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We’ll need more than one vaccine to beat the pandemic – Ars Technica

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Close-up photograph of a gloved hand holding a tiny bottle of clear liquid.
Enlarge / A medical worker holds a bottle of a candidate COVID-19 vaccine developed by Oxford University that is being tested in a trial in Soweto, South Africa.

On Monday, a press release from the transnational pharmaceutical company Pfizer dropped a rare spark of hope into the ongoing misery of the COVID-19 pandemic. Yes, new infections have hit an all-time high in the United States, and, yes, cities and states around the world are walking back their reopenings. But Pfizer says it has results from a massive clinical trial showing that its vaccine against the disease works, and works well. The release touted “a vaccine efficacy rate above 90 percent,” and it announced the company’s intention to seek from the US Food and Drug Administration an authorization to start giving people shots. The company’s ready to make 50 million doses this year and 1.3 billion doses in 2021.

That’s an ember of hope, but it’s sitting under a bucket of cold water, ready to pour. The Pfizer vaccine is finicky—hard to make, transport, and deliver. Because of desperate need, it’s in short supply even before it becomes available—1.3 billion doses is several billion short of what the world needs. The press release wasn’t peer-reviewed science, and it lacked critical details about how the vaccine works and on whom. Even the simple fact of this vaccine’s existence, some analysts have argued, might jeopardize the testing and success of potentially better vaccines down the line, a case of the imperfect being the enemy of the good.

Before the ember dies out completely, here’s a theory: no. The Pfizer vaccine’s imperfections make it a perfect prime mover, because if it works as well as the company says, it’ll help people now and require research into more, better, different vaccines for later. All the things nobody knows about the Pfizer vaccine mean that the door is wide open. “Whether its effects are durable, whether it’s effective in the elderly, whether it has safety issues, the cold chain issues, the ability to have access,” says Wayne Koff, president and CEO of the nonprofit Human Vaccines Project, “all that points to the need for a number of vaccines.”

Working with a smaller company called BioNTech, Pfizer moved off the starting block fast, and without the money from the US Operation Warp Speed program that funded other drug companies’ trials. This vaccine (like another candidate made by the company Moderna) is actually a tailored bit of genetic material called messenger RNA; give it to people, and the mRNA acts like biological software, teaching cells to manufacture the “spike” protein on the outer coat of the virus that causes COVID-19. Those people’s immune systems then learn to recognize and attack the spike, which gives them the ability to fight the virus. It’s a cool idea, and as my colleague Megan Molteni has written, it could change the future of vaccinology and infectious disease.

Cold case

But this is the first mRNA vaccine, and it turns out to be a precious little snowflake. Pfizer’s vaccine has to be stored and shipped at ultracold temperatures, less than 80 degrees below zero—it’ll keep for a few days at higher but still very cold conditions. And it needs vials made of a special glass that’s able to tolerate the freezing temperatures. (This is neat, actually—the key is that the glass is low in boron, exactly the opposite of famously temperature-change-tolerant Pyrex glass, which is a mix of boron and silicon dioxide. The glassmaker Corning has a $204 million contract with the government to make it and cut a deal in May to provide it to Pfizer. Whether Corning can make enough is the tricky part.)

All that shipping and freezing requires a level of technical sophistication that, for now at least, mostly exists in hospitals and labs—posing significant logistical challenges in rural areas and in the developing world. These are the “cold chain” problems that Koff mentioned, the problem of refrigerated shipping. (A critical Ebola vaccine needs the same deep freeze, and engineers stepped up to create specialized coolers to transport it across western Africa—but that was a pandemic that affected tens of thousands of people, not billions, and the people who made the coolers have since gotten out of the cold-chain innovation game.)

“Minus 70 is almost a nonstarter”

Those logistical challenges and an overall shortage of the vaccine are going to limit even further who gets the vaccine first. A spokesperson for Pfizer says the company has built its own network of distribution centers, freezers, and specialized shipping containers. And, meanwhile, Phase I of any vaccination plan will probably involve giving it to health care workers and first responders—the kind of people who’ll have easier access to the places that actually have the drug, and are perhaps more likely to come back for the second shot the Pfizer vaccine requires.

