Poorly conceived study designs are still a main reason for clinical trials to fail in paediatric patients. Especially, recruitment of a representative population re-mains hard to be achieved. Low recruitment rates prolong study conduct and reduce data acquisition and quality. Pharmacokinetic and pharmacodynamic investigations are mandatory in the paediatric study designs for submission to competent authorities. Therefore, non-professional tech-niques in blood sampling and patient/parent communica-tion can be main drivers for low recruitment rates. To meet these particular challenges, a novel approach for the train-ing of study teams in the EU-funded LENA project was cho-sen that goes beyond current standards. Aim of LENA (La-belling Enalapril from Newborns up to Adolescents) is to investigate pharmacokinetic (PK) and pharmacodynamics (PD) data of enalapril in children suffering from heart failure.Methods
A three-parted modular training was designed by addressing the most critical hurdles of the paediatric LENA trials by focusing on communication of study related information and blood sampling of time-critical and sensi-tive parameters. As first step, the entire team (principle inves-tigator, physicians, nurses) of every clinical centre involved in the project attended a hands-on simulation training at the specialised Medical Simulation Centre in Salzburg. During this training, LENA specific situations were exercised using manikins and original medical devices. Video-based de-briefing of the scenarios enriched the learning experience. In the second training step, the complex PK/PD sampling procedure was refreshed during an on-site training. Scope of this individualised training element was to evaluate the trial centres’ capability for obtaining samples for all pharma-cokinetic and pharmacodynamic investigations as required in the most realistic scenario possible. This phase was de-signed to resemble a regular LENA study-visit and included performance of study related procedures from sampling to bioanalysis at the central laboratory utilising healthy volun-teers. Third, -if requested-the clinical teams were accompa-nied during the first paediatric patient visits by experts to ensure the maximum support during recruitment and study conduct in the beginning. Additionally, participants’ perfor-mance and preparedness for the study as well as the useful-ness of the training were assessed using surveys based on five-point Likert scales.Results
23 participants from five different European coun-tries were trained at the simulation centre. The performance in sampling of time-critical humoral parameters was op-timised to meet the predefined time limits, and to enable maximum reliable data extraction by reducing invalid sam-ples. Participant’s abilities to communicate core elements of the studies and to successfully perform PK/PD sampling increased significantly (p=0.0003). The on-site training re-vealed results out of specification at one site. After repeating the on-site training, PD samples collected at all sites allowed for detection of sensitive parameters in low sample volumes. PK data were within the expected specifications.Conclusion
Simulation training and on-site training sub-stantially improved the participants’ performance. This tai-lored training was assessed as a helpful teaching tool in trial preparation and lead to good recruitment rates within the LENA project so far. Further follow-up surveys will evaluate the actual impact of this training on the study success.Conclusion
The research leading to these results has received funding from the EU’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°6 02 295 (LENA).