A pharmaceutical company working with another clinical research organisation (CRO) to execute their paediatric programme approached ICON’s Centre for Paediatric Clinical Development to examine their Paediatric Study Plan (iPSP) and Paediatric Investigational Plan (PIP) after multiple deadlines in their study had been missed. Recruitment in their first study was successful in adolescents 12 years and older but had stalled in younger ages from perceived insurmountable recruitment hurdles and the programme was at risk of failing. The sponsor felt that a change in the programme recruitment strategy was required in order for the ongoing study to be successful and mitigate the risk of additional deadlines being missed.

Study description 

A sponsor working with another CRO to execute their paediatric programme had missed
multiple deadlines in the agreed upon initial iPSP and PIP. Initial conflicting feedback from the Paediatric Committee (PDCO) at the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) had led to the development of divergent paediatric development plans. After prior success working with members of the Center for Paediatric Clinical Development on paediatric study plans, the sponsor reached out for a non-competive consultation to evaluate and optimise their programme. ICON reviewed and developed a new strategy, removing the need for one excess study, and streamlined the programme to fit the guidance from both agencies.

A cross-functional team of ICON paediatric drug development experts comprised of clinical, vregulatory, clinical pharmacology, and medical affairs examined the current agreed upon proposals (PIP and PSP) for both the EMA and FDA. Collectively, the team determined that a novel strategic approach would provide a greater opportunity to meet regulatory requirements and eliminate operational burden of the original, non-congruent agreements. The ICON team was able to justify modifications of ongoing studies to allow the critical first study to complete. In addition, design modifications to a second study were suggested to reduce operational burden and potentially decrease timelines and cost. Lastly, utilising the regulatory approach of extrapolation, a large efficacy study was removed from consideration, thus saving the organisation money and potentially years of clinical development, allowing patients access to medicines earlier.

The EMA’s Paediatric Committee (PDCO) agreed to the amended PIP designed by ICON,
including the addition of the extrapolation study. They requested that the sponsor provide data from completed studies before accepting the removal of the large efficacy trial. The FDA also agreed that developing alternative strategies to allow for an earlier completion of the ongoing study were warranted. They requested that the sponsor provide additional rationale to medications associated with the ongoing study, as well as an over-arching design of the second study. In addition, the FDA suggested that the sponsor could provide data from completed cohorts in the ongoing study, if appropriate, to potentially file for approval in the completed age groups. Based upon these agreements, the new strategy and harmonisation of the study plans will result in market access to this medication for children sooner.

The successes in this programme may save the sponsor years of development costs and
timelines and may allow them to approach earlier regulatory authorities and Health Technology Assessment (HTA) bodies with paediatric clinical data to support use in children and adolescents. The sponsor and ICON have since partnered on new paediatric programmes.