Exploring the promise of decentralised cancer clinical trials

An important keystone of evidence-based medicine they may be, but clinical trials are becoming increasingly difficult to deliver.

There are several reasons for this, most notable perhaps are wider pressures within the NHS, challenges in ensuring representation of the broader patient population and a need to adapt and align with current care pathways.

Traditionally, a clinical trial would typically involve a physical study site at which all trial related activity takes place. Naturally then, that dictates that all participants need to physically travel to that site. Decentralised Clinical Trials (DCTs) aim to move away from this approach to one where the need for participants to visit trial sites is reduced or completely eliminated through local delivery of trial components.

For example, monitoring blood tests can be done at GPs, patients can complete questionnaires online, and modern technology, for example smart fitness devices like a Fitbit or similar, can be used to collect data on activity or daily functioning.

DCTs are sometimes alternatively referred to as ‘remote’, ‘digital’, ‘virtual’ or ‘patient-centric’ trials and are gaining traction within the clinical research sector due to their potential to promote efficient, patient-centric and technologically enabled delivery of clinical trials. For a full DCT, all elements of trial activity are conducted away from the primary trial site. However, it is recognised that decentralisation is likely a spectrum and, for many trials, a hybrid model may be most appropriate to adopt due to sponsor and regulatory requirements.

Establishing a new normal

The Covid-19 pandemic highlighted some of the vulnerabilities of the traditional clinical trial approach and accelerated change with some clinical trials, incorporating elements of decentralisation.

The need for reduced physical contact motivated the adoption of remote methods, some of which already existed pre-pandemic and began to define the ‘new normal’. It also helped that the Medicines and Healthcare products Regulatory Agency (MHRA) introduced more flexibilities during the pandemic. E-consenting, virtual patient assessments by phone/telemedicine, courier delivery of oral trial medications to patient homes and remote safety monitoring were all adopted by some trials during the pandemic.

Now, both the US Food and Drug Administration (FDA) and European Medicines Regulatory Network are taking steps to support the move to a decentralised approach and have published recommendations.

In March 2021, the UK government set out its vision on direction of clinical trial delivery. A key theme within this is for research to take on a more patient centred approach. The recent review by Lord O’Shaughnessy of UK commercial clinical trials  further highlights the need to pursue new approaches facilitating more streamlined working and relieving pressure on the NHS. Much of this is potentially relevant to academic as well as commercial trials. The Government as part of their response, issued a notable recommendation to accelerate new and innovative ways to deliver clinical trials.

CRUK’s own Clinical Research Statement of Intent underscores a desire to work with researchers, government and the NHS to enable the best delivery of trials, and realise the opportunities afforded by new tools and technologies.

Decentralised wins…

Benefits for participants include improved access to clinical trials, particularly pertinent in rare disease subtypes where only one or two sites in the UK may have a suitable trial open.

Distance to clinical trial site is one of the biggest barriers to patient participation in trials. Indeed, studies in the UK and US show only about 30% of trial sites meet their enrolment targets and around 50% of sponsors are forced to extend their enrolment timelines. There are various reasons for a failure to meet targets, but a significant issue is the heavy burden of visits and tests on trial participants which may result in them turning down the opportunity to participate.

A decentralised approach allows trial participation from anywhere, with trial-related activities integrated into participant’s daily routine, thus lessening the burden on participants. By reducing patients’ inconvenience, DCTs have the potential to improve enrolment and reduce drop-out rates. In addition, by reducing barriers to patient participation, DCTs have the potential to promote inclusivity and improve generalisability of study results and contribute to reducing cancer inequalities by increasing accessibility to trials.

At the sponsor and clinical trial unit levels, beyond boosting recruitment targets, DCTs could improve operational efficiency and decrease costs in the long-term. They could also provide real-time safety monitoring (for example, patients self-reporting symptoms online or clinical assessments conducted via video calls) which would allow for more representative and complete data collection as patients are monitored in their natural environments.

With benefits come some challenges…

Despite the potential benefits they could offer, what is missing from past and present studies is a comprehensive and structured approach to make DCTs mainstream within cancer clinical trials.

There is a need for holistic evaluation of decentralisation within cancer trials. That is, we need to confirm whether these benefits can actually be realised and what trade-offs there are; and to also understand what patients want, which may differ from in other disease settings. For example, cancer patients may find reassurance in having hospital visits. Work with patients, carers and their families to understand what is acceptable, must be central to this.

There are also many other considerations we’ll need to take on if we are to move forward with DCTs. From a clinician perspective, one of the most important is ensuring that patient safety is not compromised. In a conventional clinical trial setting, safe handling and administration of any investigational medicinal product (IMP) is ensured by research staff.

Also, importantly, patients are reviewed regularly and monitored for adverse events. This could pose a challenge within some DCTs – for example first in human trials, and the risk of specific toxicities that may be encountered which will of course require specific knowledge and access to services.  The potential impact of reduced physical contact on the robustness of safety monitoring would require comprehensive individual risk assessment and evaluation.

We also need to address questions surrounding data privacy. For example, do Fitbits and other digital devices or apps used by participants for the purposes of the clinical trial carry specific data security risks and are there sufficient mitigating processes for potential data breaches?