IRBs contribute to study delays, but there are many other factors
Here are key strategies to reduce delay
The clinical trial industry continues to experience major delays, leading to higher costs and a slow pipeline of products making it to market, experts say. A slow IRB review process at many institutions can contribute to this problem.
In 2005, the IRB review and approval process ranked fourth in the most commonly listed cause of trial delays, says Norman M. Goldfarb, managing director of First Clinical Research of Palo Alto, CA, and editor of the Journal of Clinical Research Best Practices. Goldfarb also is the chairman of the Model Agreement Group Initiative and chairman of the Clinical Research Relief Fund.
The cause of delays most commonly listed were contract and budgets, which ranked first; enrollment and recruitment, which ranked second; and protocol amendment and refinement, which ranked third, Goldfarb says.
IRB review and approval, which is rated fourth, is followed by consent form review and approval in fifth place. Together, these are clearly significant in their impact on study delays, Goldfarb says.
"The primary problem is a cultural conflict between the objective of getting research done in a business-like manner and, number two, doing everything possible at all costs to protect the subjects," Goldfarb explains. "A number of research sites with local IRBs haven't been able to reconcile those two conflicting goals."
Another reason for delayed IRB reviews is that some local IRBs still operate in a way that worked well in past decades, but doesn't suit the current research environment, suggests Paul W. Goebel, Jr, CIP, president of Paul W. Goebel Consulting Inc. of Monrovia, MD. Goebel is on the editorial advisory board of IRB Advisor.
"They have not committed the resources necessary," Goebel says. "Some local IRBs have not increased their staff for many years while volume of work has been steadily increasing."
Meantime, the record-keeping burden has increased, and regulatory creep has set in, Goebel says.
"It's not really in the regulations, but there are new things the IRBs have been asked to do," Goebel says.
For instance, Goebel recently saw on an IRB Internet message board that some IRB members believed the regulations required them to look at a study's budget.
"I don't think that's true, but that's an example of what is happening," Goebel says. "If it's said enough times, people will think it's true."
The Office of Human Research Protection (OHRP) has begun to focus on helping IRBs find ways to increase efficiency and reduce delays.
While it could be argued that OHRP shouldn't be in the business of helping pharmaceutical companies get drugs to market faster, it also could be said that improved efficiency could lead to better quality and greater consistency in IRB reviews, the experts say.
"I think the OHRP's focus is a useful exercise," says Alan M. Sugar, MD, chairman of the New England Institutional Review Board in Wellesley, MA. Sugar also is a professor of medicine at the Boston University School of Medicine in Boston, MA, and he's the director of Infectious Disease Clinical Services at Cape Cod Hospital in Hyannis, MA. Sugar also is on the editorial advisory board of IRB Advisor.
"You make the process faster by making it more robust and focusing on the important aspects of what the IRB is meant to do, rather than simply focusing on making sure the words on a form are accurate," Sugar says.
Sugar, Goebel, and Goldfarb offer the following suggestions for ways to improve IRB response time, while maintaining or improving quality of protocol reviews:
1. Run a local or institutional IRB more professionally, like an independent IRB.
"There are a lot of unnecessary delays," Goldfarb says. "You could do the review more quickly without sacrificing quality review. And you might even improve quality by doing it quickly because IRB members won't forget what they talked about at the last meeting."
For-profit businesses improve their revenue and profit by being expeditious, so for-profit and independent IRBs typically have frequent meetings, sometimes more than once a week, Goldfarb explains.
"One of the largest sources of delays of IRB review is time between meetings," he says. "So if meetings are held every week, there are fewer delays than if they're held every month."
IRBs that meet monthly take, on average, 10 days prior to a meeting and 10 days after a meeting to handle a protocol, so that adds 20 days to the monthly 30-day cycle, Goldfarb says.
When protocols require a change, this will add another 40-plus days to the process, he adds.
