Trial Design

Item 12: Description of trial design including type of trial (e.g., parallel group, crossover), allocation ratio, and framework (e.g., superiority, equivalence, non-inferiority, exploratory).

Example

“The MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial... Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA [ulipristal acetate] group and 60 patients in the surgery group" [192].

Explanation

By “trial design” we mean the core characteristics of the type of a randomised trial planned, for example, parallel group or crossover; and the conceptual framework; for example, superiority, equivalence, or non-inferiority. Other specific aspects of the trial design, including details of randomisation and blinding, are addressed elsewhere in the SPIRIT checklist.

SPIRIT 2025 focuses primarily on trials with participants individually randomised to one of two parallel groups. While most published trials have such a design [193] the main alternative designs are multi-arm parallel, [194] factorial, [178] crossover, [195] or cluster [196]. The reporting of the planned the unit of randomisation (e.g., patient, clinic, lesion) is important. Most trials are designed to identify the superiority of an intervention, while others are designed to assess non-inferiority or equivalence [197]. It is important that researchers clearly describe these aspects of their trial.

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A review of 1,000 randomised trials indexed in PubMed in 2016 showed that 85% were parallel-group design, while the other main designs were crossover (7%) and cluster (5%). Of the 1,000 trials, 88% had two groups, 8% had three groups, and 4% had four or more groups [193]. 

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If a less common design is employed, authors should explain their choice, especially as such designs may imply the need for a larger sample size or more complex analysis and interpretation. For example, factorial and non-inferiority trials can involve more complex methods, analyses, and interpretations than parallel-group superiority trials [178,198]. In addition, the interpretation of trial results in published reports is not always consistent with the pre-specified conceptual framework, [191-201] especially among reports claiming post hoc equivalence based on a failure to demonstrate superiority rather than a specific test of equivalence [191]. Although most trials use equal randomisation (e.g., 1:1 for two groups), it is helpful to explicitly state the allocation ratio.

Summary of key elements to address

• Type of trial design (e.g., parallel group)

• Conceptual framework (e.g., superiority, non-inferiority, or equivalence)

• Unit of randomisation (e.g., individual participant)

• Allocation ratio (e.g., 1:1)