Decentralized Trials: How COVID-19 Pushed Us to Change the Clinical Trial Game
This blog was authored by Fiona Maini, global compliance and strategy principal, Medidata.
It goes without saying that the COVID-19 pandemic has had a tremendous impact on companies regardless of industry. The pandemic’s impact on clinical research globally has understandably been notable and has catalyzed greater adoption of remote strategies when conducting clinical trials.
Looking at changes in history and the influence of the internet over the last couple of decades, we can see how the clinical trial process has transformed through advances in science and technology. We’ve seen the rise of decentralized clinical trials (DCTs) and the impact of COVID-19 in changing behaviors towards the use of remote clinical trials. Going forward, the industry must continue to collaborate to ensure that we do not revert to the old methods and push forward in our approach to virtual trials. This will help to both reduce patient burden and bring treatments to market faster.
Where It All Started
The first documented controlled trial in history occurred in 582 BC and was recorded in the Old Testament’s Book of Daniel. The experiment—which resembled a clinical trial—was conducted by King Nebuchadnezzar of Babylon. He ordered his people to only eat meat and drink wine, a diet which he believed would keep them healthy. However, several men objected, reiterating their desire to continue eating vegetables. As a result, the King allowed them to follow a diet of legumes and water for 10 days. Towards the end of the 10 days, those who had a vegetarian diet appeared better nourished than the meat-eaters, which led to the King allowing them to continue with that diet beyond the 10 days. While it was a basic experiment, it was one of the first times in human history that a medical test guided a public health decision.
There have been milestones in history that have led to where we are currently. In 1787, a surgeon named James Lind began the first randomized clinical trial aboard HMS Salisbury of Britain’s Royal Navy fleet. He recruited 12 men, divided them into six groups, and subjected them to various regimens to discover what could effectively treat scurvy.
Fast forward to the 1990s, where we saw the development of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and Good Clinical Practice (GCP), the invention of the World Wide Web, and the invention of the smartphone. Moving to the mid-2000s, a swathe of international and regional regulations on clinical trials began to appear that included an update to ICH GCP Revision 2, the EU’s Clinical Trial Regulation, and the new Medical Device and Invitro Diagnostic Regulation. While in the US, we’ve seen the 21st Century Cures Act, legislation that aims to bring new medicines to market faster. The latest challenge to the industry, COVID-19, remains ongoing.
Today, ICH GCP is going through a thorough modernization and renovation to become more aligned with the scientific and technological advances of today's world. So far, ICH GCP Revision 3 looks to be very progressive with a focus and emphasis on considerations for data management, responsibilities, monitoring, and the use of technology, to name a few areas. It will seek to lay the foundation for the digital transformation of clinical research.
What’s Changed? The Internet Revolution
One of the most significant changes to have impacted clinical trials in recent history has been the internet. Mobile phones and computers have enabled us to access information from multiple sources instantly. Prior to and during the COVID-19 pandemic, people have used websites as a tool to check for their symptoms or information about their health. The internet has allowed patients to unlock access to other patients’ experiences, a specific disease or treatment, make an informed decision about their treatment options, and whether to enroll in a clinical trial. It goes without saying that with this access, patients are now more informed than ever.
The internet and the subsequent digitalization of healthcare, accelerated by COVID-19, allowed for the move from traditional clinical trial methods to Decentralized Clinical Trials (DCTs). Without the internet, such progress would not have been achieved. In contrast to traditional trials which require patients to visit sites, reducing the inclusion of diverse populations and can be burdensome for patients, DCTs offer a more patient-centric approach to leading clinical trials. DCTs enable the use of remote strategies to be deployed which, in turn, allow for further diversity of the patient sample and reduce patient burden.
What Does It Look Like from a Practical Standpoint?
DCTs have allowed for an increased sample of patients enrolled in clinical trials, and also the geographic reach and diversity of that sample. There are a few things to consider in the conduct of DCTs:
- Human interaction remains an important principle to take into account. Patients need to have a point of contact and there needs to be local support and infrastructure to guide enrolled patients. DCTs are the most successful when the rightful level of support and infrastructure is in place.
- Ensuring the process is user-friendly, as patient participation and retention in trials should be easier.
- Having an integrated technology and support service such as telemedicine or a central pharmacy.
- Patient choice is key. This is a core principle to how DCTs are successful – by enabling patients to have the freedom to choose where and when they want to partake in those trials.
Mitigating Hesitation to Enforce Adoption
In 2019, the Decentralised Clinical Trials Working Party (DCT WP), led and chaired by Medidata, was established by the Association of Clinical Research Organisations (ACRO) to examine the barriers hindering adoption of DCTs and to study the benefits of using the approach. Key insights from the working group included the need to address stakeholder hesitation in regards to modernization and change, which could be resolved through the creation of end-to-end best practices. Another issue examined is the need to identify and help resolve change management burden on trial patients. As a way to resolve the issues mentioned, the working party developed a working plan titled ‘A Toolkit Dedicated to Decentralised Clinical Trials’ which is composed of two documents created to address the issue:
- Bringing the Trial to the Patient: A Quality-by-Design Framework – a document that is aimed at providing stakeholders with guiding principles for the construction of DCTs.
- Risk Assessment Tool – which is designed to complement organizations’ risk assessment The document is designed to address mitigations by providing DCT-specific considerations that need to be taken on board.
The COVID-19 Pandemic: Impact and Regulatory Aspects in Consideration
The pandemic has had an impact on almost every company regardless of the industry. If we consider the life sciences and health care industries, the pandemic highlighted the considerable limitations of the traditional approach to clinical trials. Despite some previous hesitation from the industry, during the pandemic it had to find new solutions to the difficulties COVID-19 posed for clinical trials and found one in DCTs, recognizing the benefits of this approach.
Of note, the Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA) have played a key role in helping the industry navigate regulatory challenges during the pandemic. Regulators have been prompt and pragmatic in their approach, bridging gaps to ensure delays were minimized. In the UK, the MHRA has proven to be clear on regulatory flexibilities. Elsewhere, the US Food and Drug Administration (FDA) and the EMA were equally supportive of the industry.
The ACRO DCT WP Quality-by-Design manual and risk assessment were published in 2020. They were very timely in supporting the industry during COVID as organizations had to pivot and deploy more remote strategies, of which DCTs components have been an effective solution to continuing clinical research during regional lockdowns and restrictions.
What Does the Future Hold?
Despite challenges brought by COVID-19, the pandemic highlighted the importance of moving forward in our approach to clinical trials and in accelerating the DCT pathway. The industry worked together to deliver vaccines at unprecedented speed and has accelerated the adoption of DCTs. For instance, DCT provider Medical Research Network recorded a 200% increase in demand for their services. Looking forward, the industry must focus on adopting a singular and standardized approach of the technical qualification tools for DCT providers and increase the access and availability of technology to conduct remote trial-related activities.
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