Implementation of validated pharmacodynamic assays in multiple laboratories: challenges, successes, and limitations.
There is a "life cycle" of pharmacodynamic (PD) biomarker assays that guides the development and clinical implementation in our laboratories. The well-recognized elements of analytical assay validation and demonstration of fitness-for-purpose of the biomarker, specimen collection, handling, and assay methods are only a part of the required activities. Assay transfer across laboratories and testing on actual human clinical specimens are vital for understanding assay performance and robustness. In our experience, this patient specimen-centered approach has required assay method modifications, some unexpected, but which were critical to successful implementation in clinical trials. In addition, dispersing assays throughout the National Cancer Institute's clinical trials network has required the development of calibrator and control materials as well as formal training courses for smooth implementation. One measure of success of this approach has been that a number of the assays developed at NCI's Frederick National Laboratory have ultimately reached the stage of commercialization, enabling wide accessibility of the PD biomarker assays by the research community. See all articles in this ccr focus section, "Progress in pharmacodynamic endpoints."
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland kindersr@mail.nih.gov.
Robert
R
Kinders
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland.
Kate
K
Ferry-Galow
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland.
Lihua
L
Wang
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland.
Apurva K
AK
Srivastava
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland.
Jiuping Jay
JJ
Ji
Authors' Affiliations: Laboratory of Human Toxicology and Pharmacology; National Cancer Target Validation Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research, Inc., Frederick, Maryland.
Ralph E
RE
Parchment
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000592:standards; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards; D006801:Humans; D007753:Laboratories / Q000592:standards / Q000706:statistics & numerical data*; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000379:methods / Q000592:standards; D014481:United States
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor