Table 1.

Ethics and regulatory issues arose during the pediatric research project in the geographical areas involved.

Continent	Ethics/Regulatory Issues	Solutions
America	Acceptance of EU standards for clinical research, data protection and confidentiality	In the agreements: To refer to the international standards, e.g., ICH, “as implemented in the national legislation”. To specify that provisions apply “to the extent the EU rule is compatible with the national laws”.
Africa	Storage of samples abroad for future studies not permitted.	Biospecimens for future studies only stored locally at the clinical sites.
America	Need to comply with local laws and requirements.	The researchers were asked to comply with both EU and local laws.
Africa, Europe	Divergent classification of the clinical study (observational, non-interventional, non-pharmacological, etc.).	Upfront agreed classification among clinicians and regulatory experts on the type of clinical studies foreseen in the project, i.e., non-pharmacological clinical study.
Africa, Europe	Need to limit blood withdrawals from children according to their age and weight.	Agreement among clinicians and regulatory experts to follow European ethical recommendations on pediatric studies regarding blood withdrawals from children.
Africa, Europe	Need to transfer samples outside the country in compliance with applicable laws.	To set up regulatory-sounded Material Transfer Agreements for sharing samples.
Europe	Results of the studies mandatorily shared with parents/legal representatives.	Procedure specified in the informed consent process: parents/legal representatives informed about their right to receive study results in the informed consent document.
Europe	Future uses of samples and related data not to be broad but related to the original study and approved by an ethics committee.	Future uses of samples and data specified in protocol and informed consent documents, as approved by an ethics committee.
Europe	Informed consent more user-friendly language, limiting medico-legal terminology wherever possible.	Informed consent and assent documents adapted to use user-friendly language, minimizing medico-legal terminology and revised by ELSI experts.
Europe	Need to use user-friendly language in informed assent documents.
Africa, America, Europe	Need to update EU laws because of modifications, e.g., Directive 95/46/EC repealed by GDPR.	Investigators provided with practical information on how to comply with GDPR requirements on informed consent and assent process and documents, in particular with those not already included in the studies.