American Journal of Epidemiology Advance Access originally published online on January 27, 2006
American Journal of Epidemiology 2006 163(6):493-501; doi:10.1093/aje/kwj069
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Review |
Bias in Clinical Intervention Research
From the Copenhagen Trial Unit, Center for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Copenhagen, Denmark
Correspondence to Lise Lotte Gluud, Department 7102, Copenhagen Trial Unit, Cochrane Hepato-Biliary Group, Rigshospitalet, DK-2100 Copenhagen, Denmark (e-mail: lgluud{at}ctu.rh.dk).
Research on bias in clinical trials may help identify some of the reasons why investigators sometimes reach the wrong conclusions about intervention effects. Several quality components for the assessment of bias control have been suggested, but although they seem intrinsically valid, empirical evidence is needed to evaluate their effects on the extent and direction of bias. This narrative review summarizes the findings of methodological studies on the influence of bias in clinical trials. A number of methodological studies suggest that lack of adequate randomization in published trial reports may be associated with more positive estimates of intervention effects. The influence of double-blinding and follow-up is less clear. Several studies have found a significant association between funding sources and pro-industry conclusions. However, the methodological studies also show that bias is difficult to detect and appraise. The extent of bias in individual trials is unpredictable. A-priori exclusion of trials with certain characteristics is not recommended. Appraising bias control in individual trials is necessary to avoid making incorrect conclusions about intervention effects.
bias (epidemiology); evidence-based medicine; meta-analysis; publication bias; selection bias
Abbreviations: CI, confidence interval; ROR, relative odds ratio; SSRIs, selective serotonin reuptake inhibitors
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Hartling, M. Ospina, Y. Liang, D. M Dryden, N. Hooton, J. Krebs Seida, and T. P Klassen Risk of bias versus quality assessment of randomised controlled trials: cross sectional study BMJ, October 19, 2009; 339(oct19_1): b4012 - b4012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Liberati, D. G. Altman, J. Tetzlaff, C. Mulrow, P. C. Gotzsche, J. P.A. Ioannidis, M. Clarke, P. J. Devereaux, J. Kleijnen, and D. Moher The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration Ann Intern Med, August 18, 2009; 151(4): W-65 - W-94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boysen, L.-H. Krarup, X. Zeng, A. Oskedra, J. Korv, G. Andersen, C. Gluud, A. Pedersen, M. Lindahl, L. Hansen, et al. ExStroke Pilot Trial of the effect of repeated instructions to improve physical activity after ischaemic stroke: a multinational randomised controlled clinical trial BMJ, July 22, 2009; 339(jul20_3): b2810 - b2810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Liberati, D. G Altman, J. Tetzlaff, C. Mulrow, P. C Gotzsche, J. P A Ioannidis, M. Clarke, P J Devereaux, J. Kleijnen, and D. Moher The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration BMJ, July 21, 2009; 339(jul21_1): b2700 - b2700. [Abstract] [Full Text]
|
|
|
|
|
|
J. Little, J. P.T. Higgins, J. P.A. Ioannidis, D. Moher, F. Gagnon, E. von Elm, M. J. Khoury, B. Cohen, G. Davey-Smith, J. Grimshaw, et al. STrengthening the REporting of Genetic Association Studies (STREGA): An Extension of the STROBE Statement Ann Intern Med, February 3, 2009; 150(3): 206 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zwarenstein, S. Treweek, J. J Gagnier, D. G Altman, S. Tunis, B. Haynes, A. D Oxman, D. Moher, and for the CONSORT and Pragmatic Trials in Healthcare Improving the reporting of pragmatic trials: an extension of the CONSORT statement BMJ, December 30, 2008; 337(nov11_2): a2390 - a2390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Salanti, J. P. Higgins, A. Ades, and J. P. Ioannidis Evaluation of networks of randomized trials Statistical Methods in Medical Research, June 1, 2008; 17(3): 279 - 301. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Abrahamyan, S. R. Johnson, J. Beyene, P. S. Shah, and B. M. Feldman Quality of randomized clinical trials in juvenile idiopathic arthritis Rheumatology, May 1, 2008; 47(5): 640 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Feagan, W. J. Sandborn, U. Mittmann, S. Bar-Meir, G. D'Haens, M. Bradette, A. Cohen, C. Dallaire, T. P. Ponich, J. W. D. McDonald, et al. Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease: The EPIC Randomized Controlled Trials JAMA, April 9, 2008; 299(14): 1690 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wood, M. Egger, L. L. Gluud, K. F Schulz, P. Juni, D. G Altman, C. Gluud, R. M Martin, A. J G Wood, and J. A C Sterne Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study BMJ, March 15, 2008; 336(7644): 601 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Boutron, D. Moher, D. G. Altman, K. F. Schulz, P. Ravaud, and for the CONSORT Group Extending the CONSORT Statement to Randomized Trials of Nonpharmacologic Treatment: Explanation and Elaboration Ann Intern Med, February 19, 2008; 148(4): 295 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marmor, I. Belitskaya-Levy, and A. A. Arslan RE: LETTER TO THE EDITOR ON "BIAS IN CLINICAL INTERVENTION RESEARCH" Am. J. Epidemiol., February 15, 2008; 167(4): 500 - 501. [Full Text] [PDF]
|
|
|
|
|
|
A. Afshari, J. Wetterslev, J. Brok, and A. Moller Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis BMJ, December 15, 2007; 335(7632): 1248 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chan MD MPH A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study Can. Med. Assoc. J., December 4, 2007; 177(12): 1539 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Gluud, G. Bjelakovic, D. Nikolova, R. G. Simonetti, and C. Gluud Antioxidant Supplements and Mortality Reply JAMA, July 25, 2007; 298(4): 402 - 403. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Boutron, P. Ravaud, and R. Nizard The design and assessment of prospective randomised, controlled trials in orthopaedic surgery J Bone Joint Surg Br, July 1, 2007; 89-B(7): 858 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hemila RE: "BIAS IN CLINICAL INTERVENTION RESEARCH" Am. J. Epidemiol., May 15, 2007; 165(10): 1219 - 1219. [Full Text] [PDF]
|
|
|
|
|
|
L. L. Gluud THE AUTHOR REPLIES Am. J. Epidemiol., May 15, 2007; 165(10): 1219 - 1220. [Full Text] [PDF]
|
|
|
|
|
|
G. Bjelakovic, D. Nikolova, L. L. Gluud, R. G. Simonetti, and C. Gluud Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis JAMA, February 28, 2007; 297(8): 842 - 857. [Abstract] [Full Text] [PDF]
|
|