Imaging as a Biomarker

Background

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 .)

Report

This meeting was the largest USMS workshop held by NIST. It was attended by more than 250 researchers from the medical imaging community including: academia, clinicians and research physicians, imaging and pharmaceutical companies, contract research organizations (CROs) and trade organizations (NEMA, PhRMA Consortium), representatives from many different imaging societies (RSNA, ACR, AAPM, SNM, ISMRM), and key agencies of the federal government were represented (NIH: NCI, NIBIB, NIA, NIAMS, NIGMS, NCRR; FDA: CDRH, CDER; and NIST: CSTL, EEEL, PL, MSEL, MEL, ITL).

The workshop was organized as follows: (a) presentations from current or planned public−private partnerships that included imaging as a biomarker and the need for associated metrology and standards for Alzheimer’s disease, osteoarthritis and cancer, followed by an FDA discussion of these and related clinical trial issues associated with imaging; (b) presentations on the NIST U.S. Measurement System activity; (c) presentations from several of the key stakeholders that outlined their level of interest in supporting standards for biomedical imaging; and finally (d) presentations from the National Electronics Manufacturer’s Association (NEMA) and three leading medical imaging companies outlining their interest in collaboration with other stakeholders. Six breakout sessions were organized over the 2-day workshop to specifically address emerging imaging modalities being used in the clinical setting for drug or radiation therapy response, and related resources needed to meet the imaging metrology and standards needs for measuring change. Each breakout session was chaired by four representatives from the different stakeholder groups. The breakout session summaries are described in this report. The final workshop session summarized key points from all the speakers and breakout sessions and opened discussion with panel representatives from the stakeholder groups.

The physical measurement uncertainties for monitoring therapy response as applied to different diseases and the need for quantitative measurements were recognized as an important problem to be collectively addressed by the different agencies of the federal government, with NIST recognized as having an important role in the development of needed metrology. There was also very strong expression of interest by all the academic and industry stakeholders to become collectively engaged in finding solutions for these measurement and standards challenges, such as through the different scientific (volunteer) task groups within academic societies and industry trade organizations (PhRMA, NEMA). In addition, it was recognized that there was an opportunity to collaborate in other interagency efforts that address the role of biomarkers for drug discovery and response, including potential FDA Critical Path, and NIH roadmap and partnership initiatives, which are described at:

http://www.fnih.org/Biomarkers%20Consortium/Biomarkers_home.shtml

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AAPM American Association of Physicists in Medicine ACR American College of Radiology CDER Center for Drug Evaluation and Research CDRH Center for Devices and Radiological Health CSTL Chemical Science and Technology Laboratory DICOM Digital Imaging and Communications in Medicine EEEL Electronics and Electrical Engineering Laboratory FDA Food and Drug Administration ISMRM International Society for Magnetic Resonance in Medicine ITL Information Technology Laboratory MEL Manufacturing Engineering Laboratory MSEL Materials Science and Engineering Laboratory NCI National Cancer Institute NCRR National Center for Research Resources NEMA National Electrical Manufacturers Association NIA National Institute on Aging NIAMS National Institute of Arthritis and Musculoskeletal and Skin Diseases NIBIB National Institute of Biomedical Imaging and Bioengineering NIGMS National Institute of General Medical Sciences NIH National Institutes of Health NIST National Institute of Standards and Technology PhRMA Pharmaceutical Research and Manufacturers of America PL Physics Laboratory RSNA Radiological Society of North America SNM Society for Nuclear Medicine SPIE The International Society for Optical Engineering

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