determined whether to separate utilization from analytical validation and qualification in the recommended framework for biomarker evaluation.

On a related point, some discussants raised the concern that case studies in the report might be interpreted as questioning the value of useful biomarkers that are not appropriate surrogate endpoints (for example, C-reactive protein [CRP]). Guy Johnson remarked that the predictability and shortcomings of biomarkers such as prostate-specific antigen (PSA), CRP, and low-density lipoprotein cholesterol (LDL-C) are well known by medical professionals, and that this information should also be available to consumers. However, he said, “in a quick read of the report, I’m worried that its results could be misconstrued to undermine the value of some of these markers that are being used routinely.”

Roberta Ness replied that the committee had shared this concern, and they included information and recommendations in the report emphasizing the importance of scientific literacy, numeracy, and communication with patients regarding biomarkers. “PSA is such a perfect example, because there is so much controversy about its use,” she said, noting that physicians do not consistently interpret the results of this assay. Maria Lopes-Virella, professor of bioengineering at the Medical University of South Carolina, added that while providing information about biomarkers is important, the public needs to be made aware that the same biomarker can be valid for use in one context and not in another.

Dr. Jaffe noted that health care providers also need guidance on these issues. “Lots of physicians say, ‘That’s been in trial, [and] X showed better than Y; therefore, everybody gets X,’” he said. “That sort of thinking is a negative for the use of biomarkers, because it means when you use a biomarker, you [reduce it] to its lowest common denominator and overutilize it.” Thus, it’s important to encourage more probabilistic thinking on the part of physicians as well as the public to combat the misguided notion that a biomarker has to be good for every use or no good at all, said Dr. Jaffe.

Committee member Michelle A. Albert, assistant professor of medicine, Harvard Medical School, further noted that the phenomenon of “psychological toxicity” figured into the committee’s deliberations. In the case of very ill patients, she said, it is important to consider what effect it may have to “use the shrinkage of a tumor … to tell someone that they are improving when in fact they are not, and … what that does to them psychologically as an important endpoint.” That is an additional reason why the committee emphasized and separated context of use from biomarker validation and qualification, she stated.

Another concern raised by several discussants was the possibility that the standards established by the recommended biomarker evaluation framework will have a chilling effect on research in this area.

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