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Guidance for Clinical Trials for Children and Adolescents With Chronic Hepatitis C

Wirth, Stefan*; Kelly, Deirdre; Sokal, Etienne; Socha, Piotr§; Mieli-Vergani, Giorgina||; Dhawan, Anil||; Lacaille, Florence; Raymond, Agnès Saint#; Olivier, Sophie#; Taminiau, Jan#

Journal of Pediatric Gastroenterology & Nutrition: February 2011 - Volume 52 - Issue 2 - p 233–237
doi: 10.1097/MPG.0b013e3181f6f09c
Clinical Guideline

Most children with chronic hepatitis C are infected vertically, have a low natural seroconversion rate, and carry a lifetime risk of cirrhosis and cancer. Affected children are usually asymptomatic, and histological findings are mild with a low risk of progression, although 5% develop significant liver disease in childhood.

The use of combination treatment with pegylated interferon-α and ribavirin has changed the outcome and prognosis for this disease, with approximately 60% of children achieving sustained viral clearance. Combination therapy is not ideal for children because pegylated interferon is administered subcutaneously, impairs growth velocity, and both interferon and ribavirin have significant adverse effects that affect compliance. In addition, approximately 50% of children infected with genotype 1 do not respond to therapy. Thus, additional treatment options are required including improvement in dosing, reduction in the length of treatment, and evaluation of new drugs, such as protease inhibitors, which could be more effective for patients infected with genotype 1.

The primary goal of treatment is to eradicate the infection. The future clinical trial design should ensure that any new drugs demonstrate noninferiority to the present standard regimen in both children and adults. The measure for documenting substantial improvement above present therapy should be increased viral clearance rate or the same clearance rate, with a shorter duration of treatment and/or fewer adverse effects. We do not believe there is any need for a placebo arm because approved therapy is available and new treatments can be compared with present therapy.

Safety measures should include the standard recommended laboratory investigations, growth parameters, quality-of-life or psychological measures, and a requirement for long-term follow-up for up to 5 years.

*Clinic for Children and Adolescence, HELIOS Klinikum Wuppertal, Witten-Herdecke-University, Germany

The Liver Unit, Birmingham Children's Hospital NHS Trust, Birmingham, UK

Service de Hépatologie Pédiatrique, Cliniques Universitaires St Luc

§Department of Gastroenterology, Hepatology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland

||King's College London School at King's College Hospital, London, UK

Hôpital Necker-Enfants Malades Service de Gastroentérologie Pédiatrique, Paris, France

#European Medicines Agency, London, UK.

Received 22 May, 2010

Accepted 20 July, 2010

Address correspondence and reprint requests to Prof Dr Stefan Wirth, Clinic for Children and Adolescence, HELIOS Klinikum Wuppertal, Witten-Herdecke-University, Heusnerstr. 40, D-42283 Wuppertal, Germany (e-mail: stefan.wirth@helios-kliniken.de).

The authors report no conflicts of interest.

The views expressed in this article are the personal views of the authors and should not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties.

This Guidance is the result of a consensus meeting of a working group in November 2009 consisting of members and experts of the ESPGHAN Hepatology Committee and the EMA: Stefan Wirth, Deirdre Kelly, Etienne Sokal, Piotr Socha, Giorgina Mieli-Vergani, Anil Dhawan, and Florence Lacaille for ESPGHAN; Agnès Saint Raymond, Sophie Olivier, and Jan Taminiau for EMA.

Copyright 2011 by ESPGHAN and NASPGHAN