Finding an effective treatment in the short-term, and a vaccine in the long-term, is essential to enabling communities across the globe to restart economies and prevent poverty and starvation from lost income and resources, as well as allowing biopharma to refocus on targets such as cancer and heart disease. This vital need has meant that trials are moving faster than ever, presenting new and unique challenges.
As the field of clinical research adjusts to new conventions for conducting trials, we look at the impact of COVID-19 and the challenges that companies and their supply partners need to address.
Trials by numbers
Since the start of March 2020, 976 organizations have reported disruptions to clinical trials due to COVID-19 (1), while as of July, 3,985 new clinical trials have launched in search of a vaccine or treatment for the disease (2).
Trial areas experiencing delays include Oncology, with 31.2% of trials delayed as of May 2020, followed by Central Nervous System at 17.5%, Gastrointestinal at 8.5%, Infectious Disease at 8.1%, and Cardiovascular at 8.1% (4). The most significant impact of the pandemic on pre-COVID-19 trials has been on patient recruitment (5), with 69.9% of trials suspending enrollment. Slow enrollment and the delayed initiation of planned trials have had the next largest impact at 17.3% and 12.8% respectively, with the lack of sites and investigators playing a key role in these delays (4).
Conversely, among the thousands of new trials underway in search of effective interventions for COVID-19, clinicians and pharmaceutical companies are innovating and adapting in order to fast-track clinical studies:
• Some trials are repurposing drugs to accelerate treatment development, such as the broad-spectrum antiviral drug remdesivir developed by Gilead (6) or the steroid dexamethasone, previously used to treat asthma and other conditions (7).
• Other studies are using lessons learned from the SARS outbreak of 2002-2003 to guide vaccine development (8) and adapting vaccines originally developed for SARS (9) and MERS (10) for use on COVID-19. Using pre-existing biotechnologies can greatly speed up trials, such as with Moderna Therapeutics, who had a vaccine prospect ready for clinical trial only 42 days after the genetic sequence for SARS-CoV-2, the virus that causes COVID-19, was released (11).
• Countries across Europe have put in place ‘fast-track procedures’ for the evaluation and authorization of trials related to COVID-19 (12), while in the U.S., the FDA has launched a Coronavirus Treatment Acceleration Program (13).
Timeline to effective interventions
The world of clinical research has never faced a pandemic like the novel coronavirus that causes COVID-19. Though similar to both the SARS and MERS outbreaks, the SARS-CoV-2 coronavirus strain has spread far faster and, unlike SARS, shows no signs of dissipating (14). The prevalence and persistence of the virus have created the single greatest driver in the search for an effective intervention that humanity has yet seen.
The fastest vaccine to date – for mumps in 1948 – took four years from collection of viral samples to a licensed drug (15), but with current technological developments a COVID-19 vaccine could break that record by a large margin (16). Estimates vary widely across the scientific community, but most agree that a timeline of one to two years is possible (17). And while the search for a vaccine continues, some treatments are already being licensed for use in hospitals, such as remdesivir (18) and dexamethasone (19), with more likely to follow.
These achievements are due in large part to pre-existing research and treatments, but also to the technological innovations that are enabling the acceleration of trial timelines and procedures while mitigating the clinical disruptions occurring due to virus control measures.
The impact on clinical trials
Trials are now facing a delicate balancing act between the need to move quickly due to the essential nature of the work and maintaining the quality and validity of research results. Clinicians are adapting to new trial protocols, while suppliers and partners must be flexible enough to meet expedited timelines and reduce obstacles in the shipping and supply chains.
New challenges facing clinical research includes:
• Pressure due to shortened timelines – while a key focus is on fast-tracking evaluation and approvals, the need for quick turnarounds affects every aspect of trial management and supply.
• Remote sampling and data collection – with the need for social distancing comes travel difficulties and reduced patient contact. At-home testing and remote participant monitoring can help, but they also present logistical challenges that trial suppliers must help clinicians overcome.
• Conducting trials virtually or remotely – many trials have been forced to adopt remote trial procedures and embrace virtual tools, leading to an increasingly decentralized trial structure that requires more thorough logistics management.
• Restrictions to supply chains – changing travel restrictions and supply shortages have meant that trial suppliers have had to use alternative solutions to make sure that stocks are available
to meet trial demands.
• Conducting trial stages in parallel – speeding up the process of vaccine development may necessitate executing certain stages of development in parallel, such as early manufacturing scale-up before clinical proof of concept has been established (20).
In an effort to address these challenges, biopharma companies are embracing alternative business models that look to collaboration to speed up vaccine and treatment development. Working with research centers and universities to develop vaccines and further COVID-19 research (21, 22) has become the norm as leading pharmaceutical companies the world over pledge to work together to beat COVID-19 (23).
Driving trials forward
Despite the disruption to standard trial procedures necessitated by COVID-19, clinical trial managers can continue moving trials forward through operational innovation and the adept handling of logistics.
Important approaches to pursuing successful clinical outcomes include:
• Increased use of at-home sampling and testing. Bringing these aspects of the trial process direct to the patient eliminates the need for site visits – but in order to ensure sample integrity, clinical suppliers will need to provide effective kitting for home sample collection, along with secure tracking and tracing, and logistical support for shipping and storage.
• Adoption of drug self-administration procedures, enabling patients to participate in treatment trials without in-person clinician intervention.
• Embracing wearable technologies and mobile health (mHealth) to improve remote data collection and virtual monitoring.
• Working with partners who have the capacity to meet changing timelines and adjust to supply constraints. For example, difficult supply chain needs for a COVID-19 study led Avantor Clinical Services to develop a two-phase approach that utilized available supplies while developing customized kits leveraging in-stock and standard items to meet the trial requirements (24).
• Flexibility in equipment and kitting supply. As in the example above, the right provider will be able to help trials respond quickly to new requirements or obstacles and limit the risk of costly delays.
Summary
Across the globe, the healthcare industry is facing unprecedented challenges to developing new treatments and vaccines to tackle the COVID-19 pandemic. The thousands of new trials investigating potential interventions have opened the industry up to new collaborations, new approaches, and important innovations that will likely impact clinical trials in future.
The ability to advance trials while maintaining protocols and best practices for sample collection, study logistics, supply management, and storage and archiving will be vital to successful trial outcomes for COVID-19 and beyond. Clinical research providers with expertise in all areas of clinical supply, such as Avantor Clinical Services, will need to work proactively to help clinicians tackle the changing needs of clinical research.
Ultimately, how rapidly the essential testing and research needed to arrive at a safe and effective treatment for COVID-19, and eventually a vaccine, can be accomplished will be the biggest determinant in how quickly the world can begin to recover from the pandemic.
This article has been produced by Avantor Clinical Services as part of our ongoing commitment to setting science in motion to create a better world through the delivery of mission-critical products and services. To learn more, contact us today.
References
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