Predicting therapeutic efficacy - experimental pain in human subjects

Area of Science:

• Pharmaceutical Science
• Clinical Pharmacology
• Pain Research

Background:

• High attrition rates in drug discovery persist despite scientific advances.
• Translational research, bridging preclinical and clinical stages, is crucial for drug development.
• Current drug development faces challenges in predicting clinical efficacy from preclinical data.

Purpose of the Study:

• To review the application of human experimental pain models in early clinical development.
• To discuss challenges in Phase-II/III trial design, including sample size and placebo effects.
• To explore the potential of electroencephalography (EEG) as an objective pain assessment tool.

Main Methods:

• Utilizing human experimental pain models (capsaicin, UV-irradiation, electrical stimulation) in Phase-I volunteers.
• Analyzing data integration from early models into Phase-II efficacy trials.
• Reviewing cortical EEG studies for objective pain assessment in NSAID and opiate trials.

Main Results:

• Experimental pain models can establish hyperalgesia in human volunteers for early drug testing.
• Optimal Phase-II/III trial design requires careful consideration of sample size and placebo response.
• Cortical EEG offers an objective alternative to subjective pain assessment methods.

Conclusions:

• Human experimental pain models are valuable tools for early clinical drug development.
• Effective translational research necessitates seamless integration of preclinical and clinical data.
• Cortical EEG shows promise as an objective biomarker for pain and therapeutic response.