Example

 

“The use of central web-based randomization with permutated blocks will ensure that individual surgeons and anesthesiologists cannot determine trial allocation ahead of time. Allocation to the experimental or control interventions will take place the day of surgery. The anesthesiologist will reveal the allocation once the patient is considered “anesthesia ready,” which implies that general anesthesia has been administered, and all lines and catheters have been inserted. By revealing the allocation once the patient is in the operating room and under anesthesia, we can ensure that clinical care will not be influenced by trial allocation" [345]. 

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“The adopted concealment mechanism of the allocation sequence will use sequentially numbered (#), opaque, sealed envelopes . . ." [346]. 

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Explanation

 

Successful randomisation in practice depends on two interrelated aspects: 1) generation of an unpredictable allocation sequence (Item 21), and 2) concealment of that sequence until assignment irreversibly occurs [337, 347]. The allocation concealment mechanism aims to prevent participants and recruiters from knowing the study group to which the next participant will be assigned [337, 347]. Allocation concealment helps to ensure that a participant’s decision to provide informed consent, or a recruiter’s decision to enrol a participant, is not influenced by knowledge of the group to which they will be allocated if they join the trial. Allocation concealment should not be confused with blinding (masking) (Item 24), which seeks to prevent ascertainment, performance, and attrition biases.

 

Without adequate allocation concealment, even random, unpredictable assignment sequences can be subverted [337, 347-349]. For example, a common practice is to enclose assignments in sequentially numbered, sealed envelopes. If the envelopes are not opaque and contents are visible when held up to a light source, or if the envelopes can be unsealed and resealed, then this method of allocation concealment can be corrupted.

 

Protocols should describe the planned allocation concealment mechanism in sufficient detail to enable assessment of its adequacy. In one study of randomised trial protocols in Denmark, over half did not adequately describe allocation concealment methods [330]. In contrast, central randomisation was stated as the allocation concealment method in all phase 3 trial protocols initiated in 1968–2003 by a cooperative cancer research group that used extensive protocol review processes [331]. Improved protocol reporting was found more recently. Reviews of two samples of 108 and 292 trial protocols from 2016 found that 83% addressed the mechanism of allocation concealment [9, 10]. Similar to failure of random sequence generation, inadequate or unclear allocation concealment in trial publications has been associated with inflated effect size estimates [326, 328, 329, 337, 350, 351]. 

 

Summary of key elements to address

• How the individuals enrolling participants will be kept unaware of the next trial group assignment in the random sequence (not to be confused with blinding)