Challenging conventional wisdom that IRBs delay clinical trials
Still, steps to improve can be taken
The conventional wisdom in research circles is that IRBs are the main drag on the process, slowing down the progress of a clinical trial with an unnecessarily complicated review system.
That's what David Dilts, PhD, heard too as he started to examine the process for activating clinical oncology trials. Dilts is director of the Center for Management Research in Healthcare at Vanderbilt University in Nashville, TN. He has studied operations processes in various other industries in addition to healthcare.
Dilts and his team minutely examined all the processes involved in activating a clinical oncology trial to see what slowed things down, using the Vanderbilt-Ingram Cancer Center (VICC) and its affiliate network as an example. His goal was to find the points in the process where the most delays occurred so that trials could be opened faster.
"Before I started the entire process, I had absolutely no preconceived ideas as to what it would be and almost universally, everybody told me it was the IRB," he says. "What we found out was more often than not, it was the contracts — that contracting was a major holdup."
In fact, his data showed that the IRB process was actually faster than both the contracting and scientific review processes at VICC.
Dilts says IRBs aren't completely off the hook — he faults them for failing to gather hard data on their own operations in order to identify ways in which they could improve. And he believes that solutions currently under discussion, such as alternative models of IRB review, could help the situation.
"But if you're in an organization that thinks if we cut our IRB time in half we're going to open studies twice as fast, the answer is no," he says. "That doesn't absolve IRBs from making the processes better. But to blame the IRBs — we have not found that to be the main factor."
Dilts and his colleagues first detailed all the steps for opening a trial at VICC, using a team of experts from the cancer center, the Vanderbilt School of Engineering and the university's Owen Graduate School of Management. In total, they found more than 110 steps involved in activating a study. Then they looked at how many of those steps actually added value, and found that only 50% of them overall did so. Of the steps involved in the IRB process, less than a third were considered value added.
Dilts gives an example of what might be considered a non-value added IRB step, noting that at one organization, staff might spend a day making 25 copies of every protocol, stacking them and sorting them into envelopes, which then would get delivered to each IRB member.
"The question is how did that increase the safety of the study? How did that do anything in with regard to the efficacy of the process?" Dilts says. "It didn't. That was pure busy work. If you scanned them into a PDF, sent them out in one email, everybody's got it and you've saved yourself an enormous amount of time and effort. That's a classic non-value added activity that you can easily get rid of."
Dilts' team looked at more than 200 protocols handled by VICC and its affiliate network from January 2001 to June 2005, using archival timing data to determine how long each process took.
They found that the median time to open a trial at VICC was 171 days. The median time for the IRB process was 47 days, compared to 70 days for scientific review and 78.5 days for contracts.
Dilts and his colleagues also have studied NCI-funded cancer cooperative groups. In one case, the Cancer and Leukemia Group B, the process itself was much more complex, with more than 300 steps, and took much longer. But again, the IRB process itself (this time handled through the NCI's Central IRB) was among the fastest.
Why then do IRBs so often get blamed for slowing things down? Dilts thinks it may be because IRB delays are much more apparent to investigators than contracting problems.
"Investigators have to actually do something when the IRB makes comments," he says. "But investigators don't have to do anything when the contract is being negotiated, so the perception is, because I'm busy, this must be the problem."
A dissenting viewpoint
Not everyone agrees with Dilts' findings. Norman M. Goldfarb, CRCP, managing director of First Clinical Research of Palo Alto, CA, and editor of the Journal of Clinical Research Best Practices, says data he's seen shows that the IRB review process continues to be a major problem, particularly at local IRBs.
As an example, Goldfarb points to data from one month in 2007 reported by the clinical research organization Quintiles. It shows that for sites with a local IRB, contracts took 121 days, while the regulatory process took 157. For sites using a central IRB, contracts took 28 days, compared to 44 days for regulatory.
"So in both cases, the regulatory takes longer, and in both cases, places with local IRBs take substantially longer than places that use central IRBs," Goldfarb says. "Those numbers I would say are accurate within 20% today, for the average site."
He says it's hard to analyze data about specific processes because they're all interconnected and can affect each other.
"Let's say you're at a site and you know you're not going to have an IRB meeting for another four weeks — you just missed it," Goldfarb says. "You're not necessarily going to rush to do your contract. Similarly, if you know contracts take months to do, you're not going to rush to do the IRB review.
"There are a lot of complications in analyzing the data."
While he disagrees with Dilts' findings, Goldfarb says he's glad he's working on the problem — "because nobody else is doing it."
And he warns that this issue could become more important as the industry heads into a more stringent regulatory environment.
"That will tend to slow things down." Goldfarb says. "So the problem may be getting worse rather than better."
Reference
- Dilts DM, Sandler AB. Invisible barriers to clinical trials: the impact of structural, infrastructural and procedural barriers to opening oncology clinical trials. J Clin Oncol 2006 Oct 1;24(28):4545-52.
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