Allocation Concealment

Allocation Concealment is a technique used to prevent selection bias in Randomised Controlled Trials (RCT’s) by concealing the allocation sequence from those assigning participants to the intervention groups, until the moment of assignment. Thus it prevents researchers from (unconsciously or otherwise) influencing which participants are assigned to the intervention or control group.

The UK Medical Research Council’s famous trial of streptomycin treatment for pulmonary tuberculosis is regarded as the first properly conducted randomised clinical trial. The two steps described for allocation concealment were

  1. …random sampling numbers [were] drawn up for each sex at each centre by Professor Bradford Hill. (Allocation sequence generation)
  2. … the details of the series … were contained in a set of sealed envelopes, each bearing on the outside only the name of the hospital and a number. (Allocation sequence concealment)

Thus, Randomisation in practice depends on two important aspects:

  • Adequate generation of the allocation sequence
  • Concealment of the allocation sequence until assignment occurs

Proper allocation concealment prevents knowledge of future assignments. On average, trials with inadequate allocation concealment exaggerated estimated treatment effects, i.e. odds ratios, by 41 %. Inadequate allocation concealment is a leading cause of bias in clinical trials.

Generation of allocation sequences

  • Adequate if random numbers generated by a computer-generated number, table of random numbers, drawing of lots or envelopes, tossing a coin, shuffling cards, throwing dice etc.
  • Inadequate if sequence could be related to prognosis or introduces selection bias: case record number, date of birth, day, month or year of admission.

Concealment of allocation sequences

  • Adequate if central randomisation (site remote from trials location), sequentially numbered, sealed/opaque envelopes, coded drug containers of identical appearance prepared by an independent pharmacy.
  • Inadequate if alternation, unsealed or non-opaque envelopes.

Allocation concealment is often confused with blinding. Allocation concealment attempts to prevent selection and confounding biases and can always be implemented while blinding reduces measurement bias.

Besides the above, it is also important to know who generated the allocation sequence, who enrolled participants and who assigned them to trial groups, as at each of these stages bias could be introduced.

 

References

Allocation Concealment in RCT's

Schulz, K. F. (2000). Assessing allocation concealment and blinding in randomised controlled trials: why bother?. Evidence Based Mental Health, 3(1), 4-5.

Allocation Concealment in the First RCT

Paludan-Müller, A., Laursen, D. R. T., & Hróbjartsson, A. (2016). Mechanisms and direction of allocation bias in randomised clinical trials. BMC Medical Research Methodology, 16(1), 133.