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Analyses suggest that an enrollment sequence effect was present in the ADDRESS and PROWESS trials.
In PROWESS, this enrollment sequence effect reduced the observed treatment effect associated with DrotAA.
The enrollment sequence effect observed in two separate trials suggests the need for analyses adjusted for confounding events.
Patient enrollment, sequence generation and assignment to interventions were performed by a responsible investigator of each participating study center.
Analysis of the ADDRESS and PROWESS studies suggests that an enrollment sequence effect was present in both studies.
In ADDRESS, this enrollment sequence effect may have contributed to the decision to recommend early termination of the study for futility.
Similar(48)
A treatment-by-enrollment sequence was observed at both small (≤8 patients) and high (>8 patients) enrolling sites (data not shown).
At enrollment the sequence was concealed from researchers who confirmed consent and eligibility on an online database before allocation was revealed.
Generation of the random allocation sequence, enrollment of the patients and allocation to the assigned ventilation mode were performed by the same clinician author (JD).
An analysis of bleeding complications by sequence of enrollment in ADDRESS also indicated that sites enrolled patients at lower risk of bleeding in both the DrotAA and placebo groups.
Based on a prospectively defined analysis, there was a significant treatment-by-sequence of enrollment interaction for the first patient enrolled at each site compared with all subsequently enrolled patients at that site (P = 0.04).
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