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Real-World Study to Offer Look at How Covid-19 Vaccines Stack Up

March 9, 2021, 10:31 AM

Clues to how the three available Covid-19 vaccines compare could come through a real-world study on the long-term effects of inoculation—offering the chance to subdue fears over whether one shot is better than another.

Thousands of health-care workers will be surveyed over the next few years on their health and well-being as part of a study called HERO-Together. The first phase of the study, led by the Duke Clinical Research Institute, will address vaccine hesitancy, but over time it will address safety and health outcomes, with the potential to determine whether there are any meaningful differences among the vaccines.

“Everyone got so excited about getting their vaccine and taking a vaxxie,” said Adrian F. Hernandez, vice dean and executive director of DCRI, referring to the post-vaccination photos. “We’re really trying to paint out the movie here of how this will evolve, and how can we bring clarity or data to the story over time.”

While supply shortage remains the biggest challenge, confusion and misinformation about the three Covid-19 shots available in the U.S. threaten to stymie the level of vaccination needed to reach herd immunity. All three are highly effective, and public health leaders—as well as physician, nursing, and hospital groups—urge Americans to get vaccinated as soon as they can, with the first option available to them.

The Moderna Inc. and Pfizer Inc. vaccines are both about 95% effective. The Johnson & Johnson shot demonstrated 72% efficacy in U.S. trials and 100% efficacy against preventing deaths. But J&J’s vaccine uses a different platform, and its clinical trial took place after the coronavirus variants started circulating, and at different locations than the others.

“We don’t compare one to the other. The only way that you can effectively do that is by having head-to-head comparisons in a clinical trial, which was not done,” Anthony S. Fauci, President Joe Biden’s chief medical adviser on Covid-19 and director of the National Institute of Allergy and Infectious Diseases, said at a recent White House press briefing.

“The most important thing to do is to get vaccinated and not to try and figure out what one may be or may not be better than the other,” Fauci said.

There are no plans at this time to conduct head-to-head trials to compare efficacy rates of Covid-19 vaccines, the NIAID, part of the National Institutes of Health, said in an emailed statement.

The U.S. is administering an average of 2.17 million doses a day, and a total of 92.1 million doses have been rolled out across the country, according to Bloomberg’s vaccine tracker. More than 312 million doses have been administered in 116 countries.

‘Pretty Big Lift’

Talk of a single comparison study stems from a public perception that the different efficacy rates mean one vaccine is superior to another. Detroit Mayor Mike Duggan (D) recently expressed doubts about J&J’s vaccine, which he later walked back from.

But a clinical trial comparing the different vaccines would be costly, and manufacturers may not want to collaborate on such a study without a financial incentive to do so, Preeti N. Malani, chief health officer and an infectious diseases professor at the University of Michigan, said in an interview.

“But the more practical concern is that there’s a lot less Covid circulating right now than there was last year. And the vaccinations are rolling out,” she said. Researchers would have to study a lot of people and observe a lot of infections when designing a trial to determine if different vaccines fall within a margin of equivalency.

“I feel like it would be a pretty big lift,” Malani said.

Ideally, the best type of data would come from real-world data after the vaccine has already been rolled out, said Lee W. Riley, division head of infectious disease and vaccinology at the University of California Berkeley School of Public Health.

“Because you have millions of people who are vaccinated, there’s a lot of data to gather,” he said, acknowledging that would be an expensive undertaking.

‘HERO’ to the Rescue?

The DCRI is leading the HERO study with funding through the Patient-Centered Outcomes Research Institute, the non-governmental institute authorized by Congress under the Affordable Care Act to help patients make better decisions.

Former FDA Commissioner Robert M. Califf noted real-world data could play an important role in the availability of multiple vaccines.

“We’re all trying to understand what the different results mean,” Califf said in a virtual town hall about the study. He added that it’s impossible to draw a firm conclusion from indirect comparisons.

“In the postmarket phase, I think we’ll get distinct signals about whether there are differences in how protected we are as time goes on by the different vaccines,” he said. Califf, who leads medical strategy and policy for Google’s parent company Alphabet, is a longtime Duke cardiologist and was the founding director of DCRI.

Both Malani and Riley said the data to watch are the number of people who got vaccinated but still ended up with an infection, and the severity of infection in those people.

“That’s how you calculate the efficacy. So the number of infections in people who got vaccinated and number of infections in people who didn’t get vaccinated,” Riley said.

The data also could indicate the need for a booster shot down the line, Malani said.

“You have to pair what’s happening clinically to help inform the studies,” she said, adding that long-term data simply don’t exist with vaccines that have only been available for a few months. “Everyone has to remain patient to understand these things. But what we know now is safety is excellent and effectiveness for severe illness is also excellent.”

To contact the reporter on this story: Jeannie Baumann in Washington at

To contact the editors responsible for this story: Fawn Johnson at; Alexis Kramer at; Karl Hardy at

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