Example



“The randomization is performed using the National Cancer Institute clinical trial randomization tool (https://ctrandomization.cancer.gov/). A minimisation method is used on the allocation process to ensure the required balance across the intervention and control groups. Results are sent to an independent researcher responsible for allocation that is not involved in the recruitment nor in the delivery of the intervention. The allocation is performed right before the beginning of the intervention of each group of randomized participants (in blocks), sending the results to a local researcher in a pre-printed Excel worksheet (Microsoft, Redmond, WA, USA). Randomization and allocation of participants are carried out by different researchers" [352]. 

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“One of the leading investigators (TMS) will generate the allocation sequences using a random number generator in Excel. After eligibility is determined, the other leading investigator (AEP) will assign participants to condition (either intervention or wait-list control) according to those sequences and subsequently enroll participants in the study. . . The allocation sequence will be stored in a secure folder on a secure iRT [innovation Research & Training] server until interventions are assigned and will only be accessible to the leading investigator (TMS) who created the sequence. The other leading investigator (AEP), who assigns participants to interventions, will only see the assignments for participants ready to enroll, and will not be able to see the future allocation sequence" [320]. 

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"Randomization is performed by a statistician unrelated to the trial. The research assistant (RA) who is carrying out allocation will have no access to allocation sequence" [353].

 

“. . . the random sequence for trial group allocation in blocks will be generated by the P.I. [principal investigator] using an online tool [reference]. . . To prevent biased selection of patients, the PI will remotely screen for new patient admissions and alert the ICU [intensive care unit] staff for possible candidates. The patient’s attending physicians are responsible for applying protocol, deciding patient eligibility, and checking for inclusion/exclusion criteria and obtaining the informed consent. Once patient enrollment has been established, the attending physicians, who are blinded for the allocation blocks, will determine the corresponding stratification subgroup by using IAP [intra-abdominal pressure] and creatinine values and open the respective sealed envelope containing the group allocation" [346]. 

 

“The randomization list will be computer-generated by the biostatistician and integrated into a REDCap randomization project. Members of the study staff will not have access to the sequence prior to assignment and will utilize the REDCap project to randomly assign participants to study arm"  [354].

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Explanation

 

The process of randomising participants into a trial has three different steps: sequence generation, allocation concealment mechanism, and implementation. Investigators should strive for complete separation of the people involved with sequence generation and allocation concealment from the people involved in the implementation of assignments.

 

Failure to implement this separation may introduce bias. For example, the person who generated the allocation sequence will likely have access to a copy of the sequence list and may consult it if they were enrolling and assigning participants in a trial. Thus, that person could bias the enrolment or assignment process.

 

Authors of protocols should confirm complete separation of the people involved with sequence generation and allocation concealment from the people involved in the implementation of assignments and describe how this separation was achieved. If complete separation did not occur, then authors should describe how the people involved in the implementation will be prevented from accessing the allocation sequence (e.g., specifying that the allocation sequence will be locked in a secure location). 

 

Reviews of two samples of 108 and 292 trial protocols from 2016 found that 73% and 56% respectively did not describe the persons who will enrol or assign participants [9, 10]. 

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Summary of key elements to address

• Who will have access to the random allocation sequence

• Who will enrol participants

• Who will assign participants to interventions

• Whether the personnel enrolling and assigning participants will have no access to the random allocation sequence

When individuals involved in sequence generation and allocation concealment are the same individuals involved in the implementation of assignment:

• How and where the random allocation list will be securely stored

• Any mechanisms to prevent those enrolling and assigning participants from accessing the list