Meta-analyses offer a rigorous and transparent systematic framework for synthesizing data that can be used for a wide range of research areas, study designs, and data types. Both the outcome of meta-analyses and the meta-analysis process itself can yield useful insights for answering scientific questions and making policy decisions. Development of the National Ambient Air Quality Standards illustrates many potential applications of meta-analysis. These applications demonstrate the strengths and limitations of meta-analysis, issues that arise in various data realms, how meta-analysis design choices can influence interpretation of results, and how meta-analysis can be used to address bias and heterogeneity. Reviewing available data from a meta-analysis perspective can provide a useful framework and impetus for identifying and refining strategies for future research. Moreover, increased pervasiveness of a meta-analysis mindset—focusing on how the pieces of the research puzzle fit together—would benefit scientific research and data syntheses regardless of whether or not a quantitative meta-analysis is undertaken. While an individual meta-analysis can only synthesize studies addressing the same research question, the results of separate meta-analyses can be combined to address a question encompassing multiple data types. This observation applies to any scientific or policy area where information from a variety of disciplines must be considered to address a broader research question.
The animal testing protocols used today to evaluate the carcinogenicity of chemicals are very different from those used in the earlier part of the 20th century. To explore how cancer bioassays have changed over time, we surveyed the literature discussing test design and interpretation from the 1930s to the present. We also analyzed compendia of bioassays published by the US Public Health Service (US PHS) from 1938 to 1978, and evaluated the data to understand the evolution of testing methodology (e.g., animals used, test duration) and the types of chemicals being studied. The cancer bioassay evolved in several stages. At the beginning of the 20th century, animal bioassays were primarily used to re-create known human diseases, whereas in the 1940s to 1960s, animal bioassays were largely used to evaluate the safety of chemicals in foods, drugs, and cosmetics. Beginning in the late 1960s and 1970s, chemicals primarily associated with occupational or environmental exposures were also evaluated. Testing strategies now emphasize a suite of tests including multiple in vitro tests and both short-term and long-term animal tests. The objectives of testing are broader, too, with test goals encompassing information regarding mode of action and other parameters aimed at evaluating potential species differences (e.g., in toxicokinetics) and their relevance for evaluating human risks. It is important to consider this evolution when evaluating the testing methodology and scientific conclusions in earlier eras. As toxicology continues to develop, testing methods will continue to change in concert with increased knowledge and understanding.
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