Elsevier

The Lancet

Volume 359, Issue 9306, 16 February 2002, Pages 614-618
The Lancet

Series
Allocation concealment in randomised trials: defending against deciphering

https://doi.org/10.1016/S0140-6736(02)07750-4Get rights and content

Summary

Proper randomisation rests on adequate allocation concealment. An allocation concealment process keeps clinicians and participants unaware of upcoming assignments. Without it, even properly developed random allocation sequences can be subverted. Within this concealment process, the crucial unbiased nature of randomised controlled trials collides with their most vexing implementation problems. Proper allocation concealment frequently frustrates clinical inclinations, which annoys those who do the trials. Randomised controlled trials are anathema to clinicians. Many involved with trials will be tempted to decipher assignments, which subverts randomisation. For some implementing a trial, deciphering the allocation scheme might frequently become too great an intellectual challenge to resist. Whether their motives indicate innocent or pernicious intents, such tampering undermines the validity of a trial. Indeed, inadequate allocation concealment leads to exaggerated estimates of treatment effect, on average, but with scope for bias in either direction. Trial investigators will be crafty in any potential efforts to decipher the allocation sequence, so trial designers must be just as clever in their design efforts to prevent deciphering. Investigators must effectively immunise trials against selection and confounding biases with proper allocation concealment. Furthermore, investigators should report baseline comparisons on important prognostic variables. Hypothesis tests of baseline characteristics, however, are superfluous and could be harmful if they lead investigators to suppress reporting any baseline imbalances.

Section snippets

Allocation concealment

Researchers have many misconceptions with respect to allocation concealment. Proper allocation concealment secures strict implementation of a random allocation sequence without foreknowledge of treatment assignments. Allocation concealment refers to the technique used to implement the sequence,4 not to generate it. Nevertheless, some people discuss allocation concealment with digressions into flipping coins or use of random number tables. Those digressions amount to methodological

Baseline comparisons

Although randomisation eliminates systematic bias, it does not necessarily produce perfectly balanced groups with respect to prognostic factors. Differences due to chance remain in the intervention groups—ie, chance maldistribution. Statistical tests, however, account for these chance differences. The process of randomisation underlies significance testing and is independent of prognostic factors, known and unknown.31

Nevertheless, researchers should present distributions of baseline

Conclusion

Proper randomisation remains the only way to avoid selection and confounding biases. The crucial unbiased nature of randomised controlled trials paradoxically coincides with their most vexing implementation problems. Randomised controlled trials antagonise human beings by frustrating their clinical inclinations. Thus, many involved with trials will be tempted to undermine randomisation, if afforded the opportunity to decipher assignments. To minimise the effect of this human tendency, trialists

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