395 Million COVID Vaccines Said to Have 50.4% Efficacy. Now What?

A COVID-19 vaccine trial has led to confusion and questions by suggesting that a shot developed by China’s Sinovac has an efficacy rate of 50.4 percent, a significantly lower figure than previously expected.

The Sinovac product has attracted at least 395 million orders globally, mostly from poorer countries. It was previously said to have 78 percent efficacy, raising hopes that the easy-to-store vaccine could fill a supply gap in low- to middle-income nations.

At least nine countries including Indonesia, Brazil, Chile, Turkey, and the Philippines have made plans to buy the vaccine, called CoronaVac. Indonesia and Turkey rolled out the vaccine this week.

The Brazilian agency that runs clinical trials for the vaccine said on Tuesday it had an efficacy rate of 50.4 percent in preventing people from developing any COVID-19 symptoms. Compared with the rates of about 95 percent for vaccines made by Moderna and Pfizer-BioNTech, the relatively low efficacy of the Sinovac vaccine has disappointed some potential recipients.

But scientists say it is too early to conclude whether the results render the vaccine an undesirable candidate for mass immunization campaigns. They say Sinovac should release more data from its clinical trials in order to better assess the vaccine’s ability to protect its recipients or contain a pandemic that has killed more than 2 million people worldwide. 

Another Chinese vaccine maker, state-owned Sinopharm, said its shot was 79 percent efficacious. Similarly, it has released few details about its trials.

Scientists use “efficacy” to measure the ability of a drug, vaccine, or treatment to produce desired results in controlled experiments, while “effectiveness” is used to describe how they work under real-world conditions. In this context, the adjectives efficacious and effective have different meanings.

Vaccine efficacy measures the reduction in cases among people who were vaccinated compared to those who were not.

But what counts as a case, among other factors, can vary across studies. Numbers cited in news headlines alone often fail to capture those differences.

Most efficacy data cited in media reports refer to a vaccine’s ability to prevent symptomatic COVID-19 infection. A 50 percent efficacy rate, for example, indicates that the vaccine halved the risk of someone developing any COVID symptoms in a trial.

But it doesn’t mean the vaccine will protect 50 out of 100 people who received it from infection, because the rate did not factor in trial participants who were infected without showing or reporting any symptoms. Asymptomatic cases may spread the virus to others.

It is possible for one vaccine to have multiple efficacy rates reported for different populations. The rates can also differ if the same shots were administered differently.

In the trials for the Oxford/AstraZeneca vaccine, for example, the vaccine was found to have 90 percent efficacy for those who received a half dose followed by a full dose, but the rate was only 62 percent for those who got two full doses. Scientists have yet to fully account for the differences.

While announcements of high efficacy rates have generated much excitement, scientists say they cannot tell how well a vaccine works from their efficacy alone.

Sheena Cruickshank, an immunologist at the University of Manchester, said factors like the age and gender of the trial participants, where the trials were conducted, and the duration of the trials could all affect the final efficacy rate.

For example, a bigger proportion of older people in the trial could bring down the efficacy data, she said, because older people tend to have weaker immune responses. But if a trial does not include older people, it may not tell us enough about a vaccine’s ability to protect the senior population.

Siddharth Sridhar, a virologist at the University of Hong Kong, said he will consider taking vaccines if their developers have made trial data public and published articles in peer-reviewed journals. 

A lack of transparency has led to skepticism around vaccines produced by two Chinese companies, Sinopharm and Sinovac. The vaccines were reported to have efficacy rates of about 80 percent and 50 percent respectively, but both companies have yet to release details from their clinical trials. 

“People just want to make the best decision for their bodies,” Sridhar said. “It’s only fair to us to have some degree of data to support the conclusion that it is an effective vaccine. That responsibility lies with the researchers doing the trials and the companies.”

Only roughly.

In COVID-19 vaccine trials, participants are divided into two groups. One group gets vaccine shots and the other receives a placebo. The participants are instructed to report any COVID symptoms. And they will be counted as a symptomatic case if they test positive for the virus.

The numbers of symptomatic cases from both groups are used to calculate the efficacy rate. 

Despite the similar design, the studies recruit different groups of participants and at different locations, and they define COVID symptoms in slightly different ways.

Sridhar said the only way to directly compare two vaccines is to test them in the same trial. In clinical trials for flu shots, for example, researchers injected participants in a trial with different vaccines to directly compare their results.

But when it’s not possible, efficacy rates from different studies could provide a rough idea how the vaccines function in comparison with each other, he said. 

The rate just meets the World Health Organization’s threshold of 50 percent, the same standard the U.S. Food and Drug Administration has set for approving vaccine candidates for emergency use.

Scientists will need to look at details from the clinical trials before arriving at a verdict. The Sinovac vaccine may have another efficacy rate after including data from trials in Turkey and Indonesia.

The participants in the Brazil trials were health care workers. Sridhar said that could have dragged down the efficacy rate because medical professionals are more likely to notice and report very mild symptoms.

He said the vaccine has potential because it seems to offer good protection against severe diseases. 

The Brazilian state-run Butantan Institute, which conducts the vaccine’s trials in Brazil, said the vaccine had a 100 percent efficacy rate against severe or moderate COVID disease that requires hospitalization.

The rate dropped to 78 percent when mild cases were counted, and further fell to 50.4 percent when “very mild” cases, which do not require medical assistance, were included, according to the institute. 

Efficacy rates are not everything. Holly Seale, an infectious disease social scientist at the University of New South Wales in Australia, said the performance of a vaccine in the real world would often be different from its performance in clinical trials. 

For instance, people with underlying health conditions may not be included in the clinical trials, she said. After vaccines are rolled out to the public, more data from recipients will give scientists a better understanding of their effectiveness.

Researchers are also looking into whether the vaccines remain effective as the coronavirus evolves. Early findings have suggested that Pfizer/BioNTech’s vaccine remains effective against certain variants. 

When choosing what vaccines to buy, governments need to consider the price, storage requirements, distribution channels, and the public’s willingness to receive the vaccines.

A major drawback of Pfizer/BioNTech’s mRNA vaccines is they need to be stored at minus 70 degrees Celsius. In comparison, the Oxford/AstraZeneca vaccine, which uses another virus to deliver the genetic material of the SARS-CoV-2 virus, can be stored in regular refrigerators. Likewise, the vaccines developed by Sinovac and Sinopharm do not require extreme cold storage.

Seale said even when a vaccine has relatively low efficacy, it could still offer critical help to regions hard hit by COVID-19 by reducing the number of severe cases and deaths.

“There are cases right now where we really have to throw everything and anything we’ve got at this pandemic,” she said, “because otherwise our health care systems are getting to the point of not coping.”

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