the results. “We can be mindful with whatever specimens we have collected in the past and hope to store future ones better,” Ransohoff said. Hayes noted that NCI is developing a prospective systematic funding mechanism to answer some of the more basic questions regarding handling of samples, such as what are the implications if a sample sits for 3 days instead of 3 hours before processing or what happens if the sample is fixed for too long. One approach, Hayes said, is to develop an assay that works in the kind of tissue that is collected and archived currently. Another approach is to develop an assay that is so fundamentally powerful that it will change the way tissue is collected and archived going forward.

Trial Design

Participants discussed what is “clinically relevant.” There are multiple study designs that are valid, and which of them is clinically relevant depends on the particular research question. In the end, the goal is to cross a threshold of evidence based on a combination of observational, retrospective, prospective, and larger, more clinically oriented approaches.

As the panelists noted, many of the studies that are currently being done are not designed to contribute to the evidentiary base in the way that is needed for genomics. A question was raised about how to better train the next generation of clinical investigators to think about biomarker studies. Should the NIH develop some very specific training programs as we move into the genomics era? Ransohoff noted that the system rewards clinicians for getting grants and publishing papers, as opposed to producing products or expanding general knowledge.

Simon said that, in his experience, industry is extremely interested in new clinical trial designs that use predictive biomarkers or candidate predictive biomarkers in new drug development. Industry managers are concerned, however, about what the FDA will require (e.g., prohibitively large clinical trial sizes) and about the potential for more roadblocks in developing new drugs with companion diagnostics. He added that NIH funding is driving much of the basic research on identifying the key targets that could be candidate predictive biomarkers and drug targets.

It was noted that patients are increasingly demanding access to interventions that they regard as essential to their well being and health. Institutions are adopting technologies prematurely, and there is political pressure to approve or cover the latest technologies. This is a knowledge translation problem that needs to be addressed. It is important to consider evidence generation during the premarket phase, as trials are being designed and conducted, before product diffusion into the marketplace.

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