Many local IRBs once would shut down for the summer and not have meetings in July or August, the months when the academic institution's staff were on vacation, so some reviews would be delayed for several months, Goebel notes.
While this practice has largely stopped, institutional IRBs still are not as fast at reviewing protocols as are independent and commercial IRBs, which often can review a protocol within one week, Goebel says.
"One week is about as good as you can do with a quality review, and it takes a lot of resources to do that," Goebel says. "Local IRBs often have turnaround times of a month."
The New England IRB meets weekly, so it's able to respond fairly quickly to protocol submissions and changes, Sugar says.
"The big challenge is to get consistency among IRBs," Sugar says. "One of the problems we have is that IRBs are not consistent with one another; every IRB has its own way of doing things and is not always consistent within it, and that can drive investigators crazy and contribute to prolonged review times."
Some academic IRBs contract with independent IRBs to review studies by commercial sponsors in order to help with turnaround time, Goebel notes.
This is a good idea particularly for IRBs that meet monthly at institutions that would like to increase research, Goldfarb says.
Also, local IRBs sometimes have to devote considerable time and resources to the review of protocols created by academic researchers because these studies often are complicated and have not been vetted by staff, as have protocols written by commercial sponsors, Goebel says.
"Investigator studies at academic institutions are the hardest to review and take the most time," Goebel says. "You can't compare the turnaround time with those studies with the turnaround time of a study prepared by a commercial sponsor."
2. Invest in IRB staff to prevent some common protocol problems and causes of delay.
While smaller local IRBs have a very small staff, some of the commercial IRBs have a staff of about 80 people, and they meet three times a week, which makes it much easier to review protocols within a week, Goebel says.
Still, institutions with small IRBs could invest in technological resources, such as software to automate the submission process, to reduce paperwork and improve workflow, Goldfarb suggests.
This would free IRB staff time for other activities, such as working with investigators to improve their protocol submissions.
"What happens quite often is the IRB will send something back to the clinical investigator who will take two months to respond to the IRB, so you can't fault the IRB for that delay," Goebel says.
However, an IRB administrator could pre-review protocols, Sugar says.
"In a lot of academic institutions, you have to fill out a protocol submission form to summarize what's going on, and that can be quickly reviewed by whoever does the intake," Sugar explains.
One person who knows what the IRB does and which questions commonly arise, could pre-review protocols prior to the IRB meeting, Sugar says.
If the protocol has obvious questions that need to be answered, then the IRB administrator could notify the investigator and ask for these answers to be returned prior to the IRB meeting, he says.
"If we don't have a protocol pre-review and if there is something missing, then we lose at least a week in the review process," Sugar says.
Another way to prevent protocol problems would be for an IRB office to educate principal investigators about the proper ways to put together a protocol, Sugar adds.
"One thing that's good about our IRB's renewal and submission forms is that we've used them so long and have tweaked them, making them reasonably easy to fill out, so that if someone has serious difficulty filling out the form, it usually is an indication of other problems," Sugar says. "If the renewal form is deficient in the information we ask for, then that gets our attention."
3. Start IRB review at same time contract negotiation begins.
The clinical trial industry could reduce delays by investing a little extra funding in the process, Goldfarb says.
The contract and negotiation process now takes an average of four months, which means that much time is spent before the IRB review process can begin, Goldfarb explains.
"Ideally, you want to have the two processes go along side-by-side, so when one completes, the other will complete the same time or earlier," Goldfarb says.
However, sites may be reluctant to start the IRB review process before the contract is signed because if the contract falls through, they have lost the time and money spent in the review process, he says.
"One way sponsors can alleviate this is to say, 'If you go down both paths at the same time and don't get a contract, then we'll cover the extra costs,' and some sponsors will do that," Goldfarb says. "Others will not, but in general, sites don't ask for it."
The clinical trial industry continues to experience major delays, leading to higher costs and a slow pipeline of products making it to market, experts say.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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