The pause in a COVID-19 vaccine trial may reduce hope of its early availability; however, such a step can increase people’s faith in the safety procedures involved in vaccine development. In this novel coronavirus pandemic, political pressure and profit should not win over what is in the best interests of people.
There is no proven treatment and vaccine available as yet against COVID-19. In the last few months, most investigational therapies have moved from the ‘promising’ category to the ‘possibly not useful’ category. The latest inclusion in the list is convalescent plasma therapy. In addition to the non-pharmacological interventions of hand washing, masks wearing and observing physical distancing, one other big hope is the availability of safe and effective COVID-19 vaccines. The world is already in the fastest race in history to develop a COVID-19 vaccine.
Offline and online
But the race seems to have received a jolt. A ‘potentially unexplained illness’ in one of the volunteers for the Phase-3 clinical trial of the AstraZeneca Oxford SARS-CoV-2 vaccine, named as AZD1222, has been reported. This has been one of the front-runner COVID-19 vaccines. The report has grabbed global attention and trial was temporarily paused. But in a statement on Saturday, September 12, Oxford University said it is resuming the ‘paused’ vaccine trial of the AZD1222 (also known as ChAdOx1 nCoV-19) in clinical trial sites in the United Kingdom.
The incident of stopping the trail could delay the availability of a COVID-19 vaccine. However, it is not a reason for excessive alarm. It may have reduced our hope for the early availability of a vaccine; however, the move can increase people’s faith in crucial safety procedures in vaccine development.
Such safety incidents have been flagged in other large clinical trials in the past. Pausing a trial after such a report, for a thorough review by a Data Safety Monitoring Board (DSMB) is standard and accepted practice. Usually, a DSMB is a “group of independent individuals, external to the trial, who are experts in relevant areas. They review the accumulated data from one or more ongoing clinical trials on a regular basis and advise the sponsor about: The continued safety of the trial participants; the continued validity of the trial and the continued scientific merit of the trial”. The temporality (the timing of event and administration of vaccine are in order) does not automatically mean causality (that what happened before caused it). Such incidents are investigated in detail. The DSMB will take a decision and determine the next steps which include resuming the trial.
In fact, pausing the vaccine trial should be a rather positive sign and a very reassuring one; that there is rush but no hurry. That there is pressure but no compromise with safety. ‘Voluntary’ reporting by a manufacturer shows that systems have been put in place to pick such an incident and report it.
A scientific process
Vaccine development is a scientific process. The incident such as the AstraZeneca/Oxford case underscores the uncertainties in the vaccine development process and partly explains why it is time consuming. No one can be sure about the safety and the efficacy of a vaccine till the Phase-3 clinical trial is completed and data analysed.
Vaccine development, especially in the context of the novel coronavirus, appears to have become a global race because of the urgency created by the pandemic and the politics around both — vaccine and pandemic response. A few countries do want to become the first in the world to licence and use the vaccine.
Trial to reality
The safety incident in the AZD1222 candidate vaccine trial is a reminder not to rush where caution is needed. Clinical trials are done only on a few 1,000 people, while a vaccine, in real life, is expected to be administered to millions of healthy people. In the case of the COVID-19 vaccine, this figure could be a few billion. Therefore, the process has to be careful to study and document rare and or adverse events. In the process for a licence, safety and efficacy data from an agreed number of volunteers for reasonable follow up period should be reviewed.
The entire world wants a safe and effective vaccine. The reported incident is a stark reminder that Phase-3 clinical trials are so very essential. The idea of conditional or emergency authorisation for vaccine, without sufficient data needs to be held back. All those who were pushing for emergency authorisation of COVID-19 vaccines need to recalibrate their thoughts. It could be the time to apply the brakes on a fast-tracking of the vaccine licensing processes.
The pandemic has brought politics to the forefront. In such times, the role and independence of vaccine scientists, vaccine researchers, vaccine developers, and vaccine manufacturers and regulators become very crucial. It is not just one vaccine they are involved in manufacturing and licensing. How the world deals with licensing and the availability of a COVID-19 vaccine will determine the faith and the trust of people in all existing and future vaccines. Any wrong move can jeopardise and tarnish the promise potential vaccines hold for humankind, today and tomorrow.
Concern and some reassurance
However, in these times, the behaviour of some national regulatory authorities (NRAs) which are expected to be fully independent of any interference, appears worrying. They seem to be towing the political line. A few NRAs have given emergency or conditional authorisation, even without Phase-3 clinical trials while there are others which are in favour of manufacturers to seek early licensing even when trials are under way. This development is unprecedented and very risky. Moreover, this could put regulatory authorities in other smaller countries with no manufacturing capacity under pressure. They may have to resort to emergency licensing in order to secure some vaccine for themselves. It can become a spiralling descent into chaos.
In this context, the pledge and promise (https://bwnews.pr/3bWE2Zh) made by nine major pharmaceutical companies to adhere to high scientific and ethical standards in development of COVID-19 vaccine is reassuring. “The CEOs of AstraZeneca, BioNTech, GlaxoSmithKline plc, Johnson & Johnson, Merck (known as MSD outside the United States and Canada), Moderna, Inc., Novavax, Inc., Pfizer Inc. and Sanofi on September 8 issued a statement that said: ‘We, the undersigned biopharmaceutical companies, want to make clear our on-going commitment to developing and testing potential vaccines for COVID-19 in accordance with high ethical standards and sound scientific principles’.”
The world can live with a vaccine which is less efficacious but there cannot be a compromise on safety. Vaccines are administered to millions of healthy people and these should be free from any major adverse event. It is a combined societal responsibility and a matter of faith. If ‘due diligence’ delays vaccine availability but increases the safety profile, it will be worth the billion doses and hopes.
The good news is that a number of vaccine candidates are in the advanced stages of trials. We have every reason to be hopeful that there would be multiple COVID-19 vaccines which are both safe and effective. In this novel coronavirus pandemic, political pressure and profit should not win over what is in the best interests of people in every part of the world.
Dr. Chandrakant Lahariya is an epidemiologist and public health specialist, with more than 15 years experience in vaccines. The views expressed are personal
