病毒性肝炎研究进展f—培训课件.ppt

* Slide *. Intent-to-Treat Analysis Dropout is a common phenomenon in clinical trials of drug treatments involving longitudinal assessments for a fixed duration of follow-up. For these trials, intent-to-treat (ITT) analysis is usually preferred because time effects are seen in practice.1 The ITT analysis mandates that all subjects randomized to a treatment arm should be included in the analysis.1 It includes all randomly assigned patients enrolled in a clinical trial and uses a complete outcomes data set for each patient. Data from all patients are analyzed, and study results represent the complete analysis. Nonresponders are those who withdraw or drop out or who do not sustain a virological response. ? 1. Mazumdar S et al. J Psychiatr Res. 1999;33:87-95. * Slide *. Limitations of Conventional IFN Alfa Therapy Conventional IFN alfa administered as a subcutaneous (sc) injection is rapidly absorbed, with wide fluctuations in serum concentrations. The peak serum concentration of a single sc injection of 36 MIU of IFN alfa-2a (ROFERON?-A, Hoffmann-La Roche) ranges from 1250 to 2320 pg/mL (mean, 1730 pg/mL) within a mean time of 7.3 hours.1 The mean serum concentration following a single injection of 5 MIU/m2 of IFN alfa-2b (INTRON? A, Schering) ranges from 18 to 116 IU/mL within 3 to 12 hours after sc administration.2 As a result of such wide fluctuations in serum concentrations, conventional IFN alfa fails to provide constant antiviral coverage and can allow viral replication when its concentrations are not measurable. The widely fluctuating concentrations may also account for more peak-related side effects. Vast systemic distribution of conventional IFN alfa has been reported. For example, the volume of distribution at steady state (Vdss) for IFN alfa-2a ranges from 0.223 to 0.748 L/kg after a single intravenous dose (IFN alfa-2a 36 MIU), with a mean Vdss of 0.400 L/kg.1 Conventional IFN alfa undergoes rapid clearance (11.8 L/h for IFN alfa-2a),3 being metabolized