May 2023 • PharmaTimes Magazine • 26-27
// CLINICAL TRIALS //
Centre of the pharmaverse
Adapting to the new normal includes a wider understanding of the challenges in clinical trial decentralisation
During the pandemic virtual clinical trials were perceived by many as heralding the dawn of a new era for clinical research.
Professor Yan Yiannakou – Chief Investigator of the UK’s first fully virtual trial and Clinical Director of NIHR Patient Recruitment Centre, Newcastle – examines the evolving clinical trials landscape and reflects on whether the predictions are translating into fad or fate.
In 2020, RELIEVE IBS-D was the first interventional commercial trial in the UK to be converted to a fully virtual – also known as decentralised – clinical trial (DCT). The trial showed transformational improvement to the recruitment and retention of trial participants. A year later, the Government policy paper on clinical trials urged further development of DCTs. Despite this strong start, progress in Europe has been much slower than in the USA.
The benefits are clear. DCTs have the potential to recruit more efficiently than site-dependent trials, as they are unrestricted by geography. They are highly effective for research into common conditions and can facilitate rare disease trials by removing the need for long distance travel for participants.
Equally, DCTs can be more inclusive, allowing participation from remote areas; they can improve convenience, save time for participants and possibly even reduce the carbon footprint of clinical trials. By reducing the number of sites required to deliver a study, they can also significantly reduce costs.
Virtual reality
DCTs’ capabilities in the UK are rapidly growing. The digital technology to facilitate DCTs was available long before COVID-19, though the pandemic has made the public more accustomed to virtual consultations and hastened DCT development.
Video consultations can be linked to electronic consent. Electronic data capture records and verifies clinical data, while cloud-based platforms organise patient information and study-related materials. Remote monitoring capabilities are available and can monitor adverse events in real time.
Wearable technology has advanced rapidly, allowing a wide range of body functions to be monitored remotely, and app-based data capture via the participant’s own phone is now replacing the provision of trial-specific devices. Digital poverty, which affects about 10% of the UK population, is often perceived as a key barrier, as is digital literacy. However, provision can be made for potential participants with both hardware and IT support.
Consequently, the key challenges to decentralisation are not to do with digital connectivity, but with three other requirements: firstly, a recruitment platform that can reach a wide geographical area, linked to an efficient screening process; secondly, the logistics and infrastructure required for home-based care.
The critical elements required for successful DCTs
Key challenge 1: Recruitment
Effective recruitment and screening platforms are necessary to match the geographical reach of DCTs. Researchers can use a variety of methods to achieve this, including ‘consent for contact’ registries, digital media advertising and ‘big data’ solutions.
Registries such as Research+Me have been highly successful in facilitating trial participation and the UK-wide, Be Part of Research platform is rapidly expanding. Benefits include strong response rates and rapid recruitment, potentially starting on the day after trial opening. Invitation mail-outs can be staggered in size and frequency to match the maximal delivery capacity of the study team.
‘DCTs offer an opportunity to transform the process of clinical research by expanding access, improving patient convenience’
However, registries must be robustly managed on a secure platform with attention to information governance and data security. Registries also require maintenance by informatics staff and strategies must be put in place to continually replenish the registries with new sign-ups to avoid fatigue over time. Like all direct-to-patient recruitment modalities, they need an effective eligibility screening capability.
Digital media advertising can also be highly effective, but with response rates as low as 1%, campaigns often need to reach hundreds of thousands to recruit large numbers of trial participants. Significant multi-modal asset catalogues are required to ensure adequate penetration and marketing assets need to be approved by Research Ethics.
Media assets are disseminated by paid campaigns on a variety of social media platforms with active monitoring of analytics and public response. This requires specialist expertise and can be expensive.
Key challenge 2: Screening
As healthcare systems become more interoperable, there are opportunities to use ‘big data’ to screen populations for clinical trial participation. However, obtaining prior consent to contact potential participants remains a key challenge and response rates are low since invitations are unsolicited and come from an unfamiliar source.
Unless the process is linked to the electronic health record, invitees may be poorly characterised. NHS Digitrials overcomes some of these challenges and, in the future, it may be possible to link big data solutions to contact preferences set on the NHS app.
These direct-to-patient recruitment modalities lead to high volumes of poorly characterised respondents and therefore require powerful pre-screening capability. Online pre-screeners are commonplace, but the language used must be simple and unambiguous.
There must be provision for uncertainty and exclusion algorithms need thorough testing. Messaging needs to be informative and include considerate advice for ineligible respondents who have taken the time to volunteer and may be disappointed.
Key challenge 3: Logistics
The infrastructure of providing home-based care is rapidly developing with drug/device delivery and home-based GCP-certified nursing available to almost any part of the country. Home-based nursing allows administration of infusions and on-site monitoring.
Staff can be trained to undertake physical examinations, with or without remote video oversight from the principal investigator (PI). Participants can be taught to self-administer some injections and capillary blood testing can be successfully undertaken by about 90% of participants. Mobile research units can provide laboratory facilities and even mobile CT scanning.
However, limitations remain, particularly where acute adverse reactions are possible, or with more complex interventions and invasive assessments. MRI scanning, for example, requires the participant to travel. In such cases a more feasible approach is to have a hybrid model of site-dependent and decentralised delivery. Home-based management brings other challenges.
How do we approach would-be participants who feel uncomfortable with staff entering their home? How does a PI retain oversight and delegate tasks to staff he/she has never met? How does a PI facilitate remote management of adverse reactions, in the absence of any relationship or prior agreements with local health providers?
Most commercial trials are run in multiple countries and this produces an additional barrier, as the approvals processes for DCT-related requirements vary from country to country. The RADIAL trial, set up by the Trials@Home consortium, will compare trial processes and experiences in three arms of a trial: traditional site-dependent, hybrid and fully decentralised.
The study will run across five European countries and answer many of the questions raised in this article. Other studies are also looking at participant experience in site-dependent versus decentralised recruitment.
In conclusion, DCTs offer an opportunity to transform the process of clinical research by expanding access, improving patient convenience and reducing costs. However, successful implementation requires effective participant identification, processes to mitigate digital poverty and illiteracy, and solutions to some of the logistical barriers.
Despite those challenges, the positive benefits of DCTs will undoubtedly drive further developments in the future and consolidate their place as a permanent feature in our evolving clinical trial landscape.
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