Application of a Dynamic Map for Learning, Communicating, Navigating, and Improving Therapeutic Development

Abstract

Drug discovery and development is commonly schematized as a "pipeline," and, although appreciated by drug developers to be a useful oversimplification, this cartology may perpetuate inaccurate notions of straightforwardness and is of minimal utility for process engineering to improve efficiency. To create a more granular schema, a group of drug developers, researchers, patient advocates, and regulators developed a crowdsourced atlas of the steps involved in translating basic discoveries into health interventions, annotated with the steps that are particularly prone to difficulty or failure. This Drug Discovery, Development, and Deployment Map (4DM), provides a network view of the process, which will be useful for communication and education to those new to the field, orientation and navigation of individual projects, and prioritization of technology development and re-engineering endeavors to improve efficiency and effectiveness. The 4DM is freely available for utilization, modification, and further development by stakeholders across the translational ecosystem.

Figure 1

Therapeutic development chevron diagram. Traditional chevron diagram representation of therapeutic development. Colors in this chevron correspond to the associated “neighborhoods” on the Drug Discovery, Development, and Deployment Map. FDA, US Food and Drug Administration.

Figure 2

Drug Discovery, Development, and Deployment Map biologics map. The map comprises neighborhoods, each of which consists of a complex network of steps that interact with steps in other neighborhoods. The primary distinguishing steps between biologics and small molecules5 are in neighborhoods C (lead identification) and D (lead optimization). This file is licensed to the public under the Creative Commons Attribution‐Share Alike 4.0 license, which allows use and adaptation as long as the user provides attribution and shares any adaptations back to the public under the same license, and is available to download at https://ncats.nih.gov/translation/maps. BLA, biologics license application; cGMP, current good manufacturing practice; GLP, good laboratory practices; IND, investigational new drug; IRB, institutional review board; NBE, new biological entities; NDA, new drug application; PK/PD, pharmacokinetic/pharmacodynamic.

Figure 3

Heat map of relative ease and difficulty of steps in Drug Discovery, Development, and Deployment Map (4DM) case studies. The relative ease of the 4DM steps in different case‐studies is shown in green to indicate relative ease and in magenta to indicate relative difficulty. ADPKD, autosomal dominant polycystic kidney disease; EMR, electronic medical record; FOP, fibrodysplasia ossificans progressiva; HTS, high‐throughput screening; IND, investigational new drug; NCATS, National Center for Advancing Translational Sciences; NPY, neuropeptide Y; PKDOC, Polycystic Kidney Disease Outcomes Consortium.

Figure 4

Potential “layers” of the Drug Discovery, Development, and Deployment Map (4DM). Similar to the layers found on Google Maps, we propose that the 4DM could contain layers of information that could be toggled on or off the user depending on the question being asked.