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NCI’s PRIDE Spurs Public/Private Alliances Through Biomarker-Based Assay Validation

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Name: Sudhir Srivastava
 
Position: Chief, Cancer Biomarker Research Group, Division of Cancer Prevention, National Cancer Institute.
 
Background: program director, Division of Cancer Prevention, NCI, 1990 to present; member, American Joint Committee on Cancer; editor-in-chief, Disease Markers
 
Education: PhD, biological science, Banaras Hindu University, 1977; M.S. degree, computer science, Virginia Commonwealth University, 1987; M.P.H. degree, Johns Hopkins University, 1997; post doctoral work, University of Osaka, Japan; University of San Francisco; and the University of Arizona, Tucson.
 

 
The rising demand for more expensive targeted oncologics has inspired a flurry of biomarker-driven and PGx-based research in cancer drug development.
 
However, as this interest increases, industry observers have noted a dearth of validated efficacy-based biomarkers and diagnostics [see PGx Reporter 05-02-2007].
 
Many stakeholders have noted that what is holding back the development of biomarker-based assays in oncology is the lack of public/private collaborative research.
 
At the annual meeting of the American Association of Cancer Research in April, officials from a newly formed government group under NCI’s Early Detection Research Network outlined efforts to foster these alliances by helping diagnostic developers validate assays using clinical samples.
 
Established in 2000, the EDRN translates “molecular knowledge into practical clinical tests that identify cancers at the earliest stages of normal cells' transformations into cancer cells,” and identifies patients at risk of developing cancer.
 
The network focuses on four areas: developing new biomarkers; validating existing biomarkers, including developing technologies, standardizing and refining assay methods; conducting and supporting early clinical and epidemiological research using biomarkers; and developing statistical approaches to the simultaneous pattern analysis for multiple markers.
 
Last October, EDRN announced the establishment of the Program for Rapid, Independent Diagnostic Evaluation, or PRIDE, which aims to help extramural investigators validate biomarkers and refine their new and existing assays, reagents, methods, and tests.
 
The program invites investigators to submit proposals for their biomarkers for Phase II or Phase III validations. PRIDE reviews the applications and invites selected investigators to present the studies to the relevant EDRN group. PRIDE receives funding to support biomarker validations from the EDRN.
 
PRIDE official Sudhir Srivastava spoke to Pharmacogenomics Reporter earlier this month to discuss in detail the group’s recent efforts.
 
A lot of drug development in oncology is now biomarker driven. But there is a lot of criticism that while there are a lot of biomarkers out there, they are not validated. Can you talk a little bit about the state of biomarkers in drug development?
 
We don’t do anything with drug development, but I can tell you from a different perspective because I do interact with [drug developers]. … Biomarkers in drug discovery are still in a very nascent state. We really don’t have much control over it. Biomarkers for toxicity assessment and also for evaluating the mechanism of a given drug are far along. They are doing very well. There have been many reports that cite biomarkers for toxicity, or pharmacokinetics. Industry is very much engaged in that. But to use biomarkers as a surrogate endpoint in clinical trials, in measuring the drug’s effectiveness, is still in a very early stage.
 
Could you discuss some of the common problems you see with the applications to PRIDE?
 
Many times many of them honestly don’t understand what different things are needed [in the application]. PRIDE is not a support for discovery. PRIDE supports [research] that has gone beyond discovery stage and is ready to be tested and validated. Lots of people are asking us to substitute their own research. We are not doing that. We are not in that process. We are asking that if you have a biomarker that is ready for further testing, we’d be happy to work with you. So many times they don’t understand, because the money is tight, and they go to any place they can to get some help.
 
What are some of the improvements you’ve seen among applicants?
 
Those who are smart enough, they usually call us. They say, ‘This is what we have. Do you think this will fit within the PRIDE program?’ We either say ‘yes’ or ‘no,’ and if we can, we help them.
 
During your presentation at the AACR meeting you discussed development of an ovarian cancer biomarker panel and of a cancer biomarker database. Could you discuss some of the projects PRIDE is focusing on?
 
We currently have a panel of 15 biomarkers for ovarian cancer. … All the participating centers have been sent samples. Each will test their biomarkers with the samples given to them. Once they have conducted the assay, they will send us the data, the data will be analyzed and … then we will come up with an optimal panel of biomarkers, maybe 10. Using statistical and informatics tools we will narrow the number of biomarker panels.
 
On the cancer biomarker database, we have a demo of mock data from published literature. We are going to make a presentation of this database in our upcoming meeting in September.
 
How do you think your various efforts – from helping companies to validate their biomarker-based assays to developing the biomarker database – can fuel public/private partnerships?
 
Many companies didn’t know about EDRN two, three years ago. Now they have come to know of EDRN and they are contacting us. Now we have 15 companies who are EDRN associate members [among them Abbott, GenProbe, Eisai, and Wako].
 
They are participating with us on many, many projects. Some of them include large validation studies, some of them are simply working with us on incubator projects, meaning those projects that haven’t really reached maturity and are in an early stage. Some of them are working with us on their platforms [in cases when] they have platforms but they have no way of validating them. … So they are offering us their platforms to be tested using clinical samples. It’s happening now. As with any new infrastructure it takes time. Now that the word has gone out about EDRN to various product centers, they are coming forward and working with us.
 
What are some of the challenges in trying to fuel these public/private partnerships?
 
I think the major challenge is the IP issue. With the diagnostics you’re not going to just have one marker or two markers, you may have more than one biomarker. Some of those biomarkers may be patented by private companies. How do you deal with those multiple IPs? I think companies are going to grapple with this and we are going to grapple with it. We are trying to do [what we can], but we are limited, honestly. We are trying to say, ’Look, if the assay is successful and you are one of the primary inventors, you still have the right to take that forward for FDA approval. So you won’t lose your IP.’
 
But the major problem is [that] if it’s a collective effort, with many companies involved, then we still have to evolve a system by which all of them will discuss [the research] among themselves, or there has to be some mechanism to deal with multiple IPs on a given diagnostic assay. …
 
[For example,] EDRN’s various research centers have IP on biomarkers. But industry has IP for the platform. If it’s one-to-one research, then it’s not a problem. That’s easy to work out. We can have industry, the tech-transfer office, and NCI write the eventual engagement plan on what will happen once the technology and the biomarkers are validated.
 
But if your biomarker A, B, C, and D consists of four different institutions, and they all have IP, and then you have one platform from one company. So the company has to deal with all those institutions. Maybe they will have to come up with some kind of royalty plan. These issues we are still developing in our thought process.

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