Abstract
BACKGROUND:
The Veterans Affairs Health (VA) Administration has reported hepatitis C virus (HCV) infection rates among veterans to be twice that of the general U.S population. New HCV direct-acting antiviral (DAA) treatment options offer superior sustained virologic response (SVR) rates, improved side-effect profiles, and shortened treatment courses; yet, these new HCV DAAs are expensive, and utilization management strategies are needed to optimize use and improve clinical outcomes. A VA medical center uses pharmacist-led HCV DAA utilization management strategies that includes clinical guidance, optimizing operational flow, budget tracking and forecasting, and patient outcomes tracking.
OBJECTIVE:
To assess the economic and clinical outcomes of pharmacy-led HCV DAA utilization management in a VA medical center.
METHODS:
This was a single-center, retrospective cohort study. Patient electronic health records and the hepatitis C DAA outcomes tracking database were reviewed at a VA medical center. Patients with an HCV DAA prior authorization drug request and therapy initiated between October 1, 2014, and September 30, 2015, were included. The primary endpoint was the ratio of drug spend to cure rate calculated as the total dollars spent to the number of patients achieving SVR at least 12 weeks from end of treatment. Secondary endpoints included economic, clinical, and safety outcomes.
RESULTS:
A total of 372 patients were included in the study. The overall cost ratio of total drug spend to cure rate was $40,135.22. The overall cure rate was 94.1%, with no discontinuations due to treatment failure. The ratio of drug spend to cure rate was $41,907.35 and $38,430.77 in cirrhotic and noncirrhotic patients, respectively, and $39,481.62 and $39,178.74 in treatment-experienced and naive patients, respectively. Ten patients discontinued therapy because of the adverse effects of anemia, nausea, vomiting, and anxiety. The medication possession ratio was 98.7% (± 0.13) for all patients included in the study.
CONCLUSIONS:
This study suggests that pharmacist-led HCV DAA utilization management is an important factor in costs and cure rates. Utilization management strategies are valuable to help adequately manage patients with chronic hepatitis C (CHC) and may allow practitioners to maximize available funding for CHC, while maintaining high efficacy and safety.
What is already known about this subject
Hepatitis C virus (HCV) infection affects millions of people in the United States, and infection rates among veterans have been reported to be twice that of the general population.
Patients with chronic hepatitis C (CHC) are at increased risk of cirrhosis, hepatocellular carcinoma, and end-stage liver disease.
New HCV direct-acting antivirals (DAAs) for the treatment of CHC have better cure rates, improved side-effect profiles, and shortened treatment courses, but the high cost of these new agents is a concern for health care institutions, patients, and payers.
What this study adds
Pharmacist-led HCV DAA utilization management strategies, including clinical guidance, optimized operational flow, budgetary tracking and forecasting, and outcomes tracking, are important factors in costs and cure rates.
These utilization management strategies are valuable to manage patients with CHC and may allow practitioners to maximize available funding for CHC, while maintaining high efficacy and safety when using HCV DAAs.
Hepatitis C virus (HCV) is estimated to infect approximately 3.9 million people in the United States, according to the Centers for Disease Control and Prevention.1 Acute HCV infection is usually self-limiting and rarely causes hepatic failure. However, approximately 85% of acute HCV infection cases progress to chronic hepatitis C (CHC), which is a slow-progressing disease spanning decades and can result in cirrhosis, hepatocellular carcinoma, and end-stage liver disease.2,3 The goal of antiviral therapy in CHC is to eradicate HCV RNA, which is predicted by attainment of a sustained virologic response (SVR). SVR is defined as an undetectable HCV RNA level. SVR at 12 weeks after treatment is used to assess clinical efficacy.3
Early treatment options for CHC were composed of interferon, ribavirin, and pegylated interferon. These therapies had treatment durations of up to 48 weeks, SVR achievement rates of 6%-56%, and poor tolerability.4 In 2011, the first-generation HCV direct-acting antivirals (DAAs) boceprevir (Victrelis) and telaprevir (Incivek) became available for use in combination with pegylated interferon and ribavirin. These agents yielded improved SVR rates of 66%-79% but were associated with significant adverse effects, drug interactions, and complex dosing regimens.4,5 Second-generation HCV DAAs first came to market in the United States in 2013 and offered superior SVR achievement rates, improved side-effect profiles, and shortened treatment courses to significantly change the management of CHC. These second-generation HCV DAAs include sofosbuvir (Sovaldi), simeprevir (Olysio), ledipasvir/sofosbuvir (Harvoni), ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak), daclatasvir (Daklinza), elbasvir/grazoprevir (Zepatier), ombitasivir/paritaprevir/ritonavir (Technivie), and sofosbuvir/velpatasvir (Epclusa). These agents are used with or without ribavirin or pegylated interferon for 8-24 weeks depending on HCV genotype, previous treatment status, and severity of hepatic impairment.6-12
