Dr Paul Offit, a professor at the University of Pennsylvania and a member of the FDA’s Vaccine Advisory Group, said suspending a trial was a huge logistical challenge – especially for one such as Johnson & Johnson’s, with plans to 60,000 volunteers in 10 countries.
“It’s that big warship that you stop moving,” said Dr Offit.
Once a trial is suspended, a safety committee can ask a volunteer with an adverse event not to be blinded – in other words, whether the volunteer received the placebo or the treatment. If the volunteer received a placebo, treatment cannot be the cause of the event and the trial can continue.
If it turns out that the volunteer received the treatment, the board does a flurry of detective work. Members review medical records. They can request more information about the health of the volunteers or even order new tests – not just for people who have experienced adverse events, but for everyone participating in the trial.
The jury uses this evidence to come to a conclusion as to whether the treatment likely had something to do with the event. On very rare occasions, for example, certain vaccines can cause a nervous disorder called Guillain-Barré syndrome. But the disease takes weeks to develop. If a volunteer shows signs of Guillain-Barré syndrome on the day of a vaccine injection, this may not be the cause.
Regulators then review the decision of those boards and may accept it or request more information. For trials underway in multiple countries at once, this review may make it even more difficult to suspend a trial. After AstraZeneca suspended its global trials on September 6 for a review, regulators in Brazil, India, Japan, South Africa and the United Kingdom all gave the green light for the trial to resume. But US regulators are still keeping the US trial on hold as they continue to review the evidence.
If a safety board decides that an adverse event is unlikely to be the result of the vaccine or treatment, they may allow the trial to start over. If, on the other hand, there is an urgent problem – a contaminated batch of drugs, for example – the trial may have to stop. When the evidence is not so clear, counsel may allow the trial to resume with additional tests or examinations. A second case of the same event may be more common than you would expect, forcing the trial to end.