News in Focus NELSON ALMEIDA/AFP/GETTY NELSON Some 18,000 People Globally Have Received the Oxford Astrazeneca Vaccine So Far

The world this week News in focus NELSON ALMEIDA/AFP/GETTY NELSON Some 18,000 people globally have received the Oxford AstraZeneca vaccine so far. RELIEF AS CORONAVIRUS VACCINE TRIALS RESTART — BUT TRANSPARENCY CONCERNS REMAIN UK trials of the Oxford and AstraZeneca vaccine have resumed after a brief pause, yet key details of the events involved have not been released.

By David Cyranoski & Smriti Mallapaty Scientists say that a pause is not uncommon The University of Oxford and AstraZeneca in large trials, and that a speedy resumption of have not yet released details of the adverse he UK trials of a leading coronavirus testing was to be expected. The episode shows reaction that led to the trials’ pause and how vaccine that were abruptly halted that care is being taken with the trials, they say. the decision to resume the UK study was made. because of safety concerns have “Like anybody else who knows the impor- Regulators in Brazil announced on 12 Septem- restarted. tance of vaccines, I am very happy that the ber that trials of the vaccine have restarted The University of Oxford and phar- trial will continue,” says Klaus Stöhr, a retired there, but it is unclear when similar trials in Tmaceutical company AstraZeneca paused influenza researcher who previously headed South Africa and the United States might also enrolment in the global trials of the vaccine the World Health Organization’s research and resume. on 6 September, after a person participating epidemiology division for severe acute res- Marie-Paule Kieny, a vaccine researcher at in the UK trials experienced an adverse reac- piratory syndrome. But some scientists have INSERM, the French national health-research tion. But on 12 September, the university said criticized the trial sponsors for not releasing institute in Paris, says she hopes that research an independent committee had found that it more information about the reason for the groups working on this or other coronavirus was safe to restart. pause and about their decision-making. vaccines will share more information about

News in focus clinical-trial holds in future. The transparency individual, but still provides a summary of the released prematurely, it could present a bias bar should be set much higher than this latest clinical issues that arose, and the conclusions to the clinicians involved in them, says Griffin. example, says Kieny. “When, ultimately, a vac- the committee reached about the implications The integrity of the trials is on the line, he adds. cine will be made available, public trust will be for the study, he says. “It is of concern that they Griffin expects the pause to have little impact paramount to ensure public-health impact. sought to avoid doing so,” says Komesaroff. on the UK trials’ overall timeline. And trust needs transparency.” The University of Oxford and AstraZeneca But it has not been reported when trials of have not yet responded to requests for com- the vaccine in the United States and South Leading vaccine ment on this criticism. Africa will restart. A spokesperson for Astra- The vaccine, AZD1222, is one of the leading Although the university and AstraZeneca Zeneca told Nature that the company “will be candidates being developed to protect against have not released information about the guided by health authorities across the globe the virus that causes COVID-19, and one of a adverse event to the public, Pascal Soriot, as to when other clinical trials of the vaccine handful of immunizations in the final stages AstraZeneca’s chief executive, reportedly can resume”. of clinical testing. The pause in global trials told investors on a telephone call last week So far, some 18,000 people globally have sent a shudder around the world. that a person in the UK trials had developed received the vaccine. Phase III efficacy trials in Such a quick resumption of the trials was the symptoms of transverse myelitis, according the United Kingdom, which began in June, aim most likely outcome, says Paul Griffin, an infec- to health-news website STAT. This condition to recruit 10,000 people, and a phase III trial tious-diseases researcher at the University of involves inflammation of the spinal cord, in Brazil hopes to recruit 5,000 participants. Queensland in Brisbane, Australia. In large which can be triggered by viruses. The US trial, which started in August, is aim- trials, adverse medical events in volunteers But other scientists say there is a good rea- ing to recruit 30,000 participants. A phase I/II are common, and trial holds are designed to son why the company hasn’t released more safety and efficacy trial in South Africa wants ensure that such events are investigated and details. If information about the trials is to recruit 2,000 volunteers. volunteers are protected, he says. But, most often, it is later decided that the event was probably not related to participation in the trial and does not pose a safety concern to the rest of the volunteers, says Griffin. That seems to be what has occurred in this case, he says. THE UNDERDOG COVID‑19 It can be difficult to pin down the cause of adverse events, says Jonathan Kimmelman, a VACCINES THAT THE bioethicist who studies clinical trials at McGill University in Montreal, Canada. “Often, the WORLD MIGHT NEED best you can do is say that there is a possible link, and then proceed with collecting more Small developers struggle to get their candidates data and monitoring outcomes,” he says. The University of Oxford said in a press noticed, but they’ll be crucial if front runners stumble. release on 12 September that the pause, which applied to all trials of the vaccine, was neces- By Ewen Callaway companies rush their COVID-19 vaccines sary “to allow the review of safety data by an through clinical trials and eye up fast-track independent safety review committee, and hen it comes to developing regulatory authorization, dozens of underdog the national regulators”. vaccines, Peter Palese is no slouch. vaccines such as Palese’s have stalled, or are “The independent review process has con- A virologist at Icahn School of advancing along a slower, more conventional cluded and following the recommendations Medicine at Mount Sinai in New path. of both the independent safety review com- York City, he pioneered genetics Scientists acknowledge that it would be a mittee and the UK regulator, the MHRA [Med- Wtechniques that are used to make some of the waste of resources to take every candidate to icines and Healthcare products Regulatory billions of influenza vaccine doses produced clinical trials. But they argue that it’s essential Agency], the trials will recommence in the UK,” annually, and his team has won millions of to have a diverse selection of COVID-19 vac- the statement reads. The university also said dollars to develop a universal flu jab. cines in development. Early favourites could that it cannot disclose medical information Palese is developing a COVID-19 vaccine, fail, confer only partial protection or work about the participant’s illness for reasons of too. It consists of a bird virus that has been poorly in certain age groups; high costs and confidentiality. genetically modified to make a protein found other barriers might make some of the front It’s appropriate not to disclose information, on the surface of SARS-CoV-2. The vaccine fully runners unsuitable for wide-scale deployment for patient confidentiality and to ensure valid protects mice from an experimental model in lower-income countries. interpretation of the trial results, says Kristine of COVID-19, according to a preprint1 (the “Everyone is rooting for them to succeed Macartney, the director of Australia’s National research has not yet been peer reviewed). beyond anyone’s expectation, but it’s prudent Centre for Immunisation Research and Surveil- It also grows in chicken eggs, like most flu to think about what happens if they don’t,” says lance in Sydney. vaccines, so manufacturing could be ramped Dave O’Connor, a virologist at the University up using tried-and-tested technology. of Wisconsin–Madison. “We need to make sure Lack of details Despite its potential, Palese’s vaccine has we have back-up plans — and back-up plans to But Paul Komesaroff, a physician and bio struggled to gain the attention and funding those back-up plans.” ethicist at Monash University in Melbourne, needed to progress to human trials. “We Australia, questions the university’s claim thought this would be the best thing after Dozens of candidates that it could not release information about sliced bread, and people would break down There are more than 320 COVID-19 vaccines the adverse event on the basis of confidenti- our doors to get it. That’s not the case. We are in development, according to a tally by the ality. It is possible to provide information in very disappointed,” he says. Coalition for Epidemic Preparedness Innova- a manner that avoids identifying a particular As leading drug and biotechnology tion (CEPI) in Oslo, a fund created to finance