Existing drug–new use

One-time interventions

Follow-up limited to data collected in routine clinical care

Open-label but blinded endpoints

Risk-based monitoring

Simple source data verification

External validity (ie, results can be generalised to the population of interest) is of high interest/priority

First-in-man

Novel devices

Novel drugs

Mechanistic or complex substudies

Extensive follow-up/repeat visits needed

Subjective endpoints

Internal validity (ie, ability to attribute observed effects to a treatment or study arm rather than to confounding) is of high interest/priority

Complex hypotheses or endpoints

Complete monitoring needed

Countries without adequate health informatics systems

Areas with inadequate systems to ensure personal data protection