Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus - 19/04/17
Abstract |
Study objective |
We demonstrate the application of a Bayesian approach to a recent negative clinical trial result. A Bayesian analysis of such a trial can provide a more useful interpretation of results and can incorporate previous evidence.
Methods |
This was a secondary analysis of the efficacy and safety results of the Pediatric Seizure Study, a randomized clinical trial of lorazepam versus diazepam for pediatric status epilepticus. We included the published results from the only prospective pediatric study of status in a Bayesian hierarchic model, and we performed sensitivity analyses on the amount of pooling between studies. We evaluated 3 summary analyses for the results: superiority, noninferiority (margin <–10%), and practical equivalence (within ±10%).
Results |
Consistent with the original study’s classic analysis of study results, we did not demonstrate superiority of lorazepam over diazepam. There is a 95% probability that the true efficacy of lorazepam is in the range of 66% to 80%. For both the efficacy and safety outcomes, there was greater than 95% probability that lorazepam is noninferior to diazepam, and there was greater than 90% probability that the 2 medications are practically equivalent. The results were largely driven by the current study because of the sample sizes of our study (n=273) and the previous pediatric study (n=61).
Conclusion |
Because Bayesian analysis estimates the probability of one or more hypotheses, such an approach can provide more useful information about the meaning of the results of a negative trial outcome. In the case of pediatric status epilepticus, it is highly likely that lorazepam is noninferior and practically equivalent to diazepam.
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| Please see page 118 for the Editor’s Capsule Summary of this article. |
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| Supervising editor: Kathy N. Shaw, MD, MSCE |
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| Author contributions: JMC obtained research funding, led the original trial from which these data were derived, provided input about study design and use of published results, reviewed the statistical analyses, and drafted the article. Both authors conceived of the secondary analysis and revised the article. DBC performed primary data analyses. JMC takes responsibility for the paper as a whole. |
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| Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org/). The authors have stated that no such relationships exist. |
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| Trial registration number: NCT00621478 |
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| A 2TFFSRK survey is available with each research article published on the Web at www.annemergmed.com. |
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| A podcast for this article is available at www.annemergmed.com. |
Vol 69 - N° 1
P. 117-124 - janvier 2017 Retour au numéro
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