Traditionally, RTSM systems (also known as IRT or IxRs), have been used for Phase 2 and 3 trials where randomization and trial supply management is too complex (at scale) to handle manually. It’s not that study and supply managers love manual spreadsheets (though many do!), but rather the value of building an RTSM to manage smaller studies was cost and resource prohibitive.
With the increasing complexity of today’s trials, scale is no longer the determining factor when choosing to implement an RTSM. With the trend toward personalized medicine and gene therapies and the FDA’s flexibility with accepting creativity in Oncology designs, Phase 1 trials can be even more complex than their Phase 2 and 3 counterparts. Change is an inevitable part of the trial design process, and in some cases, protocols are undergoing revision as soon as the initial protocol version is approved.
There is a myriad of reasons for protocol amendments. For example, the addition of new cohorts, indications, or treatment arms; updates to dosing levels or changes to visit schedules; addition of combination therapies; or even adding in randomization after the initial start-up. The reality is that protocols are never set in stone, so tracking information outside of using an RTSM for complex trial designs is cumbersome and prone to human error.
Technology is no longer a barrier to utilizing RTSM in Phase 1 trials. Here are five questions to consider when planning your next Phase 1 study.
1. Is the RTSM build configurable to meet study needs?
Do you need rand-only or supply-only systems? 100% configurable systems allow you to pick and choose which features are of value by flipping on and off a switch. Do you need this feature for study A but not for study B? Not a problem. Do you know you will be adding cohorts but are unsure of the parameters yet? Or expect complex dose escalation and drug accountability down to the kit/bottle/capsule/tablet/vial/or unit level? Modern technology enables the build to match the study design.
2. Is the RTSM flexible enough to let the science lead?
Many traditional RTSMs are rigid and require added time and resources to allow for adjustments while a study is in flight. A modern, flexible RTSM is needed to quickly adapt to changes in dose, schedule, cohorts, expansion, or the multitude of ways a protocol can be amended. Accounting for flexibility from the start is key to successful execution.
3. If granted FDA Fast Track Designation, can the RTSM be implemented to meet aggressive timelines?
Speed is crucial when you are working on a novel therapy for an unmet need. If you qualify for the FDA Fast Track designation, chances are you may need to move from manual processes to RTSM quickly to accelerate the path to approval. Now more than ever, a modern and flexible RTSM can support this transition with faster build times (less than two weeks), a fully validated solution with traceability, robust quality and most importantly maintaining data integrity.
4. Will I have control to manage cohorts and enrollment caps in real-time?
You need enough patients to obtain the critical data to get results, but not so many patients that you waste resources. With cohorts, the process can be more involved since you need to manage enrollment caps and supply for each cohort vs. just focusing on meeting the enrollment target and supplying enough drug to reach the end of the study. Additionally, you may find yourself having to seed sites with supply for upcoming cohort enrollment. Add on top of that if you have different dispensing rules or dose levels per cohort, this becomes even more complex. It is critical to use a robust RTSM to help manage resupply and forecasting while reducing overage/waste – and utilize a system that provides visibility to the data in real-time and puts the control in your hands.
5. Will the RTSM enable full drug accountability throughout the entire lifecycle of the drug?
The more complex the trial, the more challenging drug accountability can be. Regardless of study phase, if your study requires meticulous tracking (especially with personalized medicine and gene therapies) it is paramount to remove the risk of human error and enable a robust audit trail (patient records which contain all dispensing information throughout the course of the trial, down to the unit level, by protocol version, etc).
More and more Phase 1 trials have benefited from an RTSM – if the system itself is savvy enough to manage the complexity and mitigate the risk of manual data entry. When considering the criticality of early-phase studies, technology should drive operational efficiencies.
Interested in learning more? Download our white paper on cohort management to see how flexibility can enable complex oncology designs.