I think it really comes down to the strength of the effect. If the anti-fungal has only a marginal effect on outcome, a large n control group helps tease out statistical significance. If the anti-fungal has a strong readily observable effect, the whole study gets un-blinded and everyone starts getting it pretty quickly anyway.
The reality is the control group and the test group are not the exact same people and often it's not even completely true everyone is dealing with the "exact same" disease (different genes, different mutations, different past treatment regimens, etc.). I definitely believe there are cases where a control is setup because "that's how it must be done" and not because it's going to actually provide any useful data at the end of the day to tell you anything about how the test group actually performed.
Another way I've seen this done which is a little less wasteful, and when you have high confidence in your new treatment, is to tweak the standard treatment marginally in some way you think might provide some small improvement in both groups, but in a way that could never justify its own full study. Like you modify the dosing schedule, add some vitimin, diet, or exercise change in some way you think will help both groups. But again you can only afford to do that if you are expecting a very strong effect from your new additive treatment which would blow away your tweak statistically, else you risk hiding a small benefit of the new treatment in your tweak.
In other words, you give every participant the best damn chance and the best care you can legally give them, and 50% of them know they are on something new which could be a blockbuster, and if it is, the whole group will get early access to it anyway.
Ok, but don't we have a body of knowledge on Alzheimer's that having another control group is redundant? Why do we keep needing new control groups for things that are going to kill people and we know are going to kill people? I cannot get by the ethical problem of knowing we're kill 50% of the people in the study to provide data we already have.
The problem is, if something related to how you run your test of the anti-fungal has an effect on the disease, you're going to assume its the anti-fungal; but maybe it's not. If you have a control group, and both groups do better than expected (compared to the body of evidence), then you've learned something you wouldn't have without a control group (and you'll have to work hard to figure out what changed in this study vs other studies). If anti-fungals are a clear winner, it's likely that the study protocol would be changed to give everyone the drug after early results.
