National Post (National Edition)
Vaccine likely a year away, experts say
It's no crystal ball, but when trying to predict when something is likely to happen, one approach is to tap the “wisdom of the crowd” — ask many people their opinions and average their responses.
When a McGill University-led team asked 28 experts, each with an average 25 years experience working with vaccines, when a COVID-19 vaccine is most likely to be available to the general public in the United States and/or Canada, their best-case guess was June 2021 for the soonest, but more likely fall of 2021.
The experts believed there was a three-in-10 chance a safety issue would be discovered only after the first vaccine is approved that will require a boxed warning, and a four-in-10 chance that the first large field study will report a null or negative result.
“Experts predicting that there's only a 40 per cent chance of a negative result, that to me actually sounds pretty optimistic,” said Jonathan Kimmelman a professor and director of the Biomedical Ethics Unit at McGill University, and the paper's senior author. Historically, fewer than five per cent of non-pandemic flu vaccines tested in humans ultimately go on to get approved.
Considering the odds, Kimmelman has been puzzled by the extreme optimism by credible public health officials like American coronavirus czar Dr. Anthony Fauci that, with almost certainty, we're going to have an effective vaccine in the near future, that help is on its way to lead us out of the COVID darkness.
Despite the cheering on of the groups in the vaccine race, it's not a sure thing that the vaccines reaching phase III trials — the final stage before potential approval — are going to deliver us back to normal. Questions are being raised about proposed FDA and international standards for COVID-19 vaccines, about how good is good enough, about the sheer logistical challenges of distributing a two-dose vaccine and getting it into tens of millions of humans in Canada alone, and about persuading the young and people at low risk of the virus to be vaccinated as an act of solidarity.
Canada is already preparing the logistics for a possible rollout in the first half of 2021. Ottawa has signed pre-order agreements with AstraZeneca, Moderna, Quebec-based Medicago and other companies for up to 358 million doses of different COVID-19 vaccine candidates.
“Work is underway in collaboration with the provinces and territories to review the capacity and capability of the existing vaccine supply chain,” Health Canada said in an email to the National Post. “Any capacity gaps will be addressed to ensure the safe and timely delivery of vaccines,” the department said, likely in an effort to avoid the massive lineups and botched shortages during the country's vast H1N1 flu vaccination campaign in 2009. One of the challenges with two-dose vaccines: how to get people to come back for the second dose.
Will the shots save lives or prevent bad outcomes? We don't yet know. According to BMJ associate editor Peter Doshi, current trials aren't set up to tell. More than 200 vaccines against the SARS-CoV-2 virus are under development; 11 are in phase III studies, each involving tens of thousands of volunteers, yet “none of those trials currently under way are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or death,” Doshi wrote last week.
The trials are double blind and placebo-controlled. No one knows who is getting the real vaccine or a pretend one. The studies are designed to end after 150 to 160 COVID infections or “events” have occurred among the study volunteers.
A data safety and monitoring board would then look to see whether there were fewer infections among the vaccinated group.
Even mild infections could qualify as an “event,” Doshi wrote. “In Pfizer and Moderna's trials, for example, people with only a cough and a positive laboratory test would bring those trials one event closer to their completion.”
What we should care about is whether a vaccine is going to prevent deaths, ICU admissions or hospitalizations, and not mild symptoms, because they don't matter as much from a public health standpoint, Kimmelman said.
“Even if you have 50 per cent protection, we still won't know whether these vaccines actually move the needle on the things we need to move the needle on.”
The difficulty is, hospital admissions and deaths from COVID-19 are uncommon, and it would require a large population over a longer period to accumulate enough deaths to see a difference between the vaccine and placebo group, Kimmelman said.
The U.S. Food and Drug Administration has set a minimum target of 50 per cent efficacy for a COVID-19 vaccine, meaning a vaccine would have to be 50 per cent better than a placebo at preventing disease.
In an early-stage study, Moderna's COVID-19 vaccine produced neutralizing antibodies in 45 healthy, 18- to 55-year-olds who received two vaccinations, 28 days apart, the company reported in the New England Journal of Medicine. Side effects — fatigue, chills, headache or muscle aches — occurred in more than half the participants.
Dr. Jacqueline Miller, head of Moderna's infectious diseases development, told last week's FDA advisory panel meeting that more than 25,000 people have received both doses of its study vaccine, or a placebo, and that the vaccine was designed to evaluate Americans “at the highest risk of severe COVID disease.”
Forty-two per cent of study participants are older adults or people with heart disease, diabetes or other underlying conditions, Miller added.
AstraZeneca's vaccine, developed with Oxford University, has produced an immune response in both the young and old, Reuters reported this week. Less clear is how well an antibody response translates into how well any vaccine can actually fend off COVID.
“We just don't know what to expect,” said Medicago president and CEO Bruce Clark. “You start asking yourself very practical questions: If something doesn't work 50 per cent (of the time), then do we really have something? Maybe we do as an emergency response initially, but a 50-per-cent level we would have to imagine over time has to get better than that.”
But even a vaccine that works half the time offers a shot at knocking down the potency of the epidemic, Clark said, especially if it can prevent severe disease and deaths.
It's possible vaccines with protection as low as 30 per cent could receive emergency authorization under FDA and international standards. The debate then becomes, how low can you go?
“The problem you could create is the following: You push a low-efficacy vaccine out on the grounds it's better than nothing. Right now, you've got zero. Thirty per cent protection? Better than zero,” said Dalhousie University philosopher and university research professor Francoise Baylis.
“The problem then becomes what if vaccine number two is 50 per cent effective, and you've now already invested how much in terms of distribution to get the first vaccine into people? What do you do to the confidence of the general public and those who have already received the vaccine,” Baylis said.
“It's a really difficult question to know at what point do you say, `it's good enough.'”
It's also not clear how well the first vaccines will be at stopping person-to-person spread
SARS-CoV-2 is a lethal pathogen, Baylis said. “What's the ideal? The ideal is we totally understand how this virus works, we get a vaccine, we know that it will stop this pathogen from being able to infect humans and we know that it lasts for a specified time, for example, 10 years, and then you get a second vaccine,” Baylis said.
The reality is that anything that gets rolled out is going to be rolled out with uncertainty. “You can't wait until you truly understand the scope of the problem because people are dying,” Baylis said.
Authorities need to communicate those uncertainties and the public needs to understand and tolerate them, Kimmelman said. “In medicine we license drugs and vaccines all the time, despite lingering uncertainties regarding impact and safety,” Kimmelman said.
We can't wait for absolute certainty. “The point is to make the best choices we can given the evidence we have and to continue collecting evidence so that we can revise our choices if the data turn southward.”
RIGHT NOW, YOU'VE GOT ZERO. 30% PROTECTION BEATS ZERO.