“We understand that Pfizer has a network of locations that it worked with to conduct its clinical trials throughout the United States,” says Anna Legried Dopp, senior director for clinical guidelines and quality improvement at the American Society of Health-System Pharmacists. Dopp says she understands there to be upwards of 100 of these locations. “They’ll leverage the ultracold freezers that were given to them for purposes of the clinical trial,” she says.

This is good; the freezers will be able to change temperatures to accommodate other, future, vaccine candidates that need cold, but not as cold, conditions (like, apparently, Moderna’s).

OK. So at least one set of weaknesses might also be a strength. So might some others. “We’ll probably figure out how to solve, in the short term, the cold chain, just because the estimates of the economic costs I’ve seen in the US are in the trillions of dollars. Longer term, in the US and globally, something that has to be at minus 70 is almost a nonstarter,” says Sam Scarpino, a mathematical epidemiologist at Northeastern University who studies disease spread. “We’ll continue to find out more and more about the vaccine as it scales up from Phase III to being injected in 100 million people, and then a billion people—whether it turns out that there are other things we need out of a vaccine, and if other stuff remains in the pipeline.”

Science by press release

What Scarpino means is, the Pfizer vaccine might be good enough to start healing the world but not good enough to finish the job. Pfizer has promised a peer-reviewed, detailed accounting of results, but for now it’s just a press release, and it leaves a lot out. (Getting science by press release is never ideal.) Pfizer and the FDA withstood extraordinary political pressure to forgo faster-moving data releases that wouldn’t encompass potential side effects, yet the press release didn’t say anything about whether the vaccine shows different levels of protection in different demographic groups (most saliently children, adults, and the elderly) or has longer-term safety issues.

How could it? The vaccine is too new, and studying vaccine efficacy in subgroups is notoriously difficult. But policymakers are going to need that data, because they’re going to have to decide how to deploy limited supplies. If they know one vaccine is better for older people, that helps tell them where to send it—and vaccines will certainly have different skill sets.

For one thing, they’ll have different levels of protection overall. The Pfizer study covered 43,538 people, 38,955 of whom got the two doses required. And the company reported only 94 cases of COVID-19. (Presumably many more of the infected were in the placebo group that didn’t get the actual vaccine; the release didn’t give the exact numbers.) But it’s probably not the case that nine times as many non-vaccinated people got the disease as vaccinated people; those numbers vary based on how many people were in each group. And that math is supposed to include a statistical range of possibility called a confidence interval. It’s sort of the possible answers the same data could account for. The smaller the confidence interval, the more sure that researchers are about a number.

People are going to want those, because they’ll make it easier to compare vaccines. Moderna spokespeople have issued a statement saying they’re about to release their initial data too. What if they say their efficacy is higher than 90 percent? Without a confidence interval, it’ll seem like Moderna’s drug is better than Pfizer’s. But if the confidence intervals of the drugs overlap, people will know that they’re actually closer to each other in terms of effectiveness.

“If Moderna comes out and it’s a 93 percent, let’s say, now we have to unwind the messaging on this. Are these numbers the same? Are they different?” says Peter Bach, director of the Center for Health Policy and Outcomes and the Drug Pricing Lab at Memorial Sloan Kettering Cancer Center. “Sure, it’s a big effect. It’s unmistakable. But because the actual numbers are pretty small, they’re just very unstable.” Confidence intervals will make the public health messaging easier later, when other vaccines come out—especially since nobody’s actually comparing these vaccines head-to-head.

Trial and errors

Comparisons will only happen after the fact, almost inferentially. “It’s very hard to do head-to-head comparisons, in part because nobody’s interested. The companies, unless they see a commercial advantage, aren’t going to do it,” says Arnold Monto, an epidemiologist at the University of Michigan School of Public Health who chairs the FDA’s Vaccines and Related Biological Products Committee. “This information is going to come from observational studies after vaccines are being used.”

At an October meeting of the FDA vaccines committee that Monto chairs, he worried that a too-early reveal of data from any of the companies might induce participants in the study to bail out. When volunteers consent to be part of a trial, they often get the right to leave the study and find out whether they received the vaccine or the placebo. As soon as one seems to work, everyone in every study might, potentially, want to just go get that—torpedoing all the other work in progress. Monto now says he’s a little less worried about that. “It may all be moot, because the trials are large in size,” Monto says. “If people do drop out, it may not really matter in terms of the long-term study of both efficacy and safety.”