Although there have been significant advances in the efficacy and safety of CHC treatment options, the costs associated with the new HCV DAAs are high.13,14 In 2011, the total estimated health care cost associated with CHC infection in the United States was $6.5 billion.15 A 2015 analysis estimated that the annual cost of ledipasvir/sofosbuvir-based therapy ranged from $66,000 to $154,000 per patient.16 Multiple cost analysis studies have been performed yielding mixed cost-effectiveness results in the long term with these newer treatments.13,16,17 These studies based their analyses on assumptions of appropriate treatment regimens allocated for patients and no progression of liver disease or relapse after achieving SVR.13,16,17 One study found that new HCV DAAs were cost-effective for genotype 1 and 3 when compared with first-generation HCV DAAs but not with other genotypes.13 Another study evaluated the cost-effectiveness of ledipasvir/sofosbuvir and found that it was not cost-effective for most patients, suggesting that treatment would cost an additional $65 billion over the next 5 years, while offsetting only $16 billion of the overall cost of CHC care.16 Because of the conflicting results of these cost analysis studies, it is extremely important for health care institutions treating CHC patients to develop strategies to contain costs.
Veterans Affairs Background
The Veterans Affairs (VA) Health Administration is considered to be the world’s largest hepatitis C care provider, with a reported HCV infection rate of 5.8% of veterans tested, which is twice the rate of the general population in the United States.18,19 This study was conducted in a 271-bed tertiary care VA medical center that serves as a referral, teaching, and research facility. The medical center provides general and specialty ambulatory and inpatient services, with several community-based outpatient clinics for veterans. At this facility, pharmacists have a major role in developing utilization management strategies to aid in cost containment of high expenses associated with new HCV DAA therapies for CHC patients. The hepatitis C utilization management program has 4 key components: clinical guidance, optimizing operational flow, budget tracking and forecasting, and outcomes tracking.
A clinical guidance document was developed to address the various aspects of clinical care, including patient selection and regimen selection. In accordance with national VA treatment guidance, published hepatitis C treatment guidelines, and primary literature, this document details patient screening criteria, inclusion and exclusion criteria, recommended regimens for specific patient subpopulations, and recommended monitoring. Clinical guides for the management of drug interactions were also developed by the pharmacist and disseminated among hepatitis C providers and staff pharmacists to prevent medication errors. The development and distribution of various clinical guides was done with the goal of improving patient management and cure rates, as well as optimizing utilization and drug spend.
Another approach to help mitigate high costs associated with medical care is to streamline and optimize the operational processes. Standard operating procedures were developed for pharmacy staff to detail the process from order initiation to dispensing of HCV DAAs. HCV DAA prior authorization drug requests were created to ensure appropriate utilization management of HCV DAAs in accordance with VA Pharmacy Benefits Management services criteria for use and the previously mentioned clinical guidance. The HCV DAA prior authorization drug request requires that a gastroenterology or infectious disease provider place an order for the drug, which is then reviewed by a clinical pharmacist. A pharmacist assesses patient history, concomitant medications for potential drug interactions, patient labs, and additional safety concerns. If approved, the initial medication order is entered for a 28-day supply with 1 refill, and an additional prior authorization drug request is then required for continued use.
Careful budget tracking and forecasting has allowed the VA medical center to stay ahead of changes in the funding environment. Budget tracking involves record maintenance of all patients approved for HCV DAAs, assessing budget allocation, and anticipating future needs based on utilization patterns. Financial reports are shared with stakeholders to notify them of additional funding requirements based on current utilization patterns. The budget is regularly assessed by the pharmacist to help determine needs and allocation by ensuring proper funding to avoid interruptions in therapy.
Furthermore, the pharmacy service is involved in the tracking of patient demographics, clinical status, HCV medication refill history, and treatment outcomes. This involvement plays a vital role in preventing unnecessary medical costs. Regimen efficacy rates can be generated with accuracy because of the detailed record keeping of patient outcomes. A clinical pharmacist tracks patients to ensure adequate treatment response and adherence to regimen. If patients are found to be noncompliant with their HCV regimens, then therapy can be discontinued. To ensure appropriate therapy for each patient, therapy can be adjusted quickly for patients who experience adverse reactions. Patient outcomes tracking also enables the facility to observe trends in regimen selection and treatment outcomes (i.e., efficacy, discontinuations, and adverse drug reactions). This capability allows the facility to adjust the treatment guidance in accordance with real-world treatment outcomes.
