Risk of selection bias in randomised trials
Tóm tắt
Selection bias occurs when recruiters selectively enrol patients into the trial based on what the next treatment allocation is likely to be. This can occur even if appropriate allocation concealment is used if recruiters can guess the next treatment assignment with some degree of accuracy. This typically occurs in unblinded trials when restricted randomisation is implemented to force the number of patients in each arm or within each centre to be the same. Several methods to reduce the risk of selection bias have been suggested; however, it is unclear how often these techniques are used in practice. We performed a review of published trials which were not blinded to assess whether they utilised methods for reducing the risk of selection bias. We assessed the following techniques: (a) blinding of recruiters; (b) use of simple randomisation; (c) avoidance of stratification by site when restricted randomisation is used; (d) avoidance of permuted blocks if stratification by site is used; and (e) incorporation of prognostic covariates into the randomisation procedure when restricted randomisation is used. We included parallel group, individually randomised phase III trials published in four general medical journals (BMJ, Journal of the American Medical Association, The Lancet, and New England Journal of Medicine) in 2010. We identified 152 eligible trials. Most trials (98 %) provided no information on whether recruiters were blind to previous treatment allocations. Only 3 % of trials used simple randomisation; 63 % used some form of restricted randomisation, and 35 % did not state the method of randomisation. Overall, 44 % of trials were stratified by site of recruitment; 27 % were not, and 29 % did not report this information. Most trials that did stratify by site of recruitment used permuted blocks (58 %), and only 15 % reported using random block sizes. Many trials that used restricted randomisation also included prognostic covariates in the randomisation procedure (56 %). The risk of selection bias could not be ascertained for most trials due to poor reporting. Many trials which did provide details on the randomisation procedure were at risk of selection bias due to a poorly chosen randomisation methods. Techniques to reduce the risk of selection bias should be more widely implemented.
Tài liệu tham khảo
Berger VW. Quantifying the magnitude of baseline covariate imbalances resulting from selection bias in randomized clinical trials. Biom J. 2005;47(2):119–27. discussion 28–39.
Berger VW, Exner DV. Detecting selection bias in randomized clinical trials. Control Clin Trials. 1999;20(4):319–27.
Follmann D, Proschan M. The effect of estimation and biasing strategies on selection bias in clinical trials with permuted blocks. J Stat Plann Inference. 1994;39(1):1–17.
Kennes LN, Cramer E, Hilgers RD, Heussen N. The impact of selection bias on test decisions in randomized clinical trials. Stat Med. 2011;30(21):2573–81.
Odgaard-Jensen J, Vist GE, Timmer A, Kunz R, Akl EA, Schunemann H, et al. Randomisation to protect against selection bias in healthcare trials. Cochrane Database Syst Rev. 2011;4:MR000012.
Rosenberger WF, Lachin JM. Randomization in clinical trials. Chichester: Wiley; 2005.
Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273(5):408–12.
Schulz KF, Grimes DA. Unequal group sizes in randomised trials: guarding against guessing. Lancet. 2002;359(9310):966–70.
Tamm M, Cramer E, Kennes LN, Heussen N. Influence of selection bias on the test decision. A simulation study. Methods Inf Med. 2012;51(2):138–43.
Kunz R, Oxman AD. The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials. BMJ. 1998;317(7167):1185–90.
Nuesch E, Reichenbach S, Trelle S, Rutjes AW, Liewald K, Sterchi R, et al. The importance of allocation concealment and patient blinding in osteoarthritis trials: a meta-epidemiologic study. Arthritis Rheum. 2009;61(12):1633–41.
Brown S, Thorpe H, Hawkins K, Brown J. Minimization – reducing predictability for multi-centre trials whilst retaining balance within centre. Stat Med. 2005;24(24):3715–27.
Schulz KF. Subverting randomization in controlled trials. JAMA. 1995;274(18):1456–8.
Berger VW. Selection bias and covariate imbalances in randomized clinical trials. Chichester: Wiley; 2005.
Berger VW, Weinstein S. Ensuring the comparability of comparison groups: is randomization enough? Control Clin Trials. 2004;25(5):515–24.
Kahan BC, Morris TP. Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ. 2012;345:e5840.
Hewitt CE, Torgerson DJ. Is restricted randomisation necessary? BMJ. 2006;332(7556):1506–8.
Hewitt CE, Torgerson DJ, Berger VW. Potential for technical errors and subverted allocation can be reduced if certain guidelines are followed: examples from a web-based survey. J Clin Epidemiol. 2009;62(3):261–9.
Parzen M, Lipsitz S, Dear K. Does clustering affect the usual test statistics of no treatment effect in a randomized clinical trial? Biom J. 1998;40(4):385–402.
Reitsma A, Chu R, Thorpe J, McDonald S, Thabane L, Hutton E. Accounting for center in the Early External Cephalic Version trials: an empirical comparison of statistical methods to adjust for center in a multicenter trial with binary outcomes. Trials. 2014;15:377.
Kahan BC. Accounting for centre-effects in multicentre trials with a binary outcome – when, why, and how? BMC Med Res Methodol. 2014;14:20.
Kahan BC, Morris TP. Analysis of multicentre trials with continuous outcomes: when and how should we account for centre effects? Stat Med. 2013;32(7):1136–49.
Berger VW. Varying the block size does not conceal the allocation. J Critical Care. 2006;21(2):229. author reply −30.
Kahan BC. Rank minimization with a two-step analysis should not replace randomization in clinical trials. J Clin Epidemiol. 2012;65(7):808–9.
Wei LJ, Lachin JM. Properties of the urn randomization in clinical trials. Control Clin Trials. 1988;9(4):345–64.
Kahan BC, Jairath V, Dore CJ, Morris TP. The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies. Trials. 2014;15:139.
Kahan BC, Morris TP. Improper analysis of trials randomised using stratified blocks or minimisation. Stat Med. 2012;31(4):328–40.
Eldridge S, Kerry S, Torgerson DJ. Bias in identifying and recruiting participants in cluster randomised trials: what can be done? BMJ. 2009;339:b4006.
Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.