Decentralised clinical trials gained momentum during the COVID-19 pandemic, and their prevalence continues to grow rapidly. In contrast to centralised or conventional clinical trials, which require study participants to take part ’in person’, decentralised clinical trials allow remote participation using state-of-the-art digital health technologies. In this article, we compare centralised and decentralised clinical trials, briefly overview how decentralised trials are performed, and outline their advantages over conventional trials.

Centralised vs. decentralised clinical trials

Centralised clinical trials are usually carried out at one or more physically central locations. While no universal format exists, a trial generally involves a number of clinical study sites where trial participants, researchers leading the trial and medical staff are physically present together for extended periods of time. These sites are controlled environments such as hospitals, medical centres, clinics, etc., where clinical research, development and testing can take place safely under supervision.

Participants in centralised trials receive investigational treatments (study drug) or placebos under medical supervision, and all follow-up testing and monitoring is carried out at a clinical site. Clinical trial data is collected centrally at the site(s) for downstream interpretation and quality control.

In a decentralised clinical trial (DCT), some or all of the trial’s activities occur at remote locations distinct from the conventional clinical trial sites mentioned above. Also known as virtual trials or direct-to-participant trials, DCTs can be defined as clinical trials that use a virtual tool to assist with any aspect of the trial, including data collection and analysis, participant enrolment and monitoring.

DCTs can take place in the participant’s home, a local health care facility, or a nearby laboratory. These trials may involve direct delivery of study drugs to participants’ homes, and usually incorporate digital health technologies to directly collect relevant medical data from participants before, during and after treatment. These typically include portable activity trackers for remote monitoring of glucose levels, blood pressure, lung function, and other health parameters. Digital health devices or sensors can be wearable, implantable, or ingestible. Interactive mobile apps may also be used; these allow participants to take part in virtual home visits by doctors, rate their quality of life, pain, mental health and daily functioning, or assess functional performance through cognition, coordination, vision and other tests.

Decentralised clinical trials surged during the COVID-19 pandemic

DCTs are not exactly a new trial format when we consider that the first fully virtual study was initiated by Pfizer in 2011 (1). However, their prevalence has grown exponentially since the COVID-19 pandemic. Not surprisingly, the travel bans and physical distancing restrictions in place during this time prevented the initiation of conventional trials, so trial sponsors needed to find alternative ways to test experimental treatments.

According to GlobalData, the decentralised clinical trials market size was 1,291 trials in 2021, and the greatest increase in DCT numbers occurred during 2020–2021 (2). Continuous advances in wearable technology and data handling, widespread access to internet and smart phones, greater focus on quality of life and public confidence in telemedicine are expected to further increase the prevalence of DCTs in future.

How are decentralised clinical trials carried out?

When it comes to planning any clinical study, it’s not an all (100 % remote) or nothing choice between a decentralised or centralised trial. In many cases, a sponsor will run a hybrid trial that encompasses remote activities as well as elements of a centralised trial. If we break down a typical clinical trial into individual components, we can see that many possibilities exist along a scale from fully centralised to fully remote.

Recruitment. This can be managed solely by the clinical site(s), or virtually, or a combination of both. The former typically involves doctor-to-doctor patient referrals and/or clinical trial recruitment agencies for patient identification and screening, while a virtual strategy could involve targeted digital campaigns to identify candidate trial participants through social media platforms.

Patient enrolment. On-site enrolment typically involves face-to-face participant screening, medical assessment, in-person training (for example, where self-sampling is necessary) and consent signing, while a virtual approach may involve live chat services to communicate with clinical study staff, virtual on-demand training, and electronic signing software for consent agreements.

Study drug distribution and administration. Participants can either receive the study drug from a medical professional at a clinical site, or the treatment can be delivered directly to the patient’s home for self-administration following appropriate in-person or virtual training.

Data collection. In a centralised clinical trial, data is collected at the clinical site(s) during scheduled appointments. Information may also be collected in diaries kept by patients as part of the trial protocol. Virtual data collection in DCTs typically includes electronic patient-reported outcomes in software programmes or smart phone apps, as well as data captured by digital health trackers or sensors as outlined earlier.

Assessment. Participants of centralised trials are assessed face-to-face by healthcare staff at clinical sites; this usually involves the use of electronic clinical outcome assessments (eCOA) using tablets or other digital devices to directly report data related to trial outcomes. In a DCT, participants are assessed virtually through mobile visits by healthcare staff (in participants’ homes or at designated clinics); this also involves the use of eCOA which may be performed remotely through smart phone apps or similar.

What are the potential benefits of decentralised clinical trials?

Some of the most notable benefits of DCTs over conventional trials include:

Lower burden for participants. A reduction in the number of clinical site visits increases participant comfort while their financial impact is decreased. This may have a positive knock-on effect on compliance and trial retention rates.  

Increased inclusivity, diversity and equitable access. By reducing or removing the need for in-person participation, DCTs eliminate geographical barriers to trial access. This potentially leads to greater overall inclusivity and representation of racial and ethnic minority populations, disabled individuals and persons of all ages, with the caveat that DCTs may not be the preferred option for individuals with reduced computer literacy.

Continuous real-life data collection. Digital health trackers can capture data much more frequently than scheduled trial visits, sometimes even continuously. Importantly, unlike scheduled testing performed at clinical sites, digital trackers and sensors also collect data during participants’ daily activities, providing insight into the efficacy and safety of the treatment in a real-life situation.   

Cost- and time-effectiveness. By downscaling or even removing the need for a clinical study site(s), a DCT can reduce the overall time and costs associated with recruitment, enrolment, data collection and analysis. These benefits are particularly relevant for larger (e.g., Phase 3) trials where the costs associated with implementing the technology and training for the DCT are quickly surpassed by the cost of running a centralised trial across many clinical sites. 

Other potential benefits include increased participant safety and safety surveillance as a result of real-time self-reporting of adverse events and daily questions about medical status through smart phone apps or similar, and easier long-term follow up (Phase 4) studies which are a crucial part of post-marketing surveillance and which are often prone to poor retention because of the burden on participants to attend long-term follow-up appointments. Finally, the continuous availability of clinical data in DCTs may facilitate a better response to hurdles and faster decision-making since sponsors can get an indication early on in a trial about how their study drug is performing.  

Although not discussed here, DCTs are faced with certain challenges and ethical considerations. In recent years, the United States FDA and other national regulatory bodies have issued guidance for DCTs to support drug developers and trial sponsors in running trials that ensure participant safety and research integrity while also reducing participant burden and trial cost. The ethical opportunities and challenges surrounding DCTs were recently discussed in a review published in Lancet Digital Health (3). 

Capitainer can help with solutions for remote sampling  

As decentralised clinical trials and remote monitoring move towards the mainstream, the self-sampling solutions offered by Capitainer can make it easier for drug developers and patients to initiate and take part in clinical trials without geographical barriers, for increased patient comfort and efficiency.  

Stay tuned for news on this topic! 

References and further reading: 

1. Orri M, Lipset CH, Jacobs BP, Costello AJ, Cummings SR. Web-based trial to evaluate the efficacy and safety of tolterodine ER 4 mg in participants with overactive bladder: REMOTE trial. Contemp Clin Trials. 2014 Jul;38(2):190-7.  
2. Clinical Trials – The Movement Towards Decentralized Clinical Trials. Source: GlobalData.  
3. Vayena E, Blasimme A, Sugarman J. Decentralised clinical trials: ethical opportunities and challenges. Lancet Digit Health. 2023 Jun;5(6):e390-e394.