Going virtual – how COVID has accelerated a real shift in clinical trial methodology
Nick Bellwood, Partner, UK Healthcare & Life Sciences, shares some critical insight from his conversation with Lilija Kircheis MD PhD. Lilija has built international teams and global clinical operations for over 22 years. She has led clinical research for much of her career and delivered over 400 trials in the last six years. Her work has led to the successful development of drugs in cardio metabolism, respiratory, immunology and oncology.
Bellwood: What have been the primary impacts of the COVID-19 pandemic on the conduct of clinical trials?
Kircheis: As healthcare providers reacted and redeployed resources to deal with the crisis, it is no surprise that clinical trial conduct was significantly affected. New trial initiation was almost impossible, and recruitment on existing studies was interrupted and slowed. Furthermore, on existing trials, it rapidly became a challenge to continue to treat and observe patients. The ability to provide medication to patients and collect biosamples and data was significantly impaired, as patients stayed away from the sites and investigators/physicians focused their capacity on the acute care of COVID patients.
Whilst this initial impact was evident, I suspect the greater impact will be seen in the next 12 – 18 months. In this timeframe, trials will be completed, and the analysis will show how heavy an impact COVID has had on the quality of study data. Multinational trials are likely to be more affected as different countries were struck at different times and how they responded adds greater variability.
Bellwood: As healthcare responded to the crisis, how did the industry and regulators react?
Kircheis: The industry reacted by evolving ad hoc and mainly remote solutions. Offsite or remote solutions included remote monitoring, patient contact with physicians via phone and video calls and using local laboratories to ensure timely processing of samples. Most urgent was the need to ensure supply of medication to patients which was complicated further when a medicine needed to be administered by a qualified healthcare practitioner. This sometimes meant having trial nurses visit patient homes to administer medication as well as carry out other necessary procedures. The entire logistical chain needed to be re-established.
To a certain degree the pharma industry had already thought about these remote solutions as there had been a growing consensus on the importance of decentralized clinical trials (DCT) and hybrid trial models in the preceding years to COVID. However, this theory had been developed to address challenges such as a lack of ethnic diversity in trials or the very small but highly disparate populations of patients associated with rare diseases, not in the context of a global pandemic. With exception of a handful of pharma early-adopters, DCT is not yet an established practice. COVID has accelerated this deployment at an unprecedented pace.
Regulatory authorities have been active stakeholders in the DCT and hybrid trial model debate with a bigger appetite for adoption in the Americas and Asia, compared to Europe. With the advent of COVID, the need to maintain and continue existing trials has meant a significant shift with regulators embracing this change. The U.S. FDA in particular, was remarkably swift in developing and issuing guidelines to support the deployment of remote ad hoc solutions and ensuring the maintenance of patient safety and the scientific integrity of trials.
Bellwood: As we enter a post-pandemic world, what will be the next steps in delivering clinical trials?
Kircheis: An array of ad hoc clinical trial solutions has been deployed in the last 18 months. In a peri-pandemic (it is too early to speak about post-pandemic times, especially in a multinational clinical research setting) or local epidemic environment, best practices and new robust processes need to be established to continue to deliver quality data while ensuring patients’ access to investigational medicines.
In the near future, we will likely see healthcare maintain a “ready for the next wave” status. Healthcare institutions will reflect on the experience and the lessons of the pandemic in how they adapted their processes for patient care in a crisis setting. Whilst healthcare sees a need to support to clinical trial activity at a certain level, it is likely to be even more selective and will also have a strong preference for DCT methodology, unless resources and infrastructure can be ringfenced to manage clinical trials on a more conventional basis. Few will have the space, people or budget to do this unaided.
Of paramount importance, industry and regulators will need establish best practice in DCTs. This will mean a critical review of what has been deployed during the acute phase of the pandemic. For pharma, this will enable benchmarking and start the journey to establishing best practices for remote procedures, DCTs and hybrid trials; for the regulatory communities, to harmonize their expectations and develop the boundary conditions to the industry and research for further progress towards remote trial settings.
Listening to patients and patient organisations and learning as well as factoring these experiences into new methodology will be a key success factor. For some patients, simply no longer needing to travel to and from centres may be a real positive, but the lack of personal contact with familiar staff is a real negative. The picture is likely to be complex but getting beyond an awareness of the expectations of patients and patient organisations will help for a smoother and more effective shift to remote methodology.
For industry and especially pharma, there remains significant need to develop medicines where patients have few or no therapeutics options. Delivering these trials with remote methodology, will drive the need for new types of roles with different skills and qualifications. These will focus on in-house nurses or para-clinicians, new types of a clinical research associate (CRA), digital experts, technical support roles for patients, etc.
In the long-term, we will see greater impact from tech companies as their focus shifts from consumer to include more clinical applications, which undoubtedly will have an impact on trials; how they are run and even designed. For now, COVID has accelerated change which means clinical trial execution is on a new course, and managed properly, this should be a significant and highly beneficial step for healthcare, industry and patients.