[BostonCard]

Another reason you might expand a trial is because the effect of the intervention is not as strong as initially hoped, or that the prevalence of the disease is not high enough to see an effect, quickly enough.


I think the expansion is an ominous sign  But more data is always welcome. 



I suspect we will see trials ended early without as clear data on efficacy and safety as we would like.

Expansion could be neutral if for example they wanted to increase representation of some particular group. If they are doing it because there is concern for the "power" of the trial you are surely correct that it is not a positive sign.
I don't think we are going to see the trials end early. If an approval was granted and they haven't actually met their endpoint (for whatever reason) the "stink" would be of immense proportions. I just don't see that happening. I do however think that a "normal" safety trial has to involve following patients for at least a year. That we aren't going to get, obviously.

It could be a sign that they simply haven't gotten enough events (that is, not enough trial participants have gotten COVID-19).  An adequately powered trial would need about 75 volunteers to get COVID-19 (by my back-of-the-envelope calculation) to have adequate power to show a 50% efficacy and a 30% lower bound to the 95% confidence interval, as required by the FDA.  If the pandemic is subsiding in the areas of the world that they are vaccinating, it is possible that they are accruing cases of COVID-19 too slowly to be powered to determine efficacy anytime soon (of course, the alternative to recruiting more patients is just to wait until you have enough cases). 

BC

[BostonCard]

Another reason you might expand a trial is because the effect of the intervention is not as strong as initially hoped, or that the prevalence of the disease is not high enough to see an effect, quickly enough.


I think the expansion is an ominous sign  But more data is always welcome. 



I suspect we will see trials ended early without as clear data on efficacy and safety as we would like.

Expansion could be neutral if for example they wanted to increase representation of some particular group. If they are doing it because there is concern for the "power" of the trial you are surely correct that it is not a positive sign.
I don't think we are going to see the trials end early. If an approval was granted and they haven't actually met their endpoint (for whatever reason) the "stink" would be of immense proportions. I just don't see that happening. I do however think that a "normal" safety trial has to involve following patients for at least a year. That we aren't going to get, obviously.

It could be a sign that they simply haven't gotten enough events (that is, not enough trial participants have gotten COVID-19).  An adequately powered trial would need about 75 volunteers to get COVID-19 (by my back-of-the-envelope calculation) to have adequate power to show a 50% efficacy and a 30% lower bound to the 95% confidence interval, as required by the FDA.  If the pandemic is subsiding in the areas of the world that they are vaccinating, it is possible that they are accruing cases of COVID-19 too slowly to be powered to determine efficacy anytime soon (of course, the alternative to recruiting more patients is just to wait until you have enough cases). 

BC