“Study startup has essentially been the same since most folks in the pharma industry can remember,” says Stephanie Petrone, executive director, medical operations for Novartis. “The paperwork is the same and the process is the same. You always have to have a contract. You always have to have a Form FDA 1572 (Statement of Investigator). TransCelerate is tackling the problem of creating a central database (the Investigator Registry) so that certain things, such as medical licenses, CVs, and GCP training, do not have to be performed every single time. Although that will accelerate identification and recruitment of qualified investigators, it does not solve the entire study start-up problem.”
According to Petrone, two stages that always seems to take up an extraordinary amount of time during study startup are establishing site contracts and the Institutional Review Board (IRB) ethics review and approval of the planned protocol. If the trial is complicated or for a life-threatening illness, the process can take even longer. More visits mean more complications which lead to a longer negotiation process on budgets.
If the scientific rationale seems rather complicated, then the trial may need a scientific review committee in addition to the IRB. Each one of those reviews could take a month or more. Petrone notes GoBalto has a solution that can make cycle-time transparent. While the solution may not change cycle-times, it will allow companies to see what processes are taking the longest. With that insight, sponsors can start to examine what can be done to shorten them.
“If the IRB review is taking a long time, we may opt to use a centralized IRB,” says Petrone. “With a centralized IRB, the protocol is approved up front, which shortens what is generally a time-consuming part of the process. While the contract can take longer due to wait times, IRB review can still take two to three months to complete. With a centralized IRB, all the board needs to do is agree a new site can perform the trial. This can knock weeks off your timeline.”
Contracts Are Still A Problem
A central IRB is not always possible. Some hospitals and clinics believe they need to retain local control over the review of the research that will be conducted in their facilities. Assuming a central IRB can be used, the only time-consuming component left is the site contracts.
When considering how the contract process could reduce time delays, the solution may be simple. Use a standard budget and language acceptable to most hospitals/physicians. Although the industry has tried to come up with one standard contract template, adoption thus far has been lackluster. Still, most institutions will agree to standards, and Petrone notes language isn't the major barrier. The standardized budget can often be the greater hurdle. She notes there is certainly a risk that a site will opt to not accept a standardized contract. Sponsors should be prepared for that reality and be willing to work with partners who are accepting of those terms.
“Those two components, a standardized contract and budget plus the use of a centralized IRB, seem to be the drivers of a quick and effective study startup,” says Petrone. “Eliminate those two things and we can take a long startup timeline and begin to whittle it down. I recently presented with someone from a pharma company that was able to cut its study startup time from 18 months to just over 12 months.”
But does this technique really work? Petrone knew the only way to know for sure was to try it herself, and the results were astounding. She notes the rapid study startup model designed by Novartis and used in the area of oncology has allowed the company to execute study startup in an average of just four weeks.
“Think about that for a moment,” says Petrone. “We are talking weeks, not months. Academic institutions generally take six months to start a trial. For us, the real moral of the story was that it definitely can be done. There are nuances that still have to be overcome, but we now know we are capable of making it a reality.”
CRO Takes A Slightly Different Approach
Novartis has a large product pipeline, and the company already had a library full of contract language with every major institution to fall back on. That certainly helped get this effort off to a great start. Once that control language was standardized, the startup effort only required the insistence on a central IRB. Quintiles/IMS has launched a similar effort using a slightly different approach. The CRO has created opt-in, precision medicine networks. If a center opts into one of their networks, they will be set up in advance via contracts with standard language. Then, each time Quintiles/IMS receives an oncology study from a sponsor, that study will be opened up to the network. Any site having access to a patient can be easily brought into the study. To have access to the trial, sites must obviously be a part of the network.
Regardless of the model used, Petrone believes the good news is that faster startups can be done. “We are breaking barriers and finding ways to perform many startup tasks very fast,” she says. “There are challenges we still need to overcome. Sites have to want to do it, and some will certainly say no. We have to open up these opportunities to all sites. For each site that says no, there will be others that say yes. The main principle behind this is resolving the steps that are rate limiting, and getting patients enrolled much faster by using this rapid study activation model. This is also a great example of bringing the trial to the patient, by working with sites that already have patients ready to enroll. Hopefully this will bring an end to the old model of opening sites and then waiting for patients to show up.”
One of the most promising aspects of the model (combining pre-identified patients with rapid site activation) is that its simple structure will eliminate the 30 percent of sites that never enroll a single patient. That alone will be a win for pharma. This model of bringing the protocol to the patient will not help with patients who need to be treated on the spot. It is not a one size fits all approach. Still, for a patient who wants to be in a trial but can’t find one within 500 miles, the model fits their lifestyle.
In any therapeutic area, but oncology especially, this principle of getting patients in the door and the sites up and running quickly will eliminate operational infrastructure problems and allow trials to get underway faster. According to Petrone, that’s a solution that will provide benefits to all sponsors and patients, especially as the model is fine-tuned over the next several years.
“Almost anyone working in clinical research would agree that the current model used in clinical research to get sites and patients is inefficient and outdated,” adds Petrone. “We need to change that model. Speeding the time to startup and opening the trial to all patients is a huge step in the right direction.”