BioPain – Functional pain biomarkers in healthy subjects and animals: standardization and pharmacological validation towards accelerated translation in analgesic drug development for better patient care
BioPain will address problems in the translation of analgesics from preclinical to early clinical drug development. The main hypothesis is that effect sizes of analgesic actions on at least some objective biomarkers of nociceptive signal processing can be translated between rodents, healthy volunteers undergoing surrogate models of pain sensitization and patients suffering from chronic pain. Powerful electro-physiological and imaging techniques are now able to accurately assess peripheral nociceptor activation as well as spinal and supra-spinal nociceptive signal processing. These objective functional biomarkers are not well standardized, and hence they are seldom used in early preclinical or clinical studies; however, it is possible that they would correlate with subjective reports of pain as a PROM. Complex statistical analyses and PK-PD-modelling of data from four prospective multi-centre studies are expected to yield a set of clinical pharmacodynamic biomarkers that are validated for effects of three standard-of-care medications in peripheral, spinal and brain compartments. These will be back-translated into animals, to provide novel models which bridge the preclinical and clinical development of analgesics.
Within its four work packages, BioPain will
- develop and standardize at least five functional pain biomarkers in human models as indicators of clinical target engagement of three standard-of-care drugs
- validate changes in the pharmacological profiles of these biomarkers for different components of the nociceptive system to pain evoked by mechanical and heat stimuli in healthy human subjects who have normal and hyperalgesic conditions (skin and/or deep tissues);
- examine differences in the modes of action and PK-PD profiles of three standard-of-care analgesics on these biomarkers;
- use the results to lay the basis for Phase 1 studies of target engagement, as well as for Phase 2 and 3 studies of the clinical efficacy, of new analgesic and anti-hyperalgesic drugs in stratified and enriched cohorts;
- apply their unique expertise in pain biomarker development, clinical trial design, pain pharmacology and data analysis to develop new and valid preclinical models which more accurately reflect the clinical situation;
- and ultimately, propose to EMA inclusion of pharmacodynamic biomarkers proven valid in BioPain into Guidelines for future clinical trials in acute and chronic pain.