Plenty of descriptions of what participation in trials involves, but there seems to be a lot of confusion about what happens if the trial you are in or some other trial is successful. Do you get the vaccine? If yes, when? If not, why not? What do ethicists & regulators want? 1/10

Let us take what is happening with the Pfizer-BioNTech, Moderna and Astra-Zeneca trials in the US. Pfizer-BioNTech and Moderna are now approved under emergency use authorization. 2/10

Pfizer has proposed gradually unblinding participants as they become eligible for vaccine per CDC priority guidelines. Moderna wants to immediately offer the vaccine to all placebo participants, regardless of whether they would be eligible. 3/10

What does this mean? Pfizer’s numbers in follow up will drop, but since they have already reached their case numbers, this means less safety data than planned as more people get the vaccine. 4/10

For Moderna, if their plans go ahead (not quite final yet--will require discussion with FDA) the efficacy and safety data will then be pretty much as they currently are. 5/10

What about Astra-Zeneca, which had an interruption in recruitment? Trial investigators are allowed to individually unblind participants who become eligible for the Pfizer or Moderna vaccines and tell them whether they received the AZ vaccine or placebo. 6/10

The participant can then decide whether to receive the authorized vaccine. Whichever they choose, they will remain in the AZ study for long-term followup. 7/10

The plan leaves the final decision up to investigators. The unblinding strategy would let trial continue while allowing volunteers to get the vaccines they are eligible for--the vast majority of participants will not be eligible for the Pfizer or Moderna vaccines for months. 8/10

Just goes to show how complicated vaccine trials can become once there are licensed vaccines available. We went through this for rotavirus vaccine trials. 9/10

All the more reason to really chase a correlate of protection. And to get trials to recruit quickly because the more vaccines we have the better for us. But the more vaccines we have, the harder it will become to get the clinical efficacy data. 10/10