TY - JOUR
T1 - Biological plausibility in environmental health systematic reviews
T2 - a GRADE concept paper
AU - Whaley, Paul
AU - Piggott, Thomas
AU - Morgan, Rebecca L.
AU - Hoffmann, Sebastian
AU - Tsaioun, Katya
AU - Schwingshackl, Lukas
AU - Ansari, Mohammed T.
AU - Thayer, Kristina A.
AU - Schünemann, Holger J.
N1 - Funding Information:
The authors would like to thank the GRADE Environmental Health Project Group and GRADE Working Group for their contributions to this manuscript, and the Evidence-based Toxicology Collaboration (EBTC) at Johns Hopkins Bloomberg School of Public Health for providing funding to cover the time of P.W. K.T. and S.H. in working on this manuscript. We would like to thank Dr Andrew Kraft and Dr Michelle Angrish for their technical review of the manuscript, and Dr Daniele Wikoff (ToxStrategies) for detailed discussion of the ideas and concepts we present here. The authors would also thank the European Food Safety Authority and EBTC for organizing the Scientific Colloquium, and the participants who contributed to discussions therein, which gave genesis to the concept of this manuscript [9]. Conflict of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Publisher Copyright:
© 2021 Paul Whaley, Thomas Piggott, Rebecca L. Morgan, Sebastian Hoffmann, Katya Tsaioun, Lukas Schwingshackl, Mohammed T. Ansari, Kristina A. Thayer, Holger Schünemann
PY - 2022/6
Y1 - 2022/6
N2 - Background: “Biological plausibility” is a concept frequently referred to in environmental and public health when researchers are evaluating how confident they are in the results and inferences of a study or evidence review. Biological plausibility is not, however, a domain of one of the most widely used approaches for assessing the certainty of evidence (CoE) which underpins the findings of a systematic review, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) CoE Framework. Objectives: Whether the omission of biological plausibility is a potential limitation of the GRADE CoE Framework is a topic that is regularly discussed, especially in the context of environmental health systematic reviews. Study Design and Setting: We analyze how the concept of “biological plausibility,” as applied in the context of assessing certainty of the evidence that supports the findings of a systematic review, is accommodated under the processes of systematic review and the existing GRADE domains. Results: We argue that “biological plausibility” is a concept which primarily comes into play when direct evidence about the effects of an exposure on a population of concern (usually humans) is absent, at high risk of bias, inconsistent, or limited in other ways. In such circumstances, researchers look toward evidence from other study designs to draw conclusions. In this respect, we can consider experimental animal and in vitro evidence as “surrogates” for the target populations, exposures, comparators, and outcomes of actual interest. Through discussion of 10 examples of experimental surrogates, we propose that the concept of biological plausibility consists of two principal aspects: a “generalizability aspect” and a “mechanistic aspect.” Conclusions: The “generalizability aspect” concerns the validity of inferences from experimental models to human scenarios, and asks the same question as does the assessment of external validity or indirectness in systematic reviews. The “mechanistic aspect” concerns certainty in knowledge of biological mechanisms and would inform judgments of indirectness under GRADE, and thus the overall CoE. Although both aspects are accommodated under the indirectness domain of the GRADE CoE Framework, further research is needed to determine how to use knowledge of biological mechanisms in the assessment of indirectness of the evidence in systematic reviews.
AB - Background: “Biological plausibility” is a concept frequently referred to in environmental and public health when researchers are evaluating how confident they are in the results and inferences of a study or evidence review. Biological plausibility is not, however, a domain of one of the most widely used approaches for assessing the certainty of evidence (CoE) which underpins the findings of a systematic review, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) CoE Framework. Objectives: Whether the omission of biological plausibility is a potential limitation of the GRADE CoE Framework is a topic that is regularly discussed, especially in the context of environmental health systematic reviews. Study Design and Setting: We analyze how the concept of “biological plausibility,” as applied in the context of assessing certainty of the evidence that supports the findings of a systematic review, is accommodated under the processes of systematic review and the existing GRADE domains. Results: We argue that “biological plausibility” is a concept which primarily comes into play when direct evidence about the effects of an exposure on a population of concern (usually humans) is absent, at high risk of bias, inconsistent, or limited in other ways. In such circumstances, researchers look toward evidence from other study designs to draw conclusions. In this respect, we can consider experimental animal and in vitro evidence as “surrogates” for the target populations, exposures, comparators, and outcomes of actual interest. Through discussion of 10 examples of experimental surrogates, we propose that the concept of biological plausibility consists of two principal aspects: a “generalizability aspect” and a “mechanistic aspect.” Conclusions: The “generalizability aspect” concerns the validity of inferences from experimental models to human scenarios, and asks the same question as does the assessment of external validity or indirectness in systematic reviews. The “mechanistic aspect” concerns certainty in knowledge of biological mechanisms and would inform judgments of indirectness under GRADE, and thus the overall CoE. Although both aspects are accommodated under the indirectness domain of the GRADE CoE Framework, further research is needed to determine how to use knowledge of biological mechanisms in the assessment of indirectness of the evidence in systematic reviews.
KW - Biological plausibility
KW - Bradford Hill
KW - Environmental health
KW - Epidemiology
KW - GRADE
KW - Surrogates
KW - Systematic review
KW - Toxicology
UR - http://www.scopus.com/inward/record.url?scp=85126848837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126848837&partnerID=8YFLogxK
U2 - 10.1016/j.jclinepi.2022.02.011
DO - 10.1016/j.jclinepi.2022.02.011
M3 - Article
C2 - 35219805
AN - SCOPUS:85126848837
SN - 0895-4356
VL - 146
SP - 32
EP - 46
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
ER -