Science Fiction Came True: Best Practices for Future Viral Pandemics – Wright – 2021 – British Journal of Clinical Pharmacology
Prior to December 2019, it might have been easy to feel complacent about the risk of a global viral pandemic. The world had not seen a truly global viral epidemic since the influenza pandemic of 1917 and the recent outbreaks of Ebola, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), although of concern, appeared to be contained or remain regional. To the general public, a truly global pandemic might have seemed something that belonged to the realm of science fiction.
Science fiction writers often explore dystopian themes and use their work as a vehicle for thought experiments on how society might cope with major world events. Unsurprisingly, uncontrolled viral pandemics are a recurring theme. The idea that a global response will be needed, uniting nations, private industry and healthcare organizations against a common (viral) enemy, is both a familiar feature of our current human existence and is evident in several works. of Science fiction. Novels such as the work of Dean Kootnz in 1981 Eyes of darkness reportedly predicted the SAR-COV-2 outbreak, although that doesn’t seem to go into the details.1 Other works (for example, Vylar Kaftan’s short story in 2012 Lion dance) now feature all-too-familiar pandemic practices such as closing schools, social distancing, requiring masks in public places and self-isolation.2 Even the 1960s television show Star Trek played with the theme of a global pandemic in an episode called “Miri” (aired October 1966). In this program, the entire population of a planet was threatened with extinction due to an invisible pathogen that required the development and rapid testing of a vaccine.
In the real world, science fiction became reality in late 2019 with the start of the current SAR-COV-2 outbreak in Wuhan, China. The World Health Organization statement in March 20203 that the outbreak was a “pandemic” signaled that a coordinated global response was going to be needed to contain the disease. What followed was an unprecedented escalation of scientific efforts to rapidly develop vaccines against the SARs-COV-2 virus, identify potential drug treatments with accelerated clinical trials, and reuse existing drugs to treat COVID-19 disease.
Reflecting on the first 6 months of the pandemic, there was confidence, and perhaps too much comfort, that our available vaccines and approved drugs, developed through sufficiently rigorous and adaptable drug development and regulatory pathways, would be sufficient to navigate the world out of the SAR-COV-2 pandemic. What has become evident is that the drug development and regulatory communities have been caught ‘flat’ by COVID-19, mired in traditional slow development agendas and regulatory pathways with little room to pivot quickly. in response to a global emergency. This despite calls for adaptive licensing and other regulatory pathways for niche diseases to accelerate the development of particularly vulnerable populations over the past decade.4
In this thematic issue, we have approached groups and researchers who have developed new best practice approaches for future pandemic planning. They provided commentary, advice and examples developed from the experience gained in 2019-2021 that will hopefully put the global community in a position of preparedness for the next global pandemic. Contributions to this issue cover vaccine development, drug reuse for treatment and prophylaxis, assaying key patient populations, and conducting clinical trials. These manuscripts should be used by researchers, drug and vaccine developers, clinicians and policy makers to form the building blocks of guidance and policy documents that were lacking at the start of the pandemic.
There are essentially three key themes that are found in much of the work presented: (1) the need to prepare for the next pandemic, (2) the importance of new and future in silico tools to accelerate antiviral treatments, and (3) the place of global cooperation between sectors in future pandemics. Each of these is summarized in more detail below.
A major concern is that the lessons learned over the past 18 months will be quickly forgotten once the SARs-COV-2 pandemic is over. This was arguably the case in the early 2000s, when SARS-COV-1 disappeared and resources to fight the epidemic were redirected elsewhere. Preparing for future pandemics therefore requires the development of policies and processes to identify, respond to and control future pandemics in a timely and effective manner. This is introduced by Dodds et al.5 and developed by Davda et al.6 which outline a five-step plan to help us prepare for and respond to future viral outbreaks. Importantly, the plan focuses on pre-pandemic preparedness, including surveillance for new pathogens, high-throughput screening of potential treatment options using human lung cells, and identification of human-derived lung cells. Key pharmacological cues such as IC50 values (or better EC90 values) using previous work on reference viruses.6 These processes can occur before a viral pandemic occurs so that realistic options for reassigning existing agents can be identified quickly in the event of a new coronavirus outbreak.
Calvo Fernandez and Zhu7 present a comprehensive review of SAR-COV-2 vaccine development around the world and emphasize the importance of vaccine access and distribution. While vaccine developers have shown that they are equipped to respond quickly to a viral outbreak, what remains unresolved is how global immunization can be achieved and how equitable and rapid access to vaccines is achieved. will be managed in future pandemics.
An area often overlooked early in the SAR-COV-2 epidemic was the profound impact that refocusing resources on developing viral treatments and vaccines would have on existing drug development programs and clinical trials. Visser et al.8 stress that drug development and clinical trials are an essential part of the global health system, so any disruption should be carefully considered and managed. A decision support framework based on ethical principles is presented by the authors which will provide invaluable advice to regulators and investigators during future pandemics.8
The use of in silico tools, including pharmacokinetics-pharmacodynamics, systems pharmacology, and physiological-pharmacokinetic models, has become common in drug development programs. In the era of COVID-19, these tools have been extended to effectively explore possible antiviral options. Patel et al.9 show how the incorporation of a model of viral kinetics, to account for the viral life cycle, can be a valuable tool to understand both the appropriate targets of action of drugs to fight the virus, but also the timeframe optimal post-infection for treatment. This concept was extended by Dodds et al.,ten who used a similar platform to show how targeting different aspects of the viral life cycle with combinations of reused (or new) agents will optimize treatment success. The use of in silico tools has also been highlighted by Dodds et al.5 and Davda et al.6 as important platforms to enable accelerated drug reorientation efforts and drug development in future pandemics. In addition, in silico tools can be used to ensure that basic principles of clinical pharmacology are not ignored in the rush to suggest possible treatments, an important lesson from the onset of the COVID-19 crisis echoed in the contribution of Smith et al.11 and the ASCEPT-BPS statement on drug reorientation.12
In terms of cooperation, the need for data sharing and transparency in clinical trials globally to tackle misinformation, poorly designed studies and fraudulent treatment claims that have occurred within the first 6-12 months. pandemic is essential. It is important to note that systems must now be put in place, as a defined act of preparedness, to ensure that this becomes a reality before the next pandemic.7 This includes a careful examination of the role of traditional medicines in the supportive care of COVID-19 disease.13 In the current pandemic, the elderly, especially those placed in care facilities for the elderly, were the population particularly vulnerable to COVID-19,14 while pediatrics were considered to be at low risk of infection and transmissibility. This highlights the need for cooperation to improve the translation of available data to under-represented populations such as pediatricians and pregnant patients.15 These populations will need prophylaxis or treatment or may even be the next vulnerable target population due to a viral antigen shift.
The current era of COVID-19 will effectively end when the SARs-COV-2 virus is contained, the world’s population is vaccinated, and life returns to a semblance of the pre-COVID world. Lessons learned during the COVID-19 pandemic, as highlighted by the articles presented here, can play an important role in how we prepare, implement and coordinate effective responses to future pandemics. When future generations look back to this time in history, they should see more than fodder for new science fiction stories. Instead, we hope this era will be recognized as the start of global science programs and practices to prepare the world for future pandemics and has provided the necessary reset in the way we develop and approve drugs and vaccines. The COVID-19 events have been the catalyst needed to align in vitro, in silico, in vivo and regulatory science in a highly coordinated fashion to answer pressing questions. These approaches should now be seen as the new “best practice” for all drugs and vaccine development in the future.
There are no competing interests to declare.