For years, sponsor companies have had access to new and emerging technologies that would ease the participation burden of patients in clinical trials. Although the technologies seemed to be well received at conferences, few companies seemed willing to take the plunge and try them out. That reluctance to adopt a new approach quickly changed when the COVID pandemic swept the world and threatened to delay or cancel many clinical studies. Hybrid and decentralized trials, and the technologies and solutions that enable them, were suddenly in high demand.
While these emerging technologies helped sponsor companies keep their trials on track, they have also been a burden for the clinical sites having to deal with the changes required to keep up with them. Do you know where your sites stand on the adoption of hybrid trials and DCTs? Are you doing enough to help them manage this new trial environment? And what advice do they have for you when implementing new technologies?
In August 2022 Clinical Leader Live featured three site experts who discussed the pain points of DCTs, including costs, budgeting, training, support, staffing, resources, and more. The participants were Jimmy Bechtel, VP of site engagement for the Society for Clinical Research Sites (SCRS); Karri Venn, COO, president, and chair of the operating board at Centricity Research; and Brad Hightower, CEO of Hightower Clinical. This Q&A highlights some of their concerns and frustrations sites have with DCTs and how you can help them manage these changes.
Ed Miseta: From a site perspective, what happened in the spring of 2020 when the pandemic began to impact North America and sponsors were scrambling to keep their trials afloat?
Karri Venn: We were a bit of anomaly because in 2015 we worked with a sponsor company on different DCT options to see how they performed versus the traditional trial model. It was an incredible learning experience and gave us a bit of a head start going into the DCT rollout during the pandemic. Still, at that time, there were not a lot of decentralized technologies being used other than ePRO and eDiaries.
When the pandemic hit, sites had to come together and figure out new processes, SOPs, and working procedures related to direct-to-patient approaches. Sites suddenly had to continue patient care through a telemedicine portal and make sure it was meeting privacy and compliance standards. When CRAs could no longer make it to our sites, we had to incorporate new paperless systems to get them access to the data. Systems that sponsors have been reluctant to adopt were suddenly moving into sites full steam ahead. It was a lot of work, but it has also opened an incredible number of doors and opportunities for CRAs, sponsors, and sites. There was a real interest in creating a remote, work-from-home concept for CRAs.
Miseta: When this was happening, did you feel you had the support of sponsor companies or were you left to figure things out on your own?
Venn: Initially we were left to figure things out on our own. Sites are smaller than many pharma companies and can be quick to pivot. I think pharma companies had to regroup and get approvals from higher ups and regulators to ensure what they were rolling out was compliant. The sites got sponsor approval where possible and simply forged ahead.
Unfortunately, what was also a delay though, was how we were compensated for the extra work we were doing. That was definitely a challenge.
Miseta: When sponsor companies were scrambling to incorporate decentralized components into their trials, what were some of the biggest challenges sites faced?
Brad Hightower: Initially things were quite chaotic. In 2020 my company was only a couple years old and still somewhat unsophisticated. We did not have a lot of our own tools and relied on the sponsor companies for some of our technology offerings they were scrambling to come up with. In a lot of ways, it was challenging to discern what was appropriate, what would work best, and how to implement solutions in a very quick timeframe. As we were trying to figure out what we were doing, we were also trying to figure out if we would have to do it 25 different ways with 25 different sponsors. It was a new world that we suddenly had to navigate.
Miseta: What were some of the things you suddenly found yourself having to do?
Hightower: We certainly saw a lot of requests for home health visits where we had to send nurses out to visit patients in their homes. There was also a need for direct to patient shipments and e-consent for those trials that were still enrolling patients. Those were probably the top three requests we were seeing.
Miseta: Karri, anything you would like to add to that?
Venn: One challenge for many sites was the entire change management process. To Brad's point, sites were dealing with multiple requests from different sponsors. As a site, you want to try and standardize processes because that is the best way to limit risk. The difficulty comes when trying to deal with those nuances and having discussions with sponsors and CROs to make sure what you're doing is sufficient. That requires a lot of training time for the teams creating the new processes, rolling out the processes, and engaging with other sites to determine what they were doing.
