The United States may be within months of a profound turning point in the country’s fight against the coronavirus: the first working vaccine.
Demonstrating in less than a year that a new vaccine is safe and effective would shatter the record for speed, the result of seven-day work weeks for scientists and billions of dollars in investment by the government of the US. Provided that enough people can get one, the vaccine may slow a pandemic that has already killed far more than one million people worldwide.
It’s tempting to look at the first vaccine as President Trump does: an on-off switch that will bring back life as we know it. “As soon as it’s given the go-ahead we will get it out, defeat the virus,” he said at a September news conference. But vaccine experts say we should prepare instead for a perplexing, frustrating year of 2021. So let’s better get prepared!
The first vaccines may provide only moderate protection, low enough to make it prudent to keep wearing masks. By next spring or summer, there may be several of these 50-50 vaccines, without a clear sense of how to choose among them. Because of this array of options, makers of a superior vaccine in early stages of development may struggle to finish clinical testing. And some vaccines may be abruptly withdrawn from the market because they turn out not to be safe.
In my opinion it has not yet dawned on hardly anybody the amount of complexity and chaos and confusion that will happen over the next couple of months. Some of this confusion is obviously inevitable, but some is the result of how coronavirus vaccine trials were designed: Each company is running its own trial, comparing its jab with placebo. But it didn’t have to be this way.
In the spring, when government scientists began discussing how to invest in vaccine research, some wanted to test a number of vaccines all at once, against each other – what’s known as a master protocol. Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, was in favor of the idea. But these mega-trials pose a business risk for any given vaccine maker because they reveal how a vaccine stacks up against its competitors.
Instead, the government offered to bankroll large vaccine trials if companies agreed to some common ground rules and shared some data. The companies were still allowed to run the trials on their own.
In simple words, a master protocol didn’t happen as you have to have the total cooperation of the pharmaceutical companies to get involved which didn’t turn out to be feasible. In the meanwhile people are suffering and are dying on daily basis. Typically, scientists take several years to prepare a vaccine before testing it on people. Early safety trails, known as Phase 1 and 2, may take several years.
If all goes well – and it often doesn’t – then Phase 3, the final stage, can begin, comparing thousands of people who receive a vaccine with thousands given a placebo. It may take three more years to get these results. Only then – a decade or more after the research has begun – will a vaccine manufacturer build a factory to make the products. When the coronavirus began to spread early this year, vaccine research around the world knew we could not afford to wait that long. The World Health Organization (W.H.O) organized a group of experts to start what came to be known as the Solidarity Vaccines Trial. Several vaccines would be given at random to one large group of volunteers, while a smaller group would receive a placebo.
All of the vaccines would be tested against the same placebo group, and all of the volunteers would be living in the same circumstances. Under such circumstances you have a fully valid comparison, not only of each of those vaccines against placebo, but against each other.
It took 9 months to get off the ground, but that trial just started with a small study in Latin America.
Around the same time that the W.H.O. was hatching plans for its mega-trial, U.S. government officials were discussing how they could best invest in – and speed up – vaccine trials. Some researchers, including Dr. Fauci, advocated a design much like the W.H.O.’s.
But Moncef Slaoui, the chief adviser of Operation Warp Speed (OWS), the multiagency effort to hasten the development of coronavirus vaccines and treatments said in a statement that such a trial would be impractical. “If OWS had tested all vaccines under one master protocol, the operation would have had to wait months before starting and recruit 200,000 volunteers at the same time.”
In the end, the government decided on what it described as a “harmonized approach”. It would allow vaccine makers to run their own trials, but only if they used protocols that followed certain guidelines and let the National Institutes of Health test all of their volunteers in the same way. The companies would get to top into to the N.I.H.’s network of clinical testing sites, and receive financial support for their trials. Through this program – believe it or not., the government has promised 10 billion USD to vaccine makers to date.
So far, AstraZeneca, Johnson & Johnson and Moderna have begun trials in the network. Novavax and Sanofi are expected to start their own Phase 3 studies in the next couple of months. But Pfizer, one of the front-runners, never joined the network, choosing to run trials completely on its own.
If Pfizer’s results turn out well, many experts expect the company to ask the Food and Drug Administration for an emergency authorization of its vaccine, potentially for just one group of high-risk people. The company might then swiftly move to apply for a license, making it widely available.
