[humfrz]

Originally Posted by AnalogMan

Yes, but unfortunately the AstraZeneca vaccine had problems in its Phase 3 clinical trial:

https://www.nature.com/articles/d41586-020-03504-w

https://www.statnews.com/2020/12/08/...rate-efficacy/

In my mind, the difficulties call the results into question. First, it seems that the mixed dosing regimen (low first dose + full second dose) was unintentional. It was given in error. This raises the question of what other errors might have occurred?

Second, the results are counter-intuitive. The low + standard dose gave greater effectiveness (90%) than the planned two standard dose regimen (62%). This suggests an inverted U-shaped dose-response curve. I spent my career in drug development, and while there are certainly examples of drugs with such inverted U-shaped dose-response curves, they are often problematic. At a minimum, it calls for questioning and looking into both whether the results are genuine, and why the lower dose regimen worked better than the higher standard dose.

The world desperately needs more SARS-CoV-2 vaccines. I fear that this dire need is pushing regulators to approve something that by customary clinical trial standards would otherwise be required to repeat the Phase 3 trial. The AstraZeneca vaccine is promising because of the easier storage conditions and lower cost, but the downside could be vaccinating millions of people with a product that turns out to be less effective than thought - putting those people at greater risk of infection.

Who did/do you work for?

PM me if you would like - or not -