Developing New Approaches for Managing Pandemics: Learnings from COVID-19

Yesterday, March 24, 2020, was a record day of events for the COVID-19 pandemic and how it is affecting every aspect of our lives as US citizens.  The dynamic nature of the current crisis is reflective across our economy and the government’s approach on managing this outbreak: The DOW JONES Futures posted a record high that has not been seen since 1993 and the FDA recommended a promising vaccine approach for COVID-19 based on all our learnings since the monumental discovery that lead to a small pox vaccine: “The FDA is facilitating access to convalescent plasma, antibody-rich blood products that are taken from blood donated by people who have recovered from the COVID-19 virus, that could shorten the length, or lessen the severity, of the illness.” [1]

In the late 18th century, Dr. Edward Jenner of Gloucestershire, England "experimented with an early version of a smallpox vaccine by utilizing the pustular material from those milkmaids exposed to cowpox who appeared to be immune to small pox”[2] with a crude inoculation that was introduced to those that contracted the virus using a skin-scratch method. Prior to Dr. Jenner’s discovery, earlier physicians were using "nasal inoculation for susceptible persons with material from smallpox lesions.”[2]
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We, as professionals working within the precision medicine field, have a responsibility to educate our US community and US politicians through this global crisis, ensuring we add to the collective understanding and assist with strategic countermeasures that consider the benefit-to-risk profile for Americans.

The US is a “melting pot” representative of a heterogenous population, which could provide a frame of reference for global scale-up during a pandemic.  As Regulatory professionals, we apply benefit-to-risk ratio analyses to development projects to ensure that safe and effective products are marketed throughout the US. Perfect diagnostic and/or therapeutic products are not achievable; we strive to commercialize and make products that outweigh the risk and provide benefits available to the patient in the context of specific intended uses.

Technical experts, who actively develop in vitro diagnostics (IVDs), understand the detection capabilities of various methodologies for COVID-19 (e.g. differential sensitivity, specificity, accuracy, pre-analytical factors, robustness, turnaround time, etc.) and the advantages and disadvantages of point-of-care testing versus centralized testing models; both models are being offered via emergency use authorization (EUA) processes. Drug development professionals have the knowledge to recommend the best distribution of treatment options for EUA vaccines. We contemporaneously develop therapeutic products based on the combined expertise of diagnostic and pharmaceutical professionals. We should apply these same co-development principles to the development and availability of medical countermeasures for COVID-19.
 
Today, March 25, 2020 the FDA Announced a: “Funding Opportunity to Explore the Use of Real-World Data (RWD) to Generate Real-World Evidence (RWE) in Regulatory Decision Making," offering a funding opportunity that could provide COVID-19 approvals to meet higher evidentiary standards versus traditional approaches and methods for data collection and evidence generation. [3] Given the long timelines typically for clinical trials, it is important to evaluate real-word evidence approaches for COVID-19.  Observational real-world data suggests that: “COVID-19 is a highly contagious viral pneumonia. In mild cases it results in few, if any symptoms, such as cough and mild fever. In severe cases, it results in life-threatening pneumonia that can be fatal, particularly in the elderly, immunocompromised and individuals with underlying medical conditions such as heart disease, lung disease and diabetes.” [4] Thus, infectious disease progression differs within our population. In order to properly manage the COVID-19 pandemic within the US, it is important to be able to collect demographics and clinical characteristics data from infected and recovered patients in order to understand the risk profile for current and future patients. Deploying RWD management and analyses solutions, such as Artificial Intelligence (AI), machine learning (ML), and software to extract data from health records (e.g., medical and pharmacy records) would facilitate the acquisition of essential data identifying predictors for COVID-19 and provides more data to accurately determine the morbidity rate.

There are some interesting clinical symptoms emerging, (lack of taste and smell) that could help identify those individuals who are at an early stage of infection with COVID-19 versus being infected with influenza. Understanding whether clinical symptoms are associated with the early onset of infection versus the late stage may be informative for determining the optimal time for diagnostic testing and whether to treat the patient or let the viral infection run its course; basing the decision on the demographic and clinical characteristics of the individual patient. Unique COVID-19 clinical symptoms, as compared to other viruses such as influenza, may also help identify potential blood donors to support the vaccine approach endorsed by FDA yesterday. 

Collecting RWD from individuals living in the US during this pandemic (for example, through a direct-to-consumer mobile diary app that captures symptoms during an outbreak) could provide data that can be analyzed to identify key clinical differentiators for this virus in addition to understanding on the length of time that symptoms persist. The US population would likely support this platform by contributing their personal experiences to this database in order to achieve beneficial disposition for the entire community. Having patient-reported outcomes in real-time would provide more data for communities and governments to integrate into their decision making process and share with other global markets. In today’s world during a health crisis like this, there needs to be mechanisms in place to collect data in real-time to ensure that decisions are made off larger datasets at earlier stages. Today’s technology can support this capability and avoid returning to a time where we rely on individual contributions by amazing physicians, as we did in the late eighteenth century. 
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Interestingly, in the patient zero area of Wuhan, China, individuals reported gastric distress; are there differences in the clinical course of the disease in specific geographies, or is this an anecdotal observation? This is why having patient reported outcomes in real-time would be beneficial.

Pandemics are part of our natural history, and as we continue to develop tools for other health burdens such as autoimmune diseases, cancer, cardiovascular disease, mental health, and neurological diseases, we should keep in mind how these modern tools could be used during times of crisis in order to make quick and necessary decisions based on the overall risk-to-benefit profile and very limited data, while still maintaining the best interests of US citizens first. It is important to maintain ethical, factual, and strategic principles when combating pandemics, and then apply the lessons learned to the next ones.


[1]https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-24-2020?utm_campaign=032420_PR_Coronavirus%20%28COVID-19%29%20Update%3A%20Daily%20Roundup%20March%2024%202020&utm_medium=email&utm_source=Eloqua

[2] Belongia, Edward A, and Allison L Naleway. “Smallpox vaccine: the good, the bad, and the ugly.” Clinical medicine & research vol. 1,2 (2003): 87-92. doi:10.3121/cmr.1.2.87

[3]https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-20-030.html?utm_campaign=FDA%20Announces%20Funding%20Opportunity%20to%20Explore%20the%20Use%20of%20Real-World%20Data&utm_medium=email&utm_source=Eloqua

[4] Terry, Mark. “Compare: 2009 H1N1 Pandemic Versus the 2020 Coronavirus Pandemic.” BioSpace. 19 MAR 2020.