ID #654 The Trial Ready Model: A Pediatric Brain Tumor Consortium (PBTC)-Informed Operational Model to Streamline Neuro-Oncology Trials from Concept to Activation

Background

The clinical trial development process is often lengthy and inefficient.[1] Pediatric neuro-oncology trials face activation barriers, including rapid bench-to-bedside translation demands, intensive safety monitoring, and limited operational capacity.[2][3][4][5] Where consortia or national trial networks are limited or unavailable, operational models can shorten time from concept to trial activation.[1][5]

Objective

To introduce the Trial Ready Model (TRM), a PBTC-developed operational model that targets predictable operational bottlenecks and streamlines trial activation.

Methods

We defined five operational bottlenecks in pediatric neuro-oncology trial activation: 1) concept-to-protocol translation, 2) scientific review and approval, 3) regulatory and ethics readiness, 4) safety review and approval, and 5) operational capacity. For each bottleneck, we identified reproducible tools and documented their impact on trial activation timelines. TRM was informed by PBTC trial experience across diverse therapeutic modalities: combination targeted, peptide vaccine, device-delivered intracranial, and CAR T cell therapies.

Results

TRM tools minimized five operational bottlenecks. Standardized protocol templates and language streamlined concept-to-protocol development and approval. Across successive PBTC protocols, time from concept approval to first protocol submission decreased 57% from 235 days (PBTC-055) to 100 days (PBTC-060); the first CAR T protocol (PBTC-059) requiring 201 days. Subject matter expert reviews improved protocol quality and scientific merit. Standardized risk lists and categorized assessments in protocols and informed consent(s) clarified research versus clinical monitoring, supporting regulatory and ethics readiness. Electronic data capture (EDC) adverse event reporting with automated email alerts enabled real-time safety review. Site readiness evaluations and PBTC operations workflows improved operational capacity and coordination across enrolling sites, operational groups, and data management, supporting treatment readiness decisions and resource allocation.

Conclusion

TRM provides a standardized operational framework to streamline trial activation while prioritizing safety. TRM is adaptable to single- and multi-site clinical trial settings and may be transferable across therapeutic areas.

1. Dilts DM, Sandler AB, Baker M, et al. Phase III clinical trial development: a process of chutes and ladders. Clinical Cancer Research. 2010;16(22):5381–5389. doi:10.1158/1078-0432.CCR-10-1273.

2. Lee EQ, Chukwueke UN, Hervey-Jumper SL, et al. Barriers to accrual and enrollment in brain tumor trials. Neuro-Oncology. 2019;21(9):1100–1117. doi:10.1093/neuonc/noz104.

3. Rahman R, Polley MYC, Alder L, et al. Current drug development and trial designs in neuro-oncology: report from the first American Society of Clinical Oncology and Society for Neuro-Oncology Clinical Trials Conference. The Lancet Oncology. 2023;24(4):e161–e171. doi:10.1016/S1470-2045(23)00005-0.

4. Boutzoukas AE, Olson R, Sellers MA, et al. Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience. Contemporary Clinical Trials. 2023;125:107067. doi:10.1016/j.cct.2022.107067.

5. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of Blood and Marrow Transplantation. 2019;25(4):625–638. doi:10.1016/j.bbmt.2018.12.758