 48 weeks. Slightly less than 10% of those who had a single course of drug
therapy maintained the treatment for the full 48 weeks. If patients who received
multiple courses of therapy are considered, the percentage of patients
achieving the full duration of treatment increased to about 13 percent. This
suggests that treated patients are poor candidates for therapy or there is
inadequate monitoring. Patients receiving drug therapy for HCV should receive
close monitoring and support to enhance the likelihood that the treatment can
be tolerated and sustained.

* This study identified a group of 1,273 individuals without a diagnosis of HCV who
were treated with drug therapy that is only indicated for the treatment of that
disease.

Recipients without ICD-9 Diagnosis of Hepatitis C
Receiving Drug Therapy for Hepatitis C
Drug therapy specific for HCV 1,260
Liver transplant with drug therapy 13
Total 1,273

A preliminary examination of possible reasons for use of drug therapy in cases
where HCV is not documented failed to produce a discernable pattern to
support the use of these agents. The need for drug therapy of HCV after a liver
transplant is not supported in the literature, although it may be appropriate for
individuals who contract the HCV after the liver transplant has occurred. There
was no diagnostic pattern apparent to account for use of these agents or a
pattern of off-label use. We recommend that this group be referred for utilization
review.

* The average annual cost to Florida Medicaid for each person with a diagnosis of
hepatitis C was $15,144 between FY 2000 and FY 2003. However, this study suffers
from the lack of a comparison population that would provide an estimate of the
marginal cost of health care services incurred due to HCV status relative to a
similar population without HCV. Additional studies, conducted over time, are
warranted in order to capture the added burden due to HCV.












M0416, Deliverable 10:3
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REFERENCES


Adinolfi LE, Utili R, Tonziello, Ruggiero. Effects of alspha interferon induction plus ribavirin
with or without amantadine in the treatment of interferon nonresponsive chronic
hepatitis C: a randomized trial. Gut 2003; 52: 701.

Allen SA, Spaulding AC, Osei AM, Taylor LE, Cabral AM, and Rich JD. Treatment of
chronic hepatitis C in a state correctional facility. Ann Intern Med 2003;138:187-191.

Alter M. Prevention of spread of hepatitis C. Hepatology 2002; 36:S93-S98.

Alter MY, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus
infection in the United State, 1988 through 1994. N Engl J Med 1999; 341: 556-562.

Alter HJ, Seeff LB. Recovery, persistence and sequelae in hepatitis C virus infection: a
perspective on long-term outcome. Seminars in Liver Disease 2000; 20:17-35.

American Liver Foundation. Hepatitis C: an information resource. 2003.
www.liverfoundation.ora. Accessed Nov. 24, 2003.

Bernstein D. Hepatitis C: advances in treatment. 54th Annual Meeting of the American
Association for the Study of Liver Diseases.
http://www.medscape.com/viewarticle/464166. Accessed Nov. 18, 2003.

Cassidy W. Hepatitis C infection in prisons.
http://www.hcvadvocate.ora/Medical Writers Circle/cassidv-1.htm. Accessed
Aug. 18, 2003.

CDC. National Hepatitis C Prevention Strategy. Summer 2001.
http://www.cdc.gov/ncidod/diseases/hepatitis/c/plan/index.htm Accessed Nov.
24, 2003.

CDC. Transmission of hepatitis B and C viruses in outpatient settings--New York,
Oklahoma, and Nebraska, 2000-2002. MMWR 2003; 52:901-906.

Davis GL, Albright JE, Cook SF, Rosenber DM. Projecting future complication of chronic
hepatitis C in the United States. LiverTranpsl 2003; 9:331-338.

Florida Department of Health. Florida Hepatitis Support Groups.
http://www.doh.state.fl.us/Disease ctrl/aids/hep/support.htm. Accessed Aug 18,
2003.

Florida Department of Health. Hepatitis Vaccine and Laboratory Testing.
http://www.doh.state.fl.us/Disease ctrl/aids/hep/index.html
Accessed Aug 18, 2003.

