Monitoring the safety and effectiveness of COVID-19 vaccines

By Dr. Seleem R. Choudhury, January 14, 2021  

Next to clean water, no single intervention has had such a dramatic effect on decreasing mortality as has the widespread introduction of vaccines (Howson, Howe, & Fineberg, 1991). The World Health Organization (WHO) describes immunization as a “key component of primary health care and an indisputable human right,” as well as “one of the best health investments money can buy” (World Health Organization, 2020). Vaccines play a critical role in the prevention and management of the outbreak of infectious diseases.  The rapid spread of COVID-19 during the months-long wait for a vaccine have highlighted their importance to public health. 

If COVID-19 were a Shakespearean play, the administration of the vaccine would ideally be the final act, and widespread adoption and effectiveness, the epilogue. However, just like Shakespeare’s Timon of Athens, this play may be also be left unfinished. According to the WHO, at least 198 COVID-19 vaccines are currently in the development pipeline, with 44 currently undergoing clinical evaluation (2020). National Institute of Allergy and Infectious Diseases Director Anthony Fauci, M.D., recently stated a date to a possible “normal” is tricky at best (McCarthy, 2020). He explains: 

“If the vaccine is reasonably if not quite effective, but not a very large proportion of the population take it, then that would really be unfortunate because it wouldn’t provide that umbrella of protection over the community so that you could feel reasonably certain that when you go to a family function, a wedding, or the like, that there’s not going to be a couple of people in there that are actually infected.”

Continued monitoring: Reasons and methods

The effectiveness of the COVID-19 vaccine to usher in a “new normal” hinges on its widespread administration. Continuous and transparent monitoring is essential to encourage the maximum number of people to choose to be vaccinated.  This article was written fully acknowledging that the SARS-CoV-2 variant exists, yet the implications of the variant remains unclear and the impact upon the vaccines remains unknown (Public Health England, 2020). 

Reasons for monitoring the vaccine

The primary reason for conducting additional vaccine effectiveness assessments is to ensure a vaccine “protects people from getting a disease under real-world conditions, outside of the strict setting of clinical trials” (National Center for Immunization and Respiratory Diseases, 2020). Numerous factors, such as how a vaccine is transported, the method of storage, or even the way patients are vaccinated, can affect a vaccine’s effectiveness in real-world situations.  

Even after administration trials of the COVID-19 vaccine, organizations will continue to monitor longer-term safety and efficacy (Cyranoski, 2020).  Teams of experts will evaluate the effectiveness of the vaccine in real-world conditions, outside of more controlled clinical environments (WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation, 2020).  Furthermore, underlying medical conditions not present in patients who participated in the clinical trials can also change the effectiveness of the vaccine in real-world use, or in groups not included or represented in clinical trials, such as children under 12, or pregnant or lactating women (National Center for Immunization and Respiratory Diseases, 2020).   

Additionally, transparent monitoring will prove essential to improve the public’s trust in the vaccine so that people will choose to vaccinate. Public trust in the storied public health institutions cited above is now deeply compromised. According to recent polls, 62% of Americans worry the U.S. Food & Drug Administration (FDA) will rush to approve vaccines without adequately assuring safety and effectiveness because of political pressure (Hamel, Kearney, Kirzinger, Lopes, Muñana, & Brodie, 2020; Miller, Ross, & Mello, 2020).  Only 25% of Americans have “a great deal” of trust in the Centers for Disease Control and Prevention (CDC), and only 21% definitely plan to get vaccinated, while 49% probably or definitely will not (Tyson, Johnson, & Funk, 2020). 

Vaccine safety is a significant concern for many, given the uncommonly rapid development and testing process, underlying suspicion about vaccines in general among segments of the population, and mistrust of the government’s pandemic response thus far (DeRoo, Pudalov, & Fu, 2020).  Efforts to provide the population with ample information addressing these reasons for apprehension should be made before and during vaccine program rollout. 

In addition to widespread misinformation about vaccines, health organizations must also contend with mistrust of vaccines borne out of the U.S.’s historical mistreatment of people of color in the spread and prevention of infectious diseases. This includes actions such as using ethnic minorities as test subjects for medical advances in the 20th century, or giving blankets laced with smallpox to indigenous peoples in Jamestown in the 1700s, to name a few examples.  In fact, some studies link mistrust of the health care system and fears of experimentation among some African American people to historical and contemporary mistreatment and disparities in care (Yancy, 2020). 

Methods for monitoring the vaccine

Clinical trial results show whether vaccines are effective.  The FDA evaluates the data from the clinical trials, as well as manufacturing information, to assess the safety and effectiveness of vaccines, then decides whether to approve a vaccine or authorize it for emergency use in the United States (National Center for Immunization and Respiratory Diseases, 2020; U.S. Food & Drug Administration, 2018). 