In fact, having a working vaccine could, in some interpretations, mean that ethically other companies can’t keep testing their own candidates—exposing people to COVID-19 when, nominally, an actual vaccine exists. That doesn’t seem to be happening either. The other trials are still ongoing. Vaccine makers know how to compare different vaccines against the same disease in “noninferiority” studies. They already do that for influenza shots. COVID-19 vaccines might have entirely different “correlates of protection,” the thing that’s actually conferring immunity. Some might induce more neutralizing antibodies, the immune system’s general infantry, while others might induce more T cells, a more specifically targeted fighter.

“Almost a miracle”

People need vaccines to do different things—to work better on old people or on kids, or to stave off different sets of symptoms. Pfizer’s end points, the things they were actually studying, were bad side effects (which they didn’t see) and a lack of mild symptoms or disease. That seems good, but it’s not the whole story.

“How does that correlate with emergence of symptoms severe enough that they require medical attention? Hospitalization? Mortality? Long-haul symptoms?” asks Llew Keltner, a drug development expert and CEO of Epistat, a health care strategy consultancy. “If we’re preventing hospitalization, preventing death, and preventing long-haul disease at 9 to 1? Oh my God, it’s almost a miracle.” Nobody knows if that’s what the Pfizer vaccine does.

For that matter, a vaccine that has lower efficacy but only requires one dose might be better. Getting two shots is no fun, and it requires an informational infrastructure to track who has gotten what and when. A single shot makes everything easier, even if it works slightly less well. “Maybe we give up a little bit in efficacy,” Bach says, “but true efficacy in the real world with Pfizer and Moderna is hampered, because it’s very hard to get people to return.”

So that’s yet another reason the Pfizer vaccine will encourage rather than block development of competitors. The market, so to speak, isn’t uniform. Two key pieces of information about any vaccine simply aren’t available yet—how long its protection lasts, and whether it prevents not only illness but actual transmission of the disease from person to person.

“I am not concerned about long-term protection initially, because we’ve got a pandemic to deal with. But I think, down the road, duration of protection is going to be very important, given the fact that the virus is not going to go away,” Monto says. “I’ve been around a number of rollouts of vaccines, and the question is always, is this lifelong protection? And we never know the answer until time passes. It’s going to be very difficult to find out, and it’s going to be different for different vaccines.”

We don’t know “longer-term health consequences”

If a vaccine can’t prevent transmission, that may likewise open a door to other candidates. A vaccine that’s 90 percent effective at preventing sickness, in conjunction with all the familiar public health “non-pharmaceutical interventions”—masks, distancing, testing, and contact tracing—might be enough to bring the US back to a new normal by late summer. But it wouldn’t be enough to allow US citizens to travel anywhere that doesn’t have the vaccine. In those places, a vaccinated person exposed to the disease and able to transmit it is just an asymptomatic superspreader.

“In terms of understanding the epidemiological consequences of the vaccine, we don’t know. The longer-term health consequences, we don’t know,” Scarpino says. “The degree to which this actually blocks transmission is going to dictate the kinds of non-pharmaceutical interventions we’ll have to layer with it.”

Even if Pfizer gets some kind of authorization to start giving people shots, as seems likely, the world will still need other COVID-19 vaccines, too. “That was the goal, to not put all our eggs in one basket. In many ways, that’s a good problem to be talking about—how the market will absorb many vaccine candidates. That’s not new to health care,” Dopp says. “Right now, there’s not enough information that would give any sort of picture to that. Right now, people are just wanting to vaccinate with an effective vaccine.” That ember of hope burns on, even with cold water raining down upon it.

This story originally appeared on wired.com.

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Tesla whistleblower Martin Tripp ordered to pay $400,000 to settle hacking case – The Verge

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Martin Tripp, the former Tesla worker who has been embroiled in a bitter legal battle with CEO Elon Musk for over two years, was ordered to pay his former employer $400,000 after admitting to leaking confidential information to a reporter.

