The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

Mechanisms in clinical practice: use and justification.

While the importance of mechanisms in determining causality in medicine is currently the subject of active debate, the role of mechanistic reasoning in clinical practice has received far less attention. In this paper we look at this question in the context of the treatment of a particular individual, and argue that evidence of mechanisms is indeed key to various aspects of clinical practice, including assessing population-level research reports, diagnostic as well as therapeutic decision making, and the assessment of treatment effects. We use the pulmonary condition bronchiectasis as a source of examples of the importance of mechanistic reasoning to clinical practice.

Evidential Proximity, Independence, and the evaluation of carcinogenicity.

This paper analyses the methods of the International Agency for Research on Cancer (IARC) for evaluating the carcinogenicity of various agents. I identify two fundamental evidential principles that underpin these methods, which I call Evidential Proximity and Independence. I then show, by considering the 2018 evaluation of the carcinogenicity of styrene and styrene-7,8-oxide, that these principles have been implemented in a way that can lead to inconsistency. I suggest a way to resolve this problem: admit a general exception to Independence and treat the implementation of Evidential Proximity more flexibly where this exception applies. I show that this suggestion is compatible with the general principles laid down in the 2019 version of IARC's methods guide, its Preamble to the Monographs.