From: Endpoints in stem cell trials in ischemic heart failure
 | Preclinical, phase I | Phase II | Phase III |
---|---|---|---|
Product-regulatory requirements | Kinetics, biodistribution of the cells. Purity, potency and karyotype stability of particular cells. Ensure traceability | Short-term side effects and risk associated with particular cell-based biologics | Performed after preliminary evidence suggesting effectiveness of particular cells |
Objective | Safety | Safety/surrogate endpoints | Safety/therapeutic benefit/improved survival |
Patient restriction/criteria | Identify target group (safety analysis) | Identify potential responders and non-responders | Include only responders |
Sample size | Usually 20 per cohort | From a few dozen to a few hundred | Several hundred or more |
Design | Randomized, open label or placebo | Randomized, placebo-controlled | Randomized, double-blinded, placebo-controlled |
End-points (feasibility - product and procedure related) | Procedure safety, biological activity of the cells | Safety/feasibility of the procedure, adequate number of cells/dose response | Long-term, substantial evidence of previously observed feasibility/safety |
Safety endpoints | Patient tolerance, abnormal cell growth, mutagenesis, tumorigenicity | Patient tolerance, tissue injury, possibility of arrhythmias | Clinically relevant objective: death, clinical events |
Efficacy endpoints | Detect surrogate endpoints sensitive to track the therapeutic benefit | 1) Further analysis of previously detected surrogate endpoints 2) Exploratory analysis of clinically relevant endpoints | 1) Clinically relevant endpoints. Objective (single or composite): improved survival, reduced clinical events/number of hospitalizations. Subjective: symptom score, health-related quality of life 2) Surrogate efficacy endpoints that meaningfully correlate with clinical endpoints |