An adaptive, phase II, dose-finding clinical trial design to evaluate l-carnitine in the treatment of septic shock based on efficacy and predictive probability of subsequent phase III success

Critical Care Medicine

Volumn 41, Issue 7, 2013, Pages 1674-1678

  Lewis, Roger J ^a,b,c,d   Viele, Kert ^d,e   Broglio, Kristine ^d   Berry, Scott M ^d   Jones, Alan E ^f  

^a HARBOR UCLA MEDICAL CENTER   (United States)

^b LOS ANGELES BIOMEDICAL RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d BERRY CONSULTANTS   (United States)

^e UNIVERSITY OF KENTUCKY   (United States)

^f UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

adaptive randomization; carnitine; clinical trial; sepsis

Indexed keywords

CARNITINE;

ARTICLE; COMPUTER SIMULATION; DOSE RESPONSE; DRUG EFFICACY; EMERGENCY WARD; INTENSIVE CARE UNIT; MONTE CARLO METHOD; MORTALITY; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROBABILITY; RANDOMIZATION; SEPTIC SHOCK; SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE; STUDY DESIGN;

ADMINISTRATION, INTRAVENOUS; CARNITINE; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; HEALTH STATUS INDICATORS; HUMANS; MONTE CARLO METHOD; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN; SHOCK, SEPTIC; VITAMIN B COMPLEX;

EID: 84880571478     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0b013e318287f850     Document Type: Article

References (15)

1. Angus DC, Linde-Zwirble WT, Lidicker J, et al: Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303-1310
2. Kochanek K, Smith B: Deaths: Preliminary Data for 2002. National Vital Statistics Report. Centers for Disease Control and Prevention 2004; 52:1-32.
3. Centers for Disease Control and Prevention: Current trends increase in national hospital discharge survey rates for septicemia - United States, 1979-1987. Morbidity and Mortality Weekly Report 1991; 39: 31-34.
4. Gallo P, Chuang-Stein C, Dragalin V, et al; PhRMA Working Group: Adaptive designs in clinical drug development - An executive summary of the PhRMA Working Group. J Biopharm Stat 2006; 16:275-283; discussion 285
5. Dragalin V: Adaptive designs: Terminology and classification. Drug Information Journal 2006;40:425-435.
6. Food and Drug Administration: Guidance for industry: Adaptive design clinical trials for drugs and biologics. Available at: http://www. fda.gov/downloads/Drugs/.../Guidances/ucm201790.pdf. Accessed February 13, 2013
7. Berry SM, Spinelli W, Littman GS, et al: A Bayesian dose-finding trial with adaptive dose expansion to flexibly assess efficacy and safety of an investigational drug. Clin Trials 2010; 7:121-135
8. Berry DA, Muller P, Grieve AP et al: Adaptive Bayesian designs for dose-ranging drug trials. In: Case Studies in Bayesian Statistics V. First Edition. Gatsonis C, Kass R, Carlin B, et al (Eds). New York, Springer-Verlag; 2001, pp 99-181
9. Bornkamp B, Bretz F, Dmitrienko A, et al: Innovative approaches for designing and analyzing adaptive dose-ranging trials. J Biopharm Stat 2007; 17:965-995
10. Vincent JL, Moreno R, Takala J et al: The SOFA (Sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996;22:707-710.
11. West M, Harrison J: Bayesian Forecasting and Dynamic Models. Second Edition. New York, Springer-Verlag, 1999
12. Dellinger RP, Levy MM, Carlet JM, et al; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical- Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296-327
13. FACTS Development Team:FACTS: Fixed and Adaptive Clinical Trial Simulator, 2012. Austin, Texas, Berry Consultants and Tessella, Inc. Available at: http://www.smarterclinicaltrials.com/wp-content/uploads/FACTS-introduction. pdf. Accessed February 13, 2013
14. Angus DC, Mira JP, Vincent JL: Improving clinical trials in the critically ill. Crit Care Med 2010; 38:527-532
15. Vincent JL: Endpoints in sepsis trials: more than just 28-day mortality? Crit Care Med 2004; 32 (5 Suppl):S209-S213