Epidemiological studies design

Deseriptive data are available from reports of humans exposed to 1,4-diehlorobenzene by inhalation (and possibly dermal contact). It is important to note that the case studies discussed in this section should be interpreted with caution since they reflect incidents in which individuals have reportedly been exposed to 1,4-dichlorobenzene, and they assume that there has been no other exposure to potentially toxic or infectious agents. There is usually little or no verification of these assumptions. Case studies in general are not scientifically equivalent to carefiilly designed epidemiological studies or to adequately controlled and monitored laboratory experiments. Thus, the case studies described below should be considered only as providing supplementary evidence that 1,4-dichlorobenzene may cause the reported effects. 

Kanitz et al. 1996 Tuthill et al. 1982). However, these studies had limitations in their designs that affect their interpretability. Well-designed epidemiological studies of populations orally exposed to chlorine dioxide in the drinking water could provide valuable information regarding safe levels. 

Evaluation of TVOC and SBS/health effects from carefully designed epidemiological studies. 

The committee concludes that there do not appear to be any serious flaws in the design and conduct of the Seychelles, Faroe Islands, and New Zealand studies that would preclude their use in a risk assessment. However, because there is a large body of scientific evidence showing adverse neurodevelopmental effects, including well-designed epidemiological studies, the committee concludes that an RfD should not be derived from a study, such as the Seychelles study, that did not observe any associations with MeHg. 

Despite the power of well-designed epidemiological studies to detect differences in disease frequencies in human populations, it is important to keep in mind that statistical significance is not the same as toxicological significance. To make a convincing connection between chemical exposure and disease, one or more additional kinds of evidence are needed. First, there must be evidence that the at-risk population was actually exposed to the chemical of concern. Second, the chemical should obey the dose-effect relationship, i.e., the incidence of the toxic effect of concern should, if possible, be shown to increase as a function of exposure, either in the... 

The United States Pharmacopeial Convention, Inc. (USP) in 2000 issued the USP criteria for levels of evidence for botanical articles [117]. While issued for botanicals, the criteria have application to all therapeutic agents. The USP criteria rank evidence from I to IV, with Level I being the strongest. Within Level I, the randomized controlled clinical trial is ranked highest, followed by meta-analysis and epidemiological studies. Level II consists of the same designs, but with methodological flaws. Level III includes inconclusive studies, and Level IV is anecdotal evidence. 

The question whether lutein and zeaxanthin can contribute to lowering the risk for AMD cannot be answered unequivocally by epidemiological studies. Only randomized controlled trials (RCTs) during the course of which xanthophylls are supplemented in a double-blind, placebo-controlled, and randomized manner, and in which results are evaluated according to clear predefined efficacy criteria (Seddon and Hennekens 1994) have the potential to provide definitive answers. The specific long-term time-course and intricate nature of AMD make the design of such studies difficult, however. 

Category IA Strongly recommended and supported by well-designed experimental, clinical, or epidemiologic studies. 

Studies in Phase IV are all studies (other than routine surveillance) performed after drug approval and related to the approved indication. They are studies that were not considered necessary for approval but are often important for optimizing the drug s use. They may be of any type but should have valid scientific objectives. Commonly conducted studies include additional drug-drug interaction, dose-response or safety studies, and studies designed to support use under the approved indication, for instance, mortality/morbidity studies, epidemiological studies. 

Simon R, Radmacher MD, Dobbin K. 2002. Design of studies using microarrays. Genetic Epidemiology 23 21. 

Studies of the reactions of population groups to photochemical smog are reviewed in Chapter 10. Such studies played a major role in the establishment of the current federal standards. Included were eye irritation studies, effects on asthmatics, and the responses of groups of high-school athletes. Uncertainties in the design of these experiments and interpretation of the data make further epidemiologic studies essential. 

Other epidemiologic studies should be designed to seek analogues in human populations of effects observed in toxicologic and clinical studies. 

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