‘Health is a political choice’, Dr Tedros Adhanom Ghebreyesus, the World Health Organization’s director general, is wont to say. Nowhere has this been more evident than in the race to develop a new Covid-19 vaccine.
Politics has propelled research at unprecedented speed. But fears are also growing that political meddling into science, particularly by United States President Donald Trump, could lead to the premature approval of a Covid-19 vaccine - without sufficient evidence that it is safe and effective.
Three of the pharma companies leading the vaccine development race, AstraZeneca, Pfizer, and Moderna, have sought to allay public fears around the clinical trials now underway, releasing unprecedented details of their Phase 3 trial protocols, each involving tens of thousands of people. However, the revelations have not allayed the safety questions altogether, and there are fears that the bar measuring a vaccine’s effectiveness before it is approved may not be set high enough. Here’s a snapshot of the issues scientists are tracking.
Safety and transparency concerns remain high after two adverse events were reported by AstraZeneca among its trial participants in the United Kingdom. Media reports said that the events both involved transverse myelitis, an inflammation of the spinal cord. Although the exact nature of the adverse events were not confirmed by AstraZeneca, the company did confirm that one of the people involved was later diagnosed with multiple sclerosis, for which transverse myelitis can be a precursor. An independent panel in the United Kingdom allowed the UK arm of the trial to resume. But the trial remains stalled in the US. If it turns out that two people among the trial’s vaccine arm (not the placebo arm) both developed the same rare condition, it would be a big concern, says Raina McIntyre, an epidemiologist at the University of New South Wales, Australia. She told Nature that the condition is also associated with viral infections, and has been observed in people with Covid-19. To rule out such a link, researchers must run a more detailed statistical analysis. Pending that, the United States Food and Drug Administration has not approved the resumption of the trial’s US arm. The fact that AstraZeneca has not been more transparent about the adverse events has added fuel to the fire of concerns. Astra Zeneca CEO Pascal Soriot, however, told a recent World Economic Forum panel that trial guidelines protecting participants’ privacy prevent disclosure of more details.
Politics and safety - unwrapping it or not. Even if the trials underway now obtain their initial results without significant adverse events, US FDA officials have already indicated that they would like to continue the trials for two months after initial results about efficacy are received to ensure that no significant adverse effects surface - such events usually emerge within the first couple of months. However, Trump’s remarks that he sees no reason to wait have fueled concerns that the White House could overrule the FDA. Meanwhile, the Secretary of Health and Human Services, Alex Azar, has already upended decades of precedent, announcing that any new FDA rules would need his personal approval.
The fact that Pfizer’s clinical trial protocol allows for an interim assessment of vaccine efficacy data after only 32 participants (vaccine and placebo arms) become infected with Covid-19, raises concerns among watchful experts. They say that opens the possibility that the company could show positive results for the vaccine, albeit from a very small sample size, within the coming month, and apply for an FDA Emergency Use Authorization for their vaccine candidate on the eve of the US presidential elections. The FDA, under pressure from the White House, might have trouble refusing the request - particularly in light of Trump’s recent statements that he sees no reason to wait as he has great confidence in the skills of “these big pharma firms.” However, the public may not be as confident. Surveys in September of the proportion of US adults likely to accept a Covid-19 vaccine if one were available had dropped from 72 per cent in May to 51 per cent. Three-quarters of those surveyed feared that the US would approve a vaccine before its safety and effectiveness had been firmly established.
Are the vaccine’s efficacy goals high enough? Even if safety concerns are allayed, critics say that the protocols of the trials underway will only measure if the vaccines reduce symptomatic cases of Covid-19, and not severe disease or death.
While the AstraZeneca, Moderna, and Pfizer trials are each enrolling 30,000-50,000 participants, more would be needed in order to determine if the vaccine candidates reduce severe disease, and that would take more time.
The companies are aiming for the vaccines to reach at least 50 per cent efficacy which is the FDA guideline part. That means a 50 per cent reduction in the proportion of vaccinated people getting Covid-19, as compared to placebo, and they are hoping that efficacy might even be higher.
But to create a viable “herd immunity” effect whereby unvaccinated people are also protected because most of those around them have been immunized, a vaccine would have to be at least 80 per cent effective, says MacIntyre.
Still, vaccinating a large portion of the population with one of these jabs would go a long way to controlling the spread of the virus if used with other interventions, such as wearing masks and contact tracing, says Thomas Lumley, a biostatistician at the University of Auckland in New Zealand: “A modestly effective vaccine would be a really big help,” he says.