Outcomes and statistical power in adult critical care randomized trials

American Journal of Respiratory and Critical Care Medicine

Volumn 189, Issue 12, 2014, Pages 1469-1478

  Harhay, Michael O ^a   Wagner, Jason ^a   Ratcliffe, Sarah J ^a   Bronheim, Rachel S ^b   Gopal, Anand ^a   Green, Sydney ^a   Cooney, Elizabeth ^a   Mikkelsen, Mark E ^a   Kerlin, Meeta Prasad ^a   Small, Dylan S ^c   Halpern, Scott D ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Critical care; Intensive care; Intensive care unit; Randomized clinical trial; Randomized controlled trial

Indexed keywords

ASSISTED VENTILATION; CRITICALLY ILL PATIENT; HUMAN; INFECTION; INTENSIVE CARE; INTENSIVE CARE UNIT; MORTALITY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STATISTICAL ANALYSIS;

CRITICAL CARE; INTENSIVE CARE; INTENSIVE CARE UNIT; RANDOMIZED CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL;

ADULT; CRITICAL CARE; DATA INTERPRETATION, STATISTICAL; HUMANS; INTENSIVE CARE UNITS; LOGISTIC MODELS; ODDS RATIO; OUTCOME ASSESSMENT (HEALTH CARE); POISSON DISTRIBUTION; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN;

EID: 84902687649     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201401-0056CP     Document Type: Review

References (53)

