By Maria João Cruz, PhD, Research Analyst, Centre for Health Solutions, and Alex Grisman, Director, Deloitte
Clinical trials are vital to find out whether a new medicine (or medical device) is safe, effective and better than existing treatments. Essentially, clinical trials serve to accumulate sufficient, robust evidence to assure regulators of the patient benefits from a new medical intervention. The COVID-19 pandemic has overwhelmed medical infrastructures and had a significant disruptive effect on the current clinical trial landscape. A number of our previous blogs have examined the response of biopharma companies in pivoting their research activities to try and develop COVID-19 treatments and vaccines.1,2 This week we take a look at the challenges COVID-19 is presenting to the operation of other clinical trials, including site and participant selection recruitment and retention, and the strategies that biopharma is adopting to mitigate these challenges.
Impact of COVID-19 on ongoing and planned clinical trials
Clinical trials are expensive, lengthy (taking on average 10-12 years) and, in the latter phases, require the participation of a large number of participants to assess the efficacy and effectiveness of a new treatment (Figure 1).3
Figure 1. Traditional approach to clinical development
At the outset of the COVID-19 pandemic, healthcare systems, and in particular hospitals, had to reorganise their services and train staff to work in new ways and in unfamiliar teams in the shortest of time frames. In addition, where clinically appropriate, they also had to discharge non-COVID-19 patients to protect them from infection and create the capacity needed for COVID-19 patients and accelerated the adoption of digital technologies to triage, support and, where possible, treat patients remotely. At the same time, most countries imposed a lockdown to curtail the spread of the disease.5 Consequently the operation of clinical trial sites and availability of participants were severely impacted.6
Since early March, when the WHO declared COVID-19 as a pandemic, biopharma companies and clinical research organisations (CROs) have had to suspend enrolment in or terminate ongoing trials, as well as delay the planned start-up of others. Research by GlobalData showed that, as of May 2020, more than 1,100 clinical trials across the US and Europe were disrupted, with the majority due to suspension of enrolment.7,8 However, after three months of increasing disruptions, between June and July the number of resumed clinical trials has started to rise (Figure 2).
Figure 2. Clinical trial disruptions and recommencements (16 April – 9 July)
Source: GlobalData’s Pharma Intelligence Center9
Moreover, at the onset of the pandemic in Europe, the UK’s National Institute for Health Research (NIHR) announced that new clinical trials were being suspended in order to prioritise COVID-19-related clinical studies and also to free-up clinical staff to be deployed to frontline care.10,11
Many biopharma companies and research organisations, especially those already working on vaccine development, considered that it was right and natural from a humanitarian viewpoint to support governments to respond to the pandemic. They, therefore, pivoted much of their research efforts into finding treatments and vaccines to combat COVID-19. Governments and other funding organisations also focused their resources on the search for a vaccine and treatments. Nevertheless, all were aware that discontinuing other clinical trials and research studies would have a significant impact on the ongoing and future care of other patients and that restarting clinical trials would be vital, but challenging.12
Transitioning to digitally-enabled trials
The primary focus during clinical trials is always the safety of patients and clinical staff. However, due to the increased risks to potential non-COVID-19 trial participants and with the necessity of social distancing measures and travel restrictions, CROs and pharma companies have had to look at alternative ways to collect trial safety and efficacy data. A crucial solution has been leveraging digital technologies that allow for safe and effective patient monitoring.13
Even before COVID-19, as we found in our February 2020 report, Intelligent clinical trials: Transforming through AI-enabled engagement, some companies were starting to explore the use of digital technologies in the recruitment and management of clinical trials. Our research showed how the adoption of advanced digital technologies presents a transformational opportunity for biopharma companies to unlock real-world data (RWD) and assist with trial design, improve patient recruitment and enrolment, optimise patient monitoring and retention, and, ultimately, use operational data through advanced analytics to drive insights.
At the end of May 2020, we interviewed Medidata’s Fiona Maini and Fareed Melhem for the first episode of our Life Sciences Connect podcast. In this episode, we discussed how sponsors and CROs have had to rethink how to conduct clinical trials during the evolving pandemic. They discussed the fact that the pandemic has emphasised the importance and need for real-time data capture for a more agile and digital approach to trial management. They also highlighted the crucial role played by industry stakeholders coming together, in informal and formal coalitions, to share data and information around COVID-19 to drive the development of new treatments. They believe that the foreseeable future is going to be a time of uncertainty, but one which offers more opportunities for flexibility and collaboration to develop new innovations.
Creating digital twins to predict clinical outcomes
The pandemic has fuelled an acceleration in the adoption of digital technologies across the life sciences and healthcare sectors. One example of using advanced technologies to help the biopharma sector adapt to the impact of COVID-19 on clinical trials is the creation of ‘digital twins’ to enable simulation of operational performance. Broadly speaking, a digital twin is a virtual replica of a physical object or a whole system, which allows the user to see how the physical object will perform in different environments or if it is changed in specific ways.14 This engineering concept uses multiple data sources, including real-time data, to enable advanced analytics and simulation experiments in a safe virtual environment.
With this technology, companies are able to accurately quantify the effect of internal and external factors such as COVID-19 or protocol complexity on site performance and patient behaviour. In addition, companies can use it to evaluate how mitigating actions, namely site selection or application of digital health tools, could contribute towards clinical trial success. Given the increasing complexity of clinical trials and the associated patient retention issues, digital twins can provide a unique insight into the balance of trial and patient needs and the likely impact and success of digital solutions.
The use of digital twins can accelerate the exploration of options and the impact of design changes and mitigation strategies, helping companies to make more informed decisions and take the best actions to overcome obstacles when designing and conducting clinical trials. This is especially important during unexpected and disruptive events, where the ability of a digital twin to predict the study wide effects of changes in specific elements of a clinical trial process sets it apart from other purely data-driven methods.
Moreover, simulations are able to predict patient loss and study delays due to COVID-19 by modelling the effect of the pandemic on hospital capacity, patient concerns, ease of movement and the number of infections in an area. Each of these factors can be modelled and applied at the site level and aggregated up, enabling the analysis of wider impacts at a country or study level to understand if and what actions need to be taken.
Clinical trials are the driving force of pharma innovation and the only safe and effective way to bring new medicines to patients. With the clinical trial landscape severely impacted by the COVID-19 pandemic, there have been serious consequences for patients, as well as for the pharma companies, governments and other funders that invest in clinical innovation each year. Indeed, we believe that connected AI-enhanced digital technologies, as well as other digital and virtual technologies, can and will transform clinical trials by making them faster, safer, more efficient and effective, and, above all, truly patient-centric. The pandemic has been a catalyst for accelerating the adoption of advanced technologies and provides an opportunity to expedite all future clinical trials to ensure patients are able to access the life-extending and life-enhancing treatments they need.