Masterarbeit

Real-life experiences with approval of pediatric clinical trials in Germany

Dr. Melanie Mühlfelder (2019)

Summary
Language: English
For decades, there was a lack of age-appropriate and safe medicines specifically approved for children for many diseases, as only few medicines had been developed and approved for this specific patient population. With the implementation of the EU Pediatric Regulation EC No 1901/2006 in 2007, the situation has continuously improved, as pharmaceutical companies have since been obliged to evaluate each of their development products for safe and effective use in children. In order to assess the efficacy and safety of a medicinal product, clinical studies in children are required in addition to studies in adults. Since children are a very vulnerable patient population, especially if they suffer from a serious or life-threatening disease, the preparation, approval and conduct of pediatric clinical trials represents a major challenge for all stakeholders involved. The health authorities and Ethics Committees, which have to review and approve clinical trial applications, have a special responsibility in this regard. With the implementation of the new EU Clinical Trial Regulation (EU) No 536/2014 in the next few years the timelines for the CTA approval process will change intensely and the sponsor will soon have only 12 days to answer on any content-related deficiencies of a CTA. In this context, this master thesis examined whether there are frequent and pediatric-specific aspects that the German health authorities and Ethics Committees pay particular attention to during their CTA assessments for pediatric clinical trials. For this purpose, the content-related deficiency letters of 24 pediatric clinical trials sponsored by Novartis Pharma AG were evaluated and analyzed. It has been shown that both institutions repeatedly expressed frequent deficiencies which the sponsor can avoid in the preparation of future pediatric studies. In particular, both institutions repeatedly raised concerns about aspects such as pregnancy testing and contraception, burdens and risk thresholds, blood collection or safe dosing of the IMP in the different pediatric age groups. In addition, it has been observed that the Ethics Committees, when reviewing patient information leaflets and ICFs, consider that parents and children are fully informed about the risks and benefits of the clinical trial in an understandable and child-friendly language. The evaluation and analysis of the deficiency letters also reveal that the health authorities and Ethics Committees pay attention to different aspects such as placebo use, the use of pediatric formulations or the individual benefit for the child participating in the trial. In summary, it can be concluded that there were frequent pediatric-specific concerns raised by the regulators and that these deficiencies aimed the safety and well-being of the children. These objections were independent of the clinical development phase of the medicinal product, the pediatric age group, the underlying disease the children suffer from and the regulatory framework under which the CTAs were assessed.
Pages: 48, Annexes: pages: 6