Cochrane Summaries

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Randomised controlled trials as a safeguard against biased estimates of treatment effects

Odgaard-Jensen J, Vist GE, Timmer A, Kunz R, Akl EA, Schünemann H, Briel M, Nordmann AJ, Pregno S, Oxman AD
Published Online: 
13 April 2011

Randomised controlled trials (RCTs) use the play of chance to allocate participants to comparison groups to prevent selection bias. Other means of treatment allocation are more prone to bias because decisions about which treatment to use can be influenced by the preferences of the physician or patient. This review compares random allocation (allocated to treatment using a random method) versus non-random allocation (allocated to treatment using a non-random method, such as alternation or external, uncontrollable factors, with no clinical judgement involved) and controlled trials with adequate versus inadequate/unclear concealment of allocation. Concealed treatment allocation is best described in general terms as the process used to prevent foreknowledge of group assignment in a controlled trial (such as the use of sequentially numbered opaque, sealed envelopes).

The results of randomised and non-randomised studies sometimes differed. Sometimes non-randomised studies yielded larger estimates of effect, and sometimes randomised trials yielded larger estimates of effect. On the other hand, not using concealed random allocation resulted in larger estimates of effect, but sometimes it resulted in similar estimates of effect (from harmful to beneficial or vice versa). It is a paradox that the unpredictability of random allocation is the best protection against the unpredictability of the extent to which non-randomised studies may be biased.

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