Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. E-mail: j.milton{at}bristol.ac.uk
Keywords Random allocation, randomized controlled trials/st[Standards]
Accepted 30 June 2003
Some 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 parapsychology, 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, parapsychology might now have something to offer in the design of orthodox medical research.
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Problems with allocation concealment |
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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 a participant who attempts to guess it. Particularly when testing participants such as Uri Geller who make strong claims about their psychic abilities, experimenters must defend against cheating so that any positive results from the study can be taken seriously.6 This is not a trivial problem in parapsychology. People have such strong opinions about psychic claims that some laboratories have been infiltrated by performance magicians posing as psychics to attempt to trick the experimenters and discredit their methods.7
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Spies, magicians, and envelopes |
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Parapsychology also draws on the expertise of the commercial security industry concerning concealment materials. Some companies manufacture special, tamper evident security envelopes to protect against industrial espionage or blackmail concerning sensitive information in transit. Many such envelopes are made out of plastics that deform or stain if solvents are used to attack the glue on the flap. Some envelopes can be opened surreptiously by freezing, which makes the glue brittle and cracked, enabling the flap to be lifted easily and the contents of the envelope to be examined. The contents can be replaced in the envelope, and the flap placed back down. As the envelope returns to room temperature the glue melts and reseals the envelope. Many security envelopes are therefore made from materials that show evidence of having been subjected to extremes of temperature.
In order to protect against another weakness of ordinary envelopestheir transparency if placed in front of an intense light source, as noted by some of Schulzs5 respondentssome commercial security envelopes are lined with black plastic. The use of plastic also protects against the use of special wetting agents, which can render transparent envelopes made out of quite thick paper. This technique has long been used by magicians to simulate psychic powers on stage. For example, a magician might ask a member of the audience to draw a picture on a sheet of paper without letting him or her see it, to seal the picture in an opaque envelope, and pass it to the magician, who then describes its contents without opening it. One of the many ways of doing this trick involves the magician unobtrusively applying a wetting agent to the envelope from a small vial through a tube to a flesh-coloured sponge attached to his or her finger. The surface becomes temporarily transparent, enabling the contents of the envelope to be read, and the wetting agent evaporates quickly, leaving little trace.9 A company in the US has recently exploited this principle to develop a spray that allows law enforcement agencies to inspect covertly suspect packages that might contain bombs, without opening them.10
Tamper-evident envelopes manufactured by specialist security firms are commercially available and could be used in clinical trials, though trialists should choose their materials carefully. Products change often, offer varying degrees of protection against interference and, even if described as being tamper evident, have not necessarily been subjected to testing. For example, some security envelopes appropriately use solvent-resistant glue on the flaps but use water-soluble glue on the seals. Trial investigators concerned about security can find a range of potentially useful and currently available materials by using search terms such as tamper evident on the internet, but should obtain sample materials and conduct their own tests on them before making a choice.
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Conclusions |
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KEY MESSAGES
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References |
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2 Kaptchuk TJ. Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med 1998;72:389433.[ISI][Medline]
3 Jüni P, Egger M. Allocation concealment in clinical trials [Letter]. JAMA 2002;288:240708.[ISI][Medline]
4 Milton J, Logan S, Gilbert R, Pindoria S, Higgins JPT. Investigation of baseline risk factor imbalance in randomised controlled trials that attempt allocation concealment at the trial site. Submitted for publication.
5 Schulz KF. Subverting randomization in controlled trials. JAMA 1995;274:145658.[Abstract]
6 Milton J, Wiseman R. Guidelines for Extrasensory Perception Research. Hatfield, UK: University of Hertfordshire Press, 1997.
7 Randi J. The Project Alpha experiment: Part 1. The first two years. Skeptical Inquirer 1983;7:2433.
8 Harrison JM. CIA Flaps and Seals Manual. Boulder, CO: Paladin Press, 1975.
9 Morris RL. What psi is not: the necessity for experiments. In Edge HL, Morris RL, Palmer J Rush JH (eds). Foundations of Parapsychology: Exploring the Boundaries of Human Capability. Boston: Routledge and Kegan Paul, 1986, pp. 70110.
10 Sample I. Letter of the law. New Scientist 16 December 2000.