@article{c63d7a2849694746a5295c007aba162c,
title = "Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: An example of a neonatal cooling trial",
abstract = "Background: Decisions to stop randomized trials are often based on traditional P value thresholds and are often unconvincing to clinicians. To familiarize clinical investigators with the application and advantages of Bayesian monitoring methods, we illustrate the steps of Bayesian interim analysis using a recent major trial that was stopped based on frequentist analysis of safety and futility. Methods: We conducted Bayesian reanalysis of a factorial trial in newborn infants with hypoxic-ischemic encephalopathy that was designed to investigate whether outcomes would be improved by deeper (32 °C) or longer cooling (120 h), as compared with those achieved by standard whole body cooling (33.5 °C for 72 h). Using prior trial data, we developed neutral and enthusiastic prior probabilities for the effect on predischarge mortality, defined stopping guidelines for a clinically meaningful effect, and derived posterior probabilities for predischarge mortality. Results: Bayesian relative risk estimates for predischarge mortality were closer to 1.0 than were frequentist estimates. Posterior probabilities suggested increased predischarge mortality (relative risk > 1.0) for the three intervention groups; two crossed the Bayesian futility threshold. Conclusions: Bayesian analysis incorporating previous trial results and different pre-existing opinions can help interpret accruing data and facilitate informed stopping decisions that are likely to be meaningful and convincing to clinicians, meta-analysts, and guideline developers. Trial registration: ClinicalTrials.gov NCT01192776. Registered on 31 August 2010.",
keywords = "Bayesian methods, Factorial trial, Hypothermia, Phase III trial, Stopping rules, Trial monitoring",
author = "{Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network} and Claudia Pedroza and Tyson, {Jon E.} and Abhik Das and Abbot Laptook and Bell, {Edward F.} and Seetha Shankaran and Martin Keszler and Hensman, {Angelita M.} and Elisa Vierira and Emilee Little and Birju Shah and Nicholas Guerina and Joseph Bliss and Hussnain Mirza and Ross Sommers and Walsh, {Michele C.} and Hibbs, {Anna Maria} and Newman, {Nancy S.} and Siner, {Bonnie S.} and Arlene Zadell and Truog, {William E.} and Pallotto, {Eugenia K.} and Kilbride, {Howard W.} and Cheri Gauldin and Anne Holmes and Kathy Johnson and Kurt Schibler and Kallapur, {Suhas G.} and Barbara Alexander and Fischer, {Estelle E.} and Gratton, {Teresa L.} and Cathy Grisby and Lenora Jackson and Jennifer Jennings and Kristin Kirker and Greg Muthig and Sandra Wuertz and {Michael Cotten}, C. and Goldberg, {Ronald N.} and Joanne Finkle and Fisher, {Kimberley A.} and Sandra Grimes and Laughon, {Matthew M.} and Bose, {Carl L.} and Janice Bernhardt and S{\'a}nchez, {Pablo J.} and Stoll, {Barbara J.} and Myra Wyckoff and Chalak, {Lina F.} and Brion, {Luc P.}",
note = "Funding Information: The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network{\textquoteright}s Optimizing Cooling Trial through cooperative agreements. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of the NICHD. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators, in addition to those listed as authors, participated in this study. NRN Steering Committee Chairs: Michael S. Caplan, MD, University of Chicago, Pritzker School of Medicine (2006–2011); Richard A. Polin, MD, Division of Neonatology, College of Physicians and Surgeons, Columbia University, (2011–present). Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (U10 HD27904): Martin Keszler, MD; Angelita M. Hensman, MS RNC-NIC; Elisa Vierira, RN BSN; Emilee Little, RN BSN; Birju Shah, MD; Nicholas Guerina, MD; Joseph Bliss, MD PhD; Hussnain Mirza, MD; Ross Sommers, MD. Case Western Reserve University, Rainbow Babies & Children{\textquoteright}s Hospital (U10 HD21364, M01 RR80): Michele C. Walsh, MD MS; Anna Maria Hibbs, MD; Nancy S. Newman, RN; Bonnie S. Siner, RN; Arlene Zadell, RN. Children{\textquoteright}s Mercy Hospital and University of Missouri Kansas City School of Medicine (U10 HD68284):William E. Truog, MD; Eugenia K. Pallotto, MD; Howard W. Kilbride, MD; Cheri Gauldin, RN BSN CCRC Anne Holmes, RN MSN MBA-HCM CCRC; Kathy Johnson, RN CCRC. Cincinnati Children{\textquoteright}s Hospital Medical Center, University of Cincinnati Medical Center, and Good Samaritan Hospital (U10 HD27853, UL1 TR77): Kurt Schibler, MD; Suhas G. Kallapur, MD; Barbara Alexander RN; Estelle E. Fischer MHSA MBA; Teresa L. Gratton, PA; Cathy Grisby, BSN CCRC; Lenora Jackson, CRC; Jennifer Jennings, RN BSN; Kristin Kirker, CRC; Greg Muthig, BA; Sandra Wuertz, RN BSN CLC. Duke University School of Medicine, University Hospital, University of North Carolina, and Duke Regional Hospital (U10 HD40492, UL1 RR24128): C. Michael Cotten, MD MHS; Ronald N. Goldberg, MD; Joanne Finkle, RN JD; Kimberley A. Fisher, PhD FNP-BC IBCLC; Sandra Grimes, RN BSN; Matthew M. Laughon, MD MPH; Carl L. Bose, MD; Janice Bernhardt, MS RN; Cindy Clark, RN. Emory University, Children{\textquoteright}s Healthcare of Atlanta, Grady Memorial Hospital, and Emory University Hospital Midtown (U10 HD27851, UL1 TR454): Barbara J. Stoll, MD; David P. Carlton, MD; Shannon E. G. Hamrick, MD; Ellen C. Hale, RN BS CCRC; Yvonne Loggins, RN. Eunice Kennedy Shriver National Institute of Child Health and Human Development: Rosemary D. Higgins, MD; Stephanie Wilson Archer, MA. Indiana University, Riley Hospital for Children at Indiana University Health and Methodist Hospital (U10 HD27856, UL1 TR6): Gregory M. Sokol, MD; Brenda B. Poindexter, MD MS; Leslie Dawn Wilson, BSN CCRC; Susan Gunn, NNP CCRC; Lucy Smiley, CCRC. Nationwide Children{\textquoteright}s Hospital and The Ohio State University (U10 HD68278): Edward G. Shepherd, MD; Leif D. Nelin, MD; Sudarshan R. Jadcherla, MD; Pablo J. S{\'a}nchez, MD; Patricia A. Luzader, RN; Christine A. Fortney, PhD RN; Nehal A. Parikh, MD; Bronte Clifford; Julie Gutentag, BSN; Marissa E. Jones, RN MBA; Jodi A. Ulloa, MSN APRN NNP-BC; L. Yossef, MD; Erin Ferns; Tiffany Sharp; Jon Wispe, MD; Elizabeth Bonachea, MD; Jonathan Slaughter, MD, MPH; Louis G. Chicoine, MD; Brandon Hart, MD; Krista Haines, MD; Ish Gulati, MD; Michael Hokenson, MD; Roopali Bapat, MD; Nahla Zaghoul, MD; Ruth Seabrook, MD; Thomas Bartman, MD; Jennifer Fuller, MS RNC; Sarah McGregor, BSN RNC; Marliese Dion Nist, BSN; Tara Wolfe, BSN; Elizabeth Ann Rodgers, BSN. RTI International (U10 HD36790): Dennis Wallace, PhD; Kristin M. Zaterka-Baxter, RN BSN CCRP; Margaret Crawford, BS CCRP; Barry Eggleston, MS; Jenna Gabrio, BS CCRP; Marie G. Gantz, PhD; Scott A. McDonald, BS; Jamie E. Newman, PhD MPH; Jeanette O{\textquoteright}Donnell Auman, BS; Carolyn M. Petrie Huitema MS CCRP. Stanford University and Lucile Packard Children{\textquoteright}s Hospital (U10 HD27880, M01 RR70, UL1 TR93): Krisa P. Van Meurs, MD; David K. Stevenson, MD; M. Bethany Ball, BS CCRC; Melinda S. Proud, RCP. University of Alabama at Birmingham Health System and Children{\textquoteright}s Hospital of Alabama (U10 HD34216, M01 RR32): Waldemar A. Carlo, MD; Namasivayam Ambalavanan, MD; Monica V. Collins, RN BSN MaEd; Shirley S. Cosby, RN BSN. University of California—Los Angeles, Mattel Children{\textquoteright}s Hospital, Santa Monica Hospital, Los Robles Hospital and Medical Center, and Olive View Medical Center (U10 HD68270): Uday Devaskar, MD; Meena Garg, MD; Teresa Chanlaw, MPH; Rachel Geller, RN BSN. University of Iowa and Mercy Medical Center (U10 HD53109, UL1 TR442): Dan L. Ellsbury, MD; Tarah T. Colaizy, MD MPH; Jane E. Brumbaugh, MD; Karen J. Johnson, RN BSN; Donia B. Campbell, RNC-NIC; Jacky R. Walker, RN; Jonathan M. Klein, MD; Jeffrey L. Segar, MD; John M. Dagle, MD PhD; Julie B. Lindower, MD MPH; Steven J. McElroy, MD; Glenda K. Rabe, MD; Robert D. Roghair, MD; Lauritz R. Meyer, MD; Cary R. Murphy, MD; Vipinchandra Bhavsar, MB BS. Publisher Copyright: {\textcopyright} 2016 Pedroza et al.",
year = "2016",
month = jul,
day = "22",
doi = "10.1186/s13063-016-1480-4",
language = "English (US)",
volume = "17",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central",
number = "1",
}