BIOMARKERS/BIOSIGNATURES Standards needed for Translational Research 1.Standardized QUESTIONS in Clinical Trials 2.Standardized PRACTICES in advancing pilot studies 3.Standardized VALIDATION/VERIFICATION studies Michael E. Berens, Ph.D.

Develop standardized QUESTIONS in Clinical Trials that position success (“low hanging fruit”) from biomarkers/biosignatures patient stratification for balancing the trial arms for equivalency (survival biomarkers) patient eligibility into clinical trial (is the target present?) tumor response/non-response to therapy (futility marker) to predict failure early Include the ecosystem of players in the design of biomarkers/biosignatures (academic, industry, advocacy, regulatory, philanthropic, etc)

Adopt standardized PRACTICES in advancing pilot studies using clinically-annotated specimens Use specimens from no more than 3 sites to ensure minimal deviation from SOPs Use best-in-class analytical partner matched to the analyte Work in close collaboration with PK and PD correlative endpoints (best-in-class partner) Operate in a parallel, blinded, limited competition model for maximal learning Include the ecosystem of players in the design of PRACTICES that enable biomarkers/biosignatures (academic, industry, advocacy, regulatory, philanthropic, etc)

Conceive, deploy, test, iterate, and improve standardized VALIDATION/VERIFICATION studies with an eye to business development Deploy Laboratory Developed Tests under CLIA (versus FDA) Harmonize test validation requirements between CMS and FDA Portability &reproducibility testing by >3 performance sites Work with regulatory groups on “gold standards” for highly complex or multi-plex analyte tests Support as a thought-leader, FDA’s requirements to launch companion diagnostics with drug trials Include the ecosystem of players in the design of VALIDATION/VERIFICATION studies for biomarkers/biosignatures (academic, industry, advocacy, regulatory, philanthropic, venture funding, etc)