Doctors who run the clinical trials know best and don’t believe it.
“Do the simple math,” said Dr. Larry Corey of the Fred Hutchinson Cancer Research Center in Seattle, who leads the team that coordinates clinical trials for federally sponsored coronavirus vaccines in the United States.
“We designed the study to hit 130, 140 endpoints seven months after starting the study,” Corey told CNN. “The first started in mid-July.”
“Endpoints” are coronavirus infections. What Corey is saying is that the trials should go on until 140 or 1
However, if you add seven months to July, you get February.
That is not to say that it is impossible to have an answer beforehand. If any of the vaccines tested are highly effective and the infection rate among volunteers is high, many people who have received placebo shots can become infected quickly. “If you had a highly effective vaccine, you would find that maybe five months after the study was designed,” Corey said.
However, if you add five months to July, you get December.
That still doesn’t get us to October.
And there are other obstacles. Dr. Paul Offit, director of the Vaccine Education Center at Philadelphia Children’s Hospital and a member of the Food and Drug Administration’s Advisory Committee on Vaccines and Related Biological Products, said most ongoing Phase 3 trials are now aimed at enrolling 30,000 people at a time. That’s because the people who designed the studies believe that it takes so many volunteers to see 140 or 150 infections.
None are fully enrolled yet, so it’s September and many, if not most, of the volunteers have yet to receive their first dose.
“Then you have to wait two weeks after the second dose to really have full immunity,” Offit told CNN.
A highly improbable – but not impossible – timeline
Why is the administration talking about results in November or even October?
“It is highly unlikely, but theoretically possible without doing something nefarious,” said Dr. Ann Falsey, Professor of Medicine at the University of Rochester Medical School in New York, who is coordinating the clinical trial for AstraZeneca’s coronavirus vaccine candidate.
For example, if the virus was spreading quickly, it would result in a lot of data very quickly. “Unfortunately, there can be a real hotspot and there can be a lot of activity,” Falsey told CNN.
And if any of the vaccines tested are highly effective, it quickly becomes clear. People in the placebo group are much more likely to get infected than people who received the real vaccine.
“You may get a definitive answer sooner than you thought,” she said. “That would be unlikely,” she added.
Offit agreed. The studies aren’t designed to detect asymptomatic or mild infections, Offit said. “The clinical endpoint is serious illness,” he said. That makes it even less likely that the studies will produce a lot of surprise data ahead of time.
And the FDA has already told companies that a vaccine must be at least 50% effective to be considered. This means that the risk of death or serious illness must be reduced by 50%.
Even when volunteers are in a virus hotspot, Offit has been advised to be careful. It is an ethical requirement of the attempts to warn volunteers of the risk of infection. “They tell people to wear face masks and social distance,” he said.
“You’re not telling them to go to a maskless biker convention in South Dakota. They want them to protect themselves.”
The FDA can’t move faster than the data
It usually takes the FDA a year to approve a vaccine after all Phase 3 data is submitted, Offit said. An expedited process would take 10 months.
In the event of a pandemic, that process will be accelerated and Operation Warp Speed has taken the necessary steps in parallel with the clinical trials to help companies make vaccines before the trials are completed and syringes and other equipment now Order Instead of Waiting Until the studies are complete, the FDA might be ready to move much, much sooner.
The only way to get enough data to queue any of the vaccines for FDA emergency approval is for one or more of the studies to get a surprising amount of data very, very quickly.
Dr. Albert Bourla, Pfizer chairman and chief executive officer, believes this could happen. He said that around 23,000 participants took part in his company’s Phase 3 clinical trial of Covid-19 vaccine, and some are already receiving the second dose of the vaccine.
Pfizer “should be able to hold enough events by the end of October to say whether the product is working or not,” Bourla said on Thursday in a statement to the International Federation of Pharmaceutical Manufacturers and Associations.
The people who make this decision are the Data and Safety Monitoring Board. This is an independent group of experts – separate from the company that makes the vaccine, separate from the doctors who run the clinical trials, and separate from the federal government – who can get an early look at the data.
“They are there to protect the safety and to determine the accuracy of the vaccine,” Corey said.
For example, if they see a clear signal that the vaccine is unsafe – if many people have severe reactions, or if people receiving the vaccine are actually more likely to become infected – they can stop the attempt. They can also stop the study if they see that the vaccine really isn’t protecting people – when as many people who are given the real vaccine get infected as those who are given a placebo.
And they can stop the study if it looks like the vaccine is working better than expected. Because of this, the CDC is asking states to be ready to distribute a vaccine in October or November, Alex Azar, secretary for health and human services, told CBS This Morning.
“God forbid we are getting great data from the Data and Safety Monitoring Board and the FDA is finding it is up to their standards and we are not ready to distribute it,” Azar said. “We have to be prepared for any eventuality and that is why the CDC is doing this.”
Corey said he doubted anyone at the DSMB would feel pressure to abandon a process and recommend an FDA review based on pressure – either political pressure or just pressure to end a pandemic that killed 185,000 Americans.
“It’s not that they don’t understand responsibility. Everyone knows how to read,” Corey said.
Falsey doesn’t think so either.
“I don’t think the message is that we’re going to look at the data mid-way through the process and if it looks anyhow good we’ll get on with it,” said Falsey. If a vaccine is found quickly, it is because there is definitive evidence, she said.
Offit agrees. He said he trusted the FDA and the approval process. But not everyone does.
“The irony is that you may have a safe vaccine by the end of the year. But you have an administration that hasn’t gained much confidence,” he said.
“We may have a safe and effective vaccine, but people still won’t trust it because they don’t trust the way the government handled science. That would be the ultimate irony.”