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Competing Interests: 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.

The use of unverified models for risk estimates and policy recommendations can be highly misleading, as their predictions may not reflect real-world health impacts. For example, a recent article states that NO 2 from gas stoves "likely causes ∼50,000 cases of current pediatric asthma from long-term NO 2 exposure alone" annually in the United States. This explicitly causal claim, which is contrary to several methodology and review articles published in this journal, among others, reflects both (a) An unverified modeling assumption that pediatric asthma burden is approximately proportional to NO 2 ; and (b) An unverified causal assumption that the assumed proportionality between exposure and response is causal. The article is devoid of any causal analysis showing that these assumptions are likely to be true. It does not show that reducing NO 2 exposure from gas stoves would reduce pediatric asthma risk. Its key references report no significant associations - let alone causation - between NO 2 and pediatric asthma. Thus, the underlying data suggests that the number of pediatric asthma cases caused by gas stoves in the United States is indistinguishable from zero. This highlights the need to rigorously validate modeling assumptions and causal claims in public health risk assessments to ensure scientifically sound foundations for policy decisions., Competing Interests: I declare no competing interests that could influence the work presented in this manuscript. Funding for this work was provided by Cox Associates, LLC. Cox Associates has reasonable expectation of receiving funds in the future from the American Gas Association (AGA) to cover part of the cost of writing up these comments and/or defraying open access charges. Cox Associates has also previously received support from the 10.13039/100000199United States Department of Agriculture (USDA) for research on statistical methods for causal analysis of observational and interventional data. The author has previously received support from the USEPA for a part of the work related to duties related to NAAQS reviews. The research questions, methods, and conclusions are solely those of the author and do not necessarily reflect the views of any funding organizations., (© 2024 The Author.)

Drawing sound causal inferences from observational data is often challenging for both authors and reviewers. This paper discusses the design and application of an Artificial Intelligence Causal Research Assistant (AIA) that seeks to help authors improve causal inferences and conclusions drawn from epidemiological data in health risk assessments. The AIA-assisted review process provides structured reviews and recommendations for improving the causal reasoning, analyses and interpretations made in scientific papers based on epidemiological data. Causal analysis methodologies range from earlier Bradford-Hill considerations to current causal directed acyclic graph (DAG) and related models. AIA seeks to make these methods more accessible and useful to researchers. AIA uses an external script (a "Causal AI Booster" (CAB) program based on classical AI concepts of slot-filling in frames organized into task hierarchies to complete goals) to guide Large Language Models (LLMs), such as OpenAI's ChatGPT or Google's LaMDA (Bard), to systematically review manuscripts and create both (a) recommendations for what to do to improve analyses and reporting; and (b) explanations and support for the recommendations. Review tables and summaries are completed systematically by the LLM in order. For example, recommendations for how to state and caveat causal conclusions in the Abstract and Discussion sections reflect previous analyses of the Study Design and Data Analysis sections. This work illustrates how current AI can contribute to reviewing and providing constructive feedback on research documents. We believe that such AI-assisted review shows promise for enhancing the quality of causal reasoning and exposition in epidemiological studies. It suggests the potential for effective human-AI collaboration in scientific authoring and review processes., Competing Interests: The research presented here was supported by the author's employer, Cox Associates. Cox Associates received seed funding from the American Chemistry Council in 2022 and 2023 to develop the core ideas and technology for the AI Causal Research Assistant (AIA) and its application to reviewing documents, as described in this paper. All research questions, technical approaches and innovations, example, and conclusions are solely those of the author. 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., (© 2023 Published by Elsevier Inc.)

Exposure-response curves are among the most widely used tools of quantitative health risk assessment. However, we propose that exactly what they mean is usually left ambiguous, making it impossible to answer such fundamental questions as whether and by how much reducing exposure by a stated amount would change average population risks and distributions of individual risks. Recent concepts and computational methods from causal artificial intelligence (CAI) and machine learning (ML) can be applied to clarify what an exposure-response curve means; what other variables are held fixed (and at what levels) in estimating it; and how much inter-individual variability there is around population average exposure-response curves. These advances in conceptual clarity and practical computational methods not only enable epidemiologists and risk analysis practitioners to better quantify population and individual exposure-response curves but also challenge them to specify exactly what exposure-response relationships they seek to quantify and communicate to risk managers and how to use the resulting information to improve risk management decisions., Competing Interests: The authors declare that they have no known competing financial interestsor personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Several recent news stories have alarmed many politicians and members of the public by reporting that indoor air pollution from gas stoves causes about 13% of childhood asthma in the United States. Research on the reproducibility and trustworthiness of epidemiological risk assessments has identified a number of common questionable research practices (QRPs) that should be avoided to draw sound causal conclusions from epidemiological data. Examples of such QRPs include claiming causation without using study designs or data analyses that allow valid causal inferences; generalizing or transporting risk estimates based on data for specific populations, time periods, and locations to different ones without accounting for differences in the study and target populations; claiming causation without discussing or quantitatively correcting for confounding, external validity bias, or other biases; and not mentioning or resolving contradictory evidence. We examine the recently estimated gas stove-childhood asthma associations from the perspective of these QRPs and conclude that it exemplifies all of them. The quantitative claim that about 13% of childhood asthma in the United States could be prevented by reducing exposure to gas stove pollution is not supported by the data collected or by the measures of association (Population Attributable Fractions) used to analyze the data. The qualitative finding that reducing exposure to gas stove pollution would reduce the burden of childhood asthma in the United States has no demonstrated validity. Systematically checking how and whether QRPs have been addressed before reporting or responding to claims that everyday exposures cause substantial harm to health might reduce social amplification of perceived risks based on QRPs and help to improve the credibility and trustworthiness of published epidemiological risk assessments., Competing Interests: 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., (© 2023 The Author(s).)

