Surrogate endpoints pharmacodynamics

Phase I Clinical pharmacology in small numbers (tens) of healthy non-patient (or patient) volunteers to assess tolerability, preliminary safety, pharmacokinetics, and pharmacodynamics where practicable (i.e. biological effect using surrogate endpoints [see later] or, rarely, therapeutic effect)... 

Ha Clinical pharmacology in patients with the target disease (small numbers - tens to 100-200) to assess pharmacodynamics, pharmacokinetics, and dose-(or concentration-) effect responses for preliminary efficacy and safety, and to validate surrogate endpoints... 

A surrogate endpoint exists (e.g., a marker that shows activity but is not predictive of therapeutic activity) so that pharmacodynamic data can be generated. For example, a drug for asthma that exerted its effect by reducing inflammatory mediator release... 

Sometimes it is not possible to measure the direct effect of the drug. Endpoints or surrogate biomarkers are used to monitor the pharmacodynamics and pharmacokinetics of the drug. These markers may be changes in blood pressure, cholesterol level, concentrations of certain enzymes, proteins, blood glucose levels, and similar factors (see Table 6.2 for serum tumor markers and Appendix 7 for general biomarkers). 

Pharmacodynamic equivalence as demonstrated by validated surrogate markers or primary clinical endpoints. 

---