Item 8: Description of trial design including type of trial (e.g., parallel group, crossover, factorial, single group), allocation ratio, and framework (e.g., superiority, equivalence, non-inferiority, exploratory).
Example
“The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery . . . randomization will be performed as block randomization with a 1:1 allocation.” 100
Explanation
The most common design for published randomised trials is the parallel group, two-arm, superiority trial with 1:1 allocation ratio.101 Other trial types include crossover, cluster, factorial, split-body, and n-of-1 randomised trials, as well as single-group trials and non-randomised comparative trials.
For trials with more than one study group, the allocation ratio reflects the intended relative number of participants in each group (e.g., 1:1 or 2:1). Unequal allocation ratios are used for a variety of reasons, including potential cost savings, allowance for learning curves, and ethical considerations when the balance of existing evidence appears to be in favour of one intervention over the other.102 Evidence also suggests a preference of some participants for enrolling in trials with an allocation ratio that favours allocation to an active treatment.92
The framework of a trial refers to its overall objective to test the superiority, non-inferiority, or equivalence of one intervention with another, or in the case of exploratory pilot trials, to gather preliminary information on the intervention (e.g., harms, pharmacokinetics) and the feasibility of conducting a full-scale trial.
It is important to specify and explain the choice of study design because of its close relation to the trial objectives (Item 7) and its influence on the study methods, conduct, costs,103 results,104-106 and interpretation. For example, factorial and non-inferiority trials can involve more complex methods, analyses, and interpretations than parallel group superiority trials.107;108 In addition, the interpretation of trial results in published reports is not always consistent with the pre-specified trial framework,6;109;110 especially among reports claiming post hoc equivalence based on a failure to demonstrate superiority rather than a specific test of equivalence.109
There is increasing interest in adaptive designs for clinical trials, defined as the use of accumulating data to decide how to modify aspects of a study as it continues, without undermining the validity and integrity of the trial.111;112 Examples of potential adaptations include stopping the trial early, modifying the allocation ratio, re-estimating the sample size, and changing the eligibility criteria. The most valid adaptive designs are those in which the opportunity to make adaptations is based on pre-specified decision rules that are fully documented in the protocol (Item 21b).
| 7: Objectives | 9: Study setting |
