Need to know:
- A remote revolution is transforming how clinical research is run. But ambiguity in decentralised clinical trial approaches can undermine impact assessment and curb adoption.
- Clinical Trials Arena established an exclusive taxonomic approach involving the review of thousands of drug trial public records to categorise different decentralised elements.
- With this analysis, we advance the understanding of which decentralised approaches are most embraced by the clinical trials industry across multiple trial characteristics.
The clinical trials industry has always been intrigued by the promise of a decentralised approach. But with the Covid-19 pandemic, many players were pushed from being attentive bystanders to becoming active players. Companies had to speedily interweave decentralised trial design elements into protocols to overcome unprecedented execution challenges.
At Clinical Trials Arena, we asked ourselves: Which organisations are the leading decentralised clinical trial (DCT) adopters? What specific forms of decentralisation elements are most utilised? And the big question: Is it time for late adopters to fully embrace decentralisation?
In an investigation that hasn’t been done before, we analysed 12 years of data on DCTs across the globe, based on clinical registry protocols, research papers, and press releases, as curated by GlobalData, the parent company of Clinical Trials Arena. We created a taxonomic system that classifies mentions of remote, virtual, or digital trial implementation methods. This way, we were able to find trends and insights on DCTs you are unlikely to find anywhere else.
Discovering DCT trends is valuable because this can pinpoint which elements are practical and which are not, says Nico O’Kuinghttons, vice president of decentralised clinical trials at Huma, a healthcare technology company. “It is important to see what piece of the puzzle will bring efficiencies.”
Use of decentralised elements in clinical trials has accelerated in the past two years.
The fastest growing form of decentralisation has been digital data collection.
GlobalData identified over 300 trials initiated during 2021 utilising digital data collection, compared with an average of just 25 per year between 2010 and 2016.
Remote monitoring of blood pressure and glucose levels – the most common form of decentralisation a decade ago – has seen the slowest growth.
We have also tracked instances of remote monitoring using sensors and devices.
These have increased from an average of 60 per year between 2010 and 2016 to more than 250 in 2021.
The use of electronic patient-reported outcomes (ePRO), electronic clinical outcome assessment (eCOA), and eConsent increased sharply from 2020 to 2021. This is largely driven by more widespread use among contract research organisations (CROs).
Decentralisation to home or alternative sites, which includes remote drug delivery and home nursing, remains rarely utilised with just 50 newly-initiated trials identified as including these elements in 2021.
In comparison, there were almost 450 new trials in 2021 utilising telemedicine, making it the most frequently used form of decentralisation.
A decade ago, Phase III trials were most likely to utilise decentralisation.
But in recent years, growth has been particularly strong for Phase II trials, which now make up one in every two trials with a decentralised approach.
Commercial sponsors used to lead most decentralised trials.
But during the past decade growth has been strongest for academic institutions.
While Covid-19 lockdown measures made decentralisation an obvious answer to keep clinical trials running, the response was not immediate. As the pandemic started, disruption to new non-Covid-19 trials was severe across the board, regardless of the trial having a decentralised element. March 2020 became the first month since 2013 where fewer than 1,000 new non-Covid-19 trials were initiated.
But the same month also marked the first signs of a shift in clinical trial design. In previous years, around 5% of all trials had utilised decentralisation components. By April 2020, 8% of the 250 new Covid-19 trials were decentralised. By May, that figure had risen by five points to 13%, and Covid-19 continued to be a hotspot for decentralisation for the remainder of 2020 and throughout 2021.
As non-Covid-19 trial activity recovered in the final quarter of 2020, the increased use of decentralisation began to spread to other disease areas. Integration of decentralised elements in trials has been particularly fast for research into the central nervous system, where 15% of trials which have started since the beginning of 2021 have utilised decentralised components.
DCT uptake according to disease
To dig deeper and examine how the use of different forms of decentralisation varies by disease area and even by organisation, we took GlobalData’s subcategorisations of decentralisation and created six groups, each reflecting a distinct form of remote or digital trial design. While our groupings are not perfect (not all decentralised trial approaches neatly fit into a single category) and our data may not be comprehensive (organisations are not obligated to publicise the decentralised elements of their trials), they provide an illuminating and in-depth view on the landscape of decentralisation.
Many of our findings help validate intuitive sense. For example, remote monitoring of blood pressure or glucose levels is by far the most popular form of decentralisation for metabolic disorder trials, with more than one in 10 utilising the approach.
But other insights are less predictable. Covid-19 trials have been the most likely to move nursing or drug delivery away from traditional trial sites. Dermatology and women’s health trials have most frequently included ePROs, eCOAs, or eConsent.
And there are disease areas where decentralisation seems yet to take off. In oncology, there are less than 1% of trials mentioning telemedicine and just one in every 150 trials note utilisation of digital data collection. Craig Lipset, Decentralized Trials and Research Alliance cochair, says that while decentralisation is occurring in oncology, it may be of a different form than in other indications. For example, patients who require imaging procedures may now go to a closer facility than their clinical trial site and have their data sent away for central review, he explained.
There may be fewer home measurement tools in oncology compared to other indications, which may explain the seemingly slower uptake in DCTs, says Rachel Colite, decentralised clinical trials vice president at Cogstate, a neuroscience company. The administration method of therapeutics in cancer, such as intravenous drugs, also make decentralisation more challenging, she added.
While DCT in oncology may be hard to keep track of, it does not mean there is lack of involvement among players, Lipset added. It is all about intent – DCT allows the opportunity for patients to participate in trials who may not have access to a typical clinical trial site, he noted.
