Key Takeaways
The Fourth Edition of the Reference Manual on Scientific Evidence is an updated resource for building, defending, and challenging scientific evidence in cases involving complex evidence. Attorneys should familiarize themselves with the Fourth Edition’s updates, as courts are likely to consult them when making potentially dispositive rulings on the admissibility of scientific evidence and expert testimony.
Since its first edition in 1994, the Reference Manual on Scientific Evidence (the “Manual”) has been the judiciary’s go‑to guide for assessing complex scientific and technical proof. The Fourth Edition, released December 31, 2025, is a joint publication of the Federal Judicial Center and the National Academies of Sciences, Engineering, and Medicine. In a new foreword, Justice Elena Kagan writes that the Manual “exemplifies the benefits that can accrue from cooperation between those proficient in legal analysis and those expert in technical subjects” and that its instruction in scientific principles and methods can “improve the quality of judicial decision making.”
The Manual is comprised of stand‑alone reference manuals that help courts critically evaluate different types of scientific and technical evidence. It spans topics from economic damages to epidemiology to mental health. Each reference manual outlines issues relevant to the specific topic, including any governing legal frameworks, relevant analytical methods and their proper application, and key considerations. The Fourth Edition adds new chapters on emerging areas, including computer science, artificial intelligence, and climate science.
Among other things, the Fourth Edition continues to provide a detailed guide to evaluating epidemiological research, with a new section on genetic and molecular epidemiological studies. The addition responds to advances in genomics, which have vastly improved scientists’ ability to identify genetic variations and other biochemical constituents, which may be associated with the incidence of disease or susceptibility to certain exposures. Importantly, the Fourth Edition notes that genetic and molecular epidemiology employ established epidemiological study designs and should be evaluated for the same potential biases and errors as other population-based research.
The Fourth Edition also significantly expands the reference manual on exposure science and exposure assessment, clarifying key distinctions between exposure and dose, and addressing the applicability of receptor-based approaches to understanding exposure. Receptor-based approaches to exposure assessments are designed to identify the “inherent variability in exposure that occurs because of factors related to human behavior and characteristics that help determine an individual’s exposure to a stressor.” The Fourth Edition further examines how individual- and population-level characteristics can influence the frequency and magnitude of exposure, as well as vulnerability to its effects. These nuances are critical to causation assessments—including the interpretation of epidemiologic studies—and should guide experts evaluating alleged harm from a stressor.
