---
title: "Randomized controlled trial"
chunk: 3/7
source: "https://en.wikipedia.org/wiki/Randomized_controlled_trial"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T04:26:23.353341+00:00"
instance: "kb-cron"
---

"It eliminates bias in treatment assignment," specifically selection bias and confounding.
"It facilitates blinding (masking) of the identity of treatments from investigators, participants, and assessors."
"It permits the use of probability theory to express the likelihood that any difference in outcome between treatment groups merely indicates chance."
There are two processes involved in randomizing patients to different interventions. First is choosing a randomization procedure to generate an unpredictable sequence of allocations; this may be a simple random assignment of patients to any of the groups at equal probabilities, may be "restricted", or may be "adaptive." A second and more practical issue is allocation concealment, which refers to the stringent precautions taken to ensure that the group assignment of patients are not revealed prior to definitively allocating them to their respective groups. Non-random "systematic" methods of group assignment, such as alternating subjects between one group and the other, can cause "limitless contamination possibilities" and can cause a breach of allocation concealment.
However empirical evidence that adequate randomization changes outcomes relative to inadequate randomization has been difficult to detect.

=== Procedures ===
The treatment allocation is the desired proportion of patients in each treatment arm.
An ideal randomization procedure would achieve the following goals:

Maximize statistical power, especially in subgroup analyses.  Generally, equal group sizes maximize statistical power, however, unequal groups sizes may be more powerful for some analyses (e.g., multiple comparisons of placebo versus several doses using Dunnett's procedure ), and are sometimes desired for non-analytic reasons (e.g., patients may be more motivated to enroll if there is a higher chance of getting the test treatment, or regulatory agencies may require a minimum number of patients exposed to treatment).
Minimize selection bias.  This may occur if investigators can consciously or unconsciously preferentially enroll patients between treatment arms.  A good randomization procedure will be unpredictable so that investigators cannot guess the next subject's group assignment based on prior treatment assignments. The risk of selection bias is highest when previous treatment assignments are known (as in unblinded studies) or can be guessed (perhaps if a drug has distinctive side effects).
Minimize allocation bias (or confounding).  This may occur when covariates that affect the outcome are not equally distributed between treatment groups, and the treatment effect is confounded with the effect of the covariates (i.e., an "accidental bias").  If the randomization procedure causes an imbalance in covariates related to the outcome across groups, estimates of effect may be biased if not adjusted for the covariates (which may be unmeasured and therefore impossible to adjust for).
However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.

==== Simple ====
This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing." Also known as "complete" or "unrestricted" randomization, it is robust against both selection and accidental biases. However, its main drawback is the possibility of imbalanced group sizes in small RCTs.  It is therefore recommended only for RCTs with over 200 subjects.

==== Restricted ====
To balance group sizes in smaller RCTs, some form of "restricted" randomization is recommended.  The major types of restricted randomization used in RCTs are:

Permuted-block randomization or blocked randomization: a "block size" and "allocation ratio" (number of subjects in one group versus the other group) are specified, and subjects are allocated randomly within each block. For example, a block size of 6 and an allocation ratio of 2:1 would lead to random assignment of 4 subjects to one group and 2 to the other. This type of randomization can be combined with "stratified randomization", for example by center in a multicenter trial, to "ensure good balance of participant characteristics in each group." A special case of permuted-block randomization is random allocation, in which the entire sample is treated as one block. The major disadvantage of permuted-block randomization is that even if the block sizes are large and randomly varied, the procedure can lead to selection bias. Another disadvantage is that "proper" analysis of data from permuted-block-randomized RCTs requires stratification by blocks.
Adaptive biased-coin randomization methods (of which urn randomization is the most widely known type): In these relatively uncommon methods, the probability of being assigned to a group decreases if the group is overrepresented and increases if the group is underrepresented. The methods are thought to be less affected by selection bias than permuted-block randomization.

==== Adaptive ====
At least two types of "adaptive" randomization procedures have been used in RCTs, but much less frequently than simple or restricted randomization:

Covariate-adaptive randomization, of which one type is minimization: The probability of being assigned to a group varies in order to minimize "covariate imbalance." Minimization is reported to have "supporters and detractors" because only the first subject's group assignment is truly chosen at random, the method does not necessarily eliminate bias on unknown factors.
Response-adaptive randomization, also known as outcome-adaptive randomization: The probability of being assigned to a group increases if the responses of the prior patients in the group were favorable. Although arguments have been made that this approach is more ethical than other types of randomization when the probability that a treatment is effective or ineffective increases during the course of an RCT, ethicists have not yet studied the approach in detail.

=== Allocation concealment ===