Personalized Medicine Webinar: Tailoring IRT/RTSM solutions to overcome challenges – Q&A

Interactive response technology (IRT) systems have simplified participant randomization, drug inventory management, and drug dispensation in traditional clinical trials for years. Randomization and trial supply management (RTSM) is a critical function of IRT used in clinical trials; it must evolve to better support personalized medicine, including clinical trials that require both just-in-time (JiT) dispensation of individual, personalized treatment, and dispensation from a stock of traditional therapies.

Perceptive eClinical experts Malcolm Morrissey, Associate Director of  Statistical Design & Trial Supplies Consultant, and Kendra Korte, Technical Solutions Consultant, discussed IRT evolution and its impact on clinical trials in a webinar, during which they responded to the following questions submitted by the audience.

What resupply strategies can be used to maintain the needs of a double-blind trial for oncology and/or rare disease?

For the most typical oncology or rare disease trials, tools exist to add random packs to shipments to maintain blinding. For example, when a like-for-like replacement shipment has been generated after a participant visit, Perceptive eClinical’s RTSM can monitor that event and add extra, random packs to shipments to protect the blinding.

Additionally, a rare disease trial may only have one participant at a site, so the challenge becomes how to avoid sending stock to the site that might not be used. For example, the depot might send the opposite treatment for a randomized, blinded trial. But, if stock is sent that is not meant for the participant at that site or is intended for later use, even its on-site storage presents an unblinding risk. IRT design features like pre-allocation and just-in-time delivery using a prediction supply method can help to avoid sending unnecessary medication. Pre-allocation of medication to an individual participant can also be used to protect blind in both typical and personalized studies. Beyond the IRT, reviews and discussion of optimal site resupply strategies during the study also can be helpful.

How can the IRT be applied to monotherapies and existing therapies, and how can that impact therapy availability and timing?

Consider the example of personalized medicine that arrived on site damaged or otherwise unfit for use. In this scenario, drug dispensation must be paused or delayed until the next cycle, extending the visit schedule by one occurrence [added at the end] each time. The additional (traditional) therapy still can take place, abiding by its own separate schedule. Perceptive eClinical’s RTSM provides options for how the different medications can be used at a visit. Those outcomes are aligned with an IRT dose level, so a participant can be assigned a study pathway label that simultaneously manages the changing schedule for their personalized therapy and assigns them what is needed for the additional therapy. It is not a challenge to handle combination therapies in Perceptive eClinical’s RTSM, but understanding what events are possible, deciding what needs must be met, and planning based on that information is very important.

How can Perceptive eClinical’s RTSM reschedule a visit for personalized medicine, along with booking a manufacturing slot?

When the IRT captures information that medication has arrived compromised and must be reordered, the trial pathway is reconfigured in the system. The flow of the next necessary action directs the user through reordering the medication, and different reasons for not being able to dispense the medication can lead to different options.

For example, if the problem is purely that the medication is not appropriate for use, a new proposed visit date is required to remanufacture. Approvals originally required as part of planning that next visit can all be captured to allow a successful order, though the order may not be allowed if it does not align with a manufacturing slot and/or the visit schedule. The visit schedule also may change, and a ‘base date’ reset within the IRT system, helping to ensure the subsequent visits [after the rescheduled one] are properly set within a specific time period in the future. However, if dispensing was not successful due to a safety concern or a participant issue, medication reorder will not be permitted.

When users update the IRT system based on real-world information, the IRT system automatically changes the path of the transaction using that information.

Radiopharmaceuticals do not have inventory; they have capacity. Can this be managed via an IRT?

Consider the example of an approval transaction related to a participant’s first enrollment visit. The site knows the participant and can propose a first visit date that starts the study chain of events, perhaps even manufacturing. The site’s preferred visit date is entered into Perceptive eClinical’s RTSM and approval of that transaction by a facility member or a specific role is required.

That scenario also can be managed through use of a slot booking system, generating the same type of approvals but handled more by the IRT than a user. In such cases, the system checks against a list of pre-agreed criteria and runs an algorithm to determine whether the site is eligible for a given manufacturing slot. This eligibility can be configured to consider whether the site is the first to choose a slot, is a ‘VIP site,’ or was rejected last time; this sits atop a priority list created to resolve conflicts when overlapping slots are requested by different sites.

The slot booking strategy is more often associated with a larger program of studies using the same manufacturing at a similar time, when there is concern demand could overwhelm capacity.

Ultimately, the preference is dictated by how the study team wishes to manage capacity and what tools Perceptive eClinical can apply to fulfill their specific needs.

How do you work with an IRT vendor to optimize design without negatively impacting overall timelines?

Current designs tend to be very specific to study team preference or the indication. In at least one case, Perceptive eClinical was engaged early by a customer who was concerned it might be difficult to set up their intended plans through an IRT system. In such cases, discussion, and information-sharing between both sides to build understanding before a standard IRT kick off meeting can be invaluable to preserving timelines. Early engagement also can help the study team feel more comfortable about expectations during the IRT build phase and its potential challenges.

Perceptive eClinical tailors each study IRT build this way. A study team may like portions of our initial proposal but want a specific mechanism around, for example, approvals. Early engagement allows us to assess the implications of such requests and to initiate our risk management process and determine necessary steps to deliver.

We always work towards First Patient In date, understanding from the study team when delivery is needed to meet this date and starting earlier if the team prefers.

Can the IRT manage studies when a single supply is utilized across multiple programs?

Numerous options exist around medication pooling in personalized medicine. In discussing capacity management above, we mentioned the IRT booking system, which effectively pools production slots for the manufacturer across a program. We accept visit date requests across studies within the program, running an algorithm to assign slots to each site that submitted requests in a way that shares and maximizes capacity.

Tracking whether stock is in short supply has been a topic of significant focus, particularly in terms of options that may exist and how to handle medication pooling across studies. For example, kits might be made available to any protocol until they are released, from which point they are exclusively for that specific protocol, guaranteeing it a certain, dedicated manufacturing volume. As noted above, the challenges are just-in-time manufacturing capacity and dispensation, not inventory, to ensure participant visits are successful. But, if quantity presents a problem, the IRT toolbox also provides options for tooling.

Key takeaways

• Personalized Medicine trials involve very specific challenges of expiry, visit & personalized shipment management
• The chain of events for patient shipments & visits differs greatly from a typical trial
• An RTSM solution which can be tailored can support specific challenges
• Engage early with IRT/RTSM experts to ensure the system can meet the challenges