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Misuse of âDeduced Ratiosâ in the Estimation of Median Effective Doses

Abstract

Dragstedt and Lang1 wrote: “It seems to us obvious that a rabbit that died from 100 mgm. would have died of any higher dose and one that survived from 150 mgm. per kilogram would have survived from any lesser dose”, and tabulated their “mortality percentages” as deduced according to “this rationale” from experienced ratios at the various doses. Behrens2, with a similar idea, pointed out its limitations: “Unter der Voraussetzung, dass es sich um ein stetiges Kollektiv handelt, dass in den einzelnen Gruppen gleichviel Tiere angesetzt werden [or percentages in place of experienced effect ratios be used] und dass, die Gruppenabstände nach beiden Seiten [of the expected median dose] gleichgross sind (arithmetische Reihe [elsewhere he correctly advocates a geometric progression]), ist zu erwarten, dass die Gesamptzahl der bei niederen Dosen Gestorbenen gleich ist derjenigen der Überlebenden bei höheren Dosen vom erwarteten Wert aus betrachtet. Selbstverständlich müssen wir die gesamte Ausdehnung unseres Kollektives mit den Gruppen erfassen”. Behrens pointed out that the deduced ratio at a given dose is not the mortality ratio except at the value 1/2 ; that the ratios deal with areas on, rather than with ordinates of, the cumulative frequency curve.

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References

  1. J. Pharmacol. and Exper. Therap., 32, 215 (1927–28).

  2. Arch. f. exper. Path. u. Pharmakol, 140, 237 (1929).

  3. "Biological Standardization" (Oxford Univ. Press, London, 1937).

  4. Brit. J. Pharmacol., 1, 265 (1946).

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WINDER, C. Misuse of âDeduced Ratiosâ in the Estimation of Median Effective Doses. Nature 159, 883 (1947). https://doi.org/10.1038/159883a0

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