IRB Reform Is Low-Hanging Fruit For FDA-Duke Clinical Trial Initiative
This article is reprinted from "The Gray Sheet" – December 10, 2007
One of the first jobs for a new FDA/Duke University partnership aimed at modernizing clinical trials will be reforming policies for institutional review boards so studies can get off the ground more quickly, participants say.
The public/private partnership will bring together government agencies, industry, and the medical and academic communities to identify strategies to make the research process more efficient and develop new standards and technologies to improve safety and enhance the quality of clinical trial data.
An important focus of the initiative, unveiled Nov. 26, will be to trim the fat off the U.S. clinical research process so larger studies can be completed more quickly and with less expense, explained Robert Califf, M.D., vice chancellor for clinical research at Duke University and co-chair of the partnership.
"What we want to do is use this as a chance to really study the clinical trials process and figure out what's not adding value or is detrimental and get rid of it," he said in an interview.
IRBs, which approve, monitor and review human clinical research for hospitals and other study sites, are a good place to start because they are now clearly obliged to do too much, says Rachel Behrman, the director of FDA's office of critical path programs. Behrman will co-chair the initiative with Califf.
"They're being asked to do a myriad of things, more than one could reasonably expect them to do," Behrman told "The Gray Sheet."
This, she and others suggest, unnecessarily slows down clinical research for devices and drugs.
"If you look at how long it takes to get through the IRB system and to get [sponsor-clinical site] contracts done in the U.S., it's completely out of control," Califf said.
He wants the collaboration to help better define the role IRBs should play and devise ways to speed up the process.
According to a recent internal Duke assessment, it takes about four-and-a-half months on average for a multicenter trial to get through the IRB review process. Negotiating a contract between a study sponsor and a Duke research site takes about four-and-a-half months as well, Califf said. Because the two processes do not always occur in sync, the total time to get a clinical trial rolling can be six-and-a-half to seven months, he estimated.
IRB Problems Are System-Wide, Chairs Say
FDA actually has limited direct oversight over IRBs, which are governed primarily by Health and Human Services' Office for Human Research Protections (OHRP) and the clinical institutions themselves.
Because IRB issues are systems-wide, Behrman and Califf say, reforms by OHRP, FDA, sponsors or review boards alone will not solve the problem. But within the context of a broad public-private partnership, the agency can wield important influence in this area, the chairs say.
"I don't think anyone would see this as assigning new responsibilities to the FDA," Califf said. "But it might very well streamline and clarify the ways responsibilities are carried out."
With the initiative planning to address information gaps between various stakeholders in clinical trials, participants see it as a way to modernize some of FDA's currently out-of-date policies.
"It's no secret that when our regulations were written, particularly focusing now on the human subject protection/bioresearch monitoring portion of clinical trials, it was the early '70s," Behrman said. "A large part of them have not been updated. So we see a need there, and we know the industry we regulate sees a need there."
In its 2006 guidance on using centralized IRBs, which are independent from clinical research sites, FDA notes that IRB requirements evolved at a time when most clinical trials were conducted at a single study site.
Rapid growth and an increased focus on human subject protection have shifted more burdens onto IRBs, sponsors and clinical investigators involved in IRB review, FDA says. Meanwhile multiple reviews by multiple IRBs lead to doubled-up efforts, delays and higher expenses for multicenter trials, the document concludes.
Local IRBs Are A Major Delay Factor, Say CROs
Ann Quinlan-Smith, president of Alquest, a contract research organization (CRO) that helps medical device companies set up studies with clinical research sites, says that process efficiency often depends on whether a study relies on a central or institution-based IRB.
For one, independent centralized IRBs significantly streamline the process by reviewing all study sites in a multicenter trial, Quinlan-Smith notes.
Using a central IRB, it can take a week to two months to get from initial collection of regulatory documents to first product use, she estimates. Institution-based, or local, IRBs take longer - about two to six months, she said in an interview.
"Central IRBs are run like businesses," agrees Norman Goldfarb, managing director of First Clinical Research, which provides consulting and training to clinical sites, sponsors and CROs. "They're very efficient and turn things around quickly. At the opposite extreme are the local IRBs. In general it takes months to get an approval through a local IRB."
"I think there are some sponsors who would move away from the large academic centers because it takes so long to get through the IRB process," Quinlan-Smith said.
Goldfarb notes that the market share of clinical research at academic medical centers has declined significantly over the past 15 years, not because of the high cost of doing research there, but because of "slow and difficult" contracting and IRB processes.
Acknowledging that local IRBs are not going away in the near term, Quinlan-Smith and Goldfarb agreed that one means of speeding up the IRB process is simply having more frequent, regular meetings, for independent and institution-based review boards alike.
The Alquest president hopes the FDA/Duke initiative will iron out a way to make IRB review a more interactive, real-time process.
Contracting Process Also Ripe For Review - Califf
A second and related area where Duke's Califf thinks the project could help reduce needless delays to trial startup is in sponsor-clinical site contract negotiation.
"Contract negotiations now take longer than the IRB," he said. "I believe that the key is like any other process: define the key steps and measure them, and then hold all sides accountable to the metrics."
Alquest estimates it takes about a week to negotiate clinical trial research agreements at private sites and about eight months at larger academic centers, primarily because the large centers each rely on their institution's own review board.
"The contract process is more difficult and more time-consuming than it ever has been in the past," Quinlan-Smith said. Though IRB review and contract negotiation are distinct processes, she says, they can overlap in important ways.
"A CRO can impact the speed of the IRB process if they know what the IRB wants and can get them that information," she said. Talking with an IRB representative before formally undergoing the review process, preparing extremely well-written protocol and meeting IRB deadlines are key to expediting the process, she says.
According to FDA, the upcoming public-private partnership will explore the creation of national, standardized contracts to simplify interactions between sites and sponsors.
The Duke and FDA-led partnership, set to begin work before the end of the year, will also consider a broad collection of other initiatives, including setting national standards for electronic data collection, improving the informed consent process and creating accreditation programs for clinical investigators and research sites (1"The Gray Sheet" Dec. 3, 2007, In Brief).
The establishment of an all-inclusive partnership will be crucial to getting any of the priorities accomplished, Behrman said. "There are investigators who actually are doing these trials, there are patients who are participating in the trials, industry is paying for many of these trials, we are regulating these trials. We all need to be at the table to chart a clear path forward."
- Jessica Bylander
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