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The main efficacy criterion was the rate of patients with a successful BZD withdrawal, defined as no BZD in urinalysis at D84 (or D98 for slow metabolisers) with no trial discontinuation due to anxiety, or due to withdrawal symptoms.
The vertebral fracture incidence was the main efficacy criterion of the study.
The main efficacy criterion was need for endotracheal intubation at 28 days.
Five subjects were excluded from efficacy analysis, three because they did not receive any injection and two because they were not evaluated for the main efficacy criterion.
The main efficacy criterion was assessed by analysis of covariance (ANCOVA) with the product, site and sequence factors as fixed effects, the subject factor as random effect and the baseline as the covariate.
The sample size calculation was based on the assumptions that mean change from baseline in VAS assessing total pain at the end of treatment was the main efficacy criterion, and the mean difference between a test treatment (μ2) and ibuprofen (μ1) was assumed to be 0 (i.e., μ2 (test) − μ1 (control) = 0).
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These estimations confirm a former meta-analysis by Trautmann et al. [19] which found that headache intensity was the main efficacy criteria in pediatric headaches.
All studies were open-label regarding physicians' assessment of outcomes, which were either hard outcomes such as ICU mortality, or relied on pre-defined objective criteria such as the main efficacy criteria (tracheal intubation).
Other recommendations are migraine-specific, such as operational diagnostic criteria and primary efficacy measure.
Fig. 2 Main efficacy outcomes.
The main efficacy results are summarized in Table 4.
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