Issues in outcomes research: an overview of randomization techniques for clinical trials

Abstract

Objective: To review and describe randomization techniques used in clinical trials, including simple, block, stratified, and covariate adaptive techniques.

Background: Clinical trials are required to establish treatment efficacy of many athletic training procedures. In the past, we have relied on evidence of questionable scientific merit to aid the determination of treatment choices. Interest in evidence-based practice is growing rapidly within the athletic training profession, placing greater emphasis on the importance of well-conducted clinical trials. One critical component of clinical trials that strengthens results is random assignment of participants to control and treatment groups. Although randomization appears to be a simple concept, issues of balancing sample sizes and controlling the influence of covariates a priori are important. Various techniques have been developed to account for these issues, including block, stratified randomization, and covariate adaptive techniques.

Advantages: Athletic training researchers and scholarly clinicians can use the information presented in this article to better conduct and interpret the results of clinical trials. Implementing these techniques will increase the power and validity of findings of athletic medicine clinical trials, which will ultimately improve the quality of care provided.

Keywords: block randomization; covariate adaptive randomization; minimization; simple randomization; stratified randomization.

Figures

Figure 1. Imbalance of sample size between treatment arms due to simple randomization (coin toss) in a small trial (n  =  10).

Figure 2. Block randomization procedure produces balanced study arms, even with a small sample size.

Figure 3. Stratified randomization procedure produces equal-sized study groups that are balanced by covariates.

Figure 4. Breakdown of the first 9 participants' group assignments by covariates: sex and body mass index.

Figure 5. Taves and Pocock and Simon covariate adaptive randomization procedures. The 10th participant is male and belongs to the underweight group. Male and underweight categories and marginal totals of initial 9 participants are shaded. Taves method (1974): A, Add marginal total in control group  =  3 (ie, 2 for male category + 1 for underweight category). Add marginal total in control group  =  5 (ie, 3 for male category + 2 for underweight category). B, Assign the 10th participant to the lower marginal total, which is the control group (ie, 3

Figure 6. Flowchart for selecting appropriate randomization technique. The gray boxes represent appropriate techniques.