What are the advantages and disadvantages of crossover designs compared to parallel designs?

When you plan an experiment, you have to choose how to assign your subjects to different treatments or conditions. One common choice is between parallel designs and crossover designs. In this article, you will learn what these designs are, how they differ, and what are their advantages and disadvantages.

1 Parallel designs

In a parallel design, each subject is randomly assigned to one of the treatments or conditions and stays in that group throughout the experiment. For example, if you want to compare two drugs, you can divide your subjects into two groups and give one drug to each group. This design is simple and straightforward, but it also has some limitations. You need a large sample size to ensure that the groups are similar and to detect any differences between them. You also have to deal with potential confounding factors, such as variations in the subjects' characteristics, compliance, or response to the treatments.

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Natalie Rodrigue

Biostatistician & Epidemiologist, Mentor for Biotechs & Medtechs. Preclinical & Clinical Research, Genomics & Aeronautics. + 30 yrs experience.
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Commonly used in clinical trials in which patients are randomised to 2 or more treatments. Because differents groups of patients are used in the various treatment groups, this design suffers from the between-patient variability and requires more subjects than the cross-over design.

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2 Crossover designs

In a crossover design, each subject receives more than one treatment or condition in a sequential order, with a washout period between them. For example, if you want to compare two drugs, you can give each subject both drugs in a random order, with a period of no drug in between. This design allows you to use each subject as their own control and to reduce the variability and confounding factors that affect parallel designs. You also need a smaller sample size to achieve the same statistical power as parallel designs.

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3 Advantages of crossover designs

Crossover designs have several advantages over parallel designs, especially when the treatments or conditions have short-term effects and are reversible. By using each subject as their own control, you can eliminate the between-subject variability and increase the sensitivity and precision of your experiment. You can also reduce the sample size and the cost of your experiment, as you need fewer subjects to achieve the same level of confidence. Crossover designs also allow you to test more than two treatments or conditions in the same experiment, which can be useful for comparing multiple options or combinations.

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Natalie Rodrigue

Biostatistician & Epidemiologist, Mentor for Biotechs & Medtechs. Preclinical & Clinical Research, Genomics & Aeronautics. + 30 yrs experience.
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A crossover design accounts for the variation between the experimental units. A crossover design is usually more powerful than a parallel design. An appropriate randomisation scheme must be used in order to correctly estimate carry-over effects.

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4 Disadvantages of crossover designs

Crossover designs also have some disadvantages and challenges that you need to consider before choosing them. One of the main drawbacks is the possibility of carryover effects, which occur when the effect of one treatment or condition persists or influences the effect of the next one. To avoid this, you need to ensure that there is a sufficient washout period between the treatments or conditions, and that they are not interacting or interfering with each other. Another challenge is the risk of period effects, which occur when the effect of a treatment or condition changes over time due to factors such as learning, fatigue, or adaptation. To control for this, you need to randomize the order of the treatments or conditions and use appropriate statistical methods to analyze the data.

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Natalie Rodrigue

Biostatistician & Epidemiologist, Mentor for Biotechs & Medtechs. Preclinical & Clinical Research, Genomics & Aeronautics. + 30 yrs experience.
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Compared with parallel group trials, cross-over trials can be very efficient with respect to sample size requirements because each patient acts as his/her own control (removes the between-patient variability present in parallel group trials). Unfortunately, cross-over trials also have several potential limitations. It assumes that differences in outcome between the treatments do not depend on the period in which the treatments are given, (no interaction between the treatment and period). Another potential cause of such an interaction is inadequacy of the length of the washout period and carry over effects.

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5 How to choose between parallel and crossover designs

When deciding which design is better for your experiment, there is no one definitive answer as it depends on the specific goals and characteristics. However, some general guidelines can help you make an informed decision. If you are testing treatments or conditions with short-term and reversible effects, dealing with a homogeneous and stable population of subjects, interested in within-subject variability and individual responses, wanting to reduce sample size and cost, or comparing more than two treatments or conditions, then a crossover design should be considered. On the other hand, if you are testing treatments or conditions with long-term or irreversible effects, dealing with a heterogeneous or unstable population of subjects, interested in between-subject variability and group differences, have a large enough sample size and budget for your experiment, or wanting to avoid the complications of carryover and period effects, then a parallel design should be considered.

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6 Here’s what else to consider

This is a space to share examples, stories, or insights that don’t fit into any of the previous sections. What else would you like to add?

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What are the advantages and disadvantages of crossover designs compared to parallel designs?

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1 Parallel designs

2 Crossover designs

3 Advantages of crossover designs

4 Disadvantages of crossover designs

5 How to choose between parallel and crossover designs

6 Here’s what else to consider

Experimental Design

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