SII pauses India trial of COVID-19 vaccine: Move may delay release but inspires confidence in process, say experts

Clinical trials for AstraZeneca’s coronavirus vaccine candidate have been paused in India , said Serum Institute of India on Thursday, days after similar trials were halted in the UK after a recipient developed a “potentially unexplained” illness. The move also comes after the company received a notice from  the Drugs Controller General of India (DCGI) for not submitting casualty analysis of the “reported serious adverse events”. Why was the vaccine trial paused? It all started when one of the vaccine recipients developed an unspecified serious illness in the UK. It is not yet clear whether the vaccine and the onset of disease are co-related. But it is standard procedure to pause trial until further information is obtained about any unexplained symptom or developments in a recipient. AstraZeneca, a Bretish-Swedish drug company, which is manufacturing the vaccine in a tie-up with Oxford University, didn’t reveal any information about the possible side effect except to call it “a potentially unexplained illness”. The health news site STAT first reported the pause in testing, saying the possible side effect occurred in the UK. It’s likely that the unexplained illness was serious enough to require hospitalisation and not a mild side effect such as fever or muscle pain, said Deborah Fuller, a University of Washington researcher who is working on a different COVID-19 vaccine that has not yet started human testing. Earlier-stage studies of the Oxford vaccine canddiate hadn’t revealed any serious side effects, but that’s a key reason for doing ever-larger phases of research — to widen the search for any reactions. Meanwhile, it is important to note that temporary holds of large medical studies aren’t unusual, and investigating any serious or unexpected reaction is a mandatory part of safety testing. AstraZeneca pointed out that it’s possible the problem could be a coincidence; illnesses of all sorts could arise in studies of thousands of people. How does it impact search for coronavirus vaccine? Even though such interruptions in last-stage trials of drugs and vaccines are not uncommon, the suspension of trials, while temporary, may offset hopes of an early vaccine. Scientists have been scrambling to develop a vaccine against the coronavirus since the outbreak began, and experts across various countries are testing several vaccine candidates. Due to the severity of the situation, the world has even witnessed calls to fast-track trials to ensure an early launch of vaccine. On average, vaccine development can take 10-15 years. The pause on the last-stage trials may offset the release date that SII and AstraZeneca were hoping for. “We are working to expedite the review of the single event to minimise any potential impact on the trial timeline,” AstraZeneca statement said. SII, which was responsible for carrying out the trials in India, however, refused to comment on how the pause will effect the production timeline. “We are reviewing the situation and pausing India trials till AstraZeneca restarts the trials. We are following DCGI’s instructions and will not be able to comment further on trials. You can connect with DCGI for more updates on this front,” SII said. Experts call pharma giant’s move to pause trial despite public glare ‘reassuring’ However, apart from a possible delay in production of vaccine, public health experts feel the decision to pause trials was actually encouraging. “This is not something to be alarmed about,” Fuller said. Instead, it’s reassuring that the company is pausing the study to figure out what’s happening and carefully monitoring the health of study participants. Dr Francis Collins, director of US National Institutes of Health said, “This ought to be reassuring… When we say we are going to focus first on safety and make no compromises, here is Exhibit A of how that is happening in practice.” Angela Rasmussen, a virologist at Columbia University in New York, tweeted that the illness may be unrelated to the vaccine, “but the important part is that this is why we do trials before rolling out a vaccine to the general public”.

So...this is why you need to do phase 3 clinical trials prior to a vaccine getting approval. https://t.co/YJGfc0jaBK

— Dr. Angela Rasmussen (@angie_rasmussen) September 8, 2020

Rasmussen’s comments bring to light the importance of sticking to the due diligence in vaccine and drug trials. During the third and final stage of testing, researchers look for any signs of possible side effects that may have gone undetected in earlier patient research. Because of their large size, these studies are considered the most important phase for picking up less common side effects and establishing safety. The trials also assess effectiveness by tracking who gets sick and who doesn’t between patients getting the vaccine and those receiving a dummy shot. This process isn’t new — phase 3 studies of vaccines and therapies are always done this way — though they are rarely in the spotlight. This especially becomes important in the backdrop of reports that countries were trying to fast-track their vaccine trials for political reasons . This week news broke that the US Centers for Disease Control and Prevention asked states to sweep away red tape that could prevent a network of vaccine distribution centres being “fully operational  by 1 November, 2020 ”. The country faces its presidential elections this year on 3 November. The US Food and Drug Administration has also raised the possibility that a vaccine might be given emergency authorisation before the end of trials. President Donald Trump dangled the possibility in front of supporters last week at the Republican National Convention saying the US “will produce a vaccine before the end of the year, or maybe even sooner”. Furthermore, Russia had launched its vaccine Sputnik V last month without conducting phase 3 trials. Reports said that human trials of the Sputnik V vaccine only began in June, at the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow, and fewer than 200 people were tested in phases 1 and 2. The vaccine was  released for public distribution on 7 September 2020 to the country’s population. Brian Oliver, who leads the Respiratory Molecular Pathogenesis Group at UTS had told  ABC News at the time of Sputnik V’s announcement_, “_In some ways, the approach reported to be taken in Russia is to have a phase 3 trial on the whole population. However, if the vaccination proves to be successful, I’m sure that people will ask why other countries didn’t also take this approach.” The roadblock in the AstraZeneca’s coronavirus vaccine trial should reinstate the importance of a larger study before a possible vaccine is released to the world population. With inputs from agencies