A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology

The hierarchy of evidence is a fundamental concept in evidence-based medicine, but existing models can be challenging to apply in laboratory-based healthcare disciplines, such as pathology, where the types of evidence and contexts are significantly different from interventional medicine. This project aimed to define a comprehensive and complementary framework of new levels of evidence for evaluating research in tumor pathology – introducing a novel Hierarchy of Research Evidence for Tumor Pathology (HETP) collaboratively designed by pathologists with help from epidemiologists, public health professionals, oncologists, and scientists, specifically tailored for use by pathologists and to aid in the production of the World Health Organization Classification of Tumours (WCT) evidence gap maps. To achieve this, we adopted a modified Delphi approach, encompassing iterative online surveys, expert oversight, and external peer review, to establish the criteria for evidence in tumor pathology, determine the optimal structure for the new hierarchy, and ascertain the levels of confidence for each type of evidence. Over a span of four months and three survey rounds we collected 1,104 survey responses, culminating in a three-day hybrid meeting in 2023, where a new hierarchy was unanimously agreed upon. The hierarchy is organized into five research theme groupings closely aligned with the subheadings of the WCT, and it consists of five levels of evidence – Level P1 representing evidence types which merit the greatest level of confidence and Level P5 reflecting the greatest risk of bias. For the first time, an international collaboration of pathology experts, supported by the International Agency for Research on Cancer (IARC), has successfully united to establish a standardized approach for evaluating evidence in tumor pathology. We intend to implement this novel HETP to map the available evidence, thereby enriching and informing the WCT effectively.