Few studies exist in the literature that evaluate pharmacists’ contributions to CHC management to optimize the utilization of HCV therapies in order to improve cure rates and lower drug expenditures.20-24 Thus, the objective of this study was to assess the overall associated cost of pharmacy-guided HCV DAA utilization management at a VA medical center and report economic, clinical, and safety parameters.
Methods
This study was a retrospective cohort study conducted at a VA medical center and approved by the center’s institutional review board. Patients with an HCV DAA prior authorization drug request and therapy initiated between October 1, 2014, and September 30, 2015, were evaluated for inclusion in the study. Patients were excluded if they completed therapy and did not have a documented HCV RNA at least 12 weeks after end of treatment (SVR12) or were not followed at this VA medical center while receiving HCV DAAs. All data were collected through a review of patient electronic health records and a HCV DAA outcomes tracking database.
The following demographics were collected at baseline: age, sex, race/ethnicity, HCV genotype, prior HCV treatment history, history of cirrhosis, human immunodeficiency virus (HIV) coinfection, and hepatitis B virus (HBV) coinfection. The primary endpoint was the overall cost ratio of drug spend to cure rate calculated as the total dollars spent for all patients receiving HCV DAA treatment divided by the number of patients achieving SVR at least 12 weeks from end of treatment. Secondary endpoints included the overall cure rate, defined as the number of patients achieving SVR at least 12 weeks after end of treatment, divided by the total number of patients included in the study. Other secondary endpoints included the cost ratio of drug spend to cure rate and the cure rate among subgroups, the number of patients discontinuing therapy because of treatment failures or adverse effects, and patient adherence. Medication pricing data were determined using the national VA drug acquisition cost. Patient adherence was measured using medication possession ratio (MPR), calculated as the sum of the days medication was supplied divided by the period of days in the refill interval. Patients were considered adherent if the MPR ratio was ≥ 0.95.23 Descriptive statistics were used to report baseline patient demographics and study outcomes.
Results
A total of 440 patients with an HCV DAA prior authorization drug request placed were reviewed for inclusion in this study; 68 patients were excluded. Reasons for exclusion were death before SVR12 could be obtained, no HCV RNA at least 12 weeks after end of therapy, or therapy initiated at an outside facility. A total of 372 patients were included in the study. The average age of patients was 62 years, and the majority were African-American male patients with no coinfection with HIV or HBV (Table 1). The most common HCV genotype was 1, with the majority in subgroup 1a. Approximately half of the patients had cirrhosis, and most patients were treatment naive.
TABLE 1.
Baseline Characteristics
| N = 372 | |
|---|---|
| Average age, years (SD) | 62.2 (+5.5) |
| Male, n (%) | 358 (96.2) |
| Race, n (%) | |
| African American | 250 (67.2) |
| Caucasian | 118 (31.7) |
| Other | 4 (1.1) |
| HCV genotype, n (%) | |
| 1 | 346 (93.0) |
| 1a | 219 (58.9) |
| 1b | 125 (33.6) |
| 1 (no subtype) | 2 (0.5) |
| 2 | 20 (5.4) |
| 3 | 8 (2.2) |
| 4 | 1 (0.3) |
| Posthepatic transplant, n (%) | 6 (1.6) |
| Cirrhosis, n (%) | 178 (47.9) |
| Prior treatment, n (%) | 81 (21.8) |
| HIV infection, n (%) | 16 (4.3) |
| HBV infection, n (%) | 8 (2.2) |
HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; SD = standard deviation.
The primary outcome of the overall cost ratio of total drug spend to cure rate was $40,135.22. The study had an overall cure rate of 94.1% (350/372), including patients who discontinued treatment. The majority of patients were on ledipasvir/sofosbuvir ± ribavirin or ombitasvir/paritaprevir/ritonavir with dasabuvir ± ribavirin, with cure rates of 97.5% (155/159) and 94.8% (145/153), respectively. Other regimens included daclatasvir + sofosbuvir ± ribavirin, sofosbuvir + simeprevir ± ribavirin, and sofosbuvir + ribavirin ± pegylated interferon, with cure rates of 100% (3/3), 91.4% (32/35), and 68.2% (15/22), respectively. For patients who completed therapy, the cure rate was 97.5% (348/357). Patients with genotype 1 had higher cure rates and lower drug spend to cure rate ratios compared with patients with genotypes 2 and 3 (Table 2). Patients with genotype 3 had the lowest cure rate and highest drug spend to cure rate ratio. Additionally, the cure rates and drug spend to cure rates for cirrhotic patients and treatment-experienced patients were similar to noncirrhotic and treatment-naive patients.
