AMSTERDAM, the Netherlands — At last year’s annual conference of the Human Proteome Organization, researchers and officials discussing clinical proteomics offered an unflinching assessment of the state of the science. But at this year’s gathering, held here this week, clinical proteomics was treated with a little more respect.
A year ago, speakers during separate panels on clinical proteomics tried to maintain a level of optimism about the direction that the field was heading. Nonetheless, some discussions describing the lack of results were scathing, and presenters said that achieving any clinical relevance remained a far-off goal for proteomics [See PM 10/11/07].
By comparison, at this year’s conference, clinical proteomics had a more welcoming reception; indeed the underlying theme of the conference was “Proteome Biology,” chosen as a way to highlight the progress proteomics has made in biology and medicine.
Also, a discussion during one session centered not on the failures of the field but on outside hurdles that may be keeping proteomics from being translated to the clinic.
According to several speakers, while the field has been overly successful in finding candidate biomarkers for a host of diseases, it has tripped up in subsequent efforts to validate them and develop them for diagnostics applications.
“Finding candidate biomarkers is easy,” said Daniel Chan, director of the Center for Biomarker Discovery at Johns Hopkins University. But validation is not, and “developing diagnostics that meet clinical and regulatory requirements is very time consuming.”
Even if promising biomarkers are found, he and others said, researchers need to ask whether they meet any clinical utility. “We need to ask, ‘What needs are not being met today that a newly discovered biomarker could meet?’”
Hanno Langen, head of biology research at the Roche Center for Medical Genomics, agreed and said that work is being done to find screening biomarkers in some disease areas where existing screening methods are already sufficient.
“We need to ask, ‘What do we need from markers?’” he said, adding that such a dialogue with the clinical world currently does not exist.
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“If your biomarker cannot be translated, it will not receive funding.” |
It is also important to differentiate the purposes of any biomarker, Langen said, by categorizing them into five types: risk-assessment, screening, prognostic, patient stratification, and therapy monitoring. From the perspective of the pharmaceutical industry, biomarkers for stratification, such as for the HER2 protein, are of particular interest, Langen said.
Chan said that during and immediately after the discovery stage, key questions need to be addressed by a researcher: How should the biomarkers be validated to meet clinical requirements? What performance criteria should be established for a clinical diagnostic? What are the steps that will be needed in developing a clinical diagnostic from the biomarker? And, finally, what are the regulatory requirements for such a clinical diagnostic?
Similarly, if the biomarker can successfully move past validation and begin taking steps toward the developmental stage as a clinical diagnostic, a researcher needs to keep in mind several criteria, Chan said. Among them, researchers must identify a targeted population for the intended test as well as pre-analytical and biological variations. Researchers must also evaluate the cost-effectiveness and clinical outcome of such a test, and determine how its results will be correlated.
Long Haul to the Clinician
The session came as proteomics continues to grapple with how to approach the clinical market. Despite years of work devoted to moving proteomics into the clinical setting, to date only a very small handful of protein-based diagnostics have been successfully commercialized, though there are signs that a batch of undisclosed tests may begin hitting the market in the coming months.
In June, Laboratory Corporation of America launched its OvaSure ovarian cancer screen, and Vermillion filed a 510(k) pre-market application with the FDA for its OVA1 ovarian tumor triage test. Also, a Correlogic spokeswoman told ProteoMonitor at the time that it planned “shortly” to file for regulatory approval for its OvaCheck test, which is designed for the early detection of epithelial ovarian cancer [See PM 06/26/08].
Meanwhile, Power3 Medical Products expects to finish its clinical-validation study for its Alzheimer’s test, called NuroPro, and could have it commercially available by the end of the year, the company’s chairman and CEO told ProteoMonitor earlier this month [See PM 08/07/08].
Still, as speakers this week said, discovering biomarkers with biological relevance is just the beginning of a long and expensive process toward clinical applicability. Much of current biomarker research is directed at seeking multiple molecules, rather than a single biomarker.
But according to Christer Wingren, an associate professor of immunotechnology at Lund University, filing a patent on multiple signatures is “much more difficult” than applying for a patent on a single biomarker. An audience member suggested, however, that though this may be true, a patent on a multiple-marker panel is also more likely to become approved.
But that doesn’t alleviate funding challenges. Finding financing resources is particularly difficult during the gray-zone phase when the biomarker or panel of biomarkers are merely basic discoveries and fully validated, or first commercial prototype, Wingren said.
Acceptance from clinicians also poses challenges. Neither public nor private payors currently reimburse for proteomics-based diagnostics, which in turn tends to make clinicians reluctant to use them. And more basically, proteomics technologies tend not to be compatible with clinical laboratories.
So what can be done to enable researchers to build their discovery-diagnostic pipelines? In addition to evaluating the necessity of a particular biomarker, researchers should judge whether a biomarker can be translated into a diagnostic.
“If your biomarker cannot be translated, it will not receive funding,” Johns Hopkins’ Chan said.
He also recommended that developers create teams with key players from both the research, funding, and diagnostic communities along the discovery, validation, development, and approval stages.
Finally, a consensus process and roadmap for the development of in vitro diagnostics need to be constructed. Currently, Chan is part of a working group that also includes members of regulatory agencies such as the FDA that is working on developing a pipeline for diagnostics for cancer.