We present a Socratic dialogue with ChatGPT, a large language model (LLM), on the causal interpretation of epidemiological associations between fine particulate matter (PM2.5) and human mortality risks. ChatGPT, reflecting probable patterns of human reasoning and argumentation in the sources on which it has been trained, initially holds that "It is well-established that exposure to ambient levels of PM2.5 does increase mortality risk" and adds the unsolicited remark that "Reducing exposure to PM2.5 is an important public health priority." After patient questioning, however, it concludes that "It is not known with certainty that current ambient levels of PM2.5 increase mortality risk. While there is strong evidence of an association between PM2.5 and mortality risk, the causal nature of this association remains uncertain due to the possibility of omitted confounders." This revised evaluation of the evidence suggests the potential value of sustained questioning in refining and improving both the types of human reasoning and argumentation imitated by current LLMs and the reliability of the initial conclusions expressed by current LLMs., Competing Interests: The authors declare that they have no known competing financial interestsor personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author.)

Population attributable fraction (PAF), probability of causation, burden of disease, and related quantities derived from relative risk ratios are widely used in applied epidemiology and health risk analysis to quantify the extent to which reducing or eliminating exposures would reduce disease risks. This causal interpretation conflates association with causation. It has sometimes led to demonstrably mistaken predictions and ineffective risk management recommendations. Causal artificial intelligence (CAI) methods developed at the intersection of many scientific disciplines over the past century instead use quantitative high-level descriptions of networks of causal mechanisms (typically represented by conditional probability tables or structural equations) to predict the effects caused by interventions. We summarize these developments and discuss how CAI methods can be applied to realistically imperfect data and knowledge - e.g., with unobserved (latent) variables, missing data, measurement errors, interindividual heterogeneity in exposure-response functions, and model uncertainty. We recommend that CAI methods can help to improve the conceptual foundations and practical value of epidemiological calculations by replacing association-based attributions of risk to exposures or other risk factors with causal predictions of the changes in health effects caused by interventions., (© 2021 The Author.)

We argue that population attributable fractions, probabilities of causation, burdens of disease, and similar association-based measures often do not provide valid estimates or surrogates for the fraction or number of disease cases that would be prevented by eliminating or reducing an exposure because their calculations do not include crucial mechanistic information. We use a thought experiment with a cascade of dominos to illustrate the need for mechanistic information when answering questions about how changing exposures changes risk. We suggest that modern methods of causal artificial intelligence (CAI) can fill this gap: they can complement and extend traditional epidemiological attribution calculations to provide information useful for risk management decisions., (© 2021 The Author.)

Causal inference regarding exposures to ambient fine particulate matter (PM 2.5 ) and mortality estimated from observational studies is limited by confounding, among other factors. In light of a variety of causal inference frameworks and methods that have been developed over the past century to specifically quantify causal effects, three research teams were selected in 2016 to evaluate the causality of PM 2.5 -mortality association among Medicare beneficiaries, using their own selections of causal inference methods and study designs but the same data sources. With a particular focus on controlling for unmeasured confounding, two research teams adopted an instrumental variables approach under a quasi-experiment or natural experiment study design, whereas one team adopted a structural nested mean model under the traditional cohort study design. All three research teams reported results supporting an estimated counterfactual causal relationship between ambient PM 2.5 and all-cause mortality, and their estimated causal relationships are largely of similar magnitudes to recent epidemiological studies based on regression analyses with omitted potential confounders. The causal methods used by all three research teams were built upon the potential outcomes framework. This framework has marked conceptual advantages over regression-based methods in addressing confounding and yielding unbiased estimates of average treatment effect in observational epidemiological studies. However, potential violations of the unverifiable assumptions underlying each causal method leave the results from all three studies subject to biases. We also note that the studies are not immune to some other common sources of bias, including exposure measurement errors, ecological study design, model uncertainty and specification errors, and irrelevant exposure windows, that can undermine the validity of causal inferences in observational studies. As a result, despite some apparent consistency of study results from the three research teams with the wider epidemiological literature on PM 2.5 -mortality statistical associations, caution seems warranted in drawing causal conclusions from the results. A possible way forward is to improve study design and reduce dependence of conclusions on untested assumptions by complementing potential outcomes methods with structural causal modeling and information-theoretic methods that emphasize empirically tested and validated relationships., (© 2021 Gradco LLC dba Gradient.)

In the first half of 2020, much excitement in news media and some peer reviewed scientific articles was generated by the discovery that fine particulate matter (PM2.5) concentrations and COVID-19 mortality rates are statistically significantly positively associated in some regression models. This article points out that they are non-significantly negatively associated in other regression models, once omitted confounders (such as latitude and longitude) are included. More importantly, positive regression coefficients can and do arise when (generalized) linear regression models are applied to data with strong nonlinearities, including data on PM2.5, population density, and COVID-19 mortality rates, due to model specification errors. In general, statistical modeling accompanied by judgments about causal interpretations of statistical associations and regression coefficients - the current weight-of-evidence (WoE) approach favored in much current regulatory risk analysis for air pollutants - is not a valid basis for determining whether or to what extent risk of harm to human health would be reduced by reducing exposure. The traditional scientific method based on testing predictive generalizations against data remains a more reliable paradigm for risk analysis and risk management., (© 2020 The Authors.)