TABLE 2.
Cure Rates and Drug Spend to Cure Rates by Subgroups
| Subgroups | Duration of Treatment Range | Cure Rate n (%) | Drug Spend/Cure Rate ($) | Cost Rangea ($) |
|---|---|---|---|---|
| Genotype | ||||
| 1 | 8-24 weeks | 331/346 (95.7) | 39,018.88 | 25,126 - 82,572 |
| 1a | 207/219 (94.5) | 37,610.04 | 25,126 - 82,572 | |
| 1b | 122/125 (97.6) | 41,126.72 | 25,126 - 82,572 | |
| 1 (no subtype) | 2/2 (100.0) | 56,254.32 | 25,126 - 82,572 | |
| 2 | 12-16 weeks | 18/20 (90.0) | 45,688.50 | 45,297 - 60,396 |
| 3 | 12-24 weeks | 3/8 (37.5) | 135,808.58 | 46,291 - 164,255 |
| 4 | 8-24 weeks | 1/1 (100.0) | 37,502.88 | 25,126 - 82,572 |
| Severity | ||||
| Cirrhosis | 12-24 weeks | 163/178 (91.6) | 41,907.35 | 25,126 - 82,572 |
| No cirrhosis | 8-12 weeks | 187/194 (96.4) | 38,430.77 | 25,126 - 45,297 |
| Treatment history | ||||
| Experienced | 8-24 weeks | 76/81 (93.8) | 39,481.62 | 25,126 - 82,572 |
| Naive | 8-12 weeks | 274/291 (94.2) | 39,178.74 | 25,126 - 45,297 |
aCost range defined by Veterans Affairs acquisition costs for full course of treatment per patient for all possible regimens recommended by local guidelines.
No patients discontinued therapy because of treatment failure. However, 10 patients discontinued therapy because of experiencing adverse effects such as anemia, nausea, vomiting, and anxiety. An additional 4 patients discontinued therapy because of nonadherence. The total calculated MPR for all patients was 98.7% (± 0.13), excluding patients who discontinued therapy because of an adverse effect, and 98.9% (358/362) of patients were considered to be adherent to their HCV treatment regimens.
Discussion
The purpose of the pharmacist-led utilization management strategies used by the VA medical center in this study was to appropriately treat and manage as many veterans as possible while balancing the costs of different regimens and the amount of funds allocated. The roles pharmacists have in CHC management vary across institutions depending on the relationships created with providers and other health care professionals. Pharmacists may be involved with ensuring that patients have access to CHC medications through insurance or assistance programs, evaluating appropriateness of provider prescribing, assessing patients for treatment eligibility, counseling patients on the HCV DAAs, ordering appropriate laboratory monitoring, and evaluating for drug interactions.22,25
At the time of this study, the national VA cost per treatment regimen ranged from $25,126 to $164,225, which varied widely depending on the selected HCV DAA and duration of treatment. The overall ratio of drug spend to cure rate of $40,135.22 for our patients indicates that the medical center was able to treat and cure patients with regimens at the lower end of the cost range. The use of lower-cost regimens allowed the medical center to treat more veterans with the available funds. When looking at the subgroups, the drug spend to cure rate ratio remained at the low end of the range despite previous treatment history, presence of cirrhosis, or genotype, with the exception of genotype 3. Historically, genotype 3 has been the harder to treat genotype with few therapeutic options. Sofosbuvir was the only available HCV DAA to treat genotype 3 for the majority of the study period. Daclatasvir offers higher rates of SVR but was not commercially available until the last month of the study.