Miseta: Did any of the sponsor companies you worked with help you cover some of these new expenses?
Venn: If you’re referring to IT infrastructure and the cost of new systems, we pass through some of those potential costs in every contract we negotiate. If a monitor doesn't have to travel to a site, that is a cost savings. If I must deploy a system that allows remote access at any time, there may be some cost sharing. Inflation is also driving up costs at the same time we are having to increase salaries. Including some of these costs in overhead is the easiest place we have been able to get some support from sponsors and CROs.
Miseta: Brad, a few listeners brought up the question of costs. Decentralized and hybrid trials were predicted to lower the cost of conducting trials. However, they do require the upfront implementation of new technologies. Will they lower the cost of conducting trials?
Hightower: It's hard to say because there seems to be a lot of opacity with this whole movement. Right now, I’m not sure we are going to see lower costs. It may depend on how intelligently these new technologies are implemented and the types of trials they run across. For example, I don't know how it can be more cost effective to always have home health on call across the country. That is not clear to me yet.
Venn: I agree with Brad. When looking at a DCT study, I think we need to ask ourselves what parts of it will accrue benefits, what parts are going to increase costs, and what parts do patients want? I think there are components of DCTs that are cost effective and will improve the patient experience. I would challenge these systems to be even more intelligent and provide information not only to sponsors but to patients and sites optimizing efficiencies and the experience.
When taking a trial to the patient’s home there are many elements that needed to be considered. When we deployed it, we had to think about the number of staff members needed to go to the patient’s home, driving time to and from the site and ultimately meaning less time on site. As well, there was additional insurance we had to purchase for staff driving. It is also difficult to hire nurses right now. To Brad's point, when you look across an entire nation, how can companies really provide those direct-to-patient services efficiently and cost effectively? And how does that improve trial costs compared to the traditional site model where the patients are coming to you?
Miseta: We have heard about site costs escalating since the stat of the pandemic. Is the move to hybrid and decentralized trials adding to those cost pressures?
Hightower: I think to some degree it is. Sites are having to staff positions with different skills than in the past. Previously our staff was primarily LPNs. Now we need people who are more tech oriented. That will cause a cost increase, especially if you don't already have those skills on your team. Inflation is impacting everyone, and sites often feel they are at the bottom of the food chain. I also feel many site coordinators are looking to move to a CRO for travel opportunities and the chance to earn a better income. Sites want to take care of their coordinators because turnover is a huge problem at the site level.
Venn: Most of our cost increases are payroll related and can be tied to retention strategies and inflation. We are losing good people to companies that are paying a higher premium, which has traditionally been pharma and CROs. Smart sites will find a way to evolve with this change. That might involve finding more entry level positions doing some traditional coordinator roles such as data entry, recruitment and outreach, and regulatory paperwork. We focus the higher premium paid coordinator/nurse roll to solely do patient visits. I believe sites are going to evolve into a different kind of infrastructure that does not have a traditional coordinator doing all the work.
Miseta: Would a centralized tech support service help manage some of those late-night phone calls?
Hightower: It might but can also create other challenges. I have been on the phone with a patient and learned of an adverse event we were not aware of. How will that be handled is a patient is talking to someone who is not affiliated with the site or the sponsor company? Will the person answering the phone recognize the adverse event and know who to report that information to? I also think a big part of patient retention is building relationships with patients. That is difficult to do if someone else is taking their calls. Patients don’t want to be told to call someone else. They will call you first. Although that call can be burdensome and challenging for the site, I think it's preferable to outsourcing it.
Miseta: Have any sponsors considered embedding staff at your site to assist with things like data entry to relieve your burden?
Venn: Yes. And that can be very valuable, especially when you experience turnover or have a ramp up of work. One of the biggest challenges for sites is managing the ebbs and flows of research, which can be unpredictable. Sites can suddenly have extra work and not enough staff to manage it. I have had embedded staff used mostly for recruitment support and data management. If that is something that can be offered, and sites need it, I think it's a great solution.
