By Turna Ray
Two genomics leaders have teamed up to create an open channel by which drug developers can access each other's non-proprietary clinical data for the purposes of advancing personalized medicine — an effort that has so far inspired pledges from several industry players to share data captured in the comparator arms of drug trials.
Drug developers have a reputation for keeping a tight hold on their clinical trial data, but this practice has proven to be detrimental when it comes to the development of genomically guided drugs. Now, with drug revenues expected to decline between $80 billion to $100 billion in the next four years due to off-patent drugs, and the pace of innovation slowing at pharmas and biotechs, the industry has become much more willing to engage in collaborations to generate and share precompetitive clinical data that can be used to jumpstart innovation.
Noticing this shift in the drug industry's psyche, Stephen Friend, CEO of Sage Bionetworks, a non-profit organization developing an open-access platform for building networked models of human disease, and Sharon Terry, CEO of the non-profit health advocacy organization Genetic Alliance, have spearheaded the Comparator Arms of Clinical Trials Program, or CTCAP. The program aims to build a genomic data-sharing community among pharmaceutical companies and other organizations willing to share data collected on patients who received a placebo or the standard of care in drug trials for investigational treatments.
In a related effort, Friend and Terry are also launching a grassroots campaign to spur drug developers to give study participants access to their own data so they have control over how that data is used in further research. If through this campaign, study participants are successful at getting drug companies to change their consent policies, it could potentially transform the data-sharing culture in drug development research.
"For virtually every clinical [drug] trial, there is a need to compare the investigational arm, which is proprietary, to something that is standard, such as placebo or a standard of care," said Friend, who was formerly senior VP and franchise head for oncology research at Merck. "So we have started going around to pharmaceutical companies asking, 'You want better maps of disease? Some of your best information is found in the comparator arms of your clinical trials. There is no proprietary information there. If we began to get people to pledge that, would you?'"
Looking back over his career in the drug industry, Friend is certain that pharmaceutical and biotech firms wouldn't have been too eager to participate in such an effort two or three years ago. But the fact that in the last six months the CTCAP program has enlisted data pledges from seven drugmakers, a contract research organization, and a pharmacy benefits manager is a sign of shifting tides in an industry that last year spent $100 billion in R&D and succeeded in garnering marketing approvals in the US for only 21 new chemical entities, compared to 26 in 2009, and 24 in 2008.
In trying to propel the pace of development, "there has been a recognition [among industry players] that some of the new tools to look at diseases provide an opportunity that is potentially awesome, but almost unaffordable," Friend observed. "So, there has been a shift in industry's attitude from, 'Why would I want to share anything?' to, 'I would really like to do this, but it's going to cost too much money, so is there any way that we might be able to do that?'"
Benefits of Sharing
Precompetitive alliances like CTCAP are one solution to pharma's drug development and productivity challenges because they allow companies to understand the pathophysiology of complex diseases without making large investments in unknown research areas. Last year, Lilly, Merck, and Pfizer, agreed to share precompetitive pharmacogenomics data for lung and gastric cancers under the auspices of the Asian Cancer Research Network. Under the partnership, the drug developers are creating "one of the most extensive pharmacogenomics cancer databases known to date" (PGx Reporter 02/24/2010).
CTCAP currently involves Pfizer, GlaxoSmithKline, Roche, Lilly, Merck, Johnson & Johnson, Genentech, Quintiles, and Medco. The project has also attracted the attention of the US Food and Drug Administration, which has expressed a desire to integrate comparator arm data sharing as a routine part of the drug development process, according to Friend. "In still keeping with the idea that information on lead compounds headed for [regulatory] filings are held close to the chest," the varied interest in CTCAP suggests "the culture is shifting around this clinical trial comparator arm data," he said.
Robert Epstein, chief clinical research and development officer of Medco, said the PBM is "very supportive of the work by Sage to assemble genomic data from a variety of sources, curate it, and make it available in an encrypted manner for researchers to abstract new knowledge."
