BALTIMORE — Researchers and investigators gathered here late last week said that after years of promising groundbreaking proteomic research without delivering the goods, the field needs to simultaneously tone down expectations and improve research methods.
Gathered for a conference hosted by the proteomics division of the American Association for Clinical Chemistry, about 150 researchers, government officials and drug, diagnostic, and biotech company representatives were treated to a steady stream of presentations on where the proteomic field has been — particularly in biomarker research and discovery — and where it needs to go.
The focus of the conference was supposed to be on opportunities that exist for proteomic research in diagnostic, pharmaceutical, and laboratory environments. Speakers patted themselves and each other on the back and highlighted work — often their own — that they said could serve as a basis for other researchers and advance proteomic methods.
But by the end of the two-day event, if there was one recurring theme it was that to date, proteomics research has failed to accomplish many of the major goals it set out to achieve, and if leaders in the field want to progress forward, change will have to happen.
David Ransohoff, a professor of medicine at the University of Carolina at Chapel Hill put it bluntly when he said, “Our methods and results are failing us,” adding that in too many experiments, even proof of principles have not been shown.
Steven Carr, a researcher who leads the proteomics platform at the Broad Institute of Harvard and the Massachusetts Institute of Technology, added that even after several years of work, one of the main goals of proteomics — to produce a complete and quantitative picture of the proteome in at least one state — has not been achieved in any organism.
Most of the shortcomings and failures of proteomics discussed were not new. Some spoke about the lack of reporting standards, others about a lack of reproducibility in experiments, and some mentioned a pie-in-the-sky mentality among researchers and entrepreneurs looking to cash in on the science.
Steven Gutman, director of the Office of In Vitro Diagnostic Device Evaluation and Safety at the US Food and Drug Administration, said that the proposals received by his office using proteomic technology and methods are often bound for failure.
“Expectations are too high. When I deal with some company with some grandiose scheme, I say [to them], ‘Why don’t you start small?’” he said.
In some instances, said Sudhir Srivastava, chief of the cancer biomarkers research group at the National Cancer Institute, researcher behavior is preventing progress in the science. Scientists are willing to share methods, he said, but asking for their data is akin to asking for a progeny.
As the industry explores ways to move the science into the clinical setting, one presenter said that proteomic diagnostic tools will interest doctors only if they impact how they can clinically manage their patients.
“They make the point over and over that understanding the biology of the disease alone is not sufficient,” said James Wittliff, professor of biochemistry and molecular biology and research professor of surgery at the Brown Cancer Center at the University of Louisville.
Looking beyond the science, John Ridge, director of reimbursement service for Roche Diagnostics, said that payment issues will pose a major obstacle to the adoption of proteomic-based tests. Currently, payors such as insurers and the federal government are not convinced about the value of proteomic testing and are struggling with how to pay for molecular tests.
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“Expectations are too high. When I deal with some company with some grandiose scheme, I say [to them], ‘Why don’t you start small?’” |
Ridge added that there are no proteomic-specific current procedural terminology codes — which are necessary for payors to reimburse for tests — and proteomic tests will most likely be paid on a method basis that can be arcane and confusing.
So what can and should be done to advance proteomics?
To begin with, the science needs to be improved, speakers said. This includes better methods of collecting and storing tissue samples, and developing better use of existing technologies to conduct hypothesis-driven research rather than broadly profiling biological substances.
Carr of the Broad Institute suggested that in the area of biomarker discovery and validation, researchers use proximal fluids rather than blood because of the complexity of serum. He also suggested using higher quality MS/MS data and technology other than mass specs for verification. The problem with mass specs, he said, is that while they have high sensitivity, they have limited dynamic range.
Omar Laterza, a research fellow at Merck Research Laboratories where he is co-director of the clinical development laboratory, said that as drug companies try to validate biomarkers, they will need to bring diagnostic firms into the process, a step that currently is not being done.
Traditionally, drug makers have been interested in biomarkers from the pharmacodynamic perspective, but more recently are seeing greater opportunities in disease biomarkers, he said.
While drug makers can offer intellectual property in the way of novel biomarkers, diagnostic firms bring expertise in assay development and validation and access to assay platforms.
On reimbursement, Ridge said that, when proteomic-based drugs or diagnostics start making their way into the clinical environment, the medical community will need to be brought into the fold, including collaboration with the American Medical Association to establish appropriate CPT codes for proteomic testing. Clinical studies will need to be designed, also, with an eye toward meeting payor needs and there will need to be a focus on health outcomes data to convince doctors and payors that new technology improves patient care, Ridge said.