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Randomised trials, human nature, and reporting guidelines

Randomisation has two parts

The prevention of selection and of confounding biases in trials hinges largely on the adequacy of allocation to the intervention. Randomisation depends on two processes: generation of an unpredictable assignment sequence and concealment of that sequence until allocation occurs. Many medical researchers mistakenly regard the sequence-generating process as randomisation, and overlook the concealment.15, 16 But without adequate concealment, even random, unpredictable assignment sequences can be

Randomisation and the human spirit

Do investigators actually confess the delicate details of subverting the intended purpose of randomisation? Some do¹⁹ but with the sensitivities involved, documentation is rare. However, when doctors responded anonymously to queries during epidemiological workshops, more than half reported deciphering an allocation concealment scheme.¹⁵ This should not be interpreted as representing more than half of all the trials, however, because many participants had been involved in multiple trials.

Double-blinding and exclusions after randomisation

Double-blinding and avoidance of exclusions after trial entry are the most important other methods for reducing bias.2, 20, 21, 22 Blinding should not be confused with allocation concealment. Concealment seeks to prevent selection bias, protects the assignment sequence before and until allocation, and can always be successfully implemented.⁷ By contrast, blinding seeks to prevent ascertainment bias, protects the sequence after allocation, and cannot always be done.⁷ We found that trials that

Reporting

Breaches of randomisation are probably more frequent than suspected. Only 32% of reports published in some specialist journals⁷ and 49% in some premier general journals⁶ specified an adequate method for generating random assignments. In both groups of journals, only about a quarter of trials reported adequate allocation concealment.6, 7 Only 9% in the specialist journals and 15% in the general journals reported both an adequate method of generating random sequences and an adequate method of

Conclusions

Authors of RCT reports often write inadequate methodological details. Anecdotal reports indicate that aspects of properly conducted RCTs annoy human beings and that researchers sometimes subvert the intended aims of randomisation. Empiric evidence suggests that inadequate methodological reporting correlates with bias in estimation of treatment effects. Faulty reporting appears to portray faulty methods.14, 26

Obviously, to assess accurately the scientific merit of RCTs, readers deserve more