Pharmacist-led pre-treatment assessment, management and outcomes in a Hepatitis C treatment patient cohort.

Background Medication reconciliation and drug-drug interaction management represent important patient safety processes completed by pharmacists as part of Hepatitis C patient care. Objectives To describe the pharmacist-led interventions of medication reconciliation and drug-drug interaction assessment, grading and management in a real-world Hepatitis C treatment cohort and to assesses the impact on patient outcomes. Setting Two Hepatitis C hospital outpatient clinics at St. James's Hospital, Dublin. Method Patients treated with Hepatitis C direct acting anti-viral agents between December 2014 and February 2017 were included in this retrospective cohort study. The study employed a standardised medication reconciliation proforma and drug-drug interaction reference list. Main outcome measures Analyse medication variances identified during pharmacist-led medication reconciliation. Assess the prevalence, type and severity of drug-drug interactions between direct acting anti-virals and co-medications. Assess the rate of prescriber acceptance of the pharmacist-developed drug-drug interaction management strategies. Results Among the 300 patients in this study, medication reconciliation identified 1543 co-medications, with 71% of patients prescribed co-medications which were subject to a potential drug-drug interaction. Drug-drug interaction assessments assigned a rating of severe to 68 interaction episodes. At least one co-medication was stopped during treatment in 25% of patients to facilitate drug-drug interaction management. Pharmacist proposed management recommendations were accepted by prescribers in 96.9% of cases. The sustained virological response rate among the cohort was 92.7%. Conclusions In this Hepatitis C pre-treatment pharmacist assessment analysis, a significant number of medication reconciliation variances and clinically significant drug-drug interactions were identified which present unique and important patient safety risks. Pharmacist-led management strategies aided the achievement of optimum treatment response while promoting patient safety and antiviral stewardship.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Effectiveness of triple therapy with direct-acting antivirals for hepatitis C genotype 1 infection: application of propensity score matching in a national HCV treatment registry.

BACKGROUND: Observational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection. A sustained virological response (SVR) 24 weeks following completion of therapy with interferon-containing regimens is considered a cure. Non-randomisation in these studies can result in confounding or selection bias. Propensity score (PS) matching is one of a number of statistical tools that can be used to mitigate the effects of confounding in observational studies. METHODS: We analysed the data of 309 patients who underwent triple therapy treatment with telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate treatment and the selection of the treatment regimen was at the discretion of the physician. To adjust for confounding, three approaches to propensity score matching were assessed Adjusted sustained-virological response rates (SVR), odds ratios, p-values and 95% confidence intervals were calculated from the three PS matched dataset. RESULTS: Prior to matching, the unadjusted sustained virological response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215) and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After matching, adjusted SVR24 rates were between 73-74% and 60-61% for telaprevir/PR and boceprevir/PR, respectively. CONCLUSION: Efficacy rates were comparable with those reported in pivotal clinical trials and real world studies. After adjusting for confounding, we conclude that there was no difference in treatment effect after PS matching. The small sample size limits the conclusions that can be made about the effect of PS matching. Propensity score adjustment remains a tool that can be applied to future analysis, however, we suggest, where possible, using a larger sample size in order to reduce the uncertainty around the outcomes.

Telementoring with project ECHO: a pilot study in Europe.

The Extension of Community Healthcare Outcomes (ECHO) project is a novel educational intervention designed in New Mexico to transfer subspecialty knowledge about hepatitis C virus (HCV) to primary care providers, thereby increasing patient access to HCV care. The ECHO model has been shown to deliver educational benefits and to result in good treatment outcomes for HCV-infected individuals in the USA; however, this approach has not been assessed in a European setting. We sought to evaluate the feasibility, acceptability and implementation of the ECHO model in Ireland using a pilot study. We present a descriptive review of recruitment, participation, retention and cost of the intervention as well as a qualitative review of the views of participants on the barriers, benefits and acceptability of the ECHO model. In the original Project ECHO in New Mexico, geographical distance posed the greatest barrier to accessing HCV care. In Ireland, people who inject drugs (PWID) were identified by interviewees as the main group facing barriers to accessing specialist HCV care. State-employed doctors and nurses caring for large numbers of HCV-infected PWID in opiate substitution treatment centres and homeless hostels were successfully recruited to participate in the project. Self-employed general practitioners did not participate, due mainly to a lack of time and the absence of reimbursement for participation. Practitioners who participated in the pilot reported benefits to themselves and their patients and would like to continue to participate in similar multidisciplinary, multisite educational interventions in the future.

Do disparities between populations in randomized controlled trials and the real world lead to differences in outcomes?

AIM: To conduct a systematic review investigating reasons for the disparity between the efficacy and effectiveness rates reported in randomized controlled trials (RCTs) and observational studies of direct-acting antiviral treatment regimens licensed for use in genotype1 hepatitis C virus-infected individuals. METHODS: This systematic review was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. RESULTS: Statistically significant (p < 0.05) differences in the baseline demographics and sustained virological response rates were observed between RCT and observational studies. CONCLUSION: In order for outcomes from RCTs to be generalizable to the real world, greater consideration needs to be taken to include patient populations that are more representative of those awaiting treatment in the clinical setting.

Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

BACKGROUND: Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs. METHODS: The staff utilisation costs associated with a Hepatitis C ambulatory visit were measured and combined with the costs of investigations to establish a mean cost per consultation. An annualised estimate of cost was produced by multiplying this by the number of consultations accessed, stratified by degree of liver impairment. Inpatient costs were established by identifying the number of inpatient episodes and multiplying by Irish diagnosis related group costs. Non-parametric bootstrapping was performed to derive mean and 95%CI values. RESULTS: Two hundred and twenty-five patients were identified. The cost of an outpatient medical review was €136 (€3.60 SD). The cost of a Hepatitis C nursing review was €128 (€7.30 SD). The annual mean costs of care were as follows (95%CI): Mild €398 (€336, €482), Moderate €417(€335, €503), Compensated cirrhosis €1790 (€990, €3164), Decompensated cirrhosis €8302 (€3945, €14,637), Transplantation Year 1 €137,176 (€136,024, €138,306), Transplantation after Year 1 €5337 (€4942, €5799), Hepatocellular carcinoma €21,992 (€15,222, €29,467), Sustained virological response €44 (€16, €73). CONCLUSIONS: The direct medical cost associated with Hepatitis C care in Ireland is substantial and increases exponentially with progression of liver disease. The follow-up costs of patients with a sustained virological response in this cohort were low in comparison to patients with chronic infection.