Florida Department of Health. Hepatitis C Treatment.
http://www.doh.state.fl.us/Disease ctrl/aids/hep/hepCtreat.htm
Accessed Aug 18, 2003.
M0416, Deliverable 10:3
Page 16










Florida Department of Health. Hepatitis C Symptoms.
http://www.doh.state.fl.us/Disease ctrl/aids/hep/hepCsymp.htm

Franciscus A. Freedom to be cured: who is driving the decisions on which groups of
patients should be eligible for hepatitis C treatments?
http://www.hcvadvocate.ora/freedom.htm Accessed Aug. 18, 2003.

Gonzalez SA, Jacobson IM. The role of hematopoietic growth factos in special
populations with chronic hepatitis C. C/eve Clin J Med 2004: 71 (supplement 3):S22-
S26.

Heathcote EJ, Shiffman ML, Cooksley WG, et al. Peginterferon alfa-2a in patients with
chronic hepatitis C and cirrhosis. N Engl J Med 2000: 343:1673-1680.

Heathcote J. Patients with hepatitis C: who should be treated?
http://www.hcvadvocate.ora/Medical Writers Circle/heathcote-1.htm
Accessed Aug. 18, 2003.

Huang K. Checkup: hepatitis C. The Wall Street Journal Online, October 9, 2003.

Jensen DM, Cotler SJ, Lam H, Harb G, Shillington A. A comparison of hepatitis C
treatment and outcomes at academic, private and Veterans' Affairs treatment
centers. Aliment Pharmacol Ther 2004; 19:69-77.

Katz D. Hepatitis C virus.
http://www.doh.state.fl.us/Disease ctrl/aids/hep/hepCbrief.html
Accessed Aug. 18, 2003.

Keuhne FC, Bethe U, Freedberg K, and Goldie SJ. Treatment for hepatitis C virus in
human immunodeficiency virus infected patients. Arch Intern Med 2002;162:2545-
2566.

Leigh JP, Bowlus CL, Leistikow BN, and Schenker M. Cost of hepatitis C. Arch Intern
Med 2001;161:2231-2237.

Malone DC. Cost-effectiveness analysis of interferon a-2b with ribavirin for chronic
hepatitis C infection. Formul/ary2000;35:681-689.

Muir A. Hepatitis C in African Americans. Hepatitis C Support Project.
http://www.hcvadvocate.org/Medical Writers Circle/muir-l.htm
Accessed Aug. 18, 2003.

Muir AJ, Provenzale D. A descriptive evaluation of eligibility for therapy among veterans
with chronic hepatitis C virus infection. J Clin Gastroenterol 2002; 34: 268-271.

Neumann UP, Berg T, Bahra N, Puhl G, Guckelberger O, Langrehr JM, Neuhaus P. Long-
term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up.
Transplantation 2004; 77:226-231.
M0416, Deliverable 10:3
Page 17










NIH Consensus Statement. Management of hepatitis C: 2002. Sep.12, 2002.
http://www.consensus.nih.aov/cons/1 16/116cdc intro.htm

Osbon C. Appropriate drug utilization in the treatment of hepatitis C. Presentation to
Florida Medicaid DUR Board. Tampa: February 8, 2003.

Pockros PJ. The management of adverse effects with PEG-interferon/ribavirin
combination therapy is a significant challenge.
http://www.hcvadvocate.ora/Medical Writers Circle/Dockros-2.htm
Accessed Aug. 18, 2003.

Rosenberg DM, Cook SF, Lanza LL. Health care, treatment patterns and cost of services
for patients infected with chronic hepatitis C virus in a large insured New England
population. J Viral Hepat 2000; 7: 361-367.

Salomon JA, Weinstein MC, Hammit JK, and Goldie SJ. Cost-Effectiveness of Treatment
for Chronic Hepatitis C Infection in an Evolving Patient Population. JAMA 2003;
290:228-237.

