Thread by @VikiLovesFACS

@willowwriter @hejaro14 @naomirwolf I guess you are arguing - as many have - that pregnant ppl should have been included in the clinical trials from the outset. We have the PREVENT guidance, developed in the context of Ebola and Zika, to help us do this. 1/

sciencedirect.com/science/articl…

@willowwriter @hejaro14 @naomirwolf Now, we can have a discussion about why it was felt that pregnant ppl should not have been included in the trials. But the long and the short of it is that they were not. 2/

@willowwriter @hejaro14 @naomirwolf This put each regulatory body in a position where it had to make its own decision about what to recommend... balancing potential risks of vaccination on one side against the known risks of COVID in pregnancy on the other. 3/

bmj.com/content/370/bm…

@willowwriter @hejaro14 @naomirwolf Different regulatory bodies made different decisions, but the fact that the USA and Israel broadly took the view that pregnant ppl could make their own decision on this, together with the fact that pregnant ppl were keen not to catch COVID... 4/

@willowwriter @hejaro14 @naomirwolf ... (with all the pregnancy-specific risks that entails) is how we end up with the enormous post-marketing safety dataset reported in the NEJM. 5/

nejm.org/doi/full/10.10…

@willowwriter @hejaro14 @naomirwolf But I think there’s another important point here, which is that even in the general population, we collect lots of safety data during the enhanced pharmacovigilance period. This is simply because for any sufficiently rare side effect, the trials are not powered to detect it. 6/

@willowwriter @hejaro14 @naomirwolf For example, even the largest of the COVID vaccine trials was only powers to detect adverse events that occur in 1/50,000 people. This is why the rare clotting disorders associated with the AZ and J&J vaccines were only detected when they started being widely used. 7/

@willowwriter @hejaro14 @naomirwolf So to answer your question. Should pregnant ppl be included in clinical trials from the outset? They probably should have been in this case. But it’s worth noting that this way of detecting adverse events is widely applied - not just to pregnant ppl - with a deal of success. 8/8

@willowwriter @hejaro14 @naomirwolf PS. I should mention, in case you didn’t know, we do now have formal trials of Pfizer and J&J during pregnancy. The Pfizer trial is powered to detect adverse events that occur at > 1/660 and the J&J at greater than 1/66. So this is a more sensitive approach than either but...

@willowwriter @hejaro14 @naomirwolf ... there is still value in doing trials with a formal, blinded control group, particularly from the point of view of being sure of immunogenicity in this population.