Rationale for a per protocol approach
SECONDARY
Analysis was carried out using a per-protocol approach. For a participant to be included in primary analysis, it was necessary to have a valid HbA1c. For intention to treat analysis, in the absence of a valid HbA1c, some form of imputation of missing values would be required. This is more challenging in a crossover setting, as parallel group approaches such as imputing with the baseline are not valid as the pre-treatment baseline is only an appropriate baseline for the first period. However, we recognise the missing data could be informative. Therefore, to address this issue, we proposed two further analyses to explore the extent to which the missing HbA1cs could affect the final results: a tipping point analysis (see sensitivity analysis) and a secondary analysis of tolerability.