Table 1. Criteria for assessing the appropriateness of using decentralized elements (FDA vs. EMA).

Categories	Attributes	FDA		EMA
Patients’ safety	Similarities	[Considerations for the use of decentralized elements]
			- Consider the type of clinical trial, the trial population, the disease being treated, the condition of the trial participant, the type of medicinal product, the clarity of its safety profile, its developmental stage, and the complexity of the procedures.
		[Considerations for off-site drug administration]
			- Consider the route of administration, whether an observation period is required, the need for emergency plans, the preparation of the drug administration, its stability, the storage conditions, the robustness of the shipping system, the ability to self-medicate, the shelf life and the return plan for unused drugs.
	Differences	[Considerations for procedures at home]		[Considerations for the use of decentralized element]
			- Only if the procedures do not cause an additional risk to trial participants or to the reliability of the data assessment.		- Weigh the burden of the decentralized elements transferred to the participants or investigators against the potential benefits.
		[Considerations for telehealth visits]		[Considerations for the use of electronic methods]
			- If the drug does not pose a significant risk to the participants and adverse events can be properly assessed in such a setting.		- Consider the burdens and potential benefits, the vulnerability of the trial population, the complexity of the trial design and the risks associated with the trial-specific interventions.
		[Hybrid DCT as an alternative to a fully DCT]
			- Drug administration at trial sites with remote follow-up.
			- Specify when a telehealth visit is appropriate and when a participant should be seen in person.
Data integrity	Similarities	[Potential error due to a decentralized element]
			- Variability of the data depending on the performer.
		[Strategies for data integrity]
			- Present an overview of the data flow in the protocol or data management plan.
	Differences	[Strategies for data integrity: quality control]		[Potential error due to decentralized element]
			- Regularly review the data entered by delegated personnel using methods tailored to its criticality and complexity.		- Exclusion of digitally illiterate people.
		[Degree of data integrity]			- Missing data.
			- A non-inferiority margin may not be reasonable to be considered as equal to an on-site trial.		- Sample handling and storage.
					- Complex data from multiple systems.
					- Malfunction of the digital tool.
					- Disrupted decentralized procedure.
				[Strategies for data integrity]
					- Make a contingency plan about decentralized elements.
					- Involve the stakeholders in advance.
				[Degree of data integrity]
					- Meet the same expectations as for an on-site trial for an authorization trial.

FDA, Food and Drug Administration; EMA, European Medicines Agency; DCT, decentralized clinical trial.