Automated summaries of serious adverse events in the hepatitis C antiviral long-term treatment against cirrhosis trial.

BACKGROUND: Even though adverse event (AE) collection and official accounting are mandatory for clinical trials, there are limited detailed guidelines specifying how to summarize the event for reporting in a timely and expeditious manner. This article details the AE and serious adverse event (SAE) reporting summary developed for a large multi-center National Institutes of Health (NIH)-sponsored clinical trial. PURPOSE: To review and analyze the large volume of AE data reported by 10 sites (806 SAEs and 19,034 AEs from August 2000 to May 2007) the automated SAE summary was developed. It was designed to ensure timeliness and clarity in the complex process of AE review and reporting. METHODS: The AE and SAE case report forms (CRFs) as well as the automated SAE summary were developed within a database management system developed by the Data Coordinating Center (DCC) which allowed for web-based data entry at the DCC and 10 sites and offered immediate overall and site-specific reports accessible by the DCC, site, and NIH project staff. RESULTS: The automated SAE summary pulled data from multiple CRFs to create a succinct and informative summary and allowed for prompt and easy reporting to the regulatory agencies. The summary was adaptable to the needs of reviewers because of the availability of multiple search options.

Response to hepatitis A and B vaccine alone or in combination in patients with chronic hepatitis C virus and advanced fibrosis.

Patients with advanced fibrosis are at increased risk of severe outcomes if they develop acute infection with hepatitis A (HAV) or hepatitis B (HBV) viruses. There are no data on the efficacy of combined HAV/HBV vaccination in patients with advanced fibrosis. Our aim was to evaluate the response to the HAV and HBV vaccine alone or in combination for patients with chronic hepatitis C (HCV) and advanced fibrosis and to evaluate the impact of administering the vaccine while patients were receiving peginterferon for treatment of chronic HCV. In this prospective study of patients with advanced fibrosis (Ishak 3-6), those without serologic evidence of prior exposure were vaccinated with either Havrix HAV, Engerix( HBV, or the TWINRIX HAV/HBV combination vaccine as appropriate, and response was defined as the development of anti-HAV or anti-HBV surface antibodies. Of the 162 eligible patients, the prevalence of prior exposure to HAV and HBV was 30 and 18%, respectively. Of the 84 patients vaccinated, 38% received Havrix, 14% Engerix, and 48% TWINRIX. The response to the HAV vaccine was 75% in those receiving Havrix compared to 78% receiving TWINRIX. In contrast, the response to HBV vaccination was 42% in patients receiving Engerix compared to 60% in those vaccinated with TWINRIX (difference 18.3%; OR 0.29; 95% CI: 0.57-7.79). The presence of diabetes was the only risk factor identified for reduced HBV response (P = 0.01). Responses to both HAV and HBV vaccines when administered alone or in combination were lower than expected in patients with HCV and advanced fibrosis, especially in those with diabetes. The observation that the decline in HBV vaccine response was somewhat lower when this was administered alone as opposed to the combination A/B vaccine suggests that the administration of a combination vaccine may enhance the vaccination response to HBV.

The spectrum of chronic hepatitis C virus infection in the Virginia Correctional System: development of a strategy for the evaluation and treatment of inmates with HCV.

BACKGROUND AND OBJECTIVE: Chronic hepatitis C virus (HCV) is common in the inmate population of the United States. Long-standing HCV can progress to cirrhosis, which can contribute to significant morbidity and mortality. However, those inmates with histologically mild disease are unlikely to develop liver-related morbidity or mortality during their period of incarceration. Our objective was to develop an economic strategy for evaluation and treatment of inmates with chronic HCV. METHODS AND MEASURES: A retrospective cohort analysis of 302 inmates within the Virginia Department of Corrections (VDOC) who underwent liver biopsy for chronic HCV at the Virginia Commonwealth University Health System between 1998 and 2002 was performed. The data from this analysis was to utilized to develop a cost model for treatment of chronic HCV in this population based upon biochemical or histologic criteria. We used the perspective of the VDOC using actual costs paid to providers, hospitals, and pharmacies. The primary endpoint was cost-effectiveness of HCV treatment. RESULTS: Eighty percent of inmates with chronic HCV were genotype 1, 49% had a normal value for serum ALT at the time of evaluation, 30% had no fibrosis, and 24% had bridging fibrosis or cirrhosis. The cost to evaluate and treat 100 consecutive inmates with peginterferon and ribavirin regardless of serum ALT and liver histology was calculated to be $1,775,900 or $35,500 per sustained virologic response (SVR). Although the cost declined by 50% if only those patients with an elevated serum ALT were treated, 45% of those inmates with varying degrees of fibrosis, and 21% with cirrhosis would not have received therapy utilizing this scenario. In contrast, the cost of performing liver biopsy and treating only those patients with any degree of fibrosis was $1,367,043; a savings of slightly more than $400,000 per 100 patients evaluated. The overall cost of treatment was most influenced by the price of peginterferon and ribavirin, which declined as the histologic criteria utilized for treatment increased. CONCLUSIONS: A strategy in which inmates with chronic HCV are evaluated and a decision regarding treatment is based upon either biochemical or histologic criteria, which appears to balance both the health-care rights of the inmate and the impact of treating this disease on the financial and other resources of the correctional system.

Treatment of chronic hepatitis C virus in the virginia department of corrections: can compliance overcome racial differences to response?

OBJECTIVE: Chronic hepatitis C virus (HCV) is common in the correctional setting and there are few data on the use of interferon (IFN)/ribavirin(RVN) combination therapy in this population. Given the high proportion of African Americans (AA) in correctional facilities, which may be associated with reduced response rates, the correctional setting allows a unique opportunity to compare the response rates of AA to Caucasians (CA). The present study describes our experience of treating HCV in the inmate population of the Virginia Department of Corrections. METHODS: Of the 119 inmates evaluated between 1998 and 2000, a retrospective analysis of 59 consecutive inmates (mean age 41, 83% male, 55% CA, 73% genotype (GT)1, and 41% with advanced fibrosis) who underwent HCV therapy with IFN a-2b (3 MU TIW) and RVN (1,000-1,200 mg/d) under direct observation was performed. Patients were followed by telemedicine and the primary endpoint was sustained virologic response (SVR) defined as an undetectable HCV RNA at least 24 wk after completion of therapy. RESULTS: All but one patient completed at least 12 wk of therapy and no patient required dose reduction. By wk 24, 34 inmates (58%) responded (negative HCV RNA) which was higher in CA compared to AA (70%vs 40%; p= 0.037). Although overall SVR was higher in CA compared to AA (41%vs 28%; p= ns), we observed no difference in SVR when comparing only GT 1 CA to AA (33%vs 29%). CONCLUSIONS: HCV can be effectively treated in the correctional setting with response rates similar to, if not better than the published literature. In this controlled setting of direct observational therapy, we observed similar SVR in CA and AA.