1. Sevransky JE, Checkley W, Martin GS. Critical care trial design and interpretation: a primer. Crit Care Med 2010;38:1882-1889.
2. Ospina-Tascon GA, Buchele GL, Vincent J-L. Multicenter, randomized, controlled trials evaluating mortality in intensive care: doomed to fail? Crit Care Med 2008;36:1311-1322. (Pubitemid 351482683)
3. Aberegg SK, Richards DR, O'Brien JM. Delta inflation: a bias in the design of randomized controlled trials in critical care medicine. Crit Care 2010;14:R77.
4. Angus DC, Mira JP, Vincent JL. Improving clinical trials in the critically ill. Crit Care Med 2010;38:527-532.
5. Annane D. Improving clinical trials in the critically ill: unique challenge-sepsis. Crit Care Med 2009;37:S117-S128.
6. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.
7. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008;371:126-134.
8. Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159-2168.
9. Dreyfuss D. Beyond randomized, controlled trials. Curr Opin Crit Care 2004;10:574-578. (Pubitemid 39620212)
10. Vincent J-L. We should abandon randomized controlled trials in the intensive care unit. Crit Care Med 2010;38:S534-S538.
11. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461. (Pubitemid 43200296)
12. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH, Elkjaer JM, Poulsen LM, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012;367:124-134.
13. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, et al.; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367:1901-1911.
14. van Meurs M, Ligtenberg JJ, Zijlstra JG. The randomized controlled trial needs critical care. Crit Care Med 2008;36:3118-3119, author reply 3119.
15. Rubenfeld GD, Abraham E. When is a negative phase II trial truly negative? Am J Respir Crit Care Med 2008;178:554-555.
16. Reade MC, Angus DC. The clinical research enterprise in critical care: what' s right, what's wrong, and what's ahead? Crit Care Med 2009;37:S1-S9.
17. McAuley DF, O'Kane C, Griffiths MJ. A stepwise approach to justify phase III randomized clinical trials and enhance the likelihood of a positive result. Crit Care Med 2010;38:S523-S527.
18. Marini JJ. Limitations of clinical trials in acute lung injury and acute respiratory distress syndrome. Curr Opin Crit Care 2006;12:25-31.
19. Harhay MO, Wagner J, Cooney E, Bronheim RS, Gopal A, Green S, Kerlin MP, Mikkelsen ME, Small D, Halpern SD. Epidemiology of published critical care randomized clinical trials, 2007-2012 [abstract]. Am J Respir Crit Care Med 2013;187:A1601.
20. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, Schulz KF. CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration. PLoS Med 2008;5:e20.
21. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12. (Pubitemid 26120810)
22. Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323:42-46. (Pubitemid 32682008)
23. Chiche JD, Angus DC. Testing protocols in the intensive care unit: complex trials of complex interventions for complex patients. JAMA 2008;299:693-695. (Pubitemid 351252731)
24. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-381.
25. Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. New York: Churchill Livingston; 1997.
26. Latronico N, Metelli M, Turin M, Piva S, Rasulo FA, Minelli C. Quality of reporting of randomized controlled trials published in Intensive Care Medicine from 2001 to 2010. Intensive Care Med 2013;39:1386-1395.
27. Deddens JA, Petersen MR. Approaches for estimating prevalence ratios. Occup Environ Med 2008;65:501-506. (Pubitemid 351969703)
28. Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752-761.
29. Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107- 1116.
30. Blackwood B, Clarke M, McAuley DF, McGuigan PJ, Marshall JC, Rose L. How outcomes are de fined in clinical trials of mechanically ventilated adults and children. Am J Respir Crit Care Med 2014;189:886-893.
31. Garland A, Connors AF. Physicians' influence over decisions to forego life support. J Palliat Med 2007;10:1298-1305.
32. Luce JM, Cook DJ, Martin TR, Angus DC, Boushey HA, Curtis JR, Heffner JE, Lanken PN, Levy MM, Polite PY, et al.; American Thoracic Society. The ethical conduct of clinical research involving critically ill patients in the United States and Canada: principles and recommendations. Am J Respir Crit Care Med 2004;170:1375-1384.
33. Halpern SD, Karlawish JH, Berlin JA. The continuing unethical conduct of underpowered clinical trials. JAMA 2002;288:358-362. (Pubitemid 34761615)
34. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*. Crit Care Med 2014;42:625-631.
35. Spragg RG, Bernard GR, Checkley W, Curtis JR, Gajic O, Guyatt G, Hall J, Israel E, Jain M, Needham DM, et al. Beyond mortality: future clinical research in acute lung injury. Am J Respir Crit Care Med 2010;181:1121-1127.
36. Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, et al. PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012;366:2055-2064.
37. Roozenbeek B, Lingsma HF, Steyerberg EW, Maas AI, Group IS. Underpowered trials in critical care medicine: how to deal with them? Crit Care 2010;14:423.
38. Roozenbeek B, Maas AI, Lingsma HF, Butcher I, Lu J, Marmarou A, McHugh GS, Weir J, Murray GD, Steyerberg EW, et al. Baseline characteristics and statistical power in randomized controlled trials: selection, prognostic targeting, or covariate adjustment? Crit Care Med 2009;37:2683-2690.
39. Hernandez AV, Steyerberg EW, Habbema JD. Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements. J Clin Epidemiol 2004;57:454-460. (Pubitemid 38758048)
40. Scales DC, Rubenfeld GD. Estimating sample size in critical care clinical trials. J Crit Care 2005;20:6-11. (Pubitemid 40602218)
41. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840-851.
42. Holloway RG, Quill TE. Mortality as a measure of quality: implications for palliative and end-of-life care. JAMA 2007;298:802-804. (Pubitemid 47263163)
43. Ferguson ND, Scales DC, Pinto R, Wilcox ME, Cook DJ, Guyatt GH, Schünemann HJ, Marshall JC, Herridge MS, Meade MO; Canadian Critical Care Trials Group. Integrating mortality and morbidity outcomes: using quality-adjusted life years in critical care trials. Am J Respir Crit Care Med 2013;187:256-261.
44. Naylor CD, Llewellyn-Thomas HA. Can there be a more patient-centred approach to determining clinically important effect sizes for randomized treatment trials? J Clin Epidemiol 1994;47:787-795. (Pubitemid 24236261)
45. Young P, Hodgson C, Dulhunty J, Saxena M, Bailey M, Bellomo R, Davies A, Finfer S, Kruger P, Lipman J, et al. End points for phase II trials in intensive care: recommendations from the Australian and New Zealand Clinical Trials Group consensus panel meeting. Crit Care Resusc 2012;14:211-215.
46. Kent DM, Hayward RA. Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. JAMA 2007;298:1209-1212. (Pubitemid 47403108)
47. Kent DM, Alsheikh-Ali A, Hayward RA. Competing risk and heterogeneity of treatment effect in clinical trials. Trials 2008;9:30.
48. Friede T, Kieser M. Sample size recalculation in internal pilot study designs: a review. Biom J 2006;48:537-555. (Pubitemid 44367892)
49. Lewis RJ, Viele K, Broglio K, Berry SM, Jones AE. 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. Crit Care Med 2013;41:1674-1678.
50. Scales DC. Research to inform the consent-to-research process. Intensive Care Med 2013;39:1484-1486.
51. Halpern SD. Financial incentives for research participation: empirical questions, available answers and the burden of further proof. Am J Med Sci 2011;342:290-293.
52. McHugh GS, Butcher I, Steyerberg EW, Marmarou A, Lu J, Lingsma HF, Weir J, Maas AI, Murray GD. A simulation study evaluating approaches to the analysis of ordinal outcome data in randomized controlled trials in traumatic brain injury: results from the IMPACT Project. Clin Trials 2010;7:44-57.
53. Rosenbaum PR. Comment: the place of death in the quality of life. Stat Sci 2006;21:313-316.