4.1.1 Maintaining the integrity of the blinding is important in particular in the design of systems, management of users’ accounts, delegation of responsibilities with respect to data handling
and provision of data access at sites, data transfers, database review prior to planned unblinding and statistical analysis across all appropriate stages of the trial.
4.1.2 Roles, responsibilities and procedures for access to unblinded information should be defined and documented by all relevant parties according to the protocol; this information may also be included in the data management plans and statistical analysis plans or other trial specific plans/instructions and site staff delegation records. For example, in blinded trials, sponsor staff or service providers who are involved in operation of the trial and directly or indirectly interact with investigator site staff should not have access to unblinding information except when justified by the trial design (e.g., use of unblinded monitors).
4.1.3 In such cases, suitable mitigation strategies should be implemented to reduce the risk of inadvertent unblinding of the blinded investigator site staff.
4.1.4 The potential for unblinding should be part of the risk assessment of a blinded trial. Any planned or unplanned unblinding, including inadvertent or emergency unblinding, should be documented. Any unplanned unblinding should be assessed for its impact on the trial results, and actions should be taken as appropriate.