The Translational Research Working Group developmental pathway for anticancer agents (drugs or biologics)

Abstract

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the National Cancer Institute's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of agents-both small molecules and biologics-for the treatment and prevention of cancer. The Agents Developmental Pathway was conceived not as a comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of an agent through the translational process to the point where it can begin definitive clinical testing. This article presents the Agents Developmental Pathway and discusses key challenges associated with the processes described.

Fig. 1

Agents Developmental Pathway. The Agents Pathway is depicted as a flowchart, a schematic process representation widely used in engineering. Top, origin of the process (rounded rectangle), activity steps (square-cornered rectangles), and conditional tests or decision steps (diamonds). Unidirectional arrows: direction of the activity sequence, and the direction of transfer of supporting tools from their parallel development paths to the main path of modality development. Bidirectional arrows : co-development or concurrent, interactive refinement. Rectangle with inset oval: an iterative refinement process (used to conserve space). The initial steps (blue) are required to proceed through the Pathway, with the credentialing steps of scientific validation, clinical need, and feasibility (blue diamonds). The Pathway includes three parallel paths, representing the development of the modality itself (green) as well as the development of two different classes of supporting tools (red): tools for characterizing and evaluating the effects of modality, and tools for defining the cohort for which the modality is appropriate. Parallel paths have been made explicit to acknowledge that some of the required tools may not exist and their parallel or co-development will be a prerequisite for the viability of the new modality. Some of the supporting tools are assessment modalities represented by either the Biospecimen-based or Imaging-based Assessment Modality Pathways. Subsequent steps include preclinical development (purple) and early stage clinical trials (yellow). For each activity, decision point, parallel path, or feedback loop, it is understood that there are many more variations which can occur, and that not all steps may occur in each instance. The Pathway does not address the ways in which insights gained from late-stage clinical trials can influence the development process. Agent interventions may be used for treatment or for primary, secondary, or tertiary prevention. The Pathways are conceived not as comprehensive descriptions of the corresponding real-world processes but as tools designed to serve specific purposes, including research program and project management, coordination of research efforts, and professional and lay education and communication.