Hightower: I'd offer a small counterpoint. We had an experience where a sponsor was insistent on providing someone to help with some of the data entry. It ended up being a bad experience for us. With embedded staff you are bringing in someone you don't know and that you haven’t vetted. Their actions can reflect poorly on the site since they are representing your site and your PI. I would caution sites to be very careful if considering accepting that help. Company culture is huge at the site level. It is one way sponsors can differentiate between sites. Anyone embedded from a sponsor company must be a fit with your culture. Much of what we do is based on open communication and working together in a seamless manner. If the wrong person is thrust upon your site, there can be challenges.
Miseta: Jimmy, we now have sites needing to know how to execute the trial protocol, getting trained on DCTs, needing to train patients, and possibly acting as tech support for some of these solutions being implemented. Are site staff members under greater stress than ever before?
Bechtel: I think so. I would argue that years before we were even thinking about DCTs, the concept of bringing in temporary staff from outside the site would have been a foreign idea. A lot of sites would have resisted it. The fact that some sites are now open to receiving support is evidence of the stress they face. Site staff is already strained. Many sites are losing staff as existing staff is being asked to do more things. The burden on site staff has increased significantly.
Hightower: I agree a hundred percent. Earlier I mentioned having to take a phone call at 11 pm to help a patient with a technical issue. That happens frequently. We are working on trials where the diary entry determines whether the patient makes it through to randomization. As a site, you feel you need to do everything you can to support the patient. It’s hard to ask a coordinator to answer their phone at midnight when a patient is calling because an eDiary is malfunctioning, especially when they never received good training on the eDiary in the first place. When that happens, the frustration and stress levels rise. Your costs also rise because you need to incentivize coordinators and ensure they're properly compensated for going that extra mile.
Miseta: With DCTs the question arises around who is responsible for what. Are there potential liability issues we need to be aware of?
Venn: Liability is a big question right now and an issue that has the least clarity. Issues can arise on a protocol-by-protocol basis. If there is a direct-to-patient situations where adverse events are being collected, that raises a lot of questions for sites on who is ultimately responsible & liable
Miseta: Are DCTs having an impact on the ability of sites to recruit more patients?
Bechtel: The potential is there. I don't think anyone can argue that performing trials in a decentralized manner will enable more patients to participate in research. If a patient can visit a site once a month instead of every week because some tasks can be performed remotely, that enables more patients to participate. However, I do not think we have gotten to that point yet. We are still working out some of the critical kinks in enabling DCTs at the site level.
Sites have been told that DCTs will make their job easier. That is the carrot that has been dangled in front of them. Eventually DCTs may make trials better and less costly, and we are moving in the right direction, but we are not there yet.
Miseta: Brad, are you hearing anything from patients?
Hightower: Most patients do not know what a DCT is. Right now, they know they must carry around an eDiary. Beyond that I have not seen anything else being used at scale that focuses on patient engagement. I have heard from patients who do not want a stranger to come into their home. I agree that there is potential here, but we have not yet begun to move the needle.
Miseta: What are the key takeaways each of you would like sponsors to get from this webinar?
Hightower: Some sponsors have done a great job of reaching out to sites and getting their feedback and opinions. Some are even coming out to sites and learning what the life of a site looks like. I would encourage more that. If we can build this DCT experience together, we can be more successful. Right now, clinical research has silos and is fragmented. If we can knock down those silos and work together, I think we can make some significant change in how research gets done.
Bechtel: Brad raises a really good point, which is to stop doing clinical trials in a box. Sponsors should not think they have all the best answers and best ways of doing things. I recommend they engage and communicate with sites early on. Let them know what you're thinking about doing with the clinical trial, what technologies you want to use, and what vendors you might opt to use. If those conversations happen early on, the sites will be better prepared to conduct the study.
Venn: In clinical research, we tend to overcomplicate things and need to remind ourselves to keep it simple. When creating a protocol, it is best to engage sites and patients. When we add too many questions and requirements to the protocol, things become more complicated. We need to collaborate more and choose the right solutions for the right reasons for the right trial. Even with DCT options, ask what is needed to answer the question and keep it simple. That will result in the most successful possible outcome.