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Background: According to the International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) guidelines for paediatric clinical trials, bridging procedures can be used if disease progression, exposure-response relationships, and clinical endpoints are similar in adults and children. In these circumstances, confirmatory efficacy trials are not necessary; the evaluation of pharmacokinetics and safety ought to be sufficient for drug approval., Purpose: The aim of this study was to assess whether the clinical trials and strategy for market approval authorisation (MAAs) in paediatric indications reflect the guidelines for bridging of adult data., Methods: A total of 95 European Public Assessment Reports (EPARs) published between 1995 and 2007 were reviewed. From every report, data extraction was performed according to the phase of development, scope of analysis, number of dose levels, dosage form, and demographics of the subjects enrolled in the trial. Data analysis consisted of an initial grouping of the studies by the degree of compliance to bridging guidelines., Results: Our analysis reveals that only 66% of the trials (n = 174) can be classified as needed, while 22% of the trials (n = 59) could have been designed and performed differently from the approved protocol (partially required). Moreover, 12% (n = 30) of the studies were deemed completely unnecessary., Limitations: A potential limitation in our study was that the dates of start and completion of the clinical studies were not available. Therefore, some EPARs have been included that may reflect common practice in the period that precedes the introduction of the ICH E11 guidelines. Yet, this should not obscure the points identified with regard to the lack of compliance to guidelines before the introduction of the paediatric legislation and the requirements for a paediatric investigation plan., Conclusions: Paediatric trials are desirable and necessary to address important unmet medical needs. However, the types of studies supporting regulatory approval do not always reflect the recommendations available in paediatric guidelines, which allow for extrapolation and bridging approaches. This situation may be explained by the lack of awareness about the prerequisites for the use of bridging concepts and of a clear process for evaluating different strategies in paediatric development.

The aim of this study is to describe the authors' experience with intra-arterial ACNU chemotherapy of malignant gliomas. The prognosis of cerebral malignant gliomas remains poor, whatever traditional therapy is applied. ACNU is a well tolerated nitrosourea with a strong antimitotic effect on neurogenic cells both in vitro and in vivo; this drug has enhanced efficacy when used at high concentrations, particularly as an intraarterial infusion. Seventy-six patients have been studied to date, 68 of whom are evaluable; these patients were treated by intra-arterial infusion of ACNU (100 mg/m2) every 6 weeks, with a mean of 2.5 courses per patient. The objective response (OR) was 28% and analysis of pretreatment factors revealed that survival was influenced by histological grade, other types of therapy applied, and age. In general IAC is well tolerated and the response and survival appear to be better than with systemic chemotherapy.