Randomization is the gold standard method for allocating participants to treatment groups in clinical trials, providing the strongest foundation for valid statistical inference about treatment effects. By using chance rather than investigator judgment or participant preference to determine assignments, randomization helps ensure that treatment groups are comparable with respect to both known and unknown factors that might affect outcomes. This balance enables investigators to attribute observed differences in outcomes to the treatments themselves rather than to baseline differences between groups.

Various randomization methods are employed depending on the trial design and practical considerations. Simple randomization uses a random sequence without constraints, analogous to flipping a coin for each assignment. Block randomization ensures that treatment groups remain balanced throughout enrollment by randomizing within blocks of predetermined size. Stratified randomization ensures balance within important subgroups by randomizing separately within strata defined by prognostic factors. Adaptive methods adjust randomization probabilities based on accumulating data to achieve specific objectives.

The integrity of the randomization process is essential for trial validity. The randomization schedule must be generated using validated methods that produce truly random sequences. The schedule must be concealed from those enrolling participants to prevent selection bias. Access to the schedule must be restricted to prevent inappropriate unblinding. Documentation must enable verification that the randomization was implemented as designed. Any departures from random assignment must be documented and considered in the analysis and interpretation of results.