title: Guidance for clinical trials for children and adolescents with chronic hepatitis C.
abstract: 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.
authors.affiliation: Clinic for Children and Adolescence, HELIOS Klinikum Wuppertal, Witten-Herdecke-University, Germany. stefan.wirth@helios-kliniken.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirth
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
authors.forename: Florence
authors.initials: F
authors.lastname: Lacaille
authors.forename: Agnès
authors.initials: A
authors.lastname: Saint Raymond
authors.forename: Sophie
authors.initials: S
authors.lastname: Olivier
authors.forename: Jan
authors.initials: J
authors.lastname: Taminiau
mesh_terms: D000293:Adolescent; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D017410:Practice Guidelines as Topic; D012107:Research Design / Q000592:standards*