According to the United States Food and Drug Administration (FDA), decentralised clinical trials (DCTs) are those in which “some or all of a clinical trial’s activities can occur at locations other than a traditional clinical trial site”1. Such locations can include the participant’s own home, their local secondary care centre or general practitioner (GP) practice. Decentralised clinical trials may also involve digitisation of processes required to carry out research at various stages, such as recruitment, informed consent, randomised interventions, collection of outcome measures and safety monitoring2. Examples of digitised processes may include the use of telemedicine for informed consent and subsequent visits, smartphone app tasks or innovative “home wearables” such as smartwatches which can sense abnormal cardiac rhythms3. Such developments have the potential to revolutionize the way that clinical trials are conducted, but they are not without pitfalls.
Over the last few years, there has been increasing interest in the concept of decentralisation, but barriers to adoption include existing digital infrastructure of facilities, lack of experience and the potential for additional legislative/regulatory requirements4. An unanticipated challenge to the traditional clinical trial methodology was the COVID-19 pandemic, where government restrictions resulted in significant disruption to on-site clinical trials, such as a reduction in patient enrollment5 and closure of facilities due to lockdown6. To mitigate this, many research facilities were forced to rapidly adopt a more decentralised approach, particularly for those trials which still required frequent patient-healthcare provider communications7. The pandemic has therefore been a catalyst in decentralisation of clinical trials. In a survey carried out by the “Trials@Home” consortium, funded by the European Innovative Medicines Initiative (EU IMI) during the early stages of the pandemic, 83% of research organisations reported that they were expecting to maintain some decentralised adaptions post-pandemic, the most common of which was telemedicine/home health visits7. In the UK, the Innovative Devices Access Pathway (IDAP) will be launched in late 2023, providing a platform for innovative device developers to seek Medicines and Healthcare Products Regulatory Agency (MHRA) approval8.
There are many potential advantages of the decentralised approach, the most widely discussed of which is the prospect of enhancing accessibility. Socioeconomic and geographical factors (including regional variation in access to healthcare) have been shown to significantly impact participation in potentially life-saving cancer trials, even in countries with outstanding centres of research and well-developed healthcare systems9. In a 2019 meta-analysis examining factors influencing participation in cancer trials, it was found that a trial was not available for patients at their institution 55.6% of the time10. Travelling long distances to a clinical trials facility may therefore be a significant barrier to willingness to participate, particularly for vulnerable patient groups. The elderly are consistently underrepresented in clinical trials11, despite the use of prescription medicines being at highest rates in those over 75 years of age12. Additionally, lack of ethnic diversity in clinical trials is a persistent issue. Despite 40% of the US population comprising minority and ethnic groups, and statistically being more likely to suffer from chronic disease, in 2020 it was found that 75% of the 32,000 participants in 53 investigational drug trials approved by the FDA were White13, 14. Adopting remote monitoring systems for the elderly or social media engagement programs with online informed consent for ethnic groups with lower healthcare access could accelerate enrolment15, and thus enhance understanding safety and efficacy of novel medicines as applied to the global population3.
Furthermore, decentralising clinical trials may prove to be highly cost-effective in the long term, despite initial costs for implementation of novel technologies which may be a source of concern for sponsors and contract research organisations (CROs)16. The Tufts Centre for Drug Development at Boston University recently completed its discounted cash flow modelling analysis for trials with and without DCT elements, and concluded that DCT for phase II drugs could result in an increase of net present value of $8.8 million per drug, and $41 million for phase III drugs17. Therefore, a decentralised approach could be of massive financial benefit to sponsors developing novel medicines17. DCTs may be completed more rapidly than traditional trials, including faster recruitment18, less travel expenses and higher retention rates, and therefore could also be of substantial financial benefit to CROs17.
Some of the drawbacks with decentralised clinical trials are particularly relevant when considering more high-risk trials, such as those recruiting patients with serious illnesses or involving high risk procedures. In a recent study involving semi-structured interviews with European regulators19, concerns included participants becoming responsible for communication of safety information, inability to assess participants’ eligibility virtually and difficulty in maintaining investigator oversight due to delegation of tasks to third parties such as home clinical staff19. Reduction of procedures difficult to carry out virtually, such as the physical examination, has the potential to reduce the accuracy of the clinical assessment and may lead to over-reliance on further diagnostic tests20,21, which may be costly to the investigator and sponsor as well as being burdensome for the patient. Chhatre et al (2018) examined factors influencing patient recruitment and retention whilst carrying out a multicentre randomised controlled trial in patients with localised prostate cancer, and found that trust in research physicians was key to both recruitment and retention, and continuous physician involvement was key in developing trust22. Furthermore, in a recent study led by the University of Cambridge, it was found that 86% of 1340 patients and 93% of 111 clinicians felt that telemedicine was inferior to face-to-face consultations23. The main reasons given were increased difficulty in building a trusting medical relationship due to reduction in non-verbal communication, inaccuracy of virtual diagnostic assessments and underreporting of symptoms by patients and difficulties in accessing urgent support for acutely unwell patients23. Both clinicians and patients felt that telemedicine disadvantaged groups including those without English as a first language, those with cognition or speech difficulties, those with complex, multi-system diseases, those without access to technology and older patients23.
Despite the demonstrated benefits of decentralisation from the sponsor or investigator viewpoint, there is a significant gap in the literature regarding perceptions of DCTs for participants in patient studies. The primary aim of this qualitative research was to establish whether a group of participants involved in patient studies at a London-based CRO would prefer their visits to be conducted in an alternative location to the main clinical trial site. Secondary outcomes include identification of the main reasons behind participants’ preferences, whether this preference changed with the purpose of the study visit and whether patients’ perceived disease burden had an impact on their choice.