Heading off headaches with multisite IRB review

Use "pre-conferences" and flexible application templates

Reams have been written about the logistical problems of dealing with local IRBs on multisite trials - the delays, the countless changes demanded by individual boards, the overall hassle.

What's rarer is to find someone who's worked out a practical strategy for dealing with this problem — one that's been proven to work.

That was the challenge taken on by Jan Blustein, MD, PhD, associate professor of health policy and medicine at New York University, New York City, and her colleagues.

Blustein, herself the chair of a social science IRB at NYU, was named in 2004 to a team conducting a multisite study as part of the Robert Wood Johnson Foundation's "Expecting Success" program. The program seeks to use quality improvement techniques to improve care to African-American and Latino heart patients.

In taking on the project, which would require individual IRB reviews at 10 sites, Blustein knew that her group could encounter problems — lengthy delays, back-and-forth negotiations with boards over consent documents and privacy concerns, differing estimations of participant risk.

Her group hit upon a novel means of addressing those problems before they came up — working with researchers and IRB representatives at each site before the applications ever were submitted, to try to work out potential problems and address IRB concerns.

"In watching the [IRB] process, it always strikes me that it's bad when people come up with a whole plan and then get shot down at the meeting," Blustein says. "The IRB world can be so capricious and so arbitrary — there's no predicting anything. Everything is so cockeyed out there, why not try to have a direct conversation first thing?"

To her surprise, IRBs were willing to have those conversations, even before their institutions had been chosen as sites for the study. And the approach helped paved the way to a smoother approval process: All 10 sites received approval within 180 days of notification of funding.

Blustein says her team's approach could work with just about any multisite protocol, as long as sites were willing to participate.

"I'm amazed that they were willing to do this," she says. "Nobody said, 'I'm too busy. I don't do stuff like that.' I was impressed by that. I think it shows a lot of effort on the part of people who are putting in their time for free."

Flexible template

The Expecting Success protocol would require post-discharge surveys of patients, patient clinical data, focus group discussions, questionnaires and interviews with physicians, other clinicians and hospital staff. Seriously debilitated patients were excluded from being contacted, and questionnaires did not ask about sensitive subjects such as illegal or stigmatizing behavior.

As a result, the greatest risks posed by the research involved the use and protection of patient data. Blustein notes that at the time of the study, IRBs still were wrapping their arms around the requirements of the Health Insurance Portability and Accountability Act (HIPAA), which put new restrictions on use of patient information.

The group contacted 16 sites that had been chosen as finalists for the protocol. They first provided a model application that researchers at the sites could tailor to meet IRB needs at their own institutions. The templates addressed the usual questions that might come up during IRB review, and included model consent forms, early drafts of the survey instruments and schedules for interviews.

Blustein's team went into great detail about potentially problematic aspects of the study, and provided some alternative approaches for dealing with them. For example, the protocol called for linking patient survey responses to clinical information, which the team knew might raise red flags at some IRBs. So sites were given the option of making those links in-house, and then sending deidentified data to the team.

The research also was broken down into modules or sub-studies, breaking apart the research questions, study design, sampling strategy, recruitment and consent process. Researchers could bind them together into one application or several.

Giving sites those alternatives helped speed the process, and, Blustein says, signaled to IRBs that her team wasn't trying to ride roughshod over individual boards.

"This was about relationship-building," she says. "I think there's a dynamic in IRBs where people start to find things [to oppose]. I think the value here is in establishing some kind of non-adversarial relationship."

Once the sites had had an opportunity to review the written packets, but before they'd actually prepared their IRB applications — and before the foundation board had begun announcing the awards to the 10 sites chosen — the team scheduled a round of conference calls with the finalist sites. Eleven calls were made before the final 10 sites were named, so the rest were discontinued as unnecessary.

Those participating in the conference calls included the site's principal investigator, project director, a member of the IRB and their legal counsel. Although one-hour calls were scheduled with each site, the calls rarely lasted more than a half hour.

In most cases, Blustein says, the project director led the conversation, with occasional input from the IRB representative.

"We would say, 'This is really for you, tell us what you need to know and what you're thinking,'" Blustein says. "And then the project director would take it from there. In some cases, the IRB person was really dominant, and in other cases, they weren't. The project director might say, 'Does this sound OK to you?' and the IRB person would say yes or no."

The calls gave Blustein's team a chance to deal with potential IRB concerns upfront, rather than submitting a proposal and having it denied.

"In one case, one [IRB representative] was absolutely convinced that there was a federal directive that was contrary to what we were suggesting," she says. "The attitude was, 'You've got to convince us.' But at least we were able to make the case on the phone, instead of just getting a letter saying: 'You've got to be crazy. Have you read Statute blah, blah, blah of Regulation blah, blah, blah?'"

'Concentrating effort'

Blustein says putting together a more flexible application and speaking with sites didn't really take more time than it would have taken had they handled the proposal in a more conventional way.

"I think it concentrated the effort we had to make into a particular time period," she says, noting that much of the template work would have been required by her team's own IRB. "I remember there was sort of this frantic week of writing all this stuff. It was a lot of work, concentrated, but in the end I'm sure it was a lot less work. And it was really worth it.

"This helped the sites to think about what they were getting into and helped us to think about what we were getting into," Blustein says. "That's not the intent of it, but it really had that effect. In that sense, it's really efficient. You sort of say, 'What? Hold it — What are we thinking about doing?'"

She notes that it would have been much more difficult to use this approach with a finished protocol already in hand.

Blustein concedes that the attraction of the foundation grant may have influenced sites to participate in the extra pre-award work.

"I think the incentive of the grant was a big deal," she says. "As a rule, the hospitals we were dealing with are not big teaching hospitals. For them, the fact that they were applying for a grant was a really big deal for them." But she notes that at least a few of the sites were at larger institutions, which presumably would be less influenced by the grant.

Blustein believes this approach could have application for other multisite studies.

"Maybe it's most useful if the [research] you're talking about is not business as usual, if it's something a little unusual for that institution."

But Blustein says IRBs in general need to think about what it's like being on the receiving end of IRB review, and to look at research, particularly multisite studies, differently.

She says that on her own IRB, she resists making changes to multisite study proposals unless she feels they're absolutely necessary.

"Because it just makes it too complicated for people," Blustein says. "We get multisite stuff and we say how much are we going to get by making things different? Are we really going to make things better or are we just going to make them marginally better?

"Maybe the message is that people who are involved in this kind of work really need to be involved in IRBs and IRBs really need to consider these as a separate class of review."

Resource

Blustein J, et al. Notes from the field: Jumpstarting the IRB approval process in multicenter studies. Health Services Research. 2007;42:1773-1782.