Document Detail


The role of the Data and Safety Monitoring Board in a clinical trial: the CRISIS study.
MedLine Citation:
PMID:  23392377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Randomized clinical trials are commonly overseen by a Data and Safety Monitoring Board comprised of experts in medicine, ethics, and biostatistics. Data and Safety Monitoring Board responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. Data and Safety Monitoring Board decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate Data and Safety Monitoring Board oversight into the design, monitoring, and reporting of randomized trials.
DESIGN: Case study, narrative review.
METHODS: The Data and Safety Monitoring Board's role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described.
FINDINGS: The National Institutes of Health-appointed CRISIS Data and Safety Monitoring Board was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested Data and Safety Monitoring Board interim review before opening CRISIS to children below 1 yr of age. The first interim analysis found higher 28-day mortality in one treatment arm. The Data and Safety Monitoring Board maintained trial closure to younger children and requested a second interim data review 6 months later. At this second meeting, mortality was no longer of concern, whereas a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the Data and Safety Monitoring Board elected to examine conditional power and unmask treatment arm identities. On finding somewhat greater efficacy in the placebo arm, the Data and Safety Monitoring Board recommended stopping CRISIS due to futility.
CONCLUSIONS: The design and operating procedures of a multicenter randomized trial must consider a pivotal Data and Safety Monitoring Board role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The Data and Safety Monitoring Board must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups.
Authors:
Richard Holubkov; T Charles Casper; J Michael Dean; K J S Anand; Jerry Zimmerman; Kathleen L Meert; Christopher J L Newth; John Berger; Rick Harrison; Douglas F Willson; Carol Nicholson;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies     Volume:  14     ISSN:  1529-7535     ISO Abbreviation:  Pediatr Crit Care Med     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-07     Completed Date:  2014-03-03     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  100954653     Medline TA:  Pediatr Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  374-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Biomedical Research / standards
Child
Child, Preschool
Clinical Trials Data Monitoring Committees*
Critical Illness
Cross Infection / prevention & control
Early Termination of Clinical Trials*
Glutamine / therapeutic use
Humans
Immune Tolerance
Infant
Intensive Care Units, Pediatric
Medical Futility
Metoclopramide / therapeutic use
Professional Role*
Randomized Controlled Trials as Topic / standards*
Research Design / standards*
Selenium / therapeutic use
Sepsis / prevention & control
Stress, Physiological / immunology
Time Factors
Zinc / therapeutic use
Grant Support
ID/Acronym/Agency:
U01 HD049934/HD/NICHD NIH HHS; U01HD049934/HD/NICHD NIH HHS; U10 HD049945/HD/NICHD NIH HHS; U10 HD049981/HD/NICHD NIH HHS; U10 HD049983/HD/NICHD NIH HHS; U10 HD050009/HD/NICHD NIH HHS; U10 HD050012/HD/NICHD NIH HHS; U10 HD050096/HD/NICHD NIH HHS; U10HD049945/HD/NICHD NIH HHS; U10HD049981/HD/NICHD NIH HHS; U10HD049983/HD/NICHD NIH HHS; U10HD050012/HD/NICHD NIH HHS; U10HD050096/HD/NICHD NIH HHS; U10HD500009/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0RH81L854J/Glutamine; H6241UJ22B/Selenium; J41CSQ7QDS/Zinc; L4YEB44I46/Metoclopramide
Investigator
Investigator/Affiliation:
Jeffrey R Fineman / ; Jeffrey Blumer / ; Thomas P Green / ; David Glidden / ; Joseph Carcillo / ; Michael Bell / ; Alan Abraham / ; Annette Seelhorst / ; Jennifer Jones / ; Jeri Burr / ; Amy Donaldson / ; Angie Webster / ; Stephanie Bisping / ; Teresa Liu / ; Brandon Jorgenson / ; Rene Enriquez / ; Jeff Yearley / ; Angela Wratney / ; Jean Reardon / ; Sabrina Heidemann / ; Maureen Frey / ; Parthak Prodhan / ; Glenda Hefley / ; David Jardine / ; Ruth Barker / ; J Francisco Fajardo / ; Tamara Jenkins /
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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