December 8, 2021

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Nature Article: Emergency use of COVID-19 Vaccines Puts Scientists in Trouble

Nature Article: Emergency use of COVID-19 Vaccines Puts Scientists in Trouble

Nature Article: Emergency use of COVID-19 Vaccines Puts Scientists in Trouble. Nature Article: Why Approval of Emergency use for  COVID-19 Vaccines Puts Scientists in Trouble? Foreword: Prior to the end of clinical trials, immunizations are accelerating approval, but scientists say this may complicate efforts to study long-term effects.

After a series of positive results in clinical trials of the COVID-19 vaccine, developers are now seeking approval for “emergency use”, which may allow tens of millions of people to receive these vaccines. But scientists worry that this early deployment may jeopardize ongoing clinical trials that try to ultimately prove how effective the vaccine is.

Nature Article: Emergency use of COVID-19 Vaccines Puts Scientists in Trouble

After the release of early data from the Phase III trial on November 9, vaccine manufacturers Pfizer and BioNTech have sought regulatory approvals to deploy their vaccines in accordance with emergency use rules. The developers of another major vaccine, Moderna, are expected to respond in a few weeks.

Once the vaccine is urgently approved, developers are under pressure to provide immunity to trial participants who receive a placebo. However, if too many people are transferred to the vaccine team, the vaccine company may not have enough data to determine long-term results, such as safety, how long the protective effect of the vaccine lasts, and whether the vaccine is used to prevent infection or just prevent disease.

“This is a real vaccine development dilemma,” said Klaus Stohr, who was responsible for vaccine design at Novartis Pharmaceuticals in Cambridge, Massachusetts and is now retired. Nevertheless, Stohr believes that the vaccine should be granted emergency use authorization because its effectiveness has been established and is urgently needed.

The vaccine dilemma

This competition between vaccine clinical trials and emergency use is new in vaccine development. Just this month, the World Health Organization approved the emergency use of an immunization for the first time, which is still being tested against a polio virus that is circulating in the southern hemisphere. But the third phase of trials of this vaccine has not yet begun.

Pfizer, headquartered in New York, and BioNTech, headquartered in Mainz, Germany, submitted an emergency use authorization (EUA) application to the U.S. Food and Drug Administration (FDA) on November 20. According to the FDA’s regulations on the COVID-19 vaccine, pharmaceutical companies can apply for EUA, provided that half of the trial participants (half of Pfizer’s 43,000 people) have been followed for two months after the last injection. Pfizer/BioNTech has reached this goal; Moderna is headquartered in Cambridge, Massachusetts. The company said it expects to achieve this milestone soon, and the company will apply for an EUA in the next few weeks.

The FDA announced that its vaccine advisory committee will meet on December 10. The committee will evaluate the data of these companies and determine whether the vaccine is safe and effective enough to restrict its use.

Many researchers expect the authorization will be approved. Once approved, a committee of the Centers for Disease Control and Prevention in Atlanta, Georgia, will decide which groups should be vaccinated first. The team is considering high-risk groups such as the elderly, people with diabetes (diabetes makes them more susceptible to COVID-19), and health care workers.

Jerome Kim, director of the Seoul International Vaccine Research Institute, said that early use of vaccines among high-risk groups will almost certainly save lives. However, he said that these vaccines have only been tested for a few months, so it is too early to know that they will be effective.

Ethical cross

Trial participants are usually “blind”, not knowing whether they received the vaccine or a placebo. But Paul Offit, a vaccine researcher at the Children’s Hospital in Philadelphia, Pennsylvania, said that once a vaccine is proven effective, it is difficult to ask participants to continue using a placebo without protection. “This is a moral issue,” he said.

On November 10, Pfizer sent a letter to participants (see “Nature” magazine), in which it said that the company is exploring ways to allow interested participants in the placebo group who meet the emergency access criteria to enter the trial Vaccine department. A spokesperson told Nature that the company “has an ethical responsibility to inform all study participants of the availability of emergency authorized vaccines.”

“Nature” interviewed more than a dozen participants who participated in the Pfizer/BioNTech or Moderna trial. Most of them said that if they learned that they were taking a placebo, they would receive the vaccine provided. Emma Bernay, a Participant of the Moderna trial from Cincinnati, Ohio, said: “One of the reasons I participated in the trial is that I think the criteria for blinded research is that if the vaccine is very effective, blinded research is not conducted and vaccines are provided to all groups. .”

However, if too many people leapfrog, then these trials may not have a large enough control group to collect results that are statistically significant for certain long-term goals, Stohr said. This includes excluding any long-term safety issues and finally determining whether the vaccine can prevent people from contracting SARS-CoV-2, or just protect the infected people from getting sick. Larry Corey, a vaccinologist at the Fred Hutchinson Research Center in Seattle, Washington, said that in addition to Pfizer/Biotech and Moderna, people in the trial are also at risk of giving up vaccination under the emergency use clause.

A Pfizer spokesperson said that if participants cross the line, the company will discuss with the FDA how to collect data to fully measure safety and effectiveness. The company’s clinical trial plan says that they intend to monitor participants for two years after the last vaccination.

Other COVID-19 vaccine developers are also working to solve these problems. Eduardo Spitzer, the scientific director of the Elea Phoenix laboratory in Buenos Aires, is convinced that Argentina will launch an emergency vaccination program. The laboratory is testing a Chinese vaccine produced by Sinopharm in Argentina in Beijing. If this happens, doctors, nurses and other important staff (many of whom have already participated in the trial) may be forced to vaccinate and therefore no longer have the qualifications to participate in the trial. Other participants in the placebo group may withdraw to get a vaccine they know is a vaccine. Spitzer said: “I am 200% convinced that the EUA will affect the trial.”

Research and judgment management confusion

Kathleen Neuzil, director of the Center for Vaccine Development and Global Health at the University of Maryland in Baltimore, said there are ways to control this interference without compromising the results of the trial. She is also the co-chair of the National Institutes of Health COVID-19 Prevention Trials Network, which arranges clinical trials for companies such as Pfizer and Moderna. She said that participants who initially took a placebo but switched to the vaccine can be monitored as a separate group, and the long-term effectiveness and safety of the vaccine can be compared between these groups. Neuzil used a similar device to determine the duration of protection provided by the first shingles vaccine.

Corey said that before lifting the veil of the trial, the company can also ask the volunteers to stay in the study and receive the vaccination immediately after the trial.

Christine Smertz from Houston, Texas, a participant in the Pfizer trial, told Nature that he understands the importance of the placebo group for further trials and will consider continuing to participate in the trial.

Eng Eong Ooi, an infectious disease researcher at the Duke-NUS Medical School in Singapore, said companies and regulators can also collect safety and effectiveness data on high-risk populations who purchase vaccines.

But such data may be biased because they cannot be compared with the control group data. However, he said they can still provide useful insights into safety and effectiveness. “We cannot have the best of both worlds. The world needs what we have now.

However, once the COVID-19 vaccine obtains emergency authorization, subsequent vaccine trials will become more complicated. Companies starting new trials must prove that their vaccines are better than emergency approved vaccines, making the trials more expensive. He said: “Any approved vaccine, even for emergency use, will change the pattern of vaccines entering the market.”

(sources: internet)