Skip to main content

Table 6 Amendments made relative to the original statistical analysis plan published in the protocol

From: Statistical analysis plan for the EuroHYP-1 trial: European multicentre, randomised, phase III clinical trial of the therapeutic hypothermia plus best medical treatment versus best medical treatment alone for acute ischaemic stroke

Topic described in original statistical analysis plan Handling of topic in the present amended statistical analysis plan Reason for action
No adjustment for nationality. Adjustment for nationality To improve the power by preventing upward bias of the standard error of the outcome.
Power calculation of secondary outcomes is missing Calculation of power conditional on sample size To be used when defining the test ordering of the secondary outcomes
Difficulties involved in interpreting an effect on a secondary outcome that can only be measured in surviving patients was not addressed The worst possible score is assigned to the dead patients A surplus of patients in one group relative to the other group may die before the outcome is measured. In the other group the corresponding surviving patients may (or may not) have very poor outcomes
No multiplicity adjustment The fixed-sequence testing procedure will be applied with the primary outcome to be tested first and followed by the secondary outcomes ordered according to falling power To keep the family-wise error rate ≤ 0.05
A search for auxiliary variables and if found followed by imputation of the primary outcome was not considered Missing value handling procedure revised accordingly To improve the efficiency of a multiple imputation of missing values of the primary outcome
The analytic potential of the exploratory temperature data was not expanded on An outline of an exploratory mixed model analyses of the temperature data and Cox analyses of time to death with censoring at end of treatment and at 91 days +/- 14 days is now included To assess if the temperature has an impact on short-term and long-term mortality and supplement the result of the analysis of the second secondary outcome
Sample size of 1500 participants Sample size reduced to 800 participants Due to exceptionally slow enrolment, we realised that this target was no longer realistic