Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: In August 2021, we published in Environmental Health a Toolkit for detecting misused epidemiological methods with the goal of providing an organizational framework for transparently evaluating epidemiological studies, a body of evidence, and resultant conclusions. Tsuda et al., the first group to utilize the Toolkit in a systematic fashion, have offered suggestions for its modification. MAIN BODY: Among the suggested modifications made by Tsuda et al., we agree that rearrangement of Part A of the Toolkit to reflect the sequence of the epidemiological study process would facilitate its usefulness. Expansion or adaptation of the Toolkit to other disciplines would be valuable but would require the input of discipline-specific expertise. We caution against using the sections of the Toolkit to produce a tally or cumulative score, because none of the items are weighted as to importance or impact. Rather, we suggest a visual representation of how a study meets the Toolkit items, such as the heat maps used to present risk of bias criteria for studies included in Cochrane reviews. We suggest that the Toolkit be incorporated in the sub-specialty known as "forensic epidemiology," as well as in graduate training curricula, continuing education programs, and conferences, with the recognition that it is an extension of widely accepted ethics guidelines for epidemiological research. CONCLUSION: We welcome feedback from the research community about ways to strengthen the Toolkit as it is applied to a broader assemblage of research studies and disciplines, contributing to its value as a living tool/instrument. The application of the Toolkit by Tsuda et al. exemplifies the usefulness of this framework for transparently evaluating, in a systematic way, epidemiological research, conclusions relating to causation, and policy decisions. POSTSCRIPT: We note that our Toolkit has, most recently, inspired authors with discipline-specific expertise in the field of Conservation Biology to adapt it for use in the Biological Sciences.

Toolkit for detecting misused epidemiological methods.

BACKGROUND: Critical knowledge of what we know about health and disease, risk factors, causation, prevention, and treatment, derives from epidemiology. Unfortunately, its methods and language can be misused and improperly applied. A repertoire of methods, techniques, arguments, and tactics are used by some people to manipulate science, usually in the service of powerful interests, and particularly those with a financial stake related to toxic agents. Such interests work to foment uncertainty, cast doubt, and mislead decision makers by seeding confusion about cause-and-effect relating to population health. We have compiled a toolkit of the methods used by those whose interests are not aligned with the public health sciences. Professional epidemiologists, as well as those who rely on their work, will thereby be more readily equipped to detect bias and flaws resulting from financial conflict-of-interest, improper study design, data collection, analysis, or interpretation, bringing greater clarity-not only to the advancement of knowledge, but, more immediately, to policy debates. METHODS: The summary of techniques used to manipulate epidemiological findings, compiled as part of the 2020 Position Statement of the International Network for Epidemiology in Policy (INEP) entitled Conflict-of-Interest and Disclosure in Epidemiology, has been expanded and further elucidated in this commentary. RESULTS: Some level of uncertainty is inherent in science. However, corrupted and incomplete literature contributes to confuse, foment further uncertainty, and cast doubt about the evidence under consideration. Confusion delays scientific advancement and leads to the inability of policymakers to make changes that, if enacted, would-supported by the body of valid evidence-protect, maintain, and improve public health. An accessible toolkit is provided that brings attention to the misuse of the methods of epidemiology. Its usefulness is as a compendium of what those trained in epidemiology, as well as those reviewing epidemiological studies, should identify methodologically when assessing the transparency and validity of any epidemiological inquiry, evaluation, or argument. The problems resulting from financial conflicting interests and the misuse of scientific methods, in conjunction with the strategies that can be used to safeguard public health against them, apply not only to epidemiologists, but also to other public health professionals. CONCLUSIONS: This novel toolkit is for use in protecting the public. It is provided to assist public health professionals as gatekeepers of their respective specialty and subspecialty disciplines whose mission includes protecting, maintaining, and improving the public's health. It is intended to serve our roles as educators, reviewers, and researchers.

Ethics Guidelines in Environmental Epidemiology: Their Development and Challenges We Face.

PURPOSE OF REVIEW: This review integrates historical developments and key events in bringing ethics into epidemiology in general and into environmental epidemiology in particular. The goal is to provide context for and discern among the various approaches and motivations that drive the need for ethical conduct in support of the public interest. RECENT FINDINGS: The need for ethics guidelines in epidemiology is different from developments in other biomedical-related fields by virtue of its focus on populations rather than on individuals. The need for ethics guidelines in environmental epidemiology as a subspecialty of epidemiology stems from the larger scale of its mission than that of epidemiology per se. Ethics guidelines in the field of environmental epidemiology have been established. They articulate not only the profession's core values and mission, but more specifically, they address the environmental epidemiologist's obligations to the participants in research, to colleagues, and to employers. They are the product of consensus, scholarship, and diligent stewardship over several decades. The next challenge is ensuring their value and impact. The forces that support professional and institutional success, and the power of special interests, are the major threats to achieving the goals of ethical conduct and research for the public good. In environmental epidemiology, these threats have global implications.

Current status of the epidemiologic evidence linking polychlorinated biphenyls and non-hodgkin lymphoma, and the role of immune dysregulation.

BACKGROUND: Although case-control studies conducted to date have largely affirmed the relationship between polychlorinated biphenyls (PCBs) and non-Hodgkin lymphoma (NHL), occupational cohort studies of PCB-exposed workers have been generally interpreted as negative, thereby raising doubts about a potential causal association. A common theme of immune dysregulation unifies many of NHL's strongest risk factors, and several authors have posited that subclinical immune dysregulation may increase NHL risk by decreasing host resistance, reducing control of cellular proliferation and differentiation, and diminishing tumor surveillance mechanisms. OBJECTIVES: The goals of this review were a) to evaluate the epidemiological research examining the association between PCB exposure and NHL and discuss the contribution to the weight of evidence of case-control studies and occupational cohort studies; and b) to summarize the evidence for immune dysregulation as a means by which PCBs may cause NHL. METHODS: We performed a literature search using PubMed and seven additional online biomedical and toxicological referencing libraries to identify literature published through August 2011. DISCUSSION AND CONCLUSIONS: Overall, we conclude that the weight of evidence supports a causal role of PCBs in lymphomagenesis. The strongest epidemiological evidence for the relationship between PCBs and NHL comes from case-control studies conducted among the general population. Epidemiological and toxicological data demonstrating immunosuppressive and inflammatory effects of PCBs further contribute to the weight of evidence by providing a plausible explanation for how PCBs can cause NHL through immune dysregulation.