By Melinda Young

The first month of the COVID-19 vaccine rollout among frontline healthcare workers was a reality check to the human research world after many people said no to the vaccine.

There are several reasons for vaccine hesitancy, including distrust in the accelerated vaccine development process.

“I think, hopefully, that this will be a wake-up call,” says Stephen B. Thomas, PhD, founding director of the Maryland Center for Health Equity and professor of health policy and management at the University of Maryland. “We spend a lot of time asking people to accept the science, helping people to understand the regulatory oversight that goes into it.”

A major reason the vaccine has not been embraced by some communities is because there is no foundation of trust. Generations of medical and research abuses among vulnerable populations and communities of color have taken a toll that is seen in the halting rollout of the COVID-19 vaccines.

“When there’s a history among communities of color of abuse, misuse, and misinformation, we argue for the research community to prove yourself trustworthy before you ask for trust,” says Rueben C. Warren, DDS, MPH, DrPH, MDiv, professor of bioethics and director of the National Center for Bioethics in Research and Health Care at Tuskegee University. “There are incidences across history in this country where the trust has been repeatedly violated. The most onerous example is the U.S. Public Health Service syphilis study at Tuskegee.”

Many Americans, including Black Americans, may be skeptical of the COVID-19 vaccines because of the term “Operation Warp Speed,” Warren notes.

Operation Warp Speed is a “terrible” name for the vaccination program, said Michael Osterholm, PhD, a member of President Biden’s COVID-19 Advisory Board. Osterholm also is the director of the Center for Infectious Disease Research and Policy at the University of Minnesota. He spoke about the vaccine distribution process in a web interview on Jan. 11. (The interview is available at: https://www.washingtonpost.com/washington-post-live/2021/01/11/coronavirus-vaccine-distribution-with-michael-osterholm/.)

“There were no safety steps shortened in this process,” Osterholm noted.

But the quick development of the vaccines and the unfortunate name of the program have led communities to think the political thumb was on the scale in developing the vaccine, he said.

“We can make all the vaccine available, and the new administration can do everything it possibly can,” Osterholm says. “In the end, it will be about Americans taking the vaccine because they believe the pandemic is real, and it is their life and safety issues and concerns.”

Research organizations and IRBs will remain involved, even as the vaccines become ubiquitous in the United States.

“The first [vaccine] clinical trials will continue,” said Kathleen M. Neuzil, MD, MPH, FIDSA, fellow with the Infectious Diseases Society of America (IDSA), and director of the Center for Vaccine Development and Global Health and Myron M. Levine professor in vaccinology at the University of Maryland School of Medicine. She spoke at IDSA’s virtual COVID-19 vaccine briefing on Dec. 3, 2020.1

“The FDA says they should continue the trials for a minimum of two years,” said Neuzil, co-director of the COVID-19 Prevention Network. “If there is any safety signal, those people will be five to six months ahead of where we are.”

Researchers will collect safety information for at least two years, she added.

The research community knows the vaccine clinical trials will be more difficult over time as the vaccine is rolled out to the public, said C. Buddy Creech, MD, MPH, FPIDS, IDSA member and director of the Vanderbilt Vaccine Research Program in Nashville, TN. Creech is a principal investigator for Phase III trials for the Moderna and Johnson & Johnson COVID-19 vaccines. He also spoke at the Dec. 3 vaccine briefing.

“The design might have to be modified over time, where we compare one vaccine to another, focus on subpopulations,” he said. “Focusing on different groups will be a challenge for us going forward.”

There also is the question of ensuring equity as the public health community rolls out the vaccine to millions of people. The research community will deal with continued enrollment for the dozens of vaccine trials underway, but have not yet been approved by any government.

“We need those second-generation vaccines,” Neuzil said. “We’ve seen an uptick in interest in being in a clinical trial.”

The first two vaccines showed such great results (95% effective at preventing COVID-19) that people have reason to believe future vaccines also will be highly effective, she explained.

“We have to be careful with the rollout,” Neuzil noted.

Since few COVID-19 vaccine doses were available to the public, it was ethical to continue with placebo-controlled vaccine trials. But the risk-benefit balance could shift once the emergency use authorization (EUA) vaccines are more plentiful.

“I see these trials continuing for the next month or two, and then there would have to be another reassessment,” Neuzil said. “It’s better to be right than consistent. This is a constantly changing field.”