The authorization of a vaccine will depend on how much protection the vaccine provides in the Phase 3 trial – what scientists refer to as its efficacy. In June, the F.D.A. set 50% efficacy as the target for a coronavirus vaccine. But the efficacy in a trial may not necessarily match its effectiveness out in the real world. That’s because, like any statistical study, Phase 3 trials have margins of error. A vaccine that met the F.D.A.’s guidelines might actually be more than 50% effective, or might be less so. It might well turn out to be only 35% effective.
Things could be even worse for vaccines in earlier stages of testing. Those products might have to prove that they are better than the newly approved vaccine. The difference between two vaccines will be smaller than between a vaccine and a placebo. As a result, these trials may have to be bigger and run longer. The steep cost may be more than many of the small start-ups working on innovative vaccines can afford. That basically prevents the development of better vaccines.
The F.D.A.’s guidelines raise the possibility of testing future vaccines against an authorized one, but they don’t give a clear sense of whether the agency would change testing requirements. Given the massive taxpayer investment, the public in my opinion should demand better.
For a long time, drug makers have been among the most hated industries in America. Companies are accused of gouging consumers with prices on life-saving drugs and of enriching themselves through the opioid crisis, among other sins.
Now, with pharmaceutical companies racing to find vaccines to end the coronavirus pandemic, the industry hopes to redeem itself in the public’s mind. The primary goals is to rescue the world from the grip of a vicious virus. But a big fringe benefit would be to get public credit – and to use an improved image to fend off government efforts to regulate the industry more heavily.
Consider Johnson & Johnson for example, one of the world’s largest healthcare companies. In recent years, its reputation has been battered by accusations that products like its artificial kips and talcum powder have harmed customers. In 2019, an Oklahoma judge ordered the company to pay 572 million USD for contributing to the opioid epidemic.
This spring, Johnson & Johnson jumped into the hunt for a Covid-19 vaccine; its candidate is now in the final stage of clinical trials. Regardless of whether the vaccine ever reaches the market, the company is looking to create a surge of positive publicity from its work.
That is in my opinion a widely held sentiment across the pharmaceutical industry. Companies are looking for public makeovers as a political battle looms in the U.S. over drug price controls. Others are seizing the once-in-a-generation opportunity to raise money for future projects from investors and the government.
Public opinion matters. To be sure, the race for a coronavirus vaccine is much more than a public relations play. Scientists at pharmaceutical companies take great pride in their work to combat human suffering. And there is immense prestige involved in being among the first to successfully conquer a devastating global pandemic. There are also potentially enormous profits on the line.
Before regulators held their ground last month, there were good reasons to be concerned about President Trump’s push for a coronavirus vaccine. He had already missed becoming the first world leader to get one approved. Vladimir Putin of Russia had already done it. And in stark contrast to Mr. Trump’s “America First” approach, Mr. Putin is using his under-tested vaccine as part of a global full-court press to win friends and enhance his country’s soft power.
On August 11, the Russian Ministry of Health formally approved the Sputnik V vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow. Its announcement was a splashy event. A website in seven languages featured a recording of the beeps broadcast from space in 1957 confirming that the first Soviet Sputnik satellite had reached orbit. Those historical echoes pointedly evoked the idea that Russia was No.1 again.
But at that point, the vaccine hadn’t even begun large-scale field trials, meaning that neither its safety nor efficacy had been fully vetted, and its early-phase clinical trial data hadn’t been released. Since then, a peer-reviewed publication of promising early results in the journal the Lancet has raised alarm bells for some scientists who are concerned about potential inconsistencies in the data, which-expected-a top Russian scientist has denied.
Still, buoyant news of the vaccine saturates Russia’s state – controlled media, and the country stands poised to leverage Sputnik into a significant diplomatic coup. It’s yet another instance – on top of America’s pullout from Syria, its exit from the Paris climate accord and its planned withdrawal from the World Health Organization – where the departure of the United States from the global stage has created a vacuum that Mr. Putin has been delighted to fill.
Because vaccines are administered to healthy people, they have especially high regulatory hurdles to clear. Full phase-three trials, designed to pick up rare side effects and to test effectiveness among diverse populations, generally involve thousands or tens of thousands of people. At approval, the Sputnik vaccine trial included – believe it or not – just 76 people.
