title: Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus.
abstract: 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.
  
  
  
  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%).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Chamberlain
authors.affiliation: Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address: jchamber@cnmc.org.
authors.forename: James M
authors.initials: JM
authors.lastname: Chamberlain
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D003975:Diazepam / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008140:Lorazepam / Q000009:adverse effects / Q000627:therapeutic use*; D013226:Status Epilepticus / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D008140:Lorazepam; D003975:Diazepam