February 24, 2023

RTSM Considerations in Rare Disease Trials: Study Length and Individualized Therapies

In an earlier blog , we discussed some randomization and trial supply management (RTSM) factors sponsors should consider when planning trials for rare disease treatments. These included the variability in how many sites are required to enroll so few patients, and how to reduce drug wastage, based on the high expense of rare disease treatments.

Here we address additional challenges, including the length of rare disease trials, the role of cell and gene therapy, and how a reliable, full-service interactive response technology (IRT) system backed by trial supply experts can tackle these and other challenges to drive trial success.

Trial Length and Support Needs

When many sites are required to meet patient enrollment goals, sponsors should be prepared for very long trials. The longer the trial, the more likely it is that design, protocol, and/or packaging changes will be needed. Being able to customize your data collection processes and make changes to the way trial supplies are managed and distributed is critical.

By working with experienced RTSM professionals, study teams receive the study support they need throughout the life of their trials. With Calyx IRT, that includes access to supply chain experts who assist the trial team as changes need to be made, providing context for the IRT system design and what options are available. They work closely with our team of professional project managers who support the study throughout its duration to ensure study continuity with no impacts to drug availability and distribution.

In addition, sponsors need to be prepared to capture a significant amount of observations and data points per patient. A thorough IRT system will enable sponsors to customize their data collection and reporting as needed, regardless of how much data is captured and/or how their data needs change throughout the trial.

“In individualized therapy trials, IRT setup is impacted by the need to manage temperature limits and expiry dates for products in both frozen and thawed states.”

— Malcolm Morrissey, Head of Statistics & Product Support Services, Calyx

Individualized Therapy Trials

When a rare disease treatment is an individualized therapy, the logistics around RTSM are even more challenging. Clinical trials involving stem cell therapies present added complexity regarding treatment logistics: the treatment is collected from a patient or donor, shipped to a manufacturing site, modified, and then shipped to the treatment facility for patient administration.

Effective treatment requires cell preservation, which is often done by cryopreservation. If the cryopreservation is not well-managed or is suboptimal, cell viability and the therapy production process can be negatively impacted. Additionally, the efficacy of the therapy may be compromised due to non-ideal frozen storage conditions.1

Frozen storage conditions may be considered extraneous to the IRT by some, but functionality such as tracking of temperature limits for the product and quarantine functionality, as well as management of a different expiry date for the product in a frozen and thawed state, all impact IRT set up and supply chain management. A robust IRT solution for handling a changing expiry date following the change of storage state/condition is a critical factor and not one that is typically seen in many clinical trials with temperature sensitive medication. It is a feature that has only gained increased use in recent years.

Additionally, the timeline of events involved in the manufacturing process could require careful oversight and in some cases a degree of control. The controls applied could be used to avoid exceeding manufacturing capabilities on a given day, for example. This would depend upon the size of recruitment within the trial or the number of protocols calling on the patient-specific manufacturing at one time.

The controls in the IRT could be as simple as applying a daily limit (or cap) to a future planned visit date entered in to the IRT for a subject’s next visit. Alternatively, Calyx has designed a booking system with bespoke rules that tackles the planning of visit slots for a given site in a trial. The booking system runs an algorithm using a set hierarchy of preference criteria to assign manufacturing slots to sites for specific planned visit dates. The algorithm can include in the assignment hierarchy, preferential sites, consideration of whether the site was allocated a slot in the last algorithm run, and other client-specific criteria for slot assignment. This booking system can manage depot capabilities and place designated limits on depots, as needed, to ensure their ability to make individualized therapies throughout this form of rare disease trials.

In both scenarios, the resupply algorithm can still include patient-focused predictive supply to cover the needs of ongoing patients across the program.

The definition of supply strategies becomes more complex if protocols include both pooled medication and protocol-specific kit types, or if the sourcing strategy varies between kit types, with some medication being locally sourced, and others sourced centrally. Thanks to their extensive experience in clinical inventory management, Calyx supply management experts understand and apply the best practices that help sponsors adapt to any requirements.

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