The rapid growth of clinical trials for COVID-19

The COVID-19 pandemic has been the catalyst for significant shifts in the clinical trial landscape. Hundreds of trials underway prior to the pandemic are on hold (1), while thousands of new trials have launched in the search for effective treatments and interventions (2). As clinicians respond to virus control measures, many of these trials are being conducted remotely using tools such as virtual assessments, home testing, and drug self-administration – per new FDA guidelines (3) – signaling a potential shift in how clinical operations are undertaken and will likely be conducted in the future.

Finding an effective treatment in the short-term, and a vaccine in the long-term has proved essential to enable communities across the globe to restart economies while allowing both public healthcare and biopharma to refocus on other health concerns, such as disease prevention and diagnosis. The vital search for a vaccine spurred global cooperation for research and distribution, which in turn has prompted a renewed industry focus for clinical trials to move faster.

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 must address.

Trials by numbers

Since the start of March 2020, research suggests almost 70% of global clinical trials have been disrupted due to COVID-19^[1], while as of July 2020 6,416 new clinical trials were launched in search of a vaccine or treatment for the disease^[2].

Trial areas experiencing delays include Oncology, with 369 related trials delayed in the USA alone as of June 2020, followed by Central Nervous System at 223 Gastrointestinal at 116 and Cardiovascular at 99^[4]. The most significant impact of the pandemic on pre-COVID-19 trials has been on patient recruitment ^[6], with 67.3% of trials suspending enrollment, the delayed start of planned trials following and slow enrollment at 18.4% and 14.4% respectively. Of the trials affected by slow enrollment, 20.7% are specifically due to the availability of sites and investigators. As of October 2020, several trials resumed. Out of these 82.4% recruited participants, with 7.3% completing recruitment and 0.5% yet to start recruiting^[5]. Trial activity is generally expected to resume at a much slower rate than originally anticipated. A report published in August 2020 by GlobalData’s Pharma Intelligence Center indicated that over 600 global trials were set to resume activity^[7].

Conversely, among the thousands of new trials underway in search of effective interventions for COVID-19, clinicians and pharmaceutical companies are innovating and adapting to fast-track clinical studies:

• Some trials repurposed drugs to accelerate treatment development, such as the broad-spectrum antiviral drug remdesivir developed by Gilead^[8] or the steroid dexamethasone, previously used to treat asthma and other conditions^[9].
• Other studies took lessons learned from the SARS outbreak of 2002-2003 to guide vaccine development^[10] and adapting vaccines originally developed for SARS^[11] and MERS^[12] for use on COVID-19. Using pre-existing biotechnologies can greatly speed up trials, such as with the Oxford University vaccine candidate that began Phase 3 trials in July^[13]. The Oxford vaccine, being developed in partnership with AstraZeneca, uses viral vector technology originally developed in the search for a MERS vaccine^[14].
• Other studies investigated the potential of targeted monoclonal antibodies designed to boost patient immunity to the virus and the method of dampening the virus’s effect while vaccines are still undergoing trials. The desire to expedite this search led six top pharma companies to request FDA permission to share information, including AstraZeneca, Lilly, and GlaxoSmithKline^[15].
• Countries across Europe put in place ‘fast-track procedures’ for the evaluation and authorization of trials related to COVID-19^[16], while in the U.S., the FDA launched a Coronavirus Treatment Acceleration Program, which became known as Operation Warp Speed^[17].

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 ^[18]. 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 the collection of viral samples to a licensed drug^[19]. Technological developments and advancements saw a COVID-19 vaccine break the record by a large margin^[20] with Pfizer and its partner BioNTech announcing their vaccine had proven 90% effective in November 2020 and was subsequently authorized for use. A timeframe of under one year.

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^[21].

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^{[22, 23]} became the norm as leading pharmaceutical companies the world over pledged to work together to beat COVID-19^[24].

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 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 can 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^[25]
• 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 in 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 accelerated adoption of the Decentralised Clinical Trial model during the pandemic is one such instance. Decentralised Clinical Trials encapsulate the elements highlighted above in driving trials forward.

Without these changes, it’s doubtful that results could have been achieved so quickly. The ability to advance trials while maintaining protocols and best practices for sample collection, study logistics, supply management, and research sample storage and archiving will be vital to successful trial outcomes beyond COVID-19. 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 the continuation of testing and effective treatment alongside a rapid rollout of the vaccines, now approved through clinical trials, will be a key 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.

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References

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