The preliminary results on the AstraZeneca vaccine were based on a total of 131 Covid-19 cases in a study involving 11,363 participants. The findings were perplexing. Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. That latter analysis was conducted on a small subset of the study participants, only 2,741.
AstraZeneca plans to explore adding the half dose-full dose regimen to its ongoing clinical trials in discussions with regulatory agencies, a spokesman told STAT in an email.
The half dose was originally administered by accident
Around the time when Astra was initiating its partnership with Oxford at the end of April, university researchers were administering doses to trial participants in Britain.
They soon noticed expected side effects such as fatigue, headaches or arm aches were milder than expected, he said.
“So we went back and checked ... and we found out that they had underpredicted the dose of the vaccine by half,” said Pangalos.
Since the half dose was not part of the originally registered trial, it's more complicated to figure out the significance of the difference here, and the future trials that will specifically test it will presumably be higher powered and able to settle the question more definitively.
Will AstraZeneca's vaccine turn out to be significantly more effective with a half-dose + full dose regimen compared to two full doses?
This question resolves positively if an RCT with over 1000 participants compares a protocol of half dose + full dose to two full doses, and finds that the former is more effective with a p-value below .05.
This question resolves negatively if an RCT with over 1000 participants compares a protocol of half dose + full dose to two full doses, and fails to find a significant difference (i.e. p>.05.)
This question resolves ambiguously if no such RCT is reported by May 1, 2021.