When the COVID pandemic hit in the spring of 2020, many drug development companies were unprepared for the changes that were about to impact their clinical trial operations.
Astellas is one company that was better prepared than most. The company had initiated a formalized, internal project on decentralized clinical trial (DCT) technologies and their use in clinical trials about nine months prior to the pandemic, in an attempt to refine its approach to DCTs and hybrid trials.
“We contemplated where we wanted to be in this space and how we would incorporate decentralized capabilities into our trials,” says Marie Rosenfeld, SVP, and head of clinical science at Astellas. “We had a study underway for pediatric patients which required an IV infusion. Because of the nature of their disease, many of those patients did not have easy access to infusion sites. We felt this was a situation where we needed to deploy a home health care solution.”
Astellas was able to deploy home health nurses to perform in-home infusions for the study drug. At the same time, the company was deploying direct-to-patient drug shipments based on individual trials and patient circumstances. According to Rosenfeld, these efforts helped Astellas establish what its strategy would be for decentralized technologies. Then the COVID pandemic hit, and the need for those solutions became very real.
“We were examining the need for DCTs with the needs of our patients, physicians, and the trial itself,” says Rosenfeld. “That was a very different situation compared to where we are today. At that time, we had full buy-in from patients and physicians on the implementation of home health visits. There was no other viable way for us to conduct the studies.”
The Pandemic was a Catalyst for Change
When the pandemic hit, Astellas conducted a thorough evaluation of every ongoing study. The company’s initial evaluation was of the assessments it had in place. For the assessments that were deemed necessary to maintain the integrity of the trial, the company would determine which needed to be conducted in an office setting versus alternative locations.
For visits that were primarily lab draws or a physical exam, but not tied to complex medical procedures, Astellas allowed patients the flexibility to have those visits done remotely via telehealth or phone calls with their physician. The company also implemented the capability for lab collections to be conducted at local facilities such as commercial lab providers. Processes were also put in place to implement remote consent forms, to avoid patients having to visit a clinic.
“Each country had a slightly different approach based on the regulations they had in place,” states Rosenfeld. “We evaluated our protocols to determine what processes could be performed remotely and part of our obligation was to inform patients of their options. This would normally be done through a formal update to the informed consent form which patients would sign in a physician’s office. We updated the content to notify patients and the institutional review boards, via mail, which assessments could be performed remotely. The signature was then obtained via telehealth or postal mail in Europe.”
Astellas’ primary focus was ensuring the safety of its patients. The company worked with established providers it already knew. For example, Astellas had a relationship with a global provider of home health capabilities, and that contract was expanded into other trials where the solution was appropriate.
Listen To Patients And Principal Investigators (PIs)
In studies where Astellas felt it could provide direct distribution of therapies to patient homes, the company proactively acted to make that capability available. It then spoke to physicians participating in studies to determine if this capability was something that would benefit them or their patients.
“We first made the capability available, and then reached out to patients to see if they had an interest in that option,” says Rosenfeld. “If patients felt the capability could benefit them, they were able to take advantage of it. Our focus was on securing patient safety and the integrity of our trial data. Then we asked patients on a case-by-case basis what factors were important to them.”
As the company was exploring the capabilities it could incorporate into trials, it was simultaneously reaching out to PIs to inform them of the options that would soon be made available to sites and patients. The company was not able to connect with patients directly, so physicians acted as the conduit to solicit their feedback.
“Our focus had to be on how we could best help our patients and sites,” says Rosenfeld. “We engaged with PIs and explained the options we felt we could best support and asked them to tell us what they were most interested in. Telehealth, remote visits, and direct-to-patient delivery were at the top of everyone’s list.”
Do All Patients Want DCTs?
Since the start of the pandemic, industry professionals have insisted that decentralized technologies be incorporated into all studies since that is what patients were demanding. Decentralized trials, they said, are the future of the industry and there would be no going back to the way studies had been conducted in the past. But are decentralized studies really what patients want?
When COVID hit, Astellas worked to engage directly with patients and patient groups to solicit their feedback on the conduct of clinical trials. The company has learned there are a lot of factors for sponsor companies to consider when thinking about deploying decentralized capabilities. Surprisingly, one of the learnings to come out of those patient interactions is that many preferred to travel to a physician’s office for their visits.
“Demographic differences and life experiences will impact what patients want from a trial. Still, we found the age of the patient was a huge factor and the primary motivator for the types of interactions they prefer to have with sites and PIs,” states Rosenfeld.
Rosenfeld admits she was a bit surprised by that finding. Like many in the industry, she assumed technology use would be a barrier to participation for many patients, especially the elderly.
“We are not seeing that,” she says. “There is a desire in older patients to have that face-to-face interface with their doctor, but it does not seem the reason is a fear of technology. Patients are telling us they prefer to have a more familial relationship. They enjoy seeing the study coordinator and they believe in-person visits result in better healthcare. They are willing to use modern technologies, if that is part of the clinical trial, but they also want to maintain that established relationship with the treating physician. The older patients preferred face-to-face meetings while younger patients were more willing to consider having medical professionals come to them.”
Much of the patient feedback Astellas gathered during COVID came from a trial for perimenopausal women taking an oral product. That places the participants in a mid to late age group, and participants often had children and/or parents living at home. Safety monitoring was straightforward and involved general labs. The study was well-suited for a decentralized trial approach.
“We tried to implement a decentralized approach very quickly,” notes Rosenfeld. “We got the contract in place and the provider was ready to go. Then we learned many women did not want strangers coming into their homes during COVID. They felt much more comfortable going into the clinic or office because they felt it was a more sterile environment. The anecdotal piece that I do not think anybody could have appreciated was these patients felt the visit was a nice escape and a reason to get out of their homes in a way that was seen as socially acceptable. We were all surprised by that result.”
When sites made home visits an option for patients, very few patients opted in. The results repeated themselves in a current, post-COVID study. Although the home visits were built into the study design, the study, conducted mainly in Europe, still had little buy-in from patients and sites.
What is and Isn’t Working?
Now that the industry has been implementing DCTs and hybrid trials for more than two and a half years, what have companies learned?
“Companies are rethinking how they design trials and changing the conversation, putting more focus on how trial protocols may impact patients and sites,” states Rosenfeld. “We now have options that weren't widely used previously. Pharma is changing the conversation about the design of a clinical trial to the burden on patients and sites. This is the first step in making trials more patient and site centric. We are learning and seeing discreet examples of the positive impact of DCTs. The conversation is moving in the right direction. Site burden is something we don't spend enough time thinking about.”
Rosenfeld also acknowledges some of the new and emerging clinical trial technologies are complicated and a bit overwhelming. While DCTs may enable trial access to diverse patients and those in remote settings, it also requires an understanding of the technology and access to a reliable Wi-Fi network. This can place a high burden on study coordinators who support patients and implement the technologies. The new DCT technologies are also driving sites to hire tech-savvy study coordinators to assist with the implementations. The industry has thus far underestimated how much burden these technologies place on sites and patients.
“I think one of the challenges the industry is still trying to understand and overcome is the concept of PI oversight,” adds Rosenfeld. “If a sponsor is using a pharmacy retail location for a patient’s standard of care, how does that impact the statement investigator form? This is also a barrier that we're seeing in the deployment of home health. Is the PI responsible for the home health nurse? The industry needs to align on the role of the PI in a hybrid environment, both from a regulator and patient perspective. That will be critical to realizing the full vision of a decentralized trial.”