Meyer-Baron Monika, Schäper Michael, van Thriel Christoph
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Neurotoxicology and Chemosensation (Working Group), Dortmund, Germany.
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Neurotoxicology and Chemosensation (Working Group), Dortmund, Germany.
Neurotoxicology. 2014 Dec;45:238-46. doi: 10.1016/j.neuro.2014.03.002. Epub 2014 Mar 19.
Neurobehavioral studies do not always gain the impact they should have, neither in the scientific nor in the regulatory field of neurotoxicology. Among others, shortcomings and inconsistencies across epidemiological studies may contribute to this situation. Examples were compiled to increase awareness of obstacles for conclusions. Meta-analyses were exploited since they sometimes allow the detection of deficits that are not obvious from individual studies. Exposure assessment, performance measures, and confounding were scrutinized among 98 primary studies included in meta-analyses on mercury, solvents, manganese and pesticides. Inconsistent and hardly comparable markers of exposure were found; figures, units or sampling periods were not always provided. The contribution of test materials to differences in test outcomes across studies could sometimes not be evaluated due to the insufficient description of the employed tests. Hypotheses for the selection of performance variables often remained undisclosed. Matching procedures prevailed with respect to the confounder age; the comparability of groups with respect to intelligence and gender remained more elusive. 8% and 16% of the studies did not even mention confounding from intelligence and gender, respectively. Only one third of the studies provided adjusted means for group comparisons; the proportion was slightly larger for studies published 2000-2010. While 50% of the studies considered confounders for their dose-response assessment, only 29% reported results for the total of test variables. The outlined deficits impede, among others, the assessment of exposure-effect relationships and confounding across studies; thereby they limit the use of the studies for toxicological risk assessment and future prevention. Some shortcomings also impede a deeper insight into the mechanisms of toxicity: tests like the Digit Symbol show that something is affected, but not what is affected. Thorough description of measures employed is among the first consequences from the data. The consideration of mechanistic insights from research on animals and neurobiology may further help to increase the significance of epidemiological studies.
神经行为学研究在神经毒理学的科学领域和监管领域，并不总能获得应有的影响力。流行病学研究中存在的缺点和不一致性等因素可能导致了这种情况。现汇编了一些例子，以提高人们对得出结论时所面临障碍的认识。之所以利用荟萃分析，是因为它们有时能发现个别研究中不明显的缺陷。在关于汞、溶剂、锰和农药的荟萃分析所纳入的98项主要研究中，对暴露评估、性能指标和混杂因素进行了审查。发现暴露指标不一致且难以比较；有时未提供数值、单位或采样周期。由于对所采用测试的描述不足，有时无法评估测试材料对不同研究中测试结果差异的影响。选择性能变量的假设往往未公开。在混杂因素年龄方面，匹配程序很常见；而在智力和性别方面，各组之间的可比性则更难确定。分别有8%和16%的研究甚至未提及智力和性别方面的混杂因素。只有三分之一的研究提供了用于组间比较的调整均值；2000 - 2010年发表的研究这一比例略高。虽然50%的研究在剂量反应评估中考虑了混杂因素，但只有29%报告了所有测试变量的结果。上述缺陷尤其妨碍了对不同研究中暴露 - 效应关系和混杂因素的评估；从而限制了这些研究在毒理学风险评估和未来预防中的应用。一些缺点还妨碍了对毒性机制的深入了解：像数字符号测试这样的测试表明某些方面受到了影响，但不清楚具体受影响的是什么。对所采用测量方法的全面描述是从这些数据得出的首要结果之一。考虑来自动物研究和神经生物学研究的机制性见解，可能进一步有助于提高流行病学研究的重要性。