Pfizer/BioNTech, which developed the first COVID-19 vaccine to receive an EUA, and Moderna, which received the second vaccine EUA, have methodically communicated with study participants about the fast-track process of making the vaccines available to the public. “They sent letters, saying, ‘We’re going forward and have filed an EUA. We understand and have an obligation to provide vaccine to the placebo group,’” she added.

The vaccine trial participants are the real heroes, she said. “We all in society owe a huge debt of gratitude to these people who have stepped forward and taken the new vaccines,” Neuzil said. “We owe the placebo group careful consideration, and at the right time, we should make sure they also have access and opportunity to get the vaccine.”

Physicians and researchers also have to build public confidence in these new vaccines.

The vaccine rollout, which began with hospital and nursing home staff, faces the tricky dual challenge of ensuring supply and demand.

“We want citizens to say, ‘Someone like me participated in these trials,’ whether that is someone with diabetes, ethnic minority,” Creech said. “When we introduce these vaccines for frontline healthcare workers, they need to know what to expect. We have a lot of work to do to educate healthcare workers in the community.”

These concerns were not addressed adequately, judging by reports of vaccine hesitancy among healthcare workers in the first phase of the vaccine rollout. In late December 2020 and early January, media reports indicated many healthcare workers were choosing not to receive the vaccine. For instance, 40% of staff at a Chicago hospital, serving a predominantly African American community, said they would not take a vaccine.2

Worse, at the end of December 2020, Ohio Gov. Mike DeWine said 60% of nursing home employees were opting out of receiving the vaccine. Nursing homes were not mandating vaccination, even though nursing homes and long-term care facilities accounted for more than half of Ohio’s COVID-19 deaths.3 California also saw large numbers of frontline workers refusing to take the vaccine.4

The groundwork for reducing vaccine hesitancy among Black Americans and other minorities can start with research sites and IRBs. The contemporary IRB’s process of informed consent exists because of a research atrocity, the U.S. Public Health Service syphilis study at Tuskegee, Thomas and Warren say.

“What made it so egregious is in the early days, there was no treatment for syphilis, but in the 1950s, they had penicillin, and then denied the men treatment,” Thomas explains. “Tuskegee needs to be contextualized; it should not be used as a blunt instrument. Yes, the Tuskegee syphilis study is the longest nontherapeutic experiment on humans, but it’s the aftermath that led to human subjects protection we have now.”

The Belmont principles of beneficence, nonmaleficence, and respect for autonomy stemmed from the Tuskegee men’s sacrifice. “The lesson to Tuskegee should be that Black people are not denied access to the vaccine and need easy access to the vaccine,” Thomas says.

Black Americans also need assurances that any long-term health consequences of the vaccine are monitored and healthcare will be equitably available, Warren says. (See article in this issue about building trust in minority communities.)

Ensuring equity in vaccine distribution will not be easy due to the need for concerted and well-planned education and outreach about the vaccine. It is important to help people understand that Operation Warp Speed did not mean researchers and IRBs were cutting corners on vaccine research, Thomas notes.

“‘Warp speed’ meant that we’ll pay companies billions of dollars before they do anything; we paid them in advance,” he explains. “We created a market for the product before we saw it, and we paid them to develop it, which is something we’ve never done like that before.”

Influencers in the research and public health community need to let people know the actual research followed protocols and went through the same oversight and review as every other research study. “We put all this effort into getting a scientifically valid vaccine,” Thomas says.

REFERENCES

  1. Infectious Diseases Society of America. IDSA media briefing: COVID-19 vaccine progress report. Dec. 3, 2020. https://www.idsociety.org/multimedia/videos/idsa-media-briefing-COVID-19-Vaccine-Progress-Report/
  2. Hopkins CD, Valentine A. Some health care workers are hesitant about getting COVID-19 vaccines. NPR. Jan. 1, 2021. https://www.npr.org/2021/01/01/952716705/some-health-care-workers-are-hesitant-about-getting-covid-19-vaccines
  3. Ingles J. Ohio governor says 60% of nursing home workers declined COVID-19 vaccine. WOSU Public Media .Dec. 31, 2020. https://radio.wosu.org/post/ohio-governor-says-60-nursing-home-workers-declined-covid-19-vaccine#stream/0
  4. Mosley T. California frontline workers are hesitant on COVID-19 vaccine, complicating state’s recovery. WBUR. Jan. 1, 2021. https://www.wbur.org/hereandnow/2021/01/01/ca-health-care-workers-vaccine