USE OF DUAL CONTROL-GROUPS TO ESTIMATE FALSE POSITIVE RATES IN LABORATORY-ANIMAL CARCINOGENICITY STUDIES
USE OF DUAL CONTROL-GROUPS TO ESTIMATE FALSE POSITIVE RATES IN LABORATORY-ANIMAL CARCINOGENICITY STUDIES
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DOI：
10.1016/0272-0590(86)90107-7
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发表时间：
1986-11-01
期刊：
影响因子：
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通讯作者：
ODONNELL, MW
中科院分区：
文献类型：
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作者：
HASEMAN, JK;WINBUSH, JS;ODONNELL, MW
检查了 18 项最近完成的使用雄性和雌性小鼠和大鼠的致癌性研究的肿瘤发生率数据，以确定这些实验中使用的两个同时对照组之间显着性 (p < 0.05) 成对差异的频率是否超出了机会预期。尽管在某些肿瘤中观察到显着的研究间变异性，但没有发现两个同时对照组之间存在二项式研究内变异性的证据。观察到的显着（p < 0.05）配对对照差异的总数实际上与通常二项式模型假设的预期相同；相应的总体观察到的假阳性率 (44%) 和预期的假阳性率 (47-50%) 基本相同。虽然人们不应该过度概括这些发现的含义，但这些结果应该减轻人们的担忧，即研究内二项式变异性导致的假阳性率升高可能会对长期实验动物致癌性研究的解释产生不利影响。另一方面，这些结果重申了其他研究人员的结论，即（特别是对于常见肿瘤）在肿瘤发病率增加被认为具有生物学意义之前，需要比孤立的 p < 0.05 效应更严格的证据；否则，该研究的假阳性率可能会高得令人无法接受。
Tumor incidence data from 18 recently completed carcinogenicity studies utilizing male and female mice and rats were examined to determine if the frequency of significant (p < 0.05) pairwise differences between the two concurrent control groups employed in these experiments exceeded chance expectation. Although marked study-to-study variability was observed for some tumors, no evidence of extra-binomial within-study variability between the two concurrent control groups was found. The total number of observed significant (p < 0.05) paired-control differences was virtually identical to what would be expected from the usual binomial model assumptions; the corresponding overall observed (44%) and expected (47-50%) false positive rates were essentially the same. While one should not overgeneralize the implications of these findings, these results should lessen concerns that elevated false positive rates resulting from extra-binomial within-study variability might be adversely affecting the interpretation of long-term laboratory animal carcinogenicity studies. On the other hand, these results reaffirm the conclusions of other investigators that (particularly for commonly occurring tumors) more stringent evidence than an isolated p < 0.05 effect should be required before an increased tumor incidence is regarded as biologically significant; otherwise, the study may have an unacceptably high false positive rate.