Challenge: Every day, patients receive drugs that are not approved according to their label. These off-label uses involve different indications, age groups, or administration routes. In the Netherlands, this is only allowed if guidelines or protocols are developed within the professional group or after consultation between the physician and pharmacist. Over 800 drugs are prescribed to children in the Netherlands. Recent research from the shows that about 60% of drug-indication-age group combinations are within the label for the specific indication and age. Of the remaining combinations, 14% was supported by a meta-analysis or high-quality clinical trial, while the remaining combinations weres only supported by moderate or low evidence of effectiveness. The availability of safety data was not investigated. Off-label prescribing in children is common, and European legislation is particularly ineffective for off-patent drugs.

Objective: Continuing the current status quo, with sporadic registration based on the Paediatric-use marketing authorisation (PUMA) method or voluntary submission by companies using published academic study data, will perpetuate off-label use on its current scale. An action plan is needed:

1. Develop an adapted decision tree to determine the necessary research for effectiveness, safety, dose, and specific pediatric formulation for each drug and indication.
2. Create a prioritization method to rank the research sequence using the decision tree.
3. Establish a research agenda for each drug and indication based on the decision tree and prioritization.
4. Implement this research agenda.

Within the project supported by FAST , exploratory conversations with (international) stakeholders are held, and input is gathered for further discussions with research funders. These conversations are essential to start the first steps.

While executing the entire action plan can lead to affordable, more effective, and safer drug therapies for children, the various program steps can also contribute to drug repurposing in other populations.

Project Status: This project started in early 2023 and was completed mid 2024.

Executor(s): Radboudumc

Role of FAST: FAST is the sponsor of the stakeholder exploration.