title: Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example.
abstract: The US National Toxicology Program (NTP) is assessed by a statistician. In the NTP-program groups of rodents are fed for a certain period of time with different doses of the substance that is being investigated. Then the animals are sacrificed and all organs are examined pathologically. Such an investigation facilitates many statistical tests. Technical Report TR 578 on Ginkgo biloba is used as an example. More than 4800 statistical tests are possible with the investigations performed. Due to a thought experiment we expect >240 false significant tests. In actuality, 209 significant pathological findings were reported. The readers of Toxicology Letters should carefully distinguish between confirmative and explorative statistics. A confirmative interpretation of a significant test rejects the null-hypothesis and delivers "statistical proof". It is only allowed if (i) a precise hypothesis was established independently from the data used for the test and (ii) the computed p-values are adjusted for multiple testing if more than one test was performed. Otherwise an explorative interpretation generates a hypothesis. We conclude that NTP-reports - including TR 578 on Ginkgo biloba - deliver explorative statistics, i.e. they generate hypotheses, but do not prove them.
authors.affiliation: University of Ulm, Epidemiology and Medical Biometry, Schwabstrasse 13, D 89070 Ulm, Baden-Württemberg, Germany. Electronic address: wilhelm.gaus@uni-ulm.de.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Gaus
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D005260:Female; D020441:Ginkgo biloba / Q000633:toxicity*; D008297:Male; D051379:Mice; D051381:Rats; D014116:Toxicology / Q000379:methods / Q000592:standards*; D014481:United States
keywords: Confirmative tests; False positive findings; Ginkgo biloba; Hypothesis generation; National Toxicology Program (NTP); Statistics