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. 2011 Aug;122(2):223-34.
doi: 10.1093/toxsci/kfr113. Epub 2011 May 10.

Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference

Hans-Olov Adami  1 , Sir Colin L Berry, Charles B Breckenridge, Lewis L Smith, James A Swenberg, Dimitrios Trichopoulos, Noel S Weiss, Timothy P Pastoor
Affiliations

Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference

Hans-Olov Adami et al. Toxicol Sci. 2011 Aug.

Abstract

Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step "Epid-Tox" process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality.

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Figures

FIG. 1.
FIG. 1.
Contribution of toxicology and epidemiology data to causal inference. Many of the same principles contribute to evidence-based decisions in the two fields. Together, causation can be more accurately inferred.
FIG. 2.
FIG. 2.
Steps 1 and 2 of the Epid-Tox framework: study identification and quality categorization.
FIG. 3.
FIG. 3.
The human relevance mode of action framework.
FIG. 4.
FIG. 4.
The causal inference grid: how strong is the evidence for or against a causal relationship in humans?
FIG. 5.
FIG. 5.
Applications of the Epid-Tox framework: HIV/Kaposi's sarcoma and EMF and brain tumors.
FIG. 6.
FIG. 6.
Applications of the Epid-Tox framework: melamine and d-limonene.
FIG. 7.
FIG. 7.
Schematic representation of the framework for causal inference based upon weight of evidence of animal and epidemiological data.
See this image and copyright information in PMC

Comment in

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