Selective Use of Decentralization Methods Best Bet for Most Trials Postpandemic
For more than a year, sponsors have been working with some form of decentralized trials (DCT) and are seeing more clearly how some protocols are benefitting — and some not — from specific elements of decentralization.
Not every trial is suited to a completely decentralized approach, says Andrew MacKinnon, decentralized trials lead at e-solutions provider Medable, but that doesn’t mean sponsors can’t adopt some of the most beneficial elements.
“Quite often, value can be put into trials that are perceived as a poor fit for these decentralized approaches,” MacKinnon says. “There isn’t really a case study or a situation we’ve seen yet where a DCT approach cannot be implemented. It’s the fact that it was the right DCT approach for this particular protocol and this particular patient population that helped bring these successful outcomes.”
The greatest value of DCT approaches, according to a recent survey conducted by WCG Avoca, is participant retention. In a poll of 229 sponsors and CROs, 55 percent of sponsors and 57 percent of CROs believe DCT elements can help boost participant retention in clinical trials, making it one of the top six drivers for adoption and effective use of DCT elements in a protocol.
The survey also found that increasing protocol compliance was another top driver for 46 percent of sponsors and 20 percent of CROs. Increasing study participant diversity was an important factor for 23 percent of sponsors and 20 percent of CROs, while accelerating timelines for individual clinical trials was cited by 24 percent of sponsors and 20 percent of CROs, and increasing data completeness and accuracy was a key factor for 23 percent of sponsors and 10 percent of CROs.
Cristin MacDonald, vice president for client delivery at WCG Avoca, says some sponsors fear that the path forward postpandemic is to use all DCT approaches “without really evaluating which ones are going to provide the most value and which are an add-on just for the sake of adding it on.” But MacKinnon said those fears can be mitigated by finding the right fit for DCT approaches to each protocol.
“Take a look at the protocol, the outcomes, what you’re looking to collect,” he said. “What are the problems with that particular patient population? Is it enrollment, compliance or retention? Then address those specific issues and deploy decentralized elements to fit that particular piece. That way you’re not throwing the decentralized kitchen sink at a protocol, you’re just picking the right elements that work and will return value.”
Speaking at a recent WCG Avoca/Medable webinar, MacKinnon offered the example of one trial that was particularly suited to the completely site-less approach. A sponsor of a rare disease study needed to screen and enroll 1,000 participants. MacKinnon said such a study would usually require a large number of sites and the enrollment period would be lengthy. But by using a single principal investigator, shipping supplies directly to patients’ homes and capturing patient-reported outcomes electronically, researchers were able to enroll more than 75 patients within three weeks. Patients were sent blood draw kits and dropped the results off at a nearby patient service center.
“This DCT approach — removing sites — works really well in these types of studies, but it may not be the approach to take for a lot of protocols,” he said. “But in this situation, it worked very effectively. What we shouldn’t do is overcomplicate things and expect the technology to take on more than what we do in a traditional approach.”
For instance, a more selective DCT approach helped revive a study of a rare genetic variant that causes age-related macular degeneration. The sponsor originally estimated it would need to screen 11,000 patients from 100 sites in a traditional trial but didn’t have the resources, so the study was shelved. To solve the problem, Medable helped deploy a completely remote screening process using a genetic screening kit and took an e-consent approach. Rather than taking a traditional approach to selecting the 100 sites for the study, once the patients were identified researchers selected about 25 sites that were close to those patients’ homes. As a result, MacKinnon said, the study that was expected to take two years and cost about $50 million took only one year and the sponsor saved about 40 percent in costs.
In another example of a selective DCT approach, Medable was able to demonstrate that DCT elements can also help protect the safety of participants. A sponsor interested in earlier detection of pulmonary adverse events (AEs) was planning a traditional approach where participants would have their blood oxygen level (SpO2) measured during on-site visits conducted weekly, monthly and quarterly as they advanced through the trial. “If you’re only taking that SpO2 measurement on a weekly, monthly or quarterly basis, those are your datapoints for identifying AEs and you’re becoming more sparse in your measurements and less able to detect that event happening,” he said.
MacKinnon said researchers sent participants a Bluetooth device that clips onto the end of their finger and can send daily SpO2 measurements to a smart phone, which in turn sends the data to sites and the study team. “We were looking at getting much quicker identification of a potential problem — ideally a quicker intervention to prevent that from becoming more problematic for the participant and retaining them in the study,” he said. “But it was really about mitigating the risk to the patient.”
But concerns about implementing DCT linger. When asked by the WCG Avoca survey to identify the top five perceived challenges to incorporating DCT elements in a clinical trial, 29 percent of sponsors and 40 percent of CROs said operational and process integration was an issue, while regulatory challenges were cited by 27 percent of sponsors and 24 percent of CROs. Another 27 percent of sponsors and 12 percent of CROs cited a lack of understanding of the DCT innovation, while 20 percent of sponsors and 30 percent of CROs said uncertainty over the value proposition or ROI of a DCT innovation gave them pause. Nineteen percent of sponsors and 20 percent of CROs cited startup costs as a factor. The survey found that 14 percent of sponsors thought lack of understanding of a DCT innovation was the top challenge overall, while 16 percent of CROs named regulatory challenges as their top concern.
Regardless of industry reservations, DCT elements will continue to be adopted because patients are going to demand the convenience they provide, says Kimberly Ray, an industry consultant who led the Association of Clinical Research Professionals (ACRP) Task Force on Decentralized Clinical Trials and Technology Competencies. “Everyone is living it. We get next-day delivery, we get food brought to our door,” Ray told CenterWatch Weekly. “Patients are going to say, ‘Why do I have to go every four weeks to your site?’”
Ray added that the ACRP task force concluded that the vast majority of trials going forward would be hybrid trials with some aspect of decentralization and a lot fewer fully decentralized trials. “But patients are going to force the issue,” she said.
A recent survey by ICON bears out that thought. Of 3,800 patients surveyed (44 percent of whom had previous clinical trial experience), only 26 percent said they would prefer clinical trial tests and procedures to be conducted at the trial site, 33 percent said they preferred a hybrid approach to trials and 58 percent said they would consider participating in a trial where all visits were conducted virtually. And 90 percent of respondents said they were willing to travel no more than one hour to participate in a trial.
Trial participants need options, the ICON survey concludes. “If we want to increase participation in clinical trials, we need to dig deep, review the protocol and the drug safety profile to choose the right model that provides patients with the options they need to participate.”
“Overall, this is a good thing for recruitment and retention,” Ray said. “It’s just a matter of working out the details. It’s not right for every [trial], but the more convenient we can make it for the patient, the better the experience they’re going to have.”