Accelerated Trial Timelines Putting Increased Pressure on Sites

“The days of sponsors waiting on sites two or three weeks is no more,” according to Jeffrey Smyth, CEO of Moore Clinical Research, a network of three sites in Florida. These days, sponsors expect study startup to begin in about five to 10 business days on almost every trial.

“You need a couple days for the feasibility.  When you get to contract negotiation, you want to do that in tandem with IRB submission so you’re not wasting any time. You want to get your regulatory documents back within two to three business days and get the budget and the contract signed hopefully in under five business days. I know that’s fast, but sponsors want everything done very quickly.”
— Jeffrey Smyth, CEO, Moore Clinical Research

The amount of time between a site getting the green light from a sponsor to proceed with a study and first-patient, first-visit can be accomplished in five to 10 business days, Smyth told attendees of MAGI’s Spring Clinical Research vConference.

Jill Johnston, president of study planning and site optimization for WCG, said independent sites or sites that are part of a private practice are more likely to be permitted to negotiate contracts and submit to IRBs concurrently, and should do so “because these two items usually take the longest in the process and can hold up a site from being activated and starting to see patients.”

But for sites that are part of a larger institution, SOPs or other processes may prohibit doing tasks like contract negotiation and IRB submission in tandem.

“Sites might need to negotiate the contract first and have it fully signed before they’d ever consider sending it to the IRB – or vice versa. From their perspective, they do not want to waste any time. If the study cannot be contracted, why would they seek IRB approval?”
—Jill Johnston, President of Study Planning and Site Optimization, WCG

She added that having a contract and budget signed within five to 10 days “is the expectation for independent sites, but at larger institutions it can take a lot longer.”

Elizabeth Weeks-Rowe, a clinical research training consultant, told CenterWatch Monthly that larger institutional sites should try to be as responsive as possible, even if they can’t perform certain tasks quickly. Large sites also typically have longer timelines, she said. “For dedicated research sites, physician’s practices with research departments and smaller institutions that can use central IRBs, they should strive for those quick timelines with regulatory, contract and budget.”

Johnston said data from CSDD and WCG show 37 percent of sites selected for studies under- enroll. She added that while 89 percent of studies eventually meet their enrollment goals, that is often accomplished at the expense of sponsors having to double their enrollment timelines, primarily due to poor enrollment. Meanwhile, WCG data show the conventional model of getting studies up and running used to take a median of 57 days between a site first being contacted and the site being selected.

“That takes too long. We could be much improved with our processes. A lot of times, we have customers that come to us that are looking for a much quicker turnaround time because they’re behind the eight ball in trying to identify key sites for their clinical trials."
—Jill Johnston, President of Study Planning and Site Optimization, WCG

JIT Accelerates Notoriously Slow Cancer Trials

Faster study startup is also a goal in oncology research, which is becoming increasingly challenging as targeted therapies and precision medicine gain traction. Rosemary McQueary, director of research for the Quality Cancer Care Alliance (QCCA) Network, said studies are becoming more complex, patient populations are very small and researchers are looking for specific molecular targets in their studies. 

As a result, study startup for oncology trials takes longer. A survey conducted in April shows a majority of oncology sites reported meeting study startup timelines in less than 120 days. Fifty percent of the sites reporting data to the WCG Knowledge Base said they met study startup timelines – defined as the amount of time between protocol delivery to trial activation – between 61 and 120 days, while 25 percent reported meeting that timeline in 121 days or more and 20 percent met timelines in 60 days or less. Five percent of sites did not measure their startup timelines.

“The traditional method of getting a site open, activated and identifying and enrolling patients just doesn’t lend itself to a lot of these rare mutations, biomarkers and patient populations that we’re looking for. What we are finding is that sites are opening, but it may take a year to find a patient or they may never find one. Anyone in operations understands that the cost of opening a site is very high, and once a site is open there's a lot of work that has to be done on a regular basis.”
—Rosemary McQueary, Director of Research, Quality Cancer Care Alliance (QCCA) Network

QCCA is a network of 16 independent, community-based oncology practices that send EHRs into a centralized data warehouse. That allows the sites to more easily identify patients who might meet their very specialized criteria, McQueary said. QCCA and its competitors in the industry offer additional centralized services to save time – a standard rate card for budgeting, master clinical trial agreements (CTAs) for contracts and standardized informed consent language. QCCA’s sites also use one central IRB, she said.

