After peaking during the Covid-19 pandemic, the clinical trial industry is re-evaluating the pros and cons of decentralised clinical trials (DCTs). At the time, decentralisation was one of the tools used to ensure clinical trials for drugs and vaccines could still take place while lockdowns were in effect. Now, sponsors and other clinical trial stakeholders are taking a pause to ensure that decentralisation tools meet the expectations of the regulators.
In the previous updates of the DCT Tracker, Clinical Trials Arena examined the key the top therapy areas using a decentralisation approach, the leaders in the space in 2022, and what to expect in 2023.
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This new edition of the DCT Tracker investigates decentralisation from the perspective of trial endpoints or outcome measures.
For this data analysis, Clinical Trials Arena looked at six different types of endpoints: efficacy, safety, quality of life (QoL), pharmacokinetics (PK) and pharmacodynamics (PD), bioequivalence, and bioavailability. An outcome measure was considered only when it was a primary endpoint, not a secondary endpoint. This analysis relied on an exclusive taxonomic approach, which involved the review of thousands of public drug trial records from 2010 to date, as curated in the Clinical Trials Database by GlobalData, the parent company of Clinical Trials Arena.
Which endpoint are DCTs measuring the most?
As expected, the data analysis reveals that QoL is the most decentralised endpoint, with 6.4% of all clinical trials measuring QoL being decentralised. Harpreet Gill, vice president of decentralised clinical trials at ICON, says it is not surprising to see QoL as the leading endpoint in DCTs. “There’s been a lot of work done in the industry around migrating paper-based patient-reported outcomes (PROs) to electronic versions,” she says, adding that electronic PROs (ePROs) are the primary candidates for a decentralised approach measuring QoL.
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By GlobalDataDigital health technologies (DHT), such as actigraphy devices, are also commonly used to assess QoL by measuring activity levels, says Keith Thomas, senior director of DCT operations at ICON. “This is a well-established use case that many people are accustomed to,” he notes. An actigraphy device is a wearable that tracks movements during sleep.
For this analysis, the percentage of decentralised trials with a particular endpoint is calculated using all virtual and non-virtual trials with the endpoint. Safety and efficacy are the next most common endpoints, with 3.3% of the trials looking at outcome measures related to both adopting decentralisation components, while 3.1% of trials measuring PK and PD have a decentralised approach.
Certain endpoints, such as QoL, are easier to measure with decentralised components than others. Thomas explains that it is much more straightforward to decentralise a PRO compared to the work that is required to validate a new digital measure or a digital endpoint that uses a DHT.
Late-stage trials are more likely to be decentralised
As per the data analysis, late-stage trials are most likely to use DCT components. The highest proportion of DCT adoption was observed in Phase III trials measuring PK and PD (8%) as a primary measure.
Moreover, Phase III and Phase IV trials tend to be more decentralised when compared to early studies, especially when trials are measuring QoL (7%). In Phase IV trials, sponsors are usually looking at the long-term impact of a treatment. As such, certain decentralised components can make it less burdensome for a patient to be involved in a long-term study, particularly if they do not live close to a trial site, Gill adds.
Gill explains that a number of factors such as cohort size, timelines, and geographic distribution are aligned better in Phase III trials to extract value from decentralised components. As the cohort population gets larger, DCTs make a lot more sense from a recruitment and cost perspective, says Craig Gravina, chief technology officer at the virtual research organisation ObvioHealth. He also notes that a patient population may be more homogeneous in a site-based trial. “As you begin to expand the reach past early stages of determining clinical efficacy, the decentralised nature [of a trial] exposes you to a wider range of population sets,” he adds.
As for earlier stage trials, there might be some hesitancy around the safety profile of an investigational product. The studies often require a lot of clinical assessments, involving positron emission tomography scans or biopsies, on a more frequent basis that cannot be readily decentralised, Gill says.
While some assessments in early stage trials can be decentralised, it might be an added complexity, especially if a patient is already going to a site. “There has to be a balance around when decentralisation is appropriate and when it is not,” Gill adds.
QoL is used across a number of different types of trials, especially oncology, but it is also a very valuable measure in indications such as pain or anything that can impact the patterns of day-to-day activities, says Gravina. “The determination of efficacy may very well impact your quality of life,” he adds. Across the therapy areas, QoL-related endpoints are the most common. Thomas says that is not surprising to see the prevalence of QoL given the way it can be measured by ePROs and DHTs.
Gravina explains that episodic conditions, such as pain, lend themselves better to a DCT environment because patients experience the symptom wherever they are. “It’s a lived experience that happens when it happens, not necessarily when you are at the site, or at the time that you sit down to fill out a questionnaire,” he says.
Telemedicine is the leading DCT component
Across all the endpoints included in this analysis, more than 20% are measured using telemedicine in some capacity. Moreover, telemedicine is used in almost 50% of DCTs measuring bioavailability, while more than 25% of PK and PD-measuring DCTs use this decentralisation component. Thomas explains that telemedicine is a tool that people are already familiar with outside clinical research given its prevalence in the healthcare industry, and it has a straightforward application compared to other components of decentralisation.
Also, sites can be hesitant to participate in a DCT because it would be a significant change from using a traditional site-based trial, which is also a big revenue model for them. However, since telemedicine could involve the sites, it can become an effective way of incorporating a decentralised component into a traditional site-based model, Gravina says.
Remote monitoring using a sensor, device, or tracker is mostly utilised in DCTs measuring bioequivalence (29.8%), QoL (27.1%), and efficacy (26.2%). Gravina says that remote patient monitoring devices are very oriented to DCTs because of the ability to continuously monitor vital signs and other types of health measurements. This becomes vital in infectious disease trials where a typical endpoint might measure fever-free time. Remote monitoring devices can catch temperature spikes at odd times better than a participant.
Decentralisation to the home or the use of alternative sites is scarcely used across all trials measuring these endpoints. This is due to unfamiliarity with this DCT component by sponsors and sites, Thomas explains. Still, the industry is slowly accepting the shift from traditional sites toward patient’s homes. “It’s all about workflow and being able to show that it works well and operationalizing it effectively,” Gill says.
Validation and regulatory certainty
While there is no technical limitation to utilising decentralisation tools to measure different endpoints, there is a lack of evidence to support their benefit. “With many of these digital endpoints, the validation work and the evidence generation that is necessary to use these is still ongoing,” Thomas says.
However, Gravina notes that it is less about clinical validity in measuring remotely or in a decentralised fashion and more about showing equivalence with current instruments and measurements. “The barrier to measuring across a lot of different endpoints is becoming lower, and the acceptance by the regulatory bodies is becoming more tolerable,” he notes.
Sponsors still want to see the value of DCTs, Gill notes. “There is a lot of good data available around the usefulness of decentralised methods, but when you start adding DHTs, there is always a concern around the cost of DCT components,” she says.
Regulatory guidance is crucial to solidify decentralisation across various endpoints. Thomas says that while regulators are developing documents, policies, and guidelines around different DCT components and research, uncertainty can slow down its adoption. The EU’s EMA released its DCT recommendations paper last year, and the FDA came out with its draft guidance on DCTs earlier this month. Gill says that these documents will help sponsors and sites to accept decentralisation as a valid way to deliver clinical trials.
More insights on DCT adoption trends:
Beyond clinical trial design: factors that impact decentralisation Remote clinical trial monitoring uptake rises but validation questions swirl DCT Adoption Tracker: Top 3 clinical trial decentralisation trends in Q1 2022 DCT Adoption Tracker reveals top therapy areas using a decentralisation approach Year in review: Who were the main DCT players in 2022?