The overall rate of SVR12 in this study was 94%, which is a conservative estimate, since it includes patients who discontinued therapy and represents patients in real-world clinical practice. Comparatively, the rate of SVR12 among patients who completed therapy was 97.5%. Cure rates for individual regimens were found to be comparable to clinical studies.26-30 Cost to cure rate ratio reported in the literature for first-generation HCV DAAs ranged from $74,380 to $189,900.26,27 A modeling study of ledipasvir/sofosbuvir for genotype 1 projected that with a cure rate of 85%-100%, cost per SVR would be anywhere from $85,813 to $124,557, based on previous treatment status and presence of cirrhosis.28 A real-world clinical study of ledipasvir/sofosbuvir in genotype 1 patients reported SVR rates of 94%-98%. The cost per SVR ranged from $81,368 in patients without cirrhosis to $101,380 in patients with compensated cirrhosis, and the average cost per SVR was $84,770.29 Another study investigated ombitasvir/paritaprevir/ritonavir with dasabuvir in genotype 1 and 4 CHC patients. The overall SVR rate ranged from 95% to 100%, and the most common side effects reported were fatigue, pruritus, headache, insomnia, nausea, and anemia, which were similar to our study.30 While these studies do not specify pharmacist involvement, and regimen cost to cure rate ratios do not provide a direct comparison of pricing with our study, they do provide a gauge for estimated comparisons.
The high MPR is in part attributed to the tracking of patient refill history for HCV regimens. Patients are required to request refills through the facility’s outpatient pharmacy and pick the prescription up in person. Additionally, the MPR strictly relies on recorded refill dates in the computer system and is not able to evaluate whether patients physically take the medication.
Limitations
This study has several limitations that primarily stem from its retrospective design and absence of a control group. With no control group, it is not possible to determine whether the pharmacist-led utilization management strategies had a direct effect on cost or cure rate. In addition, the acquisition cost of medications for the VA likely differs from other health care systems, which would affect the external application of the cost analysis to other institutions. Acquisition costs for non-VA facilities are higher; therefore, direct cost analysis comparison with the study is not possible. Despite these limitations, the study and utilization approaches are relevant to real-world clinical practice and management of CHC patients.
Conclusions
Pharmacist-led hepatitis C DAA utilization management strategies at a VA medical center are an important factor in costs and cure rates for different patient subgroups and therapies. These utilization management strategies are valuable to help pharmacists adequately manage patients with CHC and resulted in a low ratio of drug spend to cure rate. These strategies may allow practitioners to maximize available funding for CHC, while maintaining high efficacy and safety when using secondgeneration HCV DAAs.
REFERENCES
- 1.Centers for Disease Control and Prevention.. Hepatitis C FAQs for health professionals. May 23, 2016. Available at: https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#. Accessed January 24, 2017.
- 2.Kohil A, Shaffer A, Sherman A, Kottilil S.. Treatment of hepatitis C: a systematic review. JAMA. 2014;312(6):631-40. [DOI] [PubMed] [Google Scholar]
- 3.American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (ISDA) HCV Guidance Panel.. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932-54. [DOI] [PubMed] [Google Scholar]
- 4.Strader DB, Seeff LB.. A brief history of the treatment of viral hepatitis C. Clin Liver Dis. 2013;1(1):6-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Muir A. The rapid evolution of treatment strategies for hepatitis C. Am J Gastroenterol. 2014;109:628-35. [DOI] [PubMed] [Google Scholar]
- 6.Sovaldi (sofosbuvir) tablet, film coated. Gilead Sciences. August 2015. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80beab2c-396e-4a37-a4dc-40fdb62859cf. Accessed January 24, 2017.
- 7.Olysio (simeprivir) capsules, for oral use. Janssen Therapeutics. May 2016. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1816fd68-0ed7-4a37-84bb-e298c5ab6e28. Accessed January 24, 2017.
- 8.Harvoni (ledipasvir/sofosbuvir) tablets, for oral use. Gilead Sciences. May 2016. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4ec77e4-bae8-4db0-b3d5-bde09c5fa075. Accessed January 24, 2017.
- 9.Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), copackaged for oral use. AbbVie. April 2016. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab74e474-9fd6-902c-9bd9-16dc9541edd0. Accessed January 24, 2017.
- 10.Daklinza (daclatasvir) tablets, for oral use. Bristol-Myers Squibb. April 2016. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9803a6ff-8a3e-4c64-b3d0-7825c7123bf2. Accessed January 24, 2017.
- 11.Technivie (ombitasvir, paritaprevir and ritonavir) tablets, for oral use. AbbVie. February 2016. Available at: https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85130606-e6a4-cf08-4bac-a460a30b0984. Accessed January 24, 2017.
- 12.Epclusa (sofosbuvir and velpatasvir) tablets, for oral use. Gilead Sciences. June 2016. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f30631a-ee3b-4cfe-866b-964df3f0a44f. Accessed January 24, 2017.
