BackgroundThe goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used efficacy endpoint in clinical studies of hepatitis C, and represents the eradication of HCV from the body. The aim of the current review was to examine the long-term clinical, economic and quality of life benefits associated with achieving SVR.MethodsA systematic literature review was performed using the PubMed, EMBASE and Cochrane library databases to identify articles examining the clinical, economic and quality of life benefits associated with SVR, published in English language from 2002–2013. For inclusion studies were required to enroll ≥100 patients and to report clinical endpoints including hepatocellular carcinoma, overall- or liver-related mortality, or progression of disease/complications (e.g. portal hypertension, esophageal varices). Review of economic studies on cost/cost-effectiveness of achieving SVR were focused on studies assessing boceprevir/telaprevir plus pegIFN and ribavirin as this represents the current standard of care in several jurisdictions worldwide. Quality of life evidence was required to use validated quality of life instruments and provide a quantitative analysis of the impact of SVR versus no treatment or treatment failure.ResultsSVR is durable with late relapse rates over 4–5 year periods being in the range of 1–2%. Patients who achieve SVR frequently demonstrate some regression of fibrosis/cirrhosis and have a substantially reduced risk for hepatocellular carcinoma (relative risk [RR] 0.1–0.25), liver-related mortality (RR 0.03–0.2) and overall mortality (RR 0.1–0.3) in comparison with no treatment or treatment failure. In the 5 years post-treatment, medical costs for patients achieving SVR are 13-fold lower than patients not achieving SVR. Patients who achieve SVR also have health state utility values that are 0.05 to 0.31 higher than non-responders to treatment.ConclusionsSVR represents the fundamental goal of antiviral treatment for patients infected with chronic HCV, so as to reduce risk of liver disease progression. Achievement of SVR has implications beyond those of clearing viral infection; it is associated with improved long-term clinical outcomes, economic benefits and improved health-related quality of life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0748-8) contains supplementary material, which is available to authorized users.

:The National Institute for Health and Clinical Excellence (NICE) provides guidance to the National Health Service (NHS) in England and Wales on funding and use of new technologies. This study examined the impact of evidence, process and context factors on NICE decisions in [2004][2005][2006][2007][2008][2009]. A data set of NICE decisions pertaining to pharmaceutical technologies was created, including 32 variables extracted from published information. A three-category outcome variable was used, defined as the decision to 'recommend', 'restrict' or 'not recommend' a technology. With multinomial logistic regression, the relative contribution of explanatory variables on NICE decisions was assessed. A total of 65 technology appraisals (118 technologies) were analysed. Of the technologies, 27% were recommended, 58% were restricted and 14% were not recommended by NICE for NHS funding. The multinomial model showed significant associations (p < 0.10) between NICE outcome and four variables: (i) demonstration of statistical superiority of the primary endpoint in clinical trials by the appraised technology; (ii) the incremental cost-effectiveness ratio (ICER); (iii) the number of pharmaceuticals appraised within the same appraisal; and (iv) the appraisal year. Results confirm the value of a comprehensive and multivariate approach to understanding NICE decision making. New factors affecting NICE decision making were identified, including the effect of clinical superiority, and the effect of process and socio-economic factors.

Background: People with chronic infectious diseases such as hepatitis B can face stigma, which can influence everyday life as well as willingness to engage with medical professionals or disclose disease status. A systematic literature review was performed to characterize the level and type of stigma experienced by people infected with hepatitis B virus (HBV) as well as to identify instruments used to measure it. Methods: A literature review was performed using the PubMed, Embase and Cochrane Library databases to identify studies describing HBV-related stigma. For inclusion, articles were required to be published in full-text form, in English and report quantitative or qualitative data on HBV-related stigma that could be extracted. Results: A total of 23 (17 quantitative and 6 qualitative) articles examined HBV-related stigma. The scope of the review was global but nearly all identified studies were conducted in countries in the WHO Southeast Asia or Western Pacific regions or within immigrant communities in North America. Several quantitative studies utilized tools specifically designed to assess aspects of stigma. Qualitative studies were primarily conducted via patient interviews. Internalized and social stigma were common among people living with chronic HBV . Some people also perceived structural/institutional stigma, with up to 20% believing that they may be denied healthcare and up to 30% stating they may experience workplace discrimination due to HBV. Conclusion: HBV-related stigma is common, particularly in some countries in Southeast Asia and the Western Pacific region and among Asian immigrant communities, but is poorly characterized in non-Asian populations. Initiatives are needed to document and combat stigma (particularly in settings/jurisdictions where it is poorly described) as well as its clinical and socioeconomic consequences.

BackgroundFatigue is a common symptom of chronic hepatitis C virus (cHCV) infection and a common side effect of interferon-based treatment for cHCV. This study provides confirmatory evidence of the reliability and validity of the Fatigue Severity Scale (FSS) to document fatigue in cHCV research and identifies values that indicate clinically important differences in FSS to aid in interpreting fatigue in cHCV clinical trials.MethodsThe study used data from two double-blind, randomized, placebo-controlled, Phase IIb trials evaluating the efficacy and safety of simeprevir plus peginterferon-α/ribavirin in treatment-naïve (PILLAR, n = 386) and treatment-experienced patients (ASPIRE, n = 462) with cHCV infection. Patients completed the FSS and EuroQoL 5 dimension questionnaire (EQ-5D) at baseline and at regular intervals throughout both trials. Reliability was assessed using Cronbach’s coefficient α at Week 24 (internal consistency reliability) and intraclass correlation (ICC) between FSS at Weeks 12 and 24 in stable patients (<0.5 g/dL hemoglobin [Hb] change between Weeks 12/24). Correlation with the EQ-5D visual analog scale (VAS) and “Usual Activity” domain score was used to assess concurrent validity. Clinical validity was evaluated using a case-control method to link spontaneously reported fatigue and anemia adverse events (AEs) during the study to FSS scores.ResultsFSS total scores demonstrated good reliability (Cronbach’s α: 0.95, 0.96; ICC: 0.74, 0.86 for PILLAR and ASPIRE, respectively) and concurrent validity (correlation with EQ-5D VAS: -0.63, -0.66) with a monotonic relationship between the EQ-5D “Usual Activities” item response and FSS. Clinical validity was confirmed by a significant difference between cases and controls for fatigue AEs (p < 0.05); however, anemia defined by AE or Hb abnormalities was only weakly related to FSS score. Analyses indicate that a change of 0.33–0.82 in mean FSS scores represents a meaningful improvement in fatigue, and a one-point change is a conservative indicator of an important change in individual FSS scores.ConclusionA difference of ≥0.7 in mean FSS scores can be considered a clinically important difference within groups over time or between groups. A one-point change or less in individual FSS scores indicates a clinically relevant change in fatigue.

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.