Two venerable research institutions are collaborating in a far-reaching partnership that aims to safely speed research, translating trial results to patient interventions in more expedited fashion.
The newly minted Trial Innovation Center will be run by Duke Clinical Research Institute and Vanderbilt University Medical Center. The center is funded by a seven-year, $26.5 million grant from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health.
According to the project website, the goal of the center is “to create innovative methods to accelerate the implementation of multisite clinical research studies, especially those done within the national Clinical and Translational Science Award consortium.”
The collaboration will focus on the following four core tenets:
- A Study Design Core will work with investigators to develop protocols and feasible study budgets.
- A Study Start-up Core will create Master Clinical Trial Agreements and oversee a central IRB to get trials underway as quickly as possible.
- A Study Conduct Core will provide support to investigators from trial design to research results.
- An Innovations Core will create solutions to streamline and expedite interactions with the clinical trial sites.
Two principals in the project recently talked to IRB Advisor about the implications for research advancement and improved patient outcomes. Gordon Bernard, MD, is director of the Vanderbilt Institute for Clinical and Translational Research. Phillip Brian Smith, MD, is chief of the Division of Quantitative Sciences in the department of pediatrics at Duke University Medical Center.
IRB Advisor: As outlined, the project will study how multisite clinical trials of new drugs and therapies in children and adults can be conducted more rapidly and efficiently. Can you comment on some of the historical background on this issue, particularly the aspect of prolonged or multilayered IRB review?
Smith: There are lots of barriers to clinical trials — procedural things that have to be done, guidelines to be followed, institutional and FDA [requirements] — and one of the things is IRB review.
For most studies, traditionally, every site has to review the site and give approval. It’s a really cumbersome activity and it gets even more cumbersome the more sites that you have. So, you can imagine if you have, say, 30 IRBs, a handful of IRBs are going to have something they have questions about. If it’s a protocol item — what if it has already been approved by 25 sites but you need to change it for five sites?
Individual IRBs may also insert their own language in an informed consent template form that may be at odds with other sites. All of this takes a large amount of effort for questionable benefit. The central IRB models are designed to avoid that, so you have an IRB that serves as the central board and the others defer review to that central IRB.
IRB Advisor: In that regard, you call for the creation of a “Study Start-up Core to establish Master Clinical Trial Agreements and oversee a central IRB to get the trials underway as quickly as possible.” Can you explain a little more how this would work?
Bernard: Under current approaches, every site’s IRB has to review the project and every site has to negotiate a contract either with a commercial sponsor, with the NIH, or a lead investigative site. The nature of the beast is that those contract negotiations can really slow the process down. Our notion on the contract part of this is that I will oversee the contract process here at Vanderbilt for the clinical trials.
[Investigators] usually already have an agreement designed to suit them. We then need to go through the components and see what doesn’t suit us. Then we negotiate that for a period of several weeks and several months, and then meet in the middle. We say OK, and we sign it and we are good to go, but as I say sometimes that can take months.
What we are trying to do with the Accelerated Clinical Trial (ACT) agreement is write a contract that is very similar to one we end up with — in the middle. So instead of starting off at one end and meeting in the middle, we will see if we can just meet in the middle and shave off some time and have a contract that people can agree with on day one.
IRB Advisor: Of course, the other side of the coin is that some may perceive a bid to speed up trials and drug development as increasing the risk to human research subjects and, ultimately, patients. How will researchers balance the need to expedite research but proceed with caution in terms of subject/patient safety?
Smith: It’s not that the protocol and consent form wouldn’t undergo IRB review. They absolutely would. It’s just that instead of having to undergo 30 independent reviews, we would be being doing the same level of review, but there would be just one. No one has ever shown that [a multiple review process] has been more protective of study participants. The protocols we take care of and manage will look at the science and also look at the risk and benefits of the study procedures. There are additional levels of people deciding whether the research should go forward. All of the issues around conflict of interest and informed consent would still have to be managed around the central IRB.
Bernard: From the contracting perspective, I see no reason for increased risk. From the IRB side, you could conceivably have increased risk, but there is a formal IRB review. It’s not rushed — it’s just one [IRB]. It doesn’t have 29 more reviews that are unlikely to change the project significantly. So, I’m not really worried about that and each of the IRBs that are relying on the reviewing IRB get all of the documents and the minutes — the “thinking” of that IRB that they can then review.
What we’re seeing with some of the pilot work in this area is that IRBs enjoy reading about how other IRBs operate because up till now they have been very siloed. They don’t talk to each other much at the clinical, individual study level. They talk to each other about rules and regulations and working with federal authorities and that kind of thing, but when it comes down to John Smith’s protocol for congestive heart failure, they virtually never talk to each other. They don’t have a feeling for where they are on the continuum of conservative or liberal, and then in some cases they may not have a full understanding of the regulatory component of things like device trials, which can be very complicated.
IRB Advisor: This sounds like an ambitious and sweeping project that has the potential for major research transformation. Can you comment on the scope of this project and the kind of breakthroughs it could potentially lead to?
Bernard: Well, just imagine there was another outbreak of Ebola in the United States — more so than what we saw previously — and there was a treatment of possible benefit, a treatment that woud work. You would want to get that into patients as quickly as possible. With a central IRB process, you could have an IRB that says, “We’re ready to go and we will review it tomorrow.” They would be the central IRB for the project, and any other sites simply need to receive that paperwork and agree that they are applying the next day. Likewise, we would have a standard contract, a budget: “Here’s what we think it should be.” In theory, a site could sign up and be in IRB compliance in a day and enrolling patients. Right now, if you tried to do that I estimate conservatively that it would take six months for all the sites to be up and running, and maybe even a year.
Smith: There hundreds, if not thousands, of really bright investigators with great ideas that are developing things that could really have an impact on patient health. One of the barriers to getting those things to the bedside, getting the trials done that show these things are safe and effective [is the protracted and laborious current system]. Really, these trial innovation centers will be set up to help facilitate those trials and get them done in the most efficient manner.
There are a finite number of healthcare dollars that are going to get spent on research. We have to make the best use of those dollars, so our goal is to get these trials done, to make sure they don’t fail from an enrollment standpoint, and make sure that we don’t waste time and money on steps in the research process that don’t benefit the patients.
Two venerable research institutions are collaborating in a far-reaching partnership that aims to safely speed research, translating trial results to patient interventions in more expedited fashion.
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