Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the FDA's Vaccine Advisory Board, said disrupting a trial is a major logistical challenge – especially for someone like Johnson & Johnson, with plans for 60,000 volunteers in 10 countries.
"It's this big warship that you just stop moving," said Dr. Offit.
Once a study has been interrupted, a safety agency can require that a volunteer who has experienced an adverse event be “not blinded” – in other words, to find out if the volunteer received the placebo or treatment. If the volunteer was given a placebo, treatment may not be the cause of the event and the study can continue.
If the volunteer turns out to have received treatment, the board does a lot of detective work. Members review the medical records. You can request more information about the health of the volunteers or even order new tests – not just for the people who experienced adverse events, but for all participants in the study.
The board used this evidence to reach a conclusion on whether the treatment was most likely related to the event. For example, in very rare cases, some vaccines can cause a nerve disorder called Guillain-Barré syndrome. But it takes weeks for the condition to develop. If a volunteer shows signs of Guillain-Barré syndrome on the day of a vaccine injection, it may not be the cause.
The supervisory authorities then review the decision of these bodies and can accept it or request further information. This check can make stopping an experiment even more difficult for experiments being carried out in several countries at the same time. After AstraZeneca suspended its worldwide testing trials on September 6, regulators in Brazil, India, Japan, South Africa and the UK gave the go-ahead to restart the trial. But US regulators are still pausing the US trial as they continue to review the evidence.
If a safety agency determines that an adverse event is most likely not related to the vaccine or treatment, the study may be restarted. On the other hand, if there is an urgent problem – for example a contaminated batch of medication – the trial may need to be stopped. If the evidence is not as clear-cut, the board can move on to the process with additional tests or examinations. A second instance of the same event may be more frequent than randomly expected, so the process must terminate.