Imaging as a Biomarker: Standards for Change Measurements in Therapy workshop summary.

Biomarkers are biological indicators of disease or therapeutic effects that can be measured by in vivo biomedical/molecular imaging, as well as other in vitro or laboratory methods. Recent work has shown that biomedical imaging can provide an early indication of drug response by use of x-ray, computed tomography (CT), positron-emission tomography/CT (PET/CT), or magnetic resonance imaging (MRI). There are three primary sources of uncertainty in using imaging as a biomarker: 1) the biological variability, 2) the variability associated with the clinicians interpreting the images, and 3) the physical measurement variability associated with image data collection and analysis across the same or different imaging platforms. Although biological variability is a large source of error, the physical uncertainty often significantly reduces the robustness of the imaging methods and the clinical decision tools required for quantitative measurement of therapy response over time. Physical and biological measurement uncertainties may be addressed prior to designing a clinical trial and thus help in reducing the case size and cost of a clinical trial associated with a drug submission to the U.S. Food and Drug Administration (FDA). The National Institute of Standards and Technology (NIST) has been approached over the last few years by several industry and medical stakeholders to address the physical sources of measurement uncertainty. NIST's initial research discovered that the characterization of measurement uncertainty poses many complex metrology and standardization problems on a scale that appears to need significant collaboration across the different medical imaging stakeholders. Many of the issues are similar to other scientific domains that NIST has addressed as part of its mission to provide metrology standards to enhance the competitiveness of U.S. industries. To better assess the measurement and standards needs for using imaging as a biomarker, NIST engaged leading representatives from many of the different imaging societies, the imaging, pharmaceutical and e-health and other health care stakeholders, as well as other key federal agencies (the National Institutes of Health Institutes and Centers [NIH ICs], and FDA) to organize and conduct a United States Measurement System (USMS) workshop: http://usms.nist.gov/workshops. The workshop entitled Imaging as a Biomarker: Standards for Change Measurements in Therapy, was thus held on September 14-15, 2006, at NIST in Gaithersburg, Maryland. (Workshop agenda, presentations. and final workshop report will be available at http://usms.nist.gov/workshops/bioimaging.htm.)