- 13.Najafzadeh M, Andersson K, Shrank WH, et al.. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med. 2015;162(6):407-19. [DOI] [PubMed] [Google Scholar]
- 14.Davis KL, Mitra D, Medjedovic J, Beam C, Rustgi V.. Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol. 2011;45(2):e17-24. [DOI] [PubMed] [Google Scholar]
- 15.Razivi H, Elkhoury AC, Elbasha E, et al.. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164-70. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Chhatwal J, Kanwal F, Roberts MS, Dunn MA.. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015;162(6):397-406. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Chan K, Lai MN, Groessl EJ, et al.. Cost-effectiveness analysis of direct-acting antiviral therapy for treatment-naïve patients with chronic hepatitis C genotype 1 infection in the Veterans Health Administration. Clin Gastroenterol Hepatol. 2013;11(11):1503-10. [DOI] [PubMed] [Google Scholar]
- 18.U.S. Department of Veterans Affairs.. State of care for veterans with hepatitis C 2014. September 2014. Available at: http://www.hepatitis.va.gov/pdf/HCV-State-of-Care-2014.pdf. Accessed January 24, 2017.
- 19.Beste LA, Ioannou GN.. Prevalence and treatment of chronic hepatitis C virus in the US Department of Veterans Affairs. Epidemiol Rev. 2015;37:131-43. [DOI] [PubMed] [Google Scholar]
- 20.Kolor B. Patient education and treatment strategies implemented at a pharmacist-managed hepatitis C virus clinic. Pharmacotherapy. 2005;25(9):1230-41. [DOI] [PubMed] [Google Scholar]
- 21.Smith JP, Dong MH, Kaunitz JD.. Evaluation of a pharmacist-managed hepatitis C care clinic. Am J Health Syst Pharm. 2007;64(6):632-36. [DOI] [PubMed] [Google Scholar]
- 22.Sebhatu P, Martin MT.. Genotype 1 hepatitis C virus and the pharmacist’s role in treatment. Am J Health Syst Pharm. 2016;73(11):764-74. [DOI] [PubMed] [Google Scholar]
- 23.Belperio PS, Backus Ll, Ross D, Neuhauser MM, Mole LA.. A population approach to disease management: hepatitis C direct-acting antiviral use in a large health care system. J Manag Care Spec Pharm. 2014;20(6):533-40. Available at: http://www.jmcp.org/doi/10.18553/jmcp.2014.20.6.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Marino EL, Alvarez-Rubio L, Miro S, et al.. Pharmacist intervention in treatment of patients with genotype 1 chronic hepatitis C. J Manag Care Pharm. 2009;15(2):147-50. Available at: http://www.jmcp.org/doi/abs/10.18553/jmcp.2009.15.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Spooner LM. The expanding role of the pharmacist in the management of hepatitis C infection. J Manag Care Pharm. 2011;17(9):709-12. Available at: http://www.jmcp.org/doi/abs/10.18553/jmcp.2011.17.9.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Thorlund K, Druyts E, El Khoury AC, Mills EJ.. Budget impact analysis of boceprevir and telaprevir for the treatment of hepatitis C genotype 1 infection. Clinicoecon Outcomes Res. 2012;4:349-59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Barclay S, Cooke G, Holtham E, et al.. A new paradigm evaluating cost per cure of HCV infection in the UK. Hepatol Med Policy. 2016;1:2. Available at: https://hmap.biomedcentral.com/articles/10.1186/s41124-016-0002-z. Accessed January 24, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Younossi Z, Park H, Saab S, Ahmed A, Dieterich D, Gordon SC.. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2015;41(6):544-63. [DOI] [PubMed] [Google Scholar]
- 29.Younossi Z, Park H, Gordon S, et al.. Real-world outcomes of ledipasvir/sofosbuvir in treatment-naïve patients with hepatitis C. Am J Manag Care. 2016;22(6 Spec No.):Sp205-11. [PubMed] [Google Scholar]
- 30.Hinrichsen H, Wedemeyer H, Christensen S, et al.. Real-world safety and effectiveness of ombitasvir/paritaprevir/r ± dasabuvir ± ribavirin in the German Hepatitis C Registry. Poster presented at: 51st Annual Meeting of the European Association for the Study of the Liver; April 13-17, 2016; Barcelona, Spain [oral presentation #GS07]. Available at: http://www.natap.org/2016/EASL/EASL_19.htm. Accessed January 24, 2017.