The Moscow mayor’s office is currently taking up to 40,000 volunteers through final-stage trials while simultaneously offering the vaccine to frontline medics and teachers. In my opinion jumping the gun carries potentially deadly consequences, including renewed spread of the virus if a weakly effective vaccine lulls people into complacency on mask-wearing and physical distancing before herd immunity has been established.
In the United States, the vaccines that are likely to be candidates for emergency-use authorizations by the Food and Drug Administration are at least partly through phase-three testing.
Of course, Sputnik may turn out to work just fine. Russia has plenty of world-class scientists, and the Gamaleya Institute claims to have had a head start.The institute points to its development of an Ebola vaccine and says Sputnik is just a slightly modified version of its vaccine for Middle East Respiratory Syndrome. There’s no evidence, though, that those vaccines have actually been deployed in a significant way anywhere in the world.
Now the scramble by countries to secure a potential coronavirus vaccine is looking a lot like a replay of what happened in the 1990s with antiretrovirals to combat H.I.V. AIDS and in 2009 with the HINI influenza vaccine: Wealthy nations are buying up the initial supply, most likely leaving only leftovers for the rest of the world much later if at all.
The United States, for example, has secured advance purchase commitments for over 800 million doses of at least six candidate vaccines, all for itself. Compounding an image of selfishness, the Trump administration confirmed in September that it would not join Covax, an effort by dozens of countries to provide for the pooled procurement and equitable distribution of vaccines. This decision has created the political space for Russia in my opinion to cultivate the role of benefactor, even though it too has not joined Covax effort.
Russia is currently pitching dozens of countries licensing and production offers for Sputnik. These deals aren’t limited to obvious friends and neighbors like Belarus and Kazakhstan. Pending regulatory approval, India is set to produce at least 300 million doses and buy 100 million more; Brazil’s Bakia state will buy 50 million and Mexico has a purchase agreement for 32 million doses.
All told, Russia is claiming preliminary applications from at least 40 partners totaling well over a billion doses.
We don’t yet know the terms of these arrangements, and the “pending regulatory approval clause is important; the deals might break down if Sputnik’s safety and efficacy don’t pan out, though Russia is trying to quell these fears by assuming some of the legal liability for adverse reactions. If you’re the head of Mexico or the Philippines or Brazil, reeling from months of medical, social and economic shock, you might be willing to take your chances on an incompletely tested and probably relatively cheap product from Russia that you can get your hands on soon – especially if it looks like the United States and Europe are leaving you to go it alone.
Mr. Putin’s only rival for the role of global savior in my opinion is China, which is also rushing across regulatory milestones for vaccines and pushing deals, like a billion-dollar loan to help Latin America and Caribbean countries pay for them. China has also recently joined Covax.
Though the Kremlin is engaged in pandemic-related belt tightening just like everyone else, it’s carrying little debt and has 120 billion USD in liquid assets in its sovereign wealth fund. It can afford some measure of vaccine generosity. The image-burnishing would be worth the price.
Sputnik is also fodder for a disinformation campaign already showing up on Russian state-controlled media. The claim is that only the Russian vaccine is safe and effective. Russia has a long history, dating back to Soviet times, of health-related disinformation. The UGB planted “fake news” stories around the world in the early 1980s claiming that H.I.V./AIDS was an American biological weapon. Research has shown that Russian trolls and bots have actively tried to erode public confidence in vaccines in the United States since at least 2014.
For Russia, the Sputnik vaccine in my opinion goes far beyond national pride. Mr. Putin needs a showy win after a slew of recent bad press. He’s resorting to his standard playbook, leveraging a weak hand and exploiting U.S. missteps and vulnerabilities – unilateralism, neglect or abandonment of key allies, a retreat from established science – to bolster Russia’s image and global position as a great power.
Russia is betting that its short-term diplomatic gains outweigh the longer-term reputational risk should problems arise with the Sputnik vaccine. The United States could counter Russia’s gambit and contribute to an important global public good by making a relatively modest investment in the Covax vaccine effort.
Does America really want to cede this ground to Mr. Putin?
For the rest of us, we’ll have to continue to use a mask for some time to pass…