Covariate adjustment increased power in randomized controlled trials: An example in traumatic brain injury

Journal of Clinical Epidemiology

Volumn 65, Issue 5, 2012, Pages 474-481

  Turner, Elizabeth L ^a   Perel, Pablo ^a   Clayton, Tim ^a   Edwards, Phil ^a   Hernandez, Adrian V ^b   Roberts, Ian ^a   Shakur, Haleema ^a   Steyerberg, Ewout W ^c  

^a LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^b LERNER RESEARCH INSTITUTE   (United States)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Covariate adjustment; Power in clinical trials; Prognostic targeting; Relative sample size; Strict selection; Traumatic brain injury

Indexed keywords

CORTICOSTEROID; PLACEBO;

ADULT; ARTICLE; CONTROLLED STUDY; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MORTALITY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SAMPLE SIZE; TRAUMATIC BRAIN INJURY; TREATMENT DURATION; ANALYSIS OF VARIANCE; BRAIN INJURY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; GLASGOW COMA SCALE; INTENTION TO TREAT ANALYSIS; MIDDLE AGED; PHYSIOLOGY; PUPIL REFLEX; RISK; STATISTICAL ANALYSIS; STATISTICAL MODEL; STATISTICS; TREATMENT OUTCOME;

ADRENAL CORTEX HORMONES; ADULT; ANALYSIS OF VARIANCE; BRAIN INJURIES; DATA INTERPRETATION, STATISTICAL; GLASGOW COMA SCALE; HUMANS; INTENTION TO TREAT ANALYSIS; LOGISTIC MODELS; MIDDLE AGED; ODDS RATIO; PLACEBOS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REFLEX, PUPILLARY; SAMPLE SIZE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84861170204     PISSN: 08954356     EISSN: 18785921     Source Type: Journal    
DOI: 10.1016/j.jclinepi.2011.08.012     Document Type: Article

References (29)

1. Pocock S. Clinical trials: a practical approach. Chichester, UK: John Wiley and Sons; 1984.
2. 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.
3. Halpern SD, Karlawish JH, Berlin JA. The continuing unethical conduct of underpowered clinical trials. JAMA 2002;288:358-62.
4. Roozenbeek B, Lingsma HF, Steyerberg EW, Maas AIR; for the IMPACT Study Group. Underpowered trials in critical care medicine: how to deal with it? Crit Care 2010;14:423.
5. Dickinson K, Bunn F, Wentz R, Edwards P, Roberts I. Size and quality of randomized controlled trials in head injury: review of published studies. BMJ 2000;320:1308-11.
6. Maas AI, Steyerberg EW, Murray GD, Bullock R, Baethmann A, Marshall LF, et al. Why have recent trials of neuroprotective agents in head injuries failed to show convincing efficacy? A pragmatic analysis and theoretical considerations. Neurosurgery 1999;44:1286-98.
7. Brain Trauma Foundation. Joint Project of the Brain Trauma Foundation and American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS) and AANS/CNS Joint Section on Neurotrauma and Critical Care. Guidelines for the management of severe traumatic brain injury. 3rd ed. J Neurotrauma 2007;24(Suppl 1):S1-106.
8. Saatman KE, Duhaime AC, Bullock R, Maas AIR, Valadka A, Manley GT, Workshop Scientific Team And Advisory Panel Members. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008;25:719-38.
9. Machado SG, Murray GD, Teasdale GM. Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium. J Neurotrauma 1999;16:1131-8.
10. Weir CJ, Kaste M, Lees KR, Glycine Antagonist in Neuroprotection (GAIN) International Steering Committee and Investigators. Targeting neuroprotection clinical trials to ischemic stroke patients with potential to benefit from therapy. Stroke 2004;35:2111-6.
11. Altman DG Adjustment for covariate imbalance. In: Redmond C, Colton T, editors. Biostatistics in Clinical Trials. Chichester, UK: John Wiley & Sons; 2001:122-7.
12. Hernández AV, Steyerberg EW, Habema JDF. Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements. J Clin Epidemiol 2004;57:454-60.
13. Maas AI, Marmarou A, Murray GD, Teasdale SG, Steyerberg EW. Prognosis and clinical trial design in traumatic brain injury: the IMPACT study. J Neurotrauma 2007;24:232-8.
14. Marmarou A, Lu J, Butcher I, McHugh GS, Mushkadini NA, Murray GD, et al. IMPACT database of traumatic brain injury: design and description. J Neurotrauma 2007;24:232-8.
15. Roozenbeek B, Maas AIR, Lingsma HF, Butcher I, Lu J, Marmarou A, et al, Impact Study Group. Baseline characteristics and statistical power in randomized controlled trials: selection, prognostic targeting, or covariate adjustment? Crit Care Med 2009;37: 2683-90.
16. Hernandez AV, Steyerberg EW, Butcher I, Mushkadini N, Taylor GS, Murray GD, et al. Adjustment for strong predictors of outcome in traumatic brain injury trials: 25% reduction in sample size requirements in the IMPACT study. J Neurotrauma 2006;23:1295-303.
17. CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10,008 adults with clinically significant head injury (MRC CRASH trial): randomized placebo-controlled trial. Lancet 2004;364:1321-8.
18. Hauck WW, Anderson S, Marcus SM. Should we adjust for covari-ates in nonlinear regression analyses of randomized trials? Control Clin Trials 1998;19:249-56.
19. MRC Crash trial collaborators. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 2008;336:425-9.
20. Steyerberg EW, Bossuyt PMM, Lee KL. Clinical trials in acute myocardial infarction: should we adjust for baseline characteristics? Am Heart J 2000;139:745-51.
21. Davison AC, Hinkley D. Bootstrap Methods and their Application. 8th ed. Cambridge, UK: Cambridge Series in Statistical and Probabilistic Mathematics; 2006.
22. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: Development and international validation of prognostic scores based on admission characteristics. PLoS Med 2008;5(8):e165.
23. Austin PC, Manca A, Zwarenstein M, Juurlink DN, Stanbrook MB. A substantial and confusing variation exists in handling of baseline co-variates in randomized controlled trials: a review of trials published in leading medical journals. J Clin Epidemiol 2010;63:142-53.
24. Steyerberg EW, Eijkemans MJC. Heterogeneity bias: the difference between adjusted and unadjusted effects. Med Decis Making 2004;24:102-4.
25. Groenwold RH, Moons KG, Peelen LM, Knol MJ, Hoes AW. Reporting of treatment effects from randomized trials: a plea for multivari-able risk ratios. Contemp Clin Trials 2011;32:399-402.
26. Ford I, Norrie J. The role of covariates in estimating treatment effects and risk in long-term clinical trials. Stat Med 2002;21:2899-908.
27. Gail MH, Wieand S, Piantadosi S. Biased estimates of treatment effect in randomized experiments with nonlinear regressions and omitted covariates. Biometrika 1984;71:431-44.
28. Robinson LD, Jewell NP Some surprising results about covariate adjustment in logistic regression models. Int Stat Rev 1991;58: 227-40.
29. Zhang PG, Chen DG, Roe T Choice of baselines in clinical trials: a simulation study from statistical power perspective. Commun Statist Simulat Comput 2010;39:1305-17.