For instance, in the case of vaccines: What if you test the efficacy of your vaccine yet your vaccine intervention group is being more careful than the historical group simply due to behavior adaptation in the face of the pandemic? Eg: not wearing masks versus wearing masks
Conversely (but not at all equalising the errors), a study group that assumes it is vaccinated is less careful because it 'feels the benefit'. Or even actively pursues dangers to personally 'test' their protection.
That's dealt with by the 'blind' tests (depending on what you can/must test) with cohorts for the dose(s) you're trialling vs other cohorts with a competitive treatment and/or placebo[1], such that other factors (gender, age, obesity, whatever you can measure) are spread around those cohorts.
But a doctor/nurse who can see past the patient-blindness is a problem. From actually telling the subject "be careful, this is/isn't the actual/pre-approved/full-strength dose!" to unwitting facial expressions or tone of voice[2]. So the gold standard is to keep
them in the dark (about which they are administering[3]) by supplying (e.g.) lab-labelled vials of "dose for patient XYZ", "dose for patient QPR", etc.
Further behind the scenes, the layer of administration holds all the back-references. Usually there is a criteria (such as "more than 20% of participants get significantly more well/sick", or "in the event of a participant death", tuned to expectations) at which point an interim analysis is performed on the deblinded data to establish if there's an unusually good/bad outcome to one group or another - if it's
indeed significant, the protocol allows for the trial to be stopped and those with the most troublesome/least beneficial treatment to be fast-tracked onto the better alternative. That could be the hoped-for test item or not. Including back to the previous 'standard' treatment (not able to be used as the bl8nd-counter) when that's applicable.
It's interesting to consider the implications. But there are those who do that professionally, and with far more attention to the detail of the specific study (how participants can/must they recruit, how, what level of result is significant/beyond chance, what are the showstopper events (good and bad), what's the end-game, what after-care/post-trial follow-uping may be needed, etc, etc, etc...) that varies wildly according to whether it's a chemical treatment, a biological one, surgery, implantation, dressing, topical salve or any other form of therapy short of pure psychology (which may have its own system, but I've not heard details of that).
[1] The 'placebo' for acupuncture is interesting. But harder to double-blind. OTOH, they've done some decent work towards double-blinding the power of prayer.
[2] That's
also been tested, with both informed actors and unwitting personal 'administering' a global placebo (in a Phase I-ish situation) to see what placebo/nocebo effects can arise out totally independent of other causes.
[3] Not that they
are in trial situation. Except where this is specifically a test as described just above, personnel and recipients
must both know they might/might not be in the target cohort, etc, with what the possibile 'treatments' are, for ethics reasons.