However, even after a vaccine is approved by the FDA and released for public use, more assessments are necessary. According to the CDC, the goal of these assessments is “to understand more about the protection a vaccine provides under real-world conditions, outside of clinical trials” (2020).  This is accomplished by comparing groups of people who do and don’t get vaccinated, and people who do and don’t contract the COVID-19 virus to assess how well COVID-19 vaccines are working to protect people compared to other protection measures (National Center for Immunization and Respiratory Diseases, 2020). 

Future implications and vaccine resistance

These vaccine monitoring activities are the norm, but they will take place on a larger scale during this pandemic. The post-licensure vaccine evaluation will be a crucial component of an evidence-based vaccine program. This should include four aspects.

1. Collecting exposure data for COVID-19 vaccines.

The data when reviewing the efficacy of the trial is thus far encouraging and builds confidence in the continued effectiveness of the vaccine. Dedicated trials will be needed to deepen our understanding of the impact of COVID-19 vaccines among different groups, specifically children, pregnant women, and black, indigenous and people of color (Hodgson, Mansatta, Mallett, Harris, Emary, & Pollard, 2020). 

Additionally, data must be collected to assess the effectiveness of a promising administration method: heterologous prime-boost vaccination. A heterologous prime-boost vaccination is a “repeated immunization regimen designed to increase and sustain vaccine-induced immune responses” involving “sequential delivery of different vaccine platforms” (Jeyanathan, Afkhami, Smaill, Miller, Lichty, & Xing, 2020). This method has proven effective with vaccines for other diseases such as hepatitis B24 and Ebola virus (Logunov, Dolzhikova, Zubkova, Tukhvatullin, Shcheblyakov, & Dzharullaeva, et al., 2020). In past studies of other coronaviruses, “prime-boost regimens using different viral vectors expressing the same recombinant antigen proved very efficient in enhancing the target antigen-specific immune responses” (Schulze, Staib, Schätzl, Ebensen, Erfle, & Guzmana, 2008).

2. Adopting specific safety signal detection and management measures.

A vaccine safety signal is “information that indicates a potential link between a vaccine and an event previously unknown or incompletely documented, that could affect health” (World Health Organization, 2020). Experts monitor this data to decide whether changes are needed in U.S. vaccine recommendations in order to ensure that the benefits continue to outweigh the risks for people who receive vaccines (National Center for Immunization and Respiratory Diseases, 2020; European Medicines Agency, 2020). 

3. Using real-world evidence (RWE) from clinical practice.

At the beginning of the pandemic, there were well documented errors made by many countries, including notable errors in the U.S. from the CDC, the Trump administration, and hospitals (New York Times, 2020; Nather, 2020; Evans & Berzon, 2020). As a nation, the U.S. was slow to respond and react to an ever-evolving situation. Real-world evidence gathered from longitudinal studies of COVID-19 patients and vaccine recipients will play a crucial role in responding to new information quickly and effectively in clinical practice. 

4. Applying exceptional transparency measures.

The combination of data and technology makes it possible to conduct near real-time analyses of healthcare trends and, for the first time, create a more robust and accurate understanding of disease and treatments (Christian & Reynolds, 2020). This data will have to be shared in its entirety, with no detail withheld or deemed unimportant. The data must be open to criticism and analysis so that trust can be allowed to grow, and fear subsides (Nature, 2020).

Summary

Dr. Seleem R. Choudhury receiving his 1st dose of Pfizer COVID vaccine.

The COVID-19 vaccine will not be able to single-handedly eliminate the virus from our lives. It will not necessarily allow us to return to the life we led before the pandemic reared its ugly head, but it has great potential to save countless lives and make a way forward into a new normal.  The key to making this a reality is continuous monitoring of the vaccine’s effectiveness and high levels of transparency to build public trust. 

Research indicates that a majority of Americans may trust scientific research findings more if data and information were publicly shared (Funk, Hefferon, Kennedy, & Johnson, 2019; Miller, Ross, & Mello, 2020). It is essential to widen public access to information about vaccine clinical trial design, conduct, and data. This exchange of information will provide the necessary transparency and ease of interpretation of data.  

Big pharma will need to be comfortable understanding the public hesitancy and be prepared to counter this reluctance with openness and a level of transparency never seen before as the stakes could not be higher: “History has shown that once public trust in vaccines has been compromised it is difficult to win back” (Nature, 2020).

Read more from Dr. Seleem Choudhury at seleemchoudhury.com  

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