Impact of Enrollment Order on Outcomes in Sepsis Trials
Author Information
Author(s): Pierre-François Laterre, William L. Macias, Jonathan Janes, Mark D. Williams, David R. Nelson, Amand R. J. Girbes, Jean-François Dhainaut, Edward Abraham
Primary Institution: St Luc University Hospital
Hypothesis
Does the order in which patients are enrolled in clinical trials affect the observed treatment outcomes?
Conclusion
The study found that the order of patient enrollment significantly influenced mortality outcomes in the ADDRESS and PROWESS trials.
Supporting Evidence
- Higher mortality was associated with DrotAA use in the first enrolled patients.
- Subsequent patients had lower mortality rates and fewer protocol violations.
- The study suggests a learning curve effect in trial outcomes.
Takeaway
The order in which patients join a study can change how well a treatment works, especially for those who are less sick.
Methodology
The study analyzed data from two large phase 3 clinical trials, ADDRESS and PROWESS, focusing on the sequence of patient enrollment and its impact on treatment outcomes.
Potential Biases
Potential biases may arise from differences in patient characteristics as sites gained experience with the study protocol.
Limitations
The study was limited by the premature termination of the ADDRESS trial and the inability to assess protocol violations in less than 50% of patients.
Participant Demographics
Patients were from 34 countries, with varying characteristics including severity of illness and demographic factors.
Statistical Information
P-Value
0.04
Confidence Interval
1.06, 2.25
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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