Center for Drug Evaluation and Research Director Janet Woodcock put clinical trial networks on the top of her list of what could be done to speed the development of new drugs at a May 6 congressional meeting on how to modernize and accelerate biomedical innovation – and it shouldn’t require legislation to spur the change, she noted.
“If you step back and look at the whole ecosystem I think there are some major barriers that academics and developers face when they try to go from a discovery that they make in the laboratory to an actual product that is given to patients. And in order of perhaps ability to deal with this, I think number one, the clinical trials system that we have is not a system,” Woodcock told the House Energy and Commerce committee.
Instead, a new clinical trial is set up for each drug that is tested and dismantled as soon as the project is complete, she explained.
“And it takes years, it exhausts the investigators and [involves] much paperwork and often many lawyers,” Woodcock said at the committee’s first meeting on its 21stCentury Cures initiative, which is designed to examine ways to improve and accelerate biomedical innovation.
Energy and Commerce Committee Chairman Fred Upton, R-Mich., expects the initiative could help lead to legislation in about a year (“Drug Development Legislation Targeted For Next Year By Rep. Upton” —”The Pink Sheet,”Apr. 21, 2014).
Instead of reinventing the wheel for each trial, Woodcock advocates “turning the paradigm on its head,” by creating clinical trial networks, which are also referred to as standing trials or the “master protocol approach.” These networks are funded, staffed, have registries of patients and are ready to go when a new drug is ready to be plugged into an already created protocol.
Examples of such an approach include the I-SPY 2 breast cancer trial, a screening trial that exposes people with high risk breast cancer to different therapies matched to biomarkers and a Friends of Cancer Research/Brookings proposal for a multi-drug, multi-sponsor registration study of targeted cancer drugs, starting with squamous cell lung cancer (“Landmark Trial for Personalized Medicine Coming Soon: NGS Approval May Be One Offshoot of Lung Cancer “Master Protocol”” —The RPM Report,April 2013).
Credibility Advantage Possible
These trials are not only economical, but may offer a credibility advantage, Woodcock said.
“It’s much faster, it’s more independent, if I may say so, because the product … is given to the network [and] they evaluate it and so there is some distance there between the evaluators and the inventors,” she noted.
“But basically it saves a lot of money and you get to do head-to-head comparisons in this network because you are testing multiple products as well as the approved therapies at the same time,” Woodcock said.
Clinical trial networks “would be particularly important for example in the area of antibiotics, where there are real problems enrolling patients and we know clinical trials are barriers in antibiotics development,” Sarah Despres of Pew Charitable Trusts told the committee.
Woodcock credited trial networks for helping get some rare disease products on the market. The networks “have the patients ready, they have them genotyped, the investigators are trained, and everybody’s ready to go.”
Cultural, Not Legislative, Change Needed
When later asked more about what Congress could do to help develop the networks, Woodcock said legislation was not necessarily needed.
“I think a lot of the barriers have been cultural in the way we’ve done things in the past, this is how we’ve always done them so this is how we will do this. But the availability of electronic health records, the availability to reach out to clinicians all over the country to join them together and then to do trials using that infrastructure and training could provide all sorts of linked networks, it could very rapidly answer questions, which is really what drug development or device development is about – does this work, is this safe – you can very rapidly answer those questions.”
“A network is simply a group of trained people who are eager and ready and have the protocols in to evaluate something. Registries are where you identify patients and then you follow them. You can do trials in that registry; you can randomize people in that registry. These things are all linked together, this type of infrastructure that we don’t really have.”
Woodcock said FDA is working to help change the culture by participating in trial networks like I-SPY 2, and helping to develop the data standards that will enable standardized protocols by working with groups like the Coalition For Accelerating Standards and Therapies (CFAST), which is a partnership among FDA, the Clinical Data Interchange Standards Consortium and the Critical Path Institute to develop and maintain data standards tailored to individual diseases and therapeutic areas (“Rebooting Regulatory Science” —”The Pink Sheet” DAILY,Dec. 5, 2012).
Other groups FDA is assisting includeTransCelerate BioPharma Inc., an initiative started by 10 big drug firms that now has 17 member companies, that is working to develop shared R&D strategies including clinical data standards and certification of sites and investigators (“Major Pharmas To Collaborate In Non-Profit Initiative To Resolve Clinical Development Hurdles” —”The Pink Sheet” DAILY,Sep. 19, 2012).
“But there dose have to be support,” Woodcock said for the networks. “We have been encouraging people.” FDA has been thinking about how these networks can be supported and set up while at the same time stakeholders focus on their current R&D.
Trials Need To Be Efficient, Not Trashed: Pew
Woodcock has put out her call for standardization and collaboration in clinical trials multiple times in recent years (“Woodcock Pushes Standardization to Speed Rx Development, But Will Uniformity Cripple Innovation?” —”The Pink Sheet,”Jul. 22, 2013).
But as Congress considers how it might make its mark, the Energy and Commerce Committee is already considering ideas that could allow for approval of some supplemental indications without trials (“Woodcock Pushes Standardization to Speed Rx Development, But Will Uniformity Cripple Innovation?” —”The Pink Sheet,”Jul. 22, 2013).
Stakeholders like Pew’s Despres are emphasizing that clinical trials may be able to change, but should not be eliminated.
“You are going to hear a lot about the challenge of trials and the answer is not to get rid of the randomized controlled trial. It’s the gold standard and we often need it at the end of the day,” Despres said. “The regulators need the data in order to assess a product, the clinicians need the data in order to know if the product is safe and effective, and the patients need the data to know if it’s the right product for them. So the question is how to gather that data more efficiently.”