Randomization Method: Blocked (Block Randomization)
Method and Description:
This study employed block randomization (blocked randomization). In this method, participants are grouped into blocks of fixed or variable sizes, and within each block, allocation to study groups (e.g., intervention and control groups) is performed randomly and in a balanced manner. This ensures that at any point in time, the number of participants in each group is approximately equal, maintaining group balance throughout the study.
Unit of Randomization:
The unit of randomization in this study was individual. Each eligible participant was independently assigned to one of the study groups.
Stratification:
Stratified randomization was used in conjunction with the block method. Participants were divided into separate strata based on important outcome-predicting variables (such as age (age categories) and disease severity (mild/moderate/severe)). Within each stratum, an independent block randomization process was conducted to ensure group balance within each key subgroup.
Randomization Tool:
The allocation sequence was generated using the statistical software R (utilizing specialized packages such as blockrand or randomizeR). This software enables the creation of stratified block randomization sequences with precision and without bias.
Sequence Generation Process:
An independent statistician, not involved in subsequent stages of the study (such as evaluation or intervention), generated the allocation sequences. The steps were as follows:
The block size (e.g., 4, 6, or 8) and the number of groups (2 groups) were defined.
For each stratum (a specific combination of age and disease severity variables), a separate block randomization sequence was generated.
This sequence specified the exact order of group allocation (e.g., A=intervention, B=control) for each participant in that stratum.
Allocation Concealment:
To ensure that the enrolling researcher or the participant could not predict or influence future allocation, the Sequentially Numbered, Opaque, Sealed Envelopes (SNOSE) method was used:
The generated allocation for each registration number was placed in a separate, opaque, and sealed envelope.
The envelopes were arranged in sequential order according to the participants' entry sequence.
After obtaining informed consent and final confirmation of eligibility, the enrolling researcher opened the corresponding sequentially numbered envelope and assigned the participant to the designated group as indicated inside the envelope.
This process prevented any manipulation or prediction of allocation, thereby enhancing the internal validity of the study.