After hearing Fauci's recent comments on the matter, my understanding is that the phase III trials can be considered for approval once there are enough infections in the control group to do a comparative analysis.
Since the events now needed to confirm the vaccine are in the control group, not the experimental group, it seems that the blocker for approval now isn't SAFETY, as it has been continually suggested, but EFFICACY.
If that is indeed the case, what makes the most sense to me would be to allow an early approval of any vaccine that meets reasonable safety requirement (some x months in stage 3 trial), but the patient must sign a waiver saying that they understand there may be rare side effects and there is no guaranteed immunity.
It's both. The purpose of phase II trials is merely to demonstrate that the new drug is safe enough to proceed to phase III trials. That's typically a much lower bar to clear than demonstrating that it's safe enough to release onto the market.
With (typically) no more than a few hundred participants, phase II trials don't really have the statistical power to detect anything but the most serious of safety problems.
Yes, but figuring out whether something is safe is different than figuring out whether is something is effective.
To answer the efficacy question you would look at the infection and mortality rate of the experimental group and compare it to the rates of the control group. There is a minimum number of infection events needed in the control group for the comparison to be statistically significant, hence the long trial periods.
To answer the safety question I assumed you would wait some X period of time and evaluate the incidence of severe side effects that may have been caused by the vaccine. This analysis wouldn't be dependent on results to the control group. I assume this analysis can be sufficiently done with the current phase 3 trial data we have based on Fauci saying the only thing we are waiting for is events in the control group.
I didn't consider the potential safety issue that the vaccine could potentially make the vaccine worse. This safety analysis would also be dependent on control group events.
Establishing safety also involves a comparison with the control group. Otherwise you can't tell if the outcome in question is significantly more or less likely in the treatment population than in control.
Phase III examines both the efficacy and safety of the vaccine. These are independent questions.
Just because a trial takes x years to determine efficacy, it doesn't necessarily take the same amount of time to determine safety.
Fauci said certain vaccines could be approved as soon as there were enough events in the control group. Any dangerous side effects would only be in the experimental group and not dependent on events in the control group. If the only blocking factor is number of events in the control group, that to me suggest that the question of safety has already be sufficiently resolved for some of the candidate vaccines.
Yes, I directly addressed that. A potential safety issue with vaccines is making the course of the infection worse. So you have to look at vaccinated people that get infected (an 'event') to check on that.
Phase II checks if the vaccines directly causes problems, but doesn't look at a lot of events.
Phase III tests for both safety and efficacy. The efficacy portion is the bottleneck because the experimenters do not a priori know the rate of infection. So rather than waiting for a fixed amount of time, we must wait for a target number of infections.
In contrast, since we know when each person in the treatment group got the vaccine, safety can be measured after a predetermined amount of time.
Since the events now needed to confirm the vaccine are in the control group, not the experimental group, it seems that the blocker for approval now isn't SAFETY, as it has been continually suggested, but EFFICACY.
If that is indeed the case, what makes the most sense to me would be to allow an early approval of any vaccine that meets reasonable safety requirement (some x months in stage 3 trial), but the patient must sign a waiver saying that they understand there may be rare side effects and there is no guaranteed immunity.