Pharmacodynamic Biomarkers
Identifying the right biomarker to inform dose selection is critical, and with first in class agents there are always going to be unknowns.
You should do everything you can to understand the pharmacodynamic biomarker you're using. To add to the thoughts of Friends of Cancer Research, a checklist for pharmacodynamic biomarkers when used for dose selection:
✅test dynamic range and effect size in mouse studies alongside other experiments to help interpret alongside efficacy.
✅test dynamic range and effect size in procured clinical samples that have been collected using the same methods as they will be in the clinical trials.
✅test what may happen to the biomarker if the sample is delayed in transit, sent in the wrong vessel, or the requested amount/concentration was not received.
✅ establish limit of blank, limit of detection and limit of quantitation and use these limits to define the protocol.
✅ ensure you have appropriate controls in every run. Note that these may not be the same controls as those used in other studies with different sample types.
✅determine upfront what you would expect to see for a go/no-go decision.
✅if outsourcing, be very clear in your data transfer agreement which data items you expect back and make sure you have visibility into how each sample is being processed.
✅consider collection time points at the same time as PK collections and efficacy measurements.
✅don't collect more than you need! It's burdensome to patients and costly to store the samples long-term.
✅do everything you can to ensure the results are available for dose decision meetings.
✅batch carefully!