Schaefer M, Schmidt F, Folwaczny C, Lorenz R, et al. Adherence and mental side
effects during hepatitis C treatment interferon alfa and ribavirin in psychiatric risk
groups. Hepatology2003; 37:443-451.

Shatin D, Schech SD, Patel K, McHutchison JG. Population-based hepatitis C
surveillance and treatment in a national managed care organization. Am J
Manag Care 2004; 10:250-256.

Sulkowski MS, Thomas DL. Hepatitis C in the HIV-infected person. Ann Intern Med 2003:
138:197-207.

Tan SL, Pause A, Shi Y, Sonenberg N. Hepatitis C therapeutics: current status and
emerging strategies., Nature Reviews Drug Discovery 2002;1: 867-881.

Veteran's health care: standards and accountability could improve hepatitis C
screening and testing performance. GAO-01-807T, Jun. 14, 2001.

VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical
Advisory Panel. Pegylated interferon criteria for use. March 2003.
http://www.vapbm.org or http://vaww.pbm.med.va.aov Accessed Mar. 3, 2003.

Wasley A, Alter MJ. Epidemiology of hepatitis C: geographic differences and temporal
trends. Semin Liver Dis 2000; 20:1-16.

Weisbord JS, Trepka MJ, Zhang G, Smith IP, and Brewer T. Prevalence of and risk factors
for hepatitis C virus infection among STD clinic clientele in Miami, Florida. Sex
Transm Infect 2003; 79:E1.


M0416, Deliverable 10:3
Page 18









Williams T, Honeywell M, Branch E, Thompson M. Peginterferon alfa-2a: a new agent for
hepatitis C virus infection. P&T 2003; 28(5): 302-304.

Wong JB, McQuillan GM, McHutchison JG, Poynard T. Estimating future hepatitis C
morbidity, mortality, and costs in the United States. Am J Public Health 2000;
90:1562-1569.

Zeuzem S. Heterogeneous virologic response rates to interferon-based therapy in
patients with chronic hepatitis C: who responds less well? Ann Intern Med 2004;
140: 370-381.

Zeuzem S, Feinman SV, Raseneck J, et al. Peginterferon alfa2a in patients with chronic
hepatitis C. N Engl J Med 2000;343:1 666-72.







































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APPENDIX I. Specifications for Medicaid Claims Extraction and Data Definitions.


GENERAL INSTRUCTIONS
1. Data request is made with all IRB and HIPPA review and approvals in place. Data
are transferred as the encrypted files.
2. This request for a data extract begins with date of service from July 1, 1999 and
extends through June 30, 2003.
3. Do not include any personal identifiers but create a unique identifier for each
subject in the study so that we may link all claim records for an individual subject. In
addition,
Please give us the subject's age in years on the date the claims review is
initiated, i.e., July 1, 1999. Anyone 90 years or older should be coded as 90+
Exclude all geographic identifiers. If we note patterns, trends or outliers based
upon the study criteria, we will recommend that findings be forwarded to the
Prescribing Pattern Review Panel for an examination of regional trends.


DATA EXTRACTION REQUEST
1. Select recipients.
Examine paid claims with dates of service from July 1, 1999 through June 30, 2003
inclusive.
Build a list of study subjects using presence of diagnostic codes and/or drug
treatment for hepatitis C. Add all persons with liver transplant to the list of persons
eligible for study.
A list of the ICD-9, CPT/HCPCS, and NDC codes that identify the subjects is attached
to this request.
2. Retrieve claims for relevant health services use under Medicaid, i.e.,
Pharmacy claims: date of service, NDC, generic code, therapeutic class,
quantity, days supply, amt billed, amt paid, pharmacy ID
Hospital inpatient claims: date admit, provider ID, LOS, primary, secondary and
tertiary ICD-9 codes, CPT codes, amt. billed, amt paid
Hospital outpatient claims: date admit, provider ID, primary, secondary and
tertiary ICD-9 code, procedure (CPT) code, amt billed, amt paid
Physician claims: date, primary, secondary and tertiary ICD-9 code, procedure
(CPT) code, provider ID, provider type, provider specialty, amt billed, amt paid