Epstein added that Medco is exploring ways to collaborate "that would be both respectful of our members' right to their data and where and by whom it is used, as well as that of our plan sponsors. To the extent to which we are able to participate with Sage … we look forward to it."
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CTCAP data pledges so far promise to contribute significantly to genomically guided personalized medicine research. Friend and Terry have asked participants to contribute data from trials that have included whole-genome SNP analysis or whole-genome expression profiling, and have been surprised by the response.
"Three companies out of the eight, which I will keep anonymous for now, had more than forty studies, with [genomic] data on average between 100 and 2,000 patients deep … That is an order of magnitude greater than I would have guessed," Friend said.
Although FDA is seeing more and more complex genomic data submissions from drug developers, there are only a few examples of drugs that are marketed for genomically targeted subpopulation of patients — among them the colorectal cancer drugs Vectibix and Erbitux, the breast cancer treatment Herceptin, the HIV medication Abacavir, and the leukemia drug Gleevec. This might be due to the fact that pharmaceutical companies see little economic incentive for investing in large, expensive pharmacogenomic studies to launch a drug in a small patient subset that would yield a fraction of the revenue of a drug that can be marketed more broadly.
"Drug companies are only submitting genomic data when it goes to a labeling advantage. I think that's the gap," Friend observed. "The thing is the comparator arm has nothing to do with the labeling advantage either way. So, I think it's giving visibility to a set of data" that can advance research and drug development in the genomics space.
Friend projected that in the next year, CTCAP's drug partners will move from singular pledges to multiple contributions, and start organizing data submissions to try to build models of certain complex diseases and drug toxicity.
Friend and Terry are also launching the ThatsMyData campaign to encourage drug developers to give study participants access to their own data so they can control how that data is used by other researchers. This project's success will depend on the grassroots efforts of organized study participants who demand that funders and drug trial sponsors change their data access policies. If successful, ThatsMyData could foster a more open data-sharing environment among drug development researchers.
"If you think about what's keeping CTCAP from getting more momentum, it is the current culture of giving approval consent for [research] data," said Friend.
Under most data consent policies for drug trials, participants essentially give up all rights to see their own data after the trial is completed. As a result, the information cannot be used again by other researchers and is lost forever.
According to Terry and Friend, there are no real legal barriers to providing study participants more control over how their data is used after the completion of a trial. Current international and US laws include language granting study participants rights over their own data. Furthermore, the Genetic Information Non-discrimination Act would bar insurers and employers from accessing or using genetic research data on individuals for underwriting or employment decisions.
The lack of data access is more a result of the "paternalistic attitude that … others know what to do with your data, and you don't know what to do with it, and I'm going to protect you from yourself," according to Friend.
"If the public knew that this data was lost, that it wasn't recycled and shared, then they'd be pretty outraged," Terry added.
In rolling out the campaign, Terry plans to enlist the help of study participants who are willing to demand that drug trial sponsors provide access to their clinical trial data in exchange for their participation. "I can see an indigenous population saying, 'We're only going to participate in studies if we can have the data once it finishes," Terry said, adding that she plans to raise awareness for the campaign through social media and trade media outlets.
Terry said that recent advancements in the way researchers track study subjects and store data should support the effort's aims.
"Drug companies say it will be too expensive and too difficult to track individuals to return data. We know in this age of electronic interactions that that is silly and nonsense and it wouldn't be hard to do at all," she said.
She noted that another industry argument against data-sharing has been that clinical trial subjects are often lost in follow-up settings, but argued, "that is less true today because you can move a million times and still have the same e-mail address."
Terry and Friend are both Ashoka fellows, which is a recognition awarded to entrepreneurs who have found innovative solutions to social issues. During the vetting process for the fellowship, they cited their efforts on CTCAP and several other projects around drug development and sharing of genomic data.
Ashoka is not funding CTCAP or ThatsMyData; Genetic Alliance and Sage Bionetworks are actively seeking funding to advance these efforts.
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