Blinding, allocation concealment, and unblinding control

The manuals converge on preserving blinded trial conduct through strict control of information flow. Across the extracts, the common pattern is concealment of treatment assignment from participants, therapists, raters, and sometimes sponsors, together with neutral, standardised interactions that reduce expectancy bias. Several sources also converge on role separation, for example keeping dosing staff apart from outcome assessors, using independent or central blinded raters, and limiting access to allocation data to restricted personnel. They also converge on careful handling of unblinding. Most manuals treat unblinding as exceptional, usually reserved for medical emergencies, participant safety, or protocol-defined endpoints, and several require documentation of the reason and timing. Some sources add procedural safeguards such as sealed envelopes, sponsor notification, medical monitor consultation, or designated unblinded staff who hold the randomisation key. The main differences are in how blinding is operationalised. Some trials use active placebos, matched opaque capsules, or placebo procedures that mimic organoleptic features, while others rely more on role separation, standardised scripts, or centralised blinded rating. A few manuals also differ on what happens after blind break, with some requiring withdrawal if allocation is revealed to the investigator, while others allow continued blinded outcome work through an independent clinician or clinician raters who remain blinded even after participant unblinding.