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With the Paediatric Regulation in action for ten years it is becoming apparent that drug studies in children are far from what was expected. Drug studies are the restricted domain of drug companies, for drug development reasons and pharmacovigilance afterwards. Academics are only advisers to companies and executioners of submitted studies to FDA and EMA. Companies only have to prove that their drug has an effect even statistical significance of efficacy is not mandatory for acquiring market authorisation. This leads to small numbered studies that fail to elucidate specifics of children. Reasons are companies without proper knowledge of academic incentives, academics without regulatory knowledge, patient organisations not sufficiently involved, regulators with insufficient information and power to require proper studies. Advantages of large collaborations is development of disease related data bases, data bases of genetics of diseases, for whom a certain drug most likely should be selected to treat, larger more adequate numbers are possible to include in studies. Current industry cohorts for single drugs in children lack possibility to relate to national cancer registries to compare incidence cases, changes to newer drugs makes these data cohorts vulnerable for meaningful assessments. Long term follow up for adverse events in comprehensive academic databases is more appropriate, drug industry should by contract have full access to their drug related data for temporarily submission to regulatory agencies FDA and EMA. Transition into adult data bases for the same disease is of clear advantage. A European signature to these databases is mandatory. For rare diseases development of European data bases is mandatory for development of treatment strategies, to benefit most of money issues, to distribute scientific burden between industry and academia with an optimal patient, industry, academia relationship, to generate numbers, give more academic ideas a fair chance, to establish criteria for what is a meaningful improvement, to get European academics interested in drug research in children.

Chronic abdominal pain in children is a common syndrome with functional gastro intestinal symptoms. In 95% of paediatric patients no underlying disease can be identified. The yield of laboratory work up is limited and should not be initiated routinely. Besides clear red flags in symptoms and signs, which suggest underlying disease it is on the other hand adamant to confirm stress related pain as most common cause. If stress related chronic abdominal pain cannot be confirmed, the age boundaries of the child are confirmed to be within the age limits of 3–16 years as expected in most children with the symptom complex, history taking should dig into other possibilities. Possible metabolic, renal, urinary tract abnormalities should be extensively questioned, possible symptoms reviewed, and laboratory work up initiated if relevant. When the diagnosis of chronic abdominal pain is confirmed treatment options like hypnosis should not be delayed and are also effective in related functional GI disorders like functional dyspepsia and irritable bowel disease.Chronic abdominal pain in children is a common syndrome with functional gastro intestinal symptoms. In 95% of paediatric patients no underlying disease can be identified. The yield of laboratory work up is limited and should not be initiated routinely. Besides clear red flags in symptoms and signs, which suggest underlying disease it is on the other hand adamant to confirm stress related pain as most common cause. If stress related chronic abdominal pain cannot be confirmed, the age boundaries of the child are confirmed to be within the age limits of 3–16 years as expected in most children with the symptom complex, history taking should dig into other possibilities. Possible metabolic, renal, urinary tract abnormalities should be extensively questioned, possible symptoms reviewed, and laboratory work up initiated if relevant. When the diagnosis of chronic abdominal pain is confirmed treatment options like hypnosis should not be delayed and are also effective in related functional GI disorders like functional dyspepsia and irritable bowel disease.

For a paediatric development to be rationally informed by all available knowledge, it is necessary to systematically collect and learn from available data, expert knowledge and prior developments. Aspects such as drug formulation, bioanalytical methodology, pharmacokinetics/pharmacodynamics (PK/PD), study design and statistics should be considered when defining a development plan. In this context, model informed drug discovery and development (MID3) methodology [1] is likely to prove useful.

During the last 10 years the European Medicines Agency (EMA) organized a number of workshops on modeling and simulation, working towards greater integration of modeling and simulation (M&S) in the development and regulatory assessment of medicines. In the 2011 EMA - European Federation of Pharmaceutical Industries and Associations (EFPIA) Workshop on Modelling and Simulation, European regulators agreed to the necessity to build expertise to be able to review M&S data provided by companies in their dossier. This led to the establishment of the EMA Modelling and Simulation Working Group (MSWG). Also, there was agreement reached on the need for harmonization on good M&S practices and for continuing dialog across all parties. The MSWG acknowledges the initiative of the EFPIA Model-Informed Drug Discovery and Development (MID3) group in promoting greater consistency in practice, application, and documentation of M&S and considers the paper is an important contribution towards achieving this objective.