How Relevant are DCTs Post-Pandemic?
By: Sarah Hand, MSc
Interviewee: Jane Myles, Program Director, Decentralized Trials & Research Alliance (DTRA)
How Relevant are DCTs Post-Pandemic?
By: Sarah Hand, MSc
Interviewee: Jane Myles, Program Director, Decentralized Trials & Research Alliance (DTRA)
The rapid and widespread adoption of decentralized trial approaches at the height of the COVID-19 pandemic was a necessary reaction to prevent studies from ceasing to run altogether.
The number of active drug trials with a decentralized component rose by 45 percent in 2021 compared to the previous year, according to data compiled by Clinical Trials Arena.
But as the threat of COVID-19 continues to subside and clinical trial activities return to semi-normal, some question the relevance of DCTs in a post-pandemic world. The year 2022 saw considerably less DCT activity, with a nine percent dip in uptake of this methodology. And while the pandemic was a trigger point for greater interest in decentralized technology, 2020 is far from the first year that some in the industry began to investigate these methods, and many of these tools have been in the works for over a decade.
“You could say Craig [Lipset] and I are the OGs of the space,” says Jane Myles, Program Director at the Decentralized Trials & Research Alliance (DTRA), referring to her co-chair at the organization. “I think he started experimenting in 2010. I was right behind him in a different organization doing those experiments.”
Myles shared that after 10 years in DCTs, she often questions why there hasn’t been more widespread adoption of decentralized components that are built into the trial’s protocol from the beginning.
“I do think it can work in almost every setting, but it is not a cut, copy, paste,” says Myles. “And that's the challenge we're facing right now with early adopters.”
Patient-Centricity and Misconceptions About DCTs
The idea of using digital technologies to reduce the number of in-person site visits during a trial seems inherently more patient-centric than traditional protocol designs. After all, some estimates suggest that 70 percent of trial participants would need to travel two or more hours to reach their closest study center, offering a major barrier to recruitment.
But Myles explains that DCTs aren’t automatically the most patient-centric option when it comes to trial design, particularly when they’re executed in an inflexible manner.
“I want to point out that the FDA, in their definition in the guidance, actually puts in a really important phrase, which is with the intention of reducing onsite visits,” says Myles. “Doesn't eliminate them, doesn't say you have to do one thing or another. And the reason I raise that is because you can use eConsent or you can use eCOA and not change any of the site visits for a patient.”
Digital health is a spectrum and Myles stresses that the use of decentralized components doesn’t need to be all-or-nothing. After all, while some patients may appreciate the convenience of having a nurse come to their home to perform a routine blood draw, others still might prefer to have that procedure done in the clinic.
“[The] optionality you see in consumer-based settings is really where I think DCTs can align more with patient-centricity,” says Myles, pointing to the flexibility of being able to change or pause an ecommerce subscription based on your needs as an example of what healthcare could do better. “Sometimes patients will want to go see their physician, especially if they have new or treatment-emergent symptoms that they really feel need to be assessed. The trial should accommodate for that. Maybe they can see that PI by telehealth instead of in person. It depends on what has to happen for the physician to make a good assessment.”
Decentralized Components and Trial Complexity
Pursuing a decentralized or hybrid trial approach does come with a set of challenges, particularly when the industry has been entrenched in a site-centric paradigm for so long. Offering patients the opportunity to choose an at-home visit over a site visit — particularly if there’s administration of an investigation product involved — requires more than just a phone call, even if that optionality is baked into the study protocol from the beginning.
Here are just a few of the many questions that must be answered before the physician can order the study visit with a nurse and this request can be accommodated:
- Is the nurse licensed to practice in the state where the patient lives?
- Is the nurse trained on the study protocol?
- Is the nurse credentialed to administer the investigational product?
- Will the product be shipped directly to the patient or to a central site?
- What are the shipping requirements — is there cold chain storage?
There is even an added layer of complexity to DCTs if a simple blood draw is required (a procedure most nurses are capable of performing):
- Does the nurse have the required tubes?
- Does the nurse have extras in case one breaks?
- How will the samples be shipped to the central lab — do they require special handling?
- Do the samples require onsite centrifugation or other processing methods?
All of these variables must be planned for in the trial design so that physicians and patients are both clear on how and when in-home visits can take place. The complexity is taken one step further in the case of global trials, with different localities having varied regulations regarding DCTs.
“It's about adherence and compliance in a way that fits the patient preference,” says Myles. “You're not changing the protocol parameters; you're just changing where they're going to happen.”
Approaching DCTs from a Problem-Solving Perspective
There’s no avoiding that DCTs cost more than conventional trials. The average Phase II DCT costs $1.9 million, and the average Phase III study utilizing decentralized methodologies costs $3.1 million, according to a 2022 study conducted by Tufts’ Center for the Study of Drug Development (CSDD) and Medable. However, the same analysis also found profound return on investment (ROI) for DCTs of up to 25 times, largely due to shortened timelines.
