Radiologists Urge FDA To Accept PET-Based Criteria
Radiologists Urge FDA To Accept PET-Based Criteria
In May, the U.S. Food and Drug Administration will meet with two groups who have proposed that the agency accept the use of fluorodeoxyglucose–positron emission tomography (FDG–PET) imaging to measure tumor response and predict clinical outcomes in phase II and III clinical trials.
The proposal is the latest step in a campaign by the radiology community to gain acceptance of PET scans in clinical trials, along with new criteria for their use in measuring tumor response, called PERCIST (PET Response Criteria in Solid Tumors). To date, the FDA has accepted only computed tomography (CT) scans and the corresponding, widely used measurement criteria known as RECIST (Response Evaluation Criteria in Solid Tumors).
FDG–PET gauges tumor activity by measuring changes in a tumor's standardized uptake value of a glucose analogue. CT measures the percentage of shrinkage at a tumor's largest diameter. At this point, most imaging experts do not view FDG–PET as a replacement for CT but rather as another imaging method that adds molecular-level data to CT's anatomical information. For the past decade, most PET scanners have incorporated CT capabilities, so both types of scans can now be done routinely.
The authors of the new proposal, from the Foundation for the National Institutes of Health Biomarkers Consortium and the Quantitative Imaging Biomarker Alliance (QIBA), a program of the Radiological Society of North America, argue that molecular and functional imaging with FDG–PET enables evaluation of drug response sooner than with CT scans. It is particularly valuable with molecularly targeted therapies, which may stabilize a cancer without immediately shrinking the tumor. PET and PERCIST proponents also point to studies showing that FDG–PET results statistically correlate with survival times in patients with lung, head and neck, esophageal, and breast cancers, as well as lymphoma.
"While the imaging community feels as though [FDG–PET] is relatively mature, we are not able to use it in trials because of a lack of official approval and validation, so we're unable to take advantage of what is already ready for use," said QIBA program director Andrew Buckler, head of Buckler Biomedical Sciences in Wenham, Mass., a research and consulting company.
One reason that it has taken this long for FDG–PET to be considered for clinical trials may be that no individual pharmaceutical company would invest the resources needed to assemble all the data and petition the FDA to address this issue, said Daniel Sullivan, M.D., professor of radiology at Duke University in Durham, N.C. He added that no entity holds intellectual property rights to FDG–PET, so no contrast imaging company has an incentive to do this. And until now, no consortium has organized to do it.
Several organizations are involved in the current effort. The Biomarkers Consortium is a public–private research partnership that includes the FDA, National Institutes of Health, Pharmaceutical Research and Manufacturers of America, Biotechnology Industry Association, Centers for Medicare and Medicaid Services, and others. Similarly, QIBA includes representatives from a variety of stakeholders, including pharmaceutical companies, medical device (scanner) manufacturers, academicians, professional organizations, and federal agencies.
In the past, the FDA has been receptive to changes in imaging criteria, according to Sullivan. He said that in the late 1990s, the agency became concerned with the rigor of imaging data, with its subjectivity and variability, and challenged several applications of drug companies, demanding that images supporting progression-free survival be reread. With a growing emphasis on new, more quantitative, objective, and reproducible data, the FDA began pressing several pharmaceutical companies for less ambiguous results in testing certain drugs.
Abstract and Introduction
Introduction
In May, the U.S. Food and Drug Administration will meet with two groups who have proposed that the agency accept the use of fluorodeoxyglucose–positron emission tomography (FDG–PET) imaging to measure tumor response and predict clinical outcomes in phase II and III clinical trials.
The proposal is the latest step in a campaign by the radiology community to gain acceptance of PET scans in clinical trials, along with new criteria for their use in measuring tumor response, called PERCIST (PET Response Criteria in Solid Tumors). To date, the FDA has accepted only computed tomography (CT) scans and the corresponding, widely used measurement criteria known as RECIST (Response Evaluation Criteria in Solid Tumors).
FDG–PET gauges tumor activity by measuring changes in a tumor's standardized uptake value of a glucose analogue. CT measures the percentage of shrinkage at a tumor's largest diameter. At this point, most imaging experts do not view FDG–PET as a replacement for CT but rather as another imaging method that adds molecular-level data to CT's anatomical information. For the past decade, most PET scanners have incorporated CT capabilities, so both types of scans can now be done routinely.
The authors of the new proposal, from the Foundation for the National Institutes of Health Biomarkers Consortium and the Quantitative Imaging Biomarker Alliance (QIBA), a program of the Radiological Society of North America, argue that molecular and functional imaging with FDG–PET enables evaluation of drug response sooner than with CT scans. It is particularly valuable with molecularly targeted therapies, which may stabilize a cancer without immediately shrinking the tumor. PET and PERCIST proponents also point to studies showing that FDG–PET results statistically correlate with survival times in patients with lung, head and neck, esophageal, and breast cancers, as well as lymphoma.
"While the imaging community feels as though [FDG–PET] is relatively mature, we are not able to use it in trials because of a lack of official approval and validation, so we're unable to take advantage of what is already ready for use," said QIBA program director Andrew Buckler, head of Buckler Biomedical Sciences in Wenham, Mass., a research and consulting company.
One reason that it has taken this long for FDG–PET to be considered for clinical trials may be that no individual pharmaceutical company would invest the resources needed to assemble all the data and petition the FDA to address this issue, said Daniel Sullivan, M.D., professor of radiology at Duke University in Durham, N.C. He added that no entity holds intellectual property rights to FDG–PET, so no contrast imaging company has an incentive to do this. And until now, no consortium has organized to do it.
Several organizations are involved in the current effort. The Biomarkers Consortium is a public–private research partnership that includes the FDA, National Institutes of Health, Pharmaceutical Research and Manufacturers of America, Biotechnology Industry Association, Centers for Medicare and Medicaid Services, and others. Similarly, QIBA includes representatives from a variety of stakeholders, including pharmaceutical companies, medical device (scanner) manufacturers, academicians, professional organizations, and federal agencies.
In the past, the FDA has been receptive to changes in imaging criteria, according to Sullivan. He said that in the late 1990s, the agency became concerned with the rigor of imaging data, with its subjectivity and variability, and challenged several applications of drug companies, demanding that images supporting progression-free survival be reread. With a growing emphasis on new, more quantitative, objective, and reproducible data, the FDA began pressing several pharmaceutical companies for less ambiguous results in testing certain drugs.
