University of Oxford Clarifies Trial Dosing Error in COVID-19 Vaccine Co-Developed With AstraZeneca

The University of Oxford has attempted to clarify the dosing error it and AstraZeneca (AZ) made in a clinical trial assessing COVID-19 vaccine AZD1222, following divergent reports between the two of what exactly transpired.

Previously, an Oxford scientist claimed the smaller one-a-half-dose regimen was given on purpose, while AZ said it was a fortunate accident (DID, Dec. 4). Now Oxford is saying an initial dosing mistake led to a change in trial protocol once the smaller dosage was revealed to be highly effective. AZ has not responded to a request to confirm this account.

Oxford’s updated explanation coincides with the publication in the peer-reviewed The Lancet of a “pooled analysis” of phase 3 trials evaluating two different dose regimens — two doses and one-and-a-half-doses, which demonstrated an average efficacy of 70.4 percent (DID, Dec. 9).

Results were derived from 11,636 participants in the UK and Brazil, featuring three different study arms. This includes two groups who received a two-dose regimen as well as the UK group, which received the one-and-a-half dose vaccination. The one-and-a-half dose regimen showed 90 percent efficacy, while the double-dose showed only 62 percent efficacy.

The University of Oxford’s website, which was updated late Tuesday, said: “There were no problems with manufacturing the vaccine, however, due to slight differences in the materials used in the production process … [a dosing machine] over-estimated the dose, so that after adjustment a lower dose was produced.”

“This unplanned lower dosing regimen [of one-and-a-half doses] became apparent following our investigations into the different methods of dose estimation … We observed the lower vaccine dose was better tolerated by our volunteers than expected,” Oxford added.

Oxford says it “immediately discussed [the issue] with the regulators” who gave permission to update the trial protocol in order to follow the volunteer group receiving the lower dosage.

Researchers who have reviewed The Lancet article say there are lingering questions surrounding AZD1222. Chief among them, can the vaccine fight asymptomatic infections? According to the trial data, the one-and-a-half dose regimen was 60 percent effective in trial participants who were asymptomatic, but the data were unclear on the effectiveness of the two-dose regimen in asymptomatic trial participants. ― Jason Scott