DCT element more likely in Phase III
Our analysis shows that in recent years, Phase III trials have been the most likely to include decentralised approaches such as ePROs, eCOAs, or eConsent. The same is true for telemedicine, with the proportion of Phase III trials including this approach having rocketed up from 2.7% in 2019 to 5.9% in 2021. Digital data collection and remote monitoring using sensors and devices have been most common in Phase II trials.
Overall, the growth in trials involving decentralisation has been stronger for Phase III than Phase II trials. This is most evident with remote monitoring of blood pressure or glucose levels where, a decade ago, Phase III trials were far more likely than Phase II studies to involve the approach. While the proportion of Phase III trials that include these decentralised approaches have stagnated, the equivalent figure for Phase II trials has gradually caught up.
Where are we on the DCT wave?
A decade ago, when decentralisation as we know it was still in its infancy, the answer was straightforward – large commercial sponsors led the way, conducting almost half of all decentralised trials.
But in recent years the landscape has become more nuanced. Going against the grain, many of the world’s biggest pharmaceutical companies – including Novartis and GlaxoSmithKline – appear to have conducted fewer decentralised trials in recent years than they did a decade ago, according to our analysis of publicly-available information.
Meanwhile, universities, governmental organisations, and nonprofit firms have become increasingly proactive in utilising decentralisation. This has been particularly evident for digital data collection, which is now twice as likely to be included in a trial led by an institution than a commercial sponsor.
We have also seen individual universities and nonprofits develop areas of DCT specialisation. For example, Duke University has used digital data collection in over 10% of trials in the past five years. Also, the US Juvenile Diabetes Research Foundation has included remote monitoring of glucose levels in more than half of its trials. The University of Washington is a telemedicine leader, with 10% of recently initiated trials utilising the approach.
Academic centres are on the frontlines of scientific breakthroughs, so it is not surprising they are also increasingly becoming more engaged with DCT, O'Kuinghttons explains. “They are openly engaging with their own peers to try new things,” he adds.
There is also an increase in private-public partnerships that also help this trend, Colite notes. These types of partnerships are valuable as they help facilitate large-scale research that any individual institution may find challenging to execute, she explained.
CROs build DCT capacity
In support of trial sponsors, CROs have moved ahead in the use of ePROs, eCOAs, and eConsent. Since the beginning of 2021, over 50 newly initiated CRO-led trials utilised these assessment methods, equal to 4% of all CRO-led trials.
Among CROs, UK-based Synexus Clinical Research is one of the most active in utilising decentralisation with 13% of its trials including ePROs, eCOAs, or eConsent, and 7% of trials involving telemedicine. Notably, small- and medium-sized CROs have utilised decentralisation at a higher rate (14% of all trials in 2021) than the sector’s most active large CROs (8% of all trials in 2021).
DCT differences among countries
The appeal of decentralisation has been the potential to remove geographical barriers to participation in clinical research, allowing individuals from around the world to join trials. A decade ago, this narrative was clear in the data – multi-country trials were the most likely to include decentralised elements.
But in recent years, as Covid-19 studies have driven much of the increased activity in decentralisation, some countries have become especially popular locations for single-country decentralised trials. In the UK for example, 12% of all single-country trials initiated in the past three years have involved decentralised elements, compared to just 3% between 2010 and 2016. Multi-country trials including the UK have also risen over the timeframe but more slowly, from 4% to 11%.
In contrast, many countries – particularly middle-income and East Asian nations – have seen minimal growth in decentralisation. In Japan, for instance, just 1.6% of all trials that began since 2019 have included decentralised elements.
This trend can be attributed to how friendly local regulators are on engaging with decentralised clinical trials, Lipset says. “There are countries whose regulators are particularly outspoken, progressive, and engaged on this topic,” he adds. And as such, they will attract trials with DCT elements, he says.
High-income countries tend to set the pace with new approaches as their economies have the means to adapt, O'Kuinghttons explains. Data privacy also needs to be a part of the DCT conversation, Colite added. DCT uptake that requires data collection will have to be in places where data privacy regulations and compliance are also up to speed, she notes.
At the start of the Covid-19 pandemic, it would have been too premature to point to decentralisation as being the new normal, Lipset says. Organisations then were trying to adapt out of urgency, he adds. Change in pharma is not easy – you need commitment, he says, then notes: “And we saw this commitment in the past year.”
- Among decentralised trial elements, telemedicine is the most common type of decentralisation, but digital data collection has been the fastest growing category especially during the pandemic. There’s been an uptick in home nursing and remote drug delivery but are still used rarely.
- Our analysis based on public data shows oncology trials seem to be less likely to integrate decentralisation elements onto their protocol compared with other indications. But DCT experts tell Clinical Trials Arena that players in the cancer space are highly engaged with DCT approaches, and their DCT elements may look different from other disease spaces.
- Decentralisation is most common in Phase III trials than early-phase investigations, though there is a notable increasing momentum of DCT in Phase II studies. Phase III having the highest DCT use is logical as earlier studies aim to zero in on safety, and thus require higher degree of monitoring of trial participants, experts explain.
- High-income, western countries are far more likely to host trials with decentralised elements than middle-income countries, South Korea, and Japan. Counties with regulatory bodies that are progressive in terms of DCT will also attract trials with decentralisation elements, experts note.
Data visualisation by Josh Rayman and Andrew Hillman
GlobalData Media Healthcare Editor-in-Chief Alvaro Arjona wrote an editorial on our first ever DCT Adoption Tracker. You can find it here.