Spies, magicians, and Enid Blyton: how they can help improve clinical trials.

of the most important methods for preventing bias in modern clinical trials have a peculiar history. Masked assessment with placebo control seems to have appeared first during tests led by Benjamin Franklin in 1784 to investigate unorthodox claims of healing by 'animal magnetism' or 'mesmerism'. People were blindfolded and told that they were or were not receiving magnetism, when the reverse was true, and were given sham treatments of 'mesmerised water'. 1 Similar methods were used to test claims of 'higher' mesmeric phenomena such as thought-reading and precognition. 2 Two-hundred years later, the same methodology is still used to assess controversial claims in para-psychology, a subdiscipline of experimental psychology, that uses controlled laboratory techniques to examine claims of psychic abilities. Recent problems noted with the conduct of clinical trials suggest that although the two fields have diverged, para-psychology might now have something to offer in the design of orthodox medical research. In some clinical trials, patients have been allocated to interventions in such a way that clinicians could predict or control what the next eligible patient will receive, for example, by allocating patients in alternating order, or by drawing marbles out of a bag without appropriate precautions to prevent sampling until the favoured option is drawn. It is well established that treatment estimates are biased in such trials in comparison with trials in which allocations are concealed. 3 This is presumably because clinicians can assign their favoured treatment to particular patients by giving allocations out of sequence, or manipulating whether or when certain patients enter the trial, resulting in baseline risk factor imbalance. Trialists have attempted to deal with the problem by concealing allocations from clinicians until assignment. Although centralized randomization offers a relatively secure method of concealment, it still appears much more common for trialists to attempt to conceal allocations at the trial sites. 4 However, there are many anecdotes, such as those documented by Schulz, 5 of trial clinicians' attempts to breach such concealment. The methods described include holding envelopes containing allocations up to a light bulb, deciphering the allocation sequence by examining the appearance of the tablets in the sequentially numbered medication containers, and rifling through the principal investigator's filing cabinet. As in clinical trials, parapsychologists testing claims of extrasensory perception must also conceal material from people who would like to know its contents; a typical parapsychology experiment consists of concealing a random sequence of symbols from …