Myles says that when addressing the budgetary constraints that inevitably come up with the implementation of any new innovation, it’s important to address why an organization is exploring a new technology in the first place and how some of the biggest projected issues could be addressed from the onset.
Maybe the concern is getting enough data because the target patient population is small. Or sponsors might be motivated to focus on an unserved market, which could also give them a competitive advantage. Either way, DCTs can help achieve these goals.
“Depending on what you choose and how you implement it, DCTs can have an impact on many different problems,” says Myles. “You can actually increase the geographic reach of sites, reaching more patients. You can potentially get a better representation of patients that aligns with the epidemiology of the disease. You might be able to change how the patients can adhere to the protocol by putting the visits either in a local center like a pharmacy or at their homes.”
Sawtooth Adoption Curve of Innovation
Despite the buzz around DCTs in the last three years, the adoption of new technology — particularly in a risk-averse industry like clinical research — is never instantaneous, nor is it linear. In 2022, the CSDD released a report that quantified how long it takes for sponsors to move through the four phases of the innovation adoption process, which they define as initiation, evaluation, adoption decision and full implementation.
They found that on average it takes pharmaceutical and biotechnology companies 5.8 years to fully adopt a new technology, with smaller firms being the most agile, completing this process in a mean of 4.8 years. Mid-size pharmaceutical companies took the longest (mean of 6.6 years), and large organizations fell somewhere between (mean of 5.6 years).
Adding to this is the non-linear nature of the innovation adoption, which follows a “sawtooth” waveform as uptake peaks and wanes over time. Myles says she counts 2020 as year one when it comes to more widespread adoption of DCTs among organizations, which means at least a segment of the industry has another three or more years of work ahead to reach the full implementation phase referred to in the Tufts report.
“It's only natural if we're seeing this little wave in the curve,” says Myles, referring to the downturn in DCTs. “I do think over time — maybe it's 12 years, maybe it's 10 — you're going to see ‘D’ drop from ‘CT.’ It's only natural that we become more familiar with these methods, and we start to realize you have to plan this much more time to build it in.”
Data from First DCT Trials Coming Out Soon
Just like any new initiative in the pharmaceutical industry, the real proof of the DCT concept will come once the first studies to adopt the model begin to release results — something that Myles expects will start happening soon. And regardless of what the data shows, she says it will be valuable to help shape future studies that apply this methodology.
Interestingly, Myles says there’s no study registry of decentralized trials; ClinicalTrials.gov doesn’t even have a filter for these types of studies.
“Because that's really what's at risk for the sponsors,” says Myles. “Yes, they might object to cost. Yes, they might want to see ROI data. But the real risk from a sponsor perspective is that somehow the methodology used compromises the regulatory submission, timeline and package, and that is a very reasonable thing to be worried about when you're making these sorts of investments, especially if your molecular asset does have the potential to have a huge benefit to patients.”
While Myles doesn’t believe that decentralized methods will have a negative effect on the quality of data collected, she recognizes that as a major concern for the industry and says that confidence around DCTs will come from experience.
Outlook for DCTs
The flexible and non-prescriptive nature of DCTs will likely be a major focus for sponsors in the coming years as the industry continues to validate these methods. While the use of wearables, for example, might fit well with one study design or patient group, it could be completely ill-suited to another. The key is to predict what is most likely to work early on by asking some key questions. Regarding the use of wearables, these questions might be: How tech-savvy are these participants? What’s the risk to data integrity if a patient doesn’t use the device correctly?
Ultimately, Myles is optimistic about the future of DCTs, provided that trialists learn from each study to further refine and improve the way these methods are deployed.
“I'm a huge advocate for this, because I do think it's going to help patients,” says Myles. “I think it's going to help sites too, but most importantly, I think it's going to help us do better science, which is why I show up every day.”
ABOUT Jane Myles
Jane Myles is the Program Director at the Decentralized Trials & Research Alliance (DTRA). She has over 25 years of experience improving clinical trials and patient experiences. She has focused on driving innovation in trial design and execution to accelerate getting medicines to patients.
Jane transitioned from molecule focus to portfolio focus about 13 years ago, first concentrating on patient recruitment, then patient experience and input, followed by adoption of patient-facing technology. In her current role as Program Director for the DTRA, she merges these focus areas. She also serves as Chairperson for Curebase’s Strategic Advisory Board, building DCT technology and services to increase trial access and inclusion.
Most recently, Jane was VP of Innovation at Curebase from 2021 to 2023. Prior to that, she worked at Roche/Genentech for 17 years in various roles including operational program manager for hematology where she helped drive global implementation of patient-facing technology into trials. Jane has also held positions leading global trials at Lilly, Sanofi, small biotechs and niche CROs.