University tests model for six-week protocol approval
Ad hoc IRB speeds approval process
When attempting to activate a clinical trial, one of the biggest concerns an institution faces is turnaround time. At Cedars-Sinai Medical Center in Los Angeles, activation of a new clinical trial could sometimes take 118 days, including IRB review, study team response time, and non-IRB required reviews such as contract negotiations. But for some protocols, including early-stage oncology or therapeutic studies, the institution looked for other ways to bring those new therapies to patients as efficiently and safely as possible.
The Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai led an effort to respond to the institution’s challenge to develop a way to activate early-phase oncology clinical trials within six weeks. This meant completing all phases of review, from confidential disclosure agreements, IRB and non-IRB reviews, and trial site activation and enrollment, in just 42 days.
"The Cedars-Sinai cancer institute established a new mandate for Phase 1 clinical trials in oncology. Those clinical trials, sponsors and investigators expect very fast turnaround time," says Eifaang Li, DVM, MPH, CIP, director of research compliance at Cedars-Sinai. "However, we found that the six-week time frame is very difficult to achieve because many delays are coming from the sponsors’ response to IRB questions, not from the IRB or the institution."
Cedars-Sinai developed the Rapid Activation Process (RAP) in an effort to speed these protocols to approval within the new six-week time frame. Other eligible protocols include compassionate use requests, therapeutic trials with urgent need, early phase protocols with a limited activation window, and those dealing with unanticipated problems or serious noncompliance issues.
To identify the key issues and deadlines involved in getting protocols on the fast track to approval, the leadership at Cedars-Sinai formed a working group consisting of IRB administrative personnel, researchers, patient care personnel from the cancer institute, and representatives from the medical center’s Office of Sponsored Research and Funds Administration, Office of Research Compliance, and ancillary committees such as Radiation Safety.
"The team worked together and studied the overall process and each entity involved in that process," Li says. "They identified delays, errors, and how we can work together to meet the turnaround times, including engaging sponsors from the beginning to coordinate the tough issues."
In order to get RAP moving, the group developed a protocol study calendar. The calendar consists of milestones that occur in the life of each protocol, the deadline by which each milestone must be met to achieve activation within 42 days, and the personnel responsible for the task. The study calendar encourages flexibility in the milestone dates if a responsible party is having trouble meeting the goals.
"We look at milestone date, and if there’s a player who says there’s something getting in the way of meeting the date, we look and see if anyone can get their milestones done a couple of days earlier, allowing us to shift extra days to the party who needs more time," says Rebecca Flores Stella, CIP, manager, IRB Operations and Education. "One of our biggest accomplishments was seeing overall study activation as our goal, rather than focusing on issuing IRB approval versus finalizing the budget versus having the contract signed and circulated. We worked together as one unit to help our team members meet their goals. That was a very helpful process. We accomplished that by meeting regularly and tracking our milestones and identify any potential barriers. As we did this more, we got used to doing that and would do it automatically and we didn’t have to meet so much."
Ad hoc IRB
In developing the study calendar, the Cedars-Sinai IRB recognized that meeting the target dates for each RAP protocol would be difficult with the current meeting schedule. For instance, if a protocol involved research-related radiation treatments, the radiation committee would have to give approval after reviewing the IRB-approved consent form, but its next meeting may occur before the next available IRB meeting. To avoid such approval delays, a special board was formed that consists of members who could meet quickly if needed. "We developed the ad hoc IRB to give us an alternative when waiting for the next scheduled IRB meeting would add more days to the turnaround time," Flores Stella says. "We wanted to develop this flexibility without overtaxing our available resources, and without appointing and training new members."
Meetings for the ad hoc IRB can be called quickly when everyone concurs they have had enough time to review study materials, generally within 48 hours of receiving the materials. Membership consists of five seats: three clinicians, one bioethicist, and one community member to comment from a patient’s perspective. Clinician members are chosen based on expertise; for example, a cancer protocol would call for an oncologist to be on the board. The meetings can be conducted in-person or via teleconference, and meeting minutes are distributed and approved by electronic vote for greater scheduling flexibility. The ad hoc IRB meetings can be convened quickly — a protocol can be received on a Friday and the meeting held on Tuesday, Flores Stella says.
So far, the Rapid Activation Process has been used in the review of seven protocols. "These were high priority because they were high enrollment, or a therapeutic trial with patients waiting," Flores Stella says. The first four protocols were managed primarily by senior and management staff. "For tests five through seven, we were able to transfer activities to those who were highly trained but may not be in a management role. We want to be able to transfer the responsibilities from management to other staff while maintaining the same kind of turnaround time."
Constant communication is key
Li says two key practices helped the success of the program: regular RAP group meetings and frequent communication. "It’s a very comprehensive collaborative process," she says. "We also learned that the earlier we could review the protocol, the better it is for everybody. During initial assessment, the radiation safety committee, for example, provides feedback and says maybe the facility doesn’t want us to conduct this kind of protocol, then we can decide we don’t need to continue the review process. It’s very helpful. We don’t want to spend a long period of time on processing the protocol and not have it initiated. I think this process helps to address this kind of issue."
Investigator response has been very positive, Li and Flores Stella say. And while the ad hoc IRB and RAP program are in the early stages, there is hope of having the process extend to more protocols. "Based on the experiences so far, the model should be transferable to process more protocols," Li says.
"I think the biggest benefit is having the opportunity and the institutional mandate to sit down and identify issues and change the perception of the process — we’re one team with one goal of activation by day 42," Flores Stella says. "It really results in forward thinking."