Community Research and Development Information Service - CORDIS

FP6

VIRGIL Report Summary

Project ID: 503359
Funded under: FP6-LIFESCIHEALTH
Country: France

Final Report Summary - VIRGIL (European Vigilance Network for the Management of Antiviral Drug Resistance)

Antiviral drug resistance is commonly determined by relying on single specialised laboratories and high standard research groups that are often only capable of addressing one particular aspect. The main objective was to integrate clinical, technological and research networks and platforms that interact in a coherent and synergistic manner, as each provides a broad panel of specific tools for the others. The network crystallised biomedical researchers on common objectives targeting viral drug resistance that define specific activities and platforms.

The overall objective of VIRGIL Surveillance was to generate a platform enabling multicentre activities to form clinical surveillance studies in the field of virus hepatitis. Thus, the primary aim of the platform was to establish a central database system which then could be the basis for future studies on resistance in viral hepatitis.

The very first steps were to implement and to develop a specific VIRGIL Case Report Form to collect data on patients with viral hepatitis before and during antiviral treatment and to screen for resistant variants possibly being associated with different outcomes of the infection. Overall the platform had more than 20 partners who actively participated in the project. Furthermore the aim was to perform specific individual research projects on specific questions related to resistance in viral hepatitis.

Overall the general objectives of the Surveillance platform were all successfully completed. Partners were able to generate a system with central database at the IT unit in Munich. They furthermore developed and evaluated a specific eCase Report Form (eCRF) system which was constantly improved after interim analyses of the performance of the eCRF. This was the first internationally accepted and standardised e-system to collect data on resistance in viral hepatitis. We are now able to collect data in all different countries with an established data safety concept and the project was also approved by the local ethics committees. The initial purpose of establishing a database and the evaluation of the eCRF system was performed during the first two years of VIRGIL. Thereafter, partners were able to enter far more than 1 000 patients in this database.

Since the main aim of the VIRGIL network was to perform and to enable research in the field of resistance, the main focus was on hepatitis B virus (HBV) infection, as for this infection, drugs were available which were already in use in clinical practice and were associated with development of resistance.

However, the eCRF system can also be used in future for hepatitis C. For the hepatitis C virus (HCV), new direct antiviral compounds causing resistance are planned to be licensed from the year 2011. The established system can easily also adapted for HCV infection and could be used in future for similar studies. Thus, this first general objective of the platform was a big success, as for the very first time an easy-to-apply and also flexible eCRF system for viral hepatitis was successfully established.

In terms of specific individual projects, partners were able to collect for the first time so-called real-life cohorts of hepatitis B patients being treated with the antiviral compounds tenofovir and entecavir. These activities were coordinated by the Berlin group and the Rotterdam group, respectively. Both projects were of major importance for the field as patients were treated outside clinical trials and did not represent only highly selected patients, thereby fulfilling inclusion and exclusion criteria of phase-3 registration trials. Both entecavir and tenofovir proved to be safe and effective also outside clinical protocols. However, some limitations of both compounds were also detected. Both projects were highly recognised at national and international liver meetings and have just recently been submitted for publication. Publications of these important results were expected within the following few months.

The key objective for this platform was to estimate the societal impact of antiviral drug resistance in terms of mortality, morbidity and costs. A mathematical model was established that incorporated the age-specific prevalence of viral hepatitis B in a country and the progression of disease in infected individuals not receiving specific antiviral therapy over a period of 20 years (the natural history). The mortality due to hepatitis B-related causes is very high (40 % in 20 years) in those with the active, potentially progressive disease. If this cohort is fully detected and treated, mortality related to liver causes can be reduced by 90 % if an anti-HBV drug with a very low incidence of resistance is chosen from the start. The first licensed anti-HBV drug, that still had a major market share due to its low side-effect profile and relatively low price was associated with a high incidence of resistance, and was estimated to only reduce the mortality by 50%.

The impact of antiviral resistance can be large in hepatitis B since antiviral resistance can negate about 50 % of the efficacy of a major first-line anti-HBV drug. However, if second- or third-generation anti-HBV drugs with low or very low incidence of antiviral resistance are available and reimbursed in a country, antiviral resistance is then no longer a public health problem, according to mathematical modelling. The model for assessing the burden of disease in hepatitis B was developed for the Netherlands, but can be applied to all countries in the EU. Currently the model is now applied to Germany and Turkey. The situation was less clear for the impact of antiviral resistance for influenza and anti-influenza drugs, since adequate clinical data had only recently become available.

Another major objective was to develop a doctor online consultation (VirDoc) for patients with antiviral resistance. Such an e-consultation service aimed to help physicians in caring for chronic hepatitis B patients with antiviral resistance. Following evaluation, physicians indicated that VirDoc was difficult to use because physicians had to fill in time-consuming data forms and use sophisticated login and security procedures designed to protect patient privacy. To overcome these barriers, a simple form was developed which uses a rapid data entry method and anonymous patient data, thereby avoiding complex log-in procedures. A small network of consultants, that consisted of renowned hepatology experts, was maintained for several years. However, the use of this working system of online consultation was low. E-consultation is potentially effective, but Internet-consultation was not in the workflow of physicians at the time. It was estimated that A major marketing effort would be required to change the behaviour of physicians in this respect.

Evaluation of the societal impact of VIRGIL activities was a third objective. Various Internet-based knowledge tools for both influenza and hepatitis field were developed. The tools were BiBo (the online library), NarCo (the online contact persons' database), and K parK (a dedicated search engine). All tools were launched in 2006 and were maintained through 2007 and 2008.

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Contact

Fabien ZOULIM, (Group Leader)
Tel.: +33-472681974
Fax: +33-472681971
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