By now it’s pretty obvious that I’ve been disappointed with how AstraZeneca has conducted their COVID-19 vaccine clinical trials and reported the results. I was particularly concerned about their releasing partial data through press releases and making the efficacy of their vaccine sound better by referring to a subgroup of patients that I believed was caused by a dosing mistake.
All of the misgivings I had about AZ’s data announcement last Monday have now been validated through several sources, including a front-page article in the New York Times on Thanksgiving Day.
The overall trial success of the 8,900+ patients who got the intended vaccine dose was 62%. However, a small group of about 2,800 subsets was given a half dose of vaccine in their first (of two) shots in the trial. This group of patients was not an intended clinical trial subgroup, but was created by a dosing error in the experimental pharmacy.
The number of subjects in this group was so small that the “90% success rate“ suggested by AstraZeneca was likely based on a calculation that included only a couple of infections in the vaccine group. To make matters worse, no one in this “half dose” group was older than 55 years of age, and there was very little diversity in the participants.
Aside from the problems with the half dosage, in the overall trial AstraZeneca also pooled the results from two differently designed clinical trials in Britain and Brazil. This is a totally inappropriate way to report any results of multiple vaccine trials.
In my mind, the quality of this data will never be acceptable to regulators who have to approve the vaccine. In addition, since none of the subjects receiving the half-dose was in the U.S. arm of the AZ trial, this dose has not been tested in the U.S.
What does AZ do next? They could simply ignore the mistaken dose, claim victory, and present the 60% efficacy from the rest of the trial. This would be an option because the U.S. and other countries have stated that 50% efficacy is all that would be required for approval. Unfortunately, this also decreases the number of people in the trial to about 8,900, smaller than any other safety trial. Since there are no other Chimp adenovirus vaccines, we could not examine any other vaccine in development for confirmation. But they could rush the AZ vaccine given “the urgency of the pandemic.”
This may be their plan, since AstraZeneca keeps reinforcing that their vaccine could be stored for months in normal refrigerators and providing estimates they will be able to produce three billion doses next year. This amount of vaccine is attractive since it would be enough to vaccinate 20% of the world’s population.
However, what do you tell the people who get this vaccine? You are about half as likely to get COVID-19 as before? But if you take a half dose you could be 90% less likely? Who in their right mind would sign up for that?! Talk about undermining confidence in the vaccine!
No, AZ and their partner Oxford have opened up Pandora’s box by reporting their results in this manner. The only right step is to test the half dose regimen in an entirely new trial. This trial would have to involve a large and diverse enough subject population to accurately determine the vaccine’s efficacy.
The people of the world through their governments have paid for this vaccine and the clinical trials to test it. They deserve nothing less than an appropriately tested vaccine.