Table 2 5-step Model

Preclinical studies (i.e., aninal testing)

Development of a new technology or adaptation of an existing one

Phase 1, proof of safety (i.e., study of drug pharmacokinetic and pharmacodynamics)

Target population analysis; technology usability, acceptability and safety

Phase 2, proof of principle (i.e., preliminary controlled studies on drug efficacy)

Clinical research, RCTs on small selected groups*

Phase 3, pivotal studies (i.e., large effectiveness studies on heterogeneous populations)

Clinical research, pragmatic design studies on large groups in a real-world setting with effectiveness and cost-efficacy analyses*

Phase 4, post-Market monitoring

Review from a recognized Institution and Post-Market monitoring