There are exceptions for some oncology trials. In one example of an accelerated JIT study – involving a stage 4 cancer patient in her 20s who had exhausted all other opportunities for treatment – McQueary said essential documents were collected and sent to a sponsor one day after the patient was identified through QCCA’s data warehouse. On Day 2, a CTA was fully executed, and an IRB submission was completed. IRB approval was received on Day 3, a site initiation visit (SIV) was completed on Day 6, the same day that the site received a green light from the sponsor to proceed with the study, and the patient consented on Day 7 and was enrolled and dosed on Day 10.

“This really is a lifesaver – to be able to identify a patient and have them enrolled in a 10-day period. This really is a super accelerated timeline, and there are a lot of things that go into it that allow this to happen. We really strongly suggest negotiating contract language and budget upfront, so that when that patient is identified we don’t have to go back and forth with a sponsor or a CRO and get mired in all that.”
—Rosemary McQueary, Director of Research, Quality Cancer Care Alliance (QCCA) Network

JIT programs with faster timelines allow patients to stay in their home community to receive cancer treatment from their provider, rather than having to hit the road for hours to reach a site far away. “What we've tried to do is really take a patient-centric focus and bring the trials to the patients when they need them,” McQueary said. Faster JIT programs also minimize the risk of empty clinical trials, which cost money for sponsors and create headaches for sites. She said trials in this format also don’t open until a patient is identified, saving sites from study maintenance work, such as safety reports, IRB renewals and updates.

Embracing the New: Making JIT Work

Still, JIT, a longstanding practice in manufacturing, is a relatively new model for the trials industry “and that scares a lot of people,” McQueary conceded. And while sites must be able to “drop everything” in order to open quickly, quality and safety cannot be sacrificed in order to gain speed. “We still have to do everything exactly like we would with opening any other clinical trial. We have to follow every step, every process, everything needs to be done appropriately.” 

McQueary said doing anything in advance is helpful and suggested sites host sponsors for a generic assessment visit and site initiation visit at the same time. “There is a little bit of risk involved in case a sponsor or CRO were to find something that would be a real showstopper for them,” she said. “But if it’s someone you’ve worked with before I think those things can be done in parallel.”

Smyth said sites need to measure their current turnaround times, in business days, from the day they receive documents to the time they turn them in to a sponsor. They should establish, on average, the number of days it takes to complete various tasks in the startup process. “You need to understand current industry expectations for turnaround time,” he said. “What are you up against? What is your competition doing? How can I do better? After you measure your turnaround time, develop realistic goals to reduce them so you're meeting industry standards.” 

Master CTAs, which can apply to more than one study, save sites time, Smyth said, because they “already have all that language that your attorney has approved for your site to use. At that point, hopefully, you’re just negotiating terms as far as payments, the budget and those sorts of things.” He said sites should also consider completing their CTA and budget negotiation in tandem with the regulatory IRB submission process. Pricing sheets can also help expedite things, so long as sites know the fair market value for their services ahead of time and can provide a rationale or documentation on the pricing.

Electronic systems can enable sites to return confidential disclosure agreements in less than 24 hours and feasibility questionnaires in less than two business days, according to Smyth. CTAs and budgets can be received, reviewed and returned in less than three business days, he said, as can the delivery of regulatory documents and the completion of submissions to an IRB.

Johnston concurred, but added “the real key here is to have the business processes set up on the site side to enable this to happen. If they are not organized or have the right information or access to the right people at the right time, this will invite delays in that standard turnaround.  It is not the electronic systems that are enabling that to happen more quickly.”

Smyth said flowcharts should be updated and added to a site’s standard operating procedures, with site staff trained and their progress routinely checked. “This is ongoing because you always want consistency,” he said.

“Sites [need] to have high-quality services to show that they’re committed to all of these processes and procedures that support fast startup timelines. Having these enables sites to perform more clinical trials and this equates to higher revenue. It’s just good business.”
— Jeffrey Smyth, CEO, Moore Clinical Research

Weeks-Rowe added that sites can accelerate the process by making sure that the employees doing the contract, budget and regulatory work all have experience doing those tasks and aren’t learning on the job. “There’s nothing wrong with being new,” she said. “Sometimes you can’t help it, and there’s nothing wrong with that. But in an optimal situation, the person doing these tasks isn’t brand-new. It does make things go slower and there are more mistakes.”