Table 5 Content analysis of the responses on the questions related to the quality of the non-inferiority/equivalence margin including the theme, definition, and frequency in each theme

Determinants of confidence in a non-inferiority or equivalence margin quality (n = 35)

Stakeholder involvement

Involved or wanted to involve stakeholders in the elicitation

13

Supported by previous literature or guidelines

Previous literature/guidelines were used in margin design

10

Statistical considerations

Statistical limitations or comments (e.g. how large the margin is in light of observed event rates)

7

Feasibility of the trial

Feasibility of the sample size affected the margin

2

Minimal clinically important difference (MCID)

Non-inferiority margin design was clinically meaningful

2

Communication

Uncertainty about how clear the communication about the margin was

1

Suggestions to improve the definition of non-inferiority margins (n = 33)

Developing methods of involving patients and other stakeholders

Involve different groups/stakeholders in the elicitation process of the non-inferiority margin (e.g. development of formal elicitation methods; sharing of good practice case studies)

14

More guidance needed

Further guidelines on how to define the margin, including using MCID to inform the non-inferiority margin

10

Improving methods used

Improve the methods used to justify the non-inferiority margin

4

Increasing transparency

Make the justification process transparent to others

3

Pilot or pre-study

Need for pre-studies to determine the non-inferiority margin

2

Challenges in defining non-inferiority margin (n = 33)

Communication of non-inferiority trials

Challenges to explain non-inferiority trials to stakeholders

7

Lack of prior evidence or guidelines

Identifying and using the appropriate guidelines and studies to select the non-inferiority margin

6

Criteria to determine the feasibility of the trial

Possible constraints that may determine the size or feasibility of the trial

5

Implementation of results

Assessing whether the margin could inform/persuade clinical practice change

4

Different views on acceptable margin

Different opinions on what is appropriate for the margin

4

Lack of method to set the margin or to assess its relevance

Minimal methods available to identify margin and relevance

3

Variability in outcome literature

Challenges arising from different outcomes or outcome measures being used in different trials, making it harder to take meaningful conclusions regarding non-inferiority margins

3

Identifying stakeholders

Identifying the appropriate stakeholders to elicit the non-inferiority margin

1