National Cancer Institute

Introduction to the TRWG Developmental Pathways

The TRWG has constructed six "developmental pathways" that characterize the transformation of scientific discoveries into new clinical modalities for oncology. These modalities fall into two fundamental and complementary categories:

Risk assessment modalities, intended to characterize the cancer-related health status of an individual:

• Biospecimen-based risk assessment devices ¹ (protocols, reagents, instruments)
• Image-based risk assessment ² (agents or techniques)

Interventive modalities, intended to change the cancer-related health status of an individual, via prevention or treatment:

• Agents ³ (drugs or biologics)
• Immune response modifiers ⁴ (vaccines, cytokines, etc.)
• Interventive devices ⁵
• Lifestyle alterations ⁶

The developmental pathway diagrams outline the processes through which fundamental scientific discoveries are transformed into these clinical modalities. The diagrams specify key activities and decision points along the development path, clarify dependencies among different steps as well as key events that occur in parallel, and show important feedback loops and iterative processes that are embedded within the development process.

The primary purpose of these pathways was to facilitate TRWG discussions by clarifying certain essential characteristics of the early translation process. TRWG members have used them to help understand the challenges faced by translational researchers and to identify ways to help the translational research process function more effectively. For example, the pathway diagrams stimulated fruitful discussion among TRWG members and participants in the first TRWG public roundtable about relationships among different elements of the translational research effort, resources needed, and barriers that stand in the way of more rapid progress.

In creating these pathways, the TRWG was aware that such idealized representations cannot capture the full complexity of the real world. For each activity, decision point, parallel path or feedback loop, it is understood that there are many more variations that can occur - and indeed have occurred - in practice and that not all steps may occur in each instance. In addition, these diagrams do not capture the full range of possible interactions between the pathways, nor do they address the ways in which insights gained from late-stage clinical trials can influence the development process. Finally, there has been no attempt to address the influence of market conditions, projected financial return, or reimbursement considerations on development pathway decisions made in the commercial sector.

To facilitate understanding of the pathways, a generic pathway template ⁷ was also created which captures the common elements of the pathways in simplified form. The generic pathway applies equally to both the risk assessment and the interventive modalities. Note that, for interventions, some of the supporting tools required in the development process (red box in the left-hand sequence of the generic pathway) are themselves risk assessment modalities.