Veterans Affairs has had some ups and downs since launching CRADA
Agreement could set standard for industry
Despite a slow beginning, the U.S. Department of Veterans Affairs' implementation of Cooperative Research and Development Agreements (CRADAs) for clinical trials could prove to be a model for the clinical research (CR) industry.
Clinical research (CR) experts have been advocating in recent years for sponsors and clinical trial (CT) sites to expedite the negotiating process, which has been a chief factor in the industry's long research delays.
One way CT sites and sponsors could make improvements is through the use of CR agreement templates that are approved in advance by CT sites and sponsors.
Now the VA has developed just such a template that all sponsors negotiating with the VA for clinical research projects must use.
"We've always had CRADAs for basic research," says Amy Centanni, JD, director of technology transfer at the Department of Veterans Affairs in Washington, DC.
"All of our clinical trials were done through clinical trial agreements, entered into by nonprofit corporations directly with pharmaceutical companies," Centanni explains. "Then in April, 2005, the general counsel's office for the VA came out with the decision that VA nonprofit organizations have no authority to bind the VA."
The nonprofit corporations were the result of a 1980 statute that authorized nonprofit corporations with the sole job of funding VA research, accepting money from other government agencies and from private entities, Centanni says.
"Any money they accept has to go to VA-approved research projects," she adds. "So we have about 85 of these nonprofits, and they are each affiliated with a specific medical center."
After the VA general counsel's 2005 decision, the VA formed CRADA.
"We put together a working group and tried to come out with a new model that would work," Centanni says. "We pulled in people from the field, lawyers, transfer program people, and we realized it's not so easy to have a clinical trial agreement."
They ended up creating a different model for various CT scenarios, including phase I and II, phase III and IV, device trials, principal investigator-initiated trials, and other types.
The development and implementation processes have not been easy, Centanni notes.
"To be perfectly honest, it's been a struggle," Centanni says. "It's been a very big learning process for us here."
One common obstacle to CRADA buy-in is that people are resistant to change, she says.
"It's been a slow process — encouraging people to use it, talking about the benefits of it and how it works," Centanni says.
However, time has run out for those who are resistant to using CRADA: As of March 26, 2008, all clinical trials have to be done via a CRADA, Centanni says.
The VA held a conference on CRADAs on Feb. 20, 2008, in Arlington, VA.
Master agreements work at all VA centers
"The other thing we've done is we have offered CRADAs to large pharmaceutical companies that would like to enter into master agreements with us," Centanni says. "There are 13 articles in the CRADA, and all of those terms are negotiated and set and can be used at any VA medical center across the country."
Sponsors no longer need to negotiate with the local CT site each specific term of the agreement, she says.
Initially, it was difficult for VA clinical research sites to educate sponsors about CRADAs, notes Antonio Laracuente, MBA, director of research operations at the Atlanta VA Medical Center in Decatur, GA.
"Much of the work was in discussion, negotiation, explanation, and coming to an understanding that this is a much better vehicle than standard CT agreements," Laracuente says.
"It took a while for the first one to happen," he adds. "Once the first one happened for us, we were in a better position to negotiate with sponsors."
The VAs have no choice now except to use CRADAs, but obtaining sponsor buy-in still is a challenge, says David E. Johnson, PhD, deputy associate chief of staff for research and development at the VA Medical Center in Baltimore, MD.
Even when the VAs were using clinical trial agreements, there were efforts made to develop master agreements with sponsors, Johnson notes.
"Those master agreements are essentially the same now as a master's agreement would be for CRADA," Johnson says. "The sponsor company and the VA sign off on a particular contract language, and for that study that language is negotiated so there is no need for single-site negotiations."
It speeds up the process, but it does require sponsor buy-in, he adds.
"It'll take a while for legal counsel at various sponsors to read, understand, and be responsive to the CRADA format," Johnson says. "But the bottom line is that the CRADA doesn't contain any language that we haven't been insisting on in CT agreements for 10 years."
The Baltimore VA still has not obtained a CRADA contract with a sponsor, he notes.
"What we've been doing in recent attempts to negotiate CT agreements is put the CRADA language into the CT agreement, and I've gotten some push-back from that," Johnson says. "It's been a difficult transition for us, and I'm sure it's a difficult transition for the sponsors."
Integrated system with huge patient pool
However, the VAs have a big advantage when it comes to attracting clinical research. For one thing, the system is vast and spans the country, so there's a large available patient pool for CT recruitment. Secondly, the VA system has a huge electronic data system that lends itself easily to retrospective and epidemiological studies, Johnson notes.
The primary benefit to using the VA for research is the system's integration, Laracuente says.
"While we may be the Medical Center Atlanta, we're also part of integrated hospitals in the Southeast and part of a national network," Laracuente says. "So if a patient starts out in Seattle and moves to Atlanta, there's continuity in the medical record from Seattle to Atlanta."
The VA also has primary care teams that manage different diseases, and the system has a diverse patient population, he adds.
It's because of this kind of clout that the VA may be the one CR entity that could lead the way with regard to global use of a CR agreement template.
A third selling point for CRADAs and other global agreement templates is the efficiencies these bring to the CR process.
"In our negotiations with sponsors, they have indicated their willingness to have these national templates available to minimize all of the back and forth negotiation that goes on with certain clauses," Laracuente says.
While many large research institutions will allow sponsors to dictate the terms of intellectual property agreements in phase III and IV trials, the VA by statute cannot do that unless there's a CRADA, Laracuente says.
"The CRADA mechanism clarifies to the sponsor who has ownership of what's brought in and what's utilized in the study, and in the case of intellectual property development, it clearly delineates ownership rights," he explains.
Before the VA formed a technology transfer office, VA officials were not concerned about inventions, and rights were routinely waived, Centanni notes.
"Now we are more active, and we want to make sure the VA gets credit for what the VA participates in," Centanni says. "All of those terms have changed, and we're much stricter and more stringent on what we allow and don't allow."
Sponsors have to understand that the federal government cannot give away anything without first analyzing it, discussing it, and making a determination, Laracuente says.
But this is where CRADA takes away the delays and lengthy analysis of each CR agreement because these details are ironed out in advance.
"If you have the VA and sponsor agreeing on clauses that have always been difficult, such as intellectual property, data management, data security, then you have, in my opinion, won three-fourths of the battle," Laracuente says. "The indication from sponsors to us is it would be great — getting the central agreement out of our hands and in the central offices."
For example, one of the pharmaceutical company sponsors who came on board early is Novartis, which negotiated a CRADA with the VA's Washington, DC, office, Centanni says.
"Novartis is very happy with the agreement and went out and contacted 12 of our sites to participate in different studies," Centanni says. "We've had nothing but positive contact from both sides."
While the Novartis model is for phase III and IV studies, they're planning to do a CRADA for phase I and II studies, also," Centanni says.
Still, challenges remain.
"Companies are used to doing things through clinical trial agreements," Centanni says. "Now there's a new agreement they haven't seen before, and they have to get their legal department to look at it and review it."
For instance, it's been challenging convincing sponsors to look at CRADA from the VA's perspective, Centanni says.
"I expect there will be growing pains, things we didn't anticipate," Centanni says. "We have learned a lot from negotiations with Novartis about things we didn't include in our model, things we'll need to fix."
Despite a slow beginning, the U.S. Department of Veterans Affairs' implementation of Cooperative Research and Development Agreements (CRADAs) for clinical trials could prove to be a model for the clinical research (CR) industry.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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