The settlement is intended to bring an end to one of the more sordid stories at Tesla, in which Tripp, a former process technician, locked horns with the billionaire CEO over allegations that Tesla was wasting a “jaw-dropping” amount of raw material as it ramped up production of the Model 3 sedan.

Musk later accused Tripp of “sabotage” and personally ordered investigators to hack Tripp’s phone and spy on his messages. Tesla even misled local police about a potential mass shooting by Tripp at the company’s Nevada factory.

But in the end, Tripp came out on the losing side. The payment is part of a proposed settlement to a lawsuit filed by Tesla in 2018 alleging that Tripp hacked the electric car company’s system and transferred “gigabytes” of data to third parties. As part of the agreement, Tripp admitted to violating laws related to trade secrets and computer crimes when he told a Business Insider reporter that Tesla was wasting a significant amount of raw materials during production of its Model 3.

Tripp also agreed to pay $25,000 to Tesla for continuing to reveal information about the company, despite being ordered to stop by a judge. Tripp had been publishing a large number of documents and videos online, including many under a confidentiality order in the case. In August, Tripp fired his lawyers and set about representing himself in the case. It was also revealed that a Tesla short seller, The Funicular Fund, was financing Tripp’s legal defense.

Earlier this year, a judge dismissed Tripp’s defamation case against Tesla, in which the former technician accused the company of spreading false rumors about him. After Tripp filed for whistleblower status with the Securities and Exchange Commission, Musk emailed a reporter at The Guardian telling them a tipster had contacted Tesla to say that Tripp might “come back and shoot people,” at the Nevada Gigafactory. The local sheriff determined the threat was not real, but Tesla issued a press release, which was picked up by several media outlets.

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Canada's economy bounced back at record 40% pace in third quarter — but GDP still below pre-COVID level – CBC.ca

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Statistics Canada said Tuesday the economy grew at a record annualized pace of 40.5 per cent in the third quarter as businesses came out of COVID-19 lockdowns.

The previous record for quarterly growth in real gross domestic product was 13.2 per cent in the first quarter of 1965, the agency said.

As historic as the rebound was, it fell short of expectations.

Financial data firm Refinitiv said the average economist estimate was for an annualized growth rate of 47.6 per cent for the quarter.

The rebound over July, August and September was a sharp turnaround from the preceding three-month stretch, which saw a record drop.

Driving the rebound were the further rolling back of public health restrictions that allowed businesses to reopen.

Statistics Canada also said there was a substantial increase in the housing market owing to low interest rates, as well as household spending on goods like cars.

GDP still lower than it was in February

Despite the overall increase, the national statistics office said real gross domestic product still remains shy of where it was before the pandemic.

The third quarter ended with the fifth consecutive monthly increase in real GDP after the steepest monthly drops on record in March and April when widespread lockdowns were instituted to slow the spread of COVID-19.

September saw a 0.8 per cent increase in real GDP, Statistics Canada said, a slight slowing from the 0.9 per cent recorded in August.

The agency also provided a preliminary estimate for October’s figures, saying early indicators point to a 0.2 per cent increase in the month. The figure will be finalized at the end of this month.

“The fourth quarter of 2020 is still beginning with some growth, though less than we had anticipated,” CIBC senior economist Royce Mendes wrote in a note.

“Looking ahead, the economy faces a December with harsh restrictions that will likely see another contraction in economic activity.”

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Statistics Canada says economy grew at a record pace in Q3 – CityNews Toronto

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Statistics Canada says the economy grew at a record annualized pace of 40.5 per cent in the third quarter as businesses came out of COVID-19 lockdowns.

Financial data firm Refinitiv says the average economist estimate was for an annualized growth rate of 47.6 per cent for the quarter.

The rebound over July, August and September was a sharp turnaround from the preceding three-month stretch saw a record drop.

Driving the bounce-back were the further rolling back of public health restrictions that allowed businesses to reopen.

Statistics Canada also says there was a substantial increase in the housing market owing to low interest rates and household spending on goods like cars.

Despite the overall increase, the national statistics office says real gross domestic product still remains shy of where it was before the pandemic.

More to come

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