3. Use recipient eligibility file to generate a file for each subject including the following
Age; Sex; Race; NH status; Medicaid eligibility dates; Medicare eligibility (0 or 1);
Death if recorded; AIDS waiver flag; CMS flag; Organ transplant indicator (0 or 1)

M0416, Deliverable 10:3
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DATA DEFINITIONS
Positive HCV identification
ICD-9-CM
070.41 Acute Hepatitis C with coma
070.44 Chronic Hepatitis C with coma
070.51 Acute Hepatitis C without coma
070.54 Chronic Hepatitis C without coma

CPT/HCPCS
J9212 Infergen

Identification of Liver Transplant Recipient
ICD-DM-9 Disease Name
V42.7 Liver transplant status

ICD-9 Codes Used to Identify Selected Co-morbidities
ICD-DM-9 Disease Name
042 HIV/AIDS
303, 305, 571 Alcohol abuse
304 Drug Dependence
295, 296, 297 Psychosis including schizophrenia
300.4 Depression
456.2, 572, 573.1, Fibrosis or cirrhosis of the liver, esophageal varices
573.8, 573.9

Diagnoses Used to Identify Advanced Liver Disease
ICD-DM-9 Disease Name
155.0 Hepatocelluar Cancer
286.9 Coagulopathy
289.4 Hypersplenism
456.0/572.2 Esophageal varices
571.5 Cirrhosis
572.2 Hepatic encephalopathy
572.3 Portal hypertension
573.8 Liver failure
782.4 Jaundice
789.5 Ascites


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Drug Treatment for Hepatitis C
Therapeutic Code Generic Code NDC Drug
W5G 22222 00085-1236-01 Rebetron
(Z2G in before 22221 00085-1236-02 (pegylated
2001) 22220 00085-1236-03 interferon and
22222 00085-1241-01 ribavirin)
22221 00085-1241-02
22220 00085-1241-03
22225 00085-1258-01
22224 00085-1258-02
22223 00085-1258-03
14179 00085-1194-03 Rebetol
14179 00085-1327-04 (ribavirin)
14179 00085-1351-05
14179 00085-1385-07
Z2G 89389 00085-1368-01 Peg-lntron
&W5G 89391 00085-1291-01 (pegylated
14752 00085-1304-01 interferon)
14753 00085-1270-01
18926 00004-0350-39 Pegasys
18287 00004-3500-09 (ribavirin)
51624 55513-0554-06 Infergen
Z2G 51623 55513-0562-06 (interferon alfacon-
51623 64116-0031-01 1)
51623 64116-0031-06
Z2G 46472 00085-1168-04 Intron A
47525 00085-1133-01 (interferon alfa-2b)
47528 00085-1179-02
47602 00085-0571-02
47604 00085-0539-01
47605 00085-1110-01
47661 00085-1234-01
47663 00085-1242-01
47512 00004-2016-09 Roferon-A
47513 00004-2017-07 (interferon alfa-2a)


M0416, Deliverable 10:3
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APPENDIX II.

Count of Eligible Recipients in FFS and MediPass

Member Member
Plan CNTof Unique Members Plan CNTof Unique Members
FY9900 December '99
FFS 1,535,688 FFS 696,708
MediPass 842,779 MediPass 519,849

FY0001 December '00
FFS 1,587,457 FFS 745,550
MediPass 903,052 MediPass 592,203

FY0102 December'01
FFS 1,765,708 FFS 789,010
MediPass 895,140 MediPass 599,509

FY0203 December '02
FFS 1,787,439 FFS 813,149
MediPass 944,617 MediPass 642,631


Not Shown: HMO Recips, PSN Recips and Children's Medical Services


Data provided by ACHA (Chris Mallison): May, 20, 2004.


M0416, Deliverable 10:3
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