Guardrails to Ensure a Safe and Effective COVID-19 Vaccine: Dr. Ruth Karron’s Written Testimony

Written testimony from the House Committee on Oversight and Reform Virtual Briefing:

Chairman Krishnamoorthi, Ranking Member Cloud, and Members of the Committee, thank you for the opportunity to speak with you today about COVID-19 vaccine development and evaluation. My name is Ruth Karron. I am a pediatrician, trained in infectious diseases, and am a Professor in the Johns Hopkins Bloomberg School of Public Health, where I lead the Center for Immunization Research and the Johns Hopkins Vaccine Initiative. The opinions expressed are my own and do not necessarily reflect the views of Johns Hopkins University. My work has focused on respiratory virus vaccines, vaccine policy, and vaccine ethics. With respect to COVID- 19 vaccines, I have served on the Data and Safety Monitoring Board for the phase 2 trial of the Moderna mRNA vaccine, and will likely be a coinvestigator on 2 of the vaccine trials scheduled to begin in the coming months. I have also had the honor and privilege of serving on 2 Federal Advisory Committees: I chaired the Vaccines and Related Biologic Products Advisory Committee (VRBPAC; 2006-2008), which advises the FDA on issues related to vaccine licensure, and served as a member of the Advisory Committee on Immunization Practices (ACIP; 2012-2016), which advises the CDC on vaccine deployment.

As I write this testimony, more than 3 million Americans have been infected with SARS-CoV2 and more than 137,000 have died. This virus has profoundly affected us all, but it has been especially devastating for the elderly, the poor, and for racial and ethnic minorities. While it is critical to implement and enforce social distancing practices now, development and deployment of COVID-19 vaccines is essential, since these vaccines will be the best tools we have to control and ultimately end this pandemic. Outstanding scientists in government, industry, academia, and in non-governmental organizations have worked together to develop COVID-19 vaccine candidates, and a number of large-scale vaccine efficacy trials will begin this summer and fall. This is not a competition, but a “yes, and” moment: testing multiple vaccines now will increase the chances that we will have effective vaccines in sufficient quantity to protect people in our country and around the world. As these trials are launched, we need to make sure that diverse populations are included, so that we have the necessary vaccine safety and efficacy data to inform decisions about vaccine authorization, licensure, and use. We also need to plan for the careful, open, and transparent evaluation of all vaccine trial data, so that these vaccines will be used in the safest and most effective way possible to protect all members of our society.

VRBPAC’s advice will be critically important as the FDA reviews the data generated from these many efficacy trials, and makes decisions about Emergency Use Authorizations (EUAs) and licensure. Collectively, VRBPAC’s expert members are pediatricians, internists, obstetricians, basic scientists, and biostatisticians, who are particularly knowledgeable about infectious diseases, vaccine trial design and conduct, and public health. VRBPAC also has an industry representative and a consumer representative. In my experience, VRBPAC’s input on vaccine trial design , review of vaccine trial data, and development of recommendations regarding vaccine licensure has served two very important purposes: the public and the FDA have had the opportunity to hear the thinking, questions, and concerns of some of our country’s leading independent vaccine scientists; equally important, the FDA and VRBPAC members have the opportunity to hear and respond to the public’s concerns in an open public forum. For decisions regarding vaccine licensure, briefing documents, including data analyses by the vaccine manufacturer and an independent data analysis by the FDA, are typically made available to VRBPAC members and to the public at least 2 days in advance of the meeting. At the meeting, the vaccine manufacturer and the FDA each present their analyses of the vaccine safety and efficacy data. There is an open public hearing, during which the public has the opportunity to pose questions to the manufacturer, the FDA, and VRBPAC members. Following the open public hearing, the committee members first discuss and then vote on the licensure- related questions posed by the FDA. Typically, these are 2 separate questions: “Are the available data adequate to support the efficacy of the product [for the indicated population]?” “Are the available data adequate to support the safety of the product [for the indicated population]?” . Meetings are webcast, and summaries and transcripts of the meetings are posted on the FDA website.

With respect to COVID-19 vaccine authorization and licensure, VRBPAC’s input would be especially valuable. This fall and winter, safety and efficacy data will be emerging from COVID- 19 vaccine trials, as the pandemic continues, with its terrible impact on the health and well-being of people everywhere. Decisions may need to be made about issuing EUAs for one or more vaccines, with data that are promising but incomplete. Questions about risk and benefit, either for entire populations or for high-risk subgroups, must be discussed openly, among independent experts, using all available data, with clear acknowledgment of what is known and what is as yet unknown. Decisions about licensure of COVID-19 vaccines should similarly be made with VRBPAC engagement, review, and advice.

We also need to make certain that the information about vaccine safety and efficacy that is reviewed by FDA, VRBPAC, and other advisory committees is representative of our society, which means that trials must include volunteers from diverse racial, ethnic, geographic, and age groups. We need to know if these vaccines are safe and if they work in each of these groups, which will lay the foundation for equitable access and for widespread acceptance and uptake. In particular, we need to ensure that Black, Latinx, and American Indian populations, who are far more likely to become infected with the virus and far more likely to die from COVID, are not only offered opportunities to participate in these vaccine trials, but also choose to participate in these studies. For this to happen, we must acknowledge the high levels of mistrust that exist in many communities, and work urgently to engage communities and build trust.

As we begin efficacy trials of COVID-19 vaccines, we must also devise a clear plan to meet the needs of pregnant women. A recent report from the CDC indicates that pregnant women, particularly Black and Latina women, may be at increased risk for hospitalization and ICU admission compared to their non-pregnant counterparts; moreover, many pregnant women suffer from comorbidities such as obesity, diabetes, and hypertension, which are known to increase the risk for severe COVID disease. If we don’t have a vaccine that we can offer to pregnant women, then we don’t have a vaccine for our frontline workers, because pregnant women are doctors, nurses, EMTs, and hospital workers; police, teachers, and nursing home aides; grocery store clerks and factory workers. All of these women deserve to be protected against COVID-19. We must act now to ensure that we develop and evaluate vaccines that can be given safely to pregnant women. Our PREVENT guidance, which we developed with an international group of experts 2 years ago, provides a roadmap for the inclusion of the interests of pregnant women in the development and deployment of vaccines for epidemics and pandemics. As outlined in the guidance, we need to plan for systematic data collection from women who may become pregnant during the course of the vaccine trials that are about to begin, require vaccine manufacturers to perform developmental and reproductive toxicology (DART) studies as needed, and engage experts in obstetrics, pediatrics, and research ethics to consider how to safely design studies to include pregnant women.

Building confidence in COVID-19 vaccines is critical, because the best vaccine in the world won’t work if it isn’t used. There are many partners in that process, but it begins here, by soliciting public engagement and developing public trust for the ways in which these vaccines are evaluated in clinical trials, and providing open, transparent, independent expert review and analysis of clinical trial data, to be included in the decision-making process for vaccine licensure or Emergency Use Authorization.

Thank you again for the opportunity to speak with you today.  I look forward to your questions.

-Dr. Ruth A. Karron 7/14/20
Directory of the Center for Immunization Research