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Clinical trial design: the neglected problem of asymmetrical transfer in cross-over trials

Published online by Cambridge University Press:  09 July 2009

Keith Millar
Keith Millar*
Affiliation:
Behavioural Science Section, Department of Psychiatry, University Hospital and Medical School, Nottingham
*
1Address for correspondence: Dr K. Millar, Behavioural Science Section, Department of Psychiatry, University Hospital and Medical School, Clifton Boulevard, Nottingham NG7 2UH.
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Synopsis

The paper illustrates drawbacks of the popular cross-over design in clinical trials in psychiatry where treatment effects become distorted by, and confounded with, the effects of their order of administration. It is argued that research workers should analyse data from cross-over trials for asymmetries due to order of treatment and seriously doubt the reliability of data if such effects are found. The problem is avoided by the use of separate-groups designs.

Type
Research Article
Information
Psychological Medicine , Volume 13 , Issue 4 , November 1983 , pp. 867 - 873
Copyright
Copyright © Cambridge University Press 1983

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References

Armitage, P. & Hills, M. (1982). The two-period crossover trial. The Statistician 31, 119–131.CrossRefGoogle Scholar
Barker, N., Hews, R. J., Huitson, A. & Poloniecki, J. (1982). The two-period crossover trial. Bulletin in Applied Statistics 9, 67–116.CrossRefGoogle Scholar
Brown, B. W. (1980). The crossover experiment for clinical trials. Biometrics 36, 69–80.CrossRefGoogle ScholarPubMed
File, S. E. & Lister, R. G. (1982). Do lorazepam-induced deficits in learning result from impaired rehearsal, reduced motivation or increased sedation? British Journal of Clinical Pharmacology 14, 545–550.CrossRefGoogle ScholarPubMed
Friedman, L. M., Furberg, C. D. & DeMets, D. L. (1981). Fundamentals of Clinical Trials. John Wright: Bristol.Google Scholar
Gart, J. J. (1969). An exact test for comparing matched proportions in crossover designs. Biometrika 56, 75–80.CrossRefGoogle Scholar
Gore, S. M. (1981). Assessing clinical trials – rash adventures. British Medical Journal ii, 426–428.CrossRefGoogle Scholar
Grimm, V. & Hershkowitz, M. (1981). The effect of chronic diazepam treatment on discrimination performance and 3H-flunitrazepam binding in the brains of shocked and non-shocked rats. Psychopharmacology 74, 132–136.CrossRefGoogle Scholar
Heel, R. C., Brogden, R. M., Speight, T. M. & Avery, G. S. (1981). Temazepam: a review of its pharmacological properties and therapeutic efficiency as an hypnotic. Drugs 21, 321–340.CrossRefGoogle Scholar
Hills, M. & Armitage, P. (1979). The two-period cross-over clinical trial. British Journal of Clinical Pharmacology 8, 7–20.CrossRefGoogle ScholarPubMed
Hindmarch, I. (1980). Psychomotor function and psychoactive drugs. British Journal of Clinical Pharmacology 10, 189–209.CrossRefGoogle ScholarPubMed
Johnson, A. L. (1983). Clinical trials in psychiatry. Psychological Medicine 13, 1–8.CrossRefGoogle ScholarPubMed
Johnson, F. N. & Johnson, S. (1977). Clinical Trials. Blackwell: Oxford.Google Scholar
Jones, D. M., Lewis, M. J. & spriggs, T. L. B. (1978). The effects of low doses of diazepam on human performance in groupadministered tasks. British Journal of Clinical Pharmacology 6, 333–337.CrossRefGoogle Scholar
Kershner, R. P. & Federer, W. T. (1981). Two-treatment crossover designs for estimating a variety of effects. Journal of the American Statistical Association 76, 612–619.CrossRefGoogle Scholar
Ley, P., Jain, V. K., Swinson, R. P., Eaves, D., Bradshaw, P. W., Kincey, J. A., Crowder, R. & Abbiss, S. (1972). A state-dependent learning effect produced by amylobarbitone sodium. British Journal of Psychiatry 120, 511–515.CrossRefGoogle ScholarPubMed
Liljequist, R. & Mattila, M. J. (1979). Acute effects of temazepam and nitrazepam on psychomotor skills and memory. Acta Pharmacologica et Toxicologica 44, 364–369.CrossRefGoogle Scholar
Millar, K. (1983). Asymmetrical transfer: an inherent weakness of repeated-measure drug experiments. British Journal of Psychiatry 143, 480–486.CrossRefGoogle ScholarPubMed
Millar, K. & Standen, P. J. (1982). Differences in performance impairment due to brompheniramine maleate as a function of the sustained release system. British Journal of Clinical Pharmacology 14, 49–55.CrossRefGoogle ScholarPubMed
Millar, K. & Wilkinson, R. T. (1981). The effects upon vigilance and reaction speed of the addition of ephedrine hydrochloride to chlorpheniramine maleate. European Journal of Clinical Pharmacology 20, 351–357.CrossRefGoogle ScholarPubMed
Poulton, E. C. (1973). Unwanted range effects from using within- subject experimental designs. Psychological Bulletin 80, 113–121.CrossRefGoogle Scholar
Poulton, E. C. (1975). Range effects in experiments on people. American Journal of Psychology 88, 3–32.CrossRefGoogle Scholar
Poulton, E. C. (1982). Influential companions: effects of one strategy on another in the within-subjects designs of cognitive psychology. Psychological Bulletin 91, 673–690.CrossRefGoogle Scholar
Poulton, E. C. & Edwards, R. S. (1974). Interactions, range effects, and comparisons between tasks in experiments measuring performance with pairs of stresses: mild heat and 1 mg of L-hyoscine hydrobromide. Aviation, Space and Environmental Medicine 45, 735–741.Google ScholarPubMed
Poulton, E. C. & Edwards, R. S. (1979). Asymmetric transfer in within-subjects experiments on stress interactions. Ergonomics 22, 945–961.CrossRefGoogle ScholarPubMed
Poulton, E. C. & Freeman, P. R. (1966). Unwanted asymmetrical transfer effects with balanced experimental designs. Psychological Bulletin 66, 1–8.CrossRefGoogle ScholarPubMed
Wilkinson, R. T. (1969). Some factors influencing the effect of environmental stressors on performance. Psychological Bulletin 72, 260–272.CrossRefGoogle ScholarPubMed
Winer, B. J. (1970). Statistical Principles in Experimental Design. McGraw-Hill: London.Google Scholar