Part 1 – Central vs. Local Medication Sourcing

The randomization and trial supply management (RTSM) needs of clinical trials are complex. But, sponsors who leverage robust interactive response technology (IRT) systems can tackle the complexities – often without knowing they exist – in even the most complicated study designs, those involving oncology treatments.

There are many RTSM challenges in oncology trials, including the inherent unknowns regarding the number of visits each patient will complete, the need for different visit schedules per arm (as well as the difference between visits and cycles), and the topic we cover here: central vs local sourcing of standard-of-care treatments.

Tracking Different Medication Types

Multi-center oncology studies recruit across many countries and may require the management of many different medication types, as patients receive the standard of care treatment for their diagnosis in addition to the investigational medical product (IMP). The sourcing of standard-of-care treatments can differ based on each site’s location and may vary from IMP that’s sourced centrally. Sites in one country may need the IRT system to track and manage stocks of centrally sourced treatments, whereas sites in another country may be able to buy sufficient stocks locally.

In the scenario where medication is locally sourced, the labels on that medication do not include unique kit numbers that are identifiable by the IRT system. So, while the centrally sourced medication labels include specific kit numbers assigned to subjects, dispensing information, and expiration dates that are maintained in the IRT system, the same is not true for locally sourced medications.

Local Sourcing	→	Medication that is not uniquely labelled and is not allocated by IRT (assumed available)
Central Sourcing	→	Medication that is uniquely labelled and is assigned by IRT (specific kit numbers assigned to subjects)

In some circumstances, medication sourced locally could be labeled and released into the IRT or, alternatively, the medication could be released into the IRT as a pure “quantity” of non-uniquely labeled kits via dummy kit numbers. However, these options are not generally utilized, as they assume the medication is stored at a central depot.  Shipments to the sites may not be required when the medication is truly sourced local to the site.

Other solutions may be investigated, such as a stock level adjustment transaction to update the IRT with local site stocks. However, the risk of non-compliance may negate the benefits of its application.  Instead, the most common case is that medications sourced locally are handled external to the IRT entirely for shipping and dispensing considerations.

When this becomes challenging is at the beginning of each medication assignment visit, the IRT conducts a medication requirement check to ensure that suitable medication is available on-site for a successful visit. If medication is sourced locally and not tracked in the IRT, it will not be included in these checks, and is assumed to always be available.

Inappropriate medication checks can be detrimental to the course of the trial, as they could result in a failed patient visit if the medication that the IRT does not track isn’t available. It could also result in a skipped randomization record and forcing to the treatment that we assume is always available, in the case where forcing is allowed and the medication type we track is depleted.

Trial Length

Oncology trials are typically very long, with patients remaining in the protocol until disease progression. Monitoring patient progression will be a key focus and there could be an extension of the IRT visit schedule to accommodate survival beyond initial expectations.

In addition, the longer the trial, the more likely that circumstances will arise dictating changes in how medication is sourced. This could occur if the availability of the locally sourced medication changes, for example, the need to centrally source is removed through greater local availability of the standard of care treatment, or alternatively, the local source has become scarce or burdensome for the sites to source. And/or the country could also need to change from local sourcing to central sourcing or vice versa for an individual medication type during the live study.

Any change to medication sourcing will have an impact on medication checks, IRT dispensing schedules, visit reporting information, and shipments to sites; if not managed well, the IRT could resupply sites with kits they do not require, which contributes to excessive drug wastage, or alternatively fail to supply the medication that is needed by the site.

The Need for Flexibility

It’s important that your IRT system has the flexibility needed to accommodate central and locally sourced medication, as well as supply changes that can occur during lengthy oncology trials.

Calyx’s IRT solution can apply both central and local sourcing within the same trial and is adaptable to switch on a per-kit type basis within a country from central to local sourcing (and vice versa) during lengthy oncology trials. When sourcing is switched for an individual kit type within a country, Calyx IRT also automatically changes all the associated functionality discussed, which avoids the need for clinical supply manager action &/or programming changes.

Successfully used in over 600 oncology trials to date, Calyx IRT conducts intelligent medication checks during dispensing visits to avoid “false” failed randomizations and is designed to distribute all remaining kits at sites before switching to local sourcing to reduce excessive medication wastage.

What is Calyx’s approach to sending Data/Reports that are requested by DTRF (e.g., via email, to a safe location) or does it only lie on the requestor’s (sponsor) decision?

How does stratifying by site impact the blind? Does it make it better or worse?

What is Calyx’s stance on randomization caps? Specifically, treatment arm caps?

Do you see an up-tick in usage of baseline adaptive algorithms (e.g., minimization and its extensions) to mitigate the risks associated with a rand list? Any specific blinding considerations with baseline adaptive algorithms?

Supply chain experts behind Calyx IRT deliver valuable service to improve clinical trial efficiencies

Nottingham, England and Morrisville, NC – March 7, 2023 – Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced the availability of Calyx Supply Simulation, a clinical trial supply forecasting service available through Calyx’s in-house expert statistical design and trial supplies consultants.

Clinical trial sponsors can leverage the simulation service to inform decision-making related to the quantity of medication produced for use in clinical development. The service helps sponsors improve clinical trial efficiencies by evaluating the amount of medication required to start and maintain clinical trial enrolment, predicting how long an existing amount of study medication will last, and determining the optimal site and depot buffer stock quantities required to ensure dispensation while reducing the cost and burden of excessive drug wastage.

“We’re pleased to offer this valuable service so that global clinical trial sponsors can reduce the risk of drug availability impacting their clinical studies as patients progress through the dispensing events of clinical trials,” said Juan Munoz Pujol. “In addition, by optimizing supply requirements upfront with Calyx Supply Simulation, sponsors can minimize the amount of drugs that end up destroyed during clinical trials, which will reduce excessive drug wastage and help sponsors meet their corporate sustainability goals.”

Calyx’s team of expert supply chain analysts – who bring a collective 100 years of experience in Randomization and Trial Supply Management (RTSM) – work closely with each trial sponsor to understand their specific challenges and tailor the simulation to meet their unique needs. Based on sophisticated simulation modelling methodology and using over 50 design parameters that closely mimic an Interactive Response Technology (IRT) system, Calyx Supply Simulation considers multiple, real-life fixed and variable domains and the ‘what if’ scenarios that often occur during clinical trials.

Click here for more information on Calyx Supply Simulation.

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

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.

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.

Calyx advanced inventory management strategies can reduce clinical trial drug wastage by up to 50%

Nottingham, England and Morrisville, NC – November 22, 2022 – Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, announced today that a Top 10 pharmaceutical company is leveraging medication pooling, an advanced inventory management strategy available through Calyx IRT (interactive response technology), to improve drug distribution efficiencies and reduce drug wastage in an ongoing, global clinical development program.

The Top 10 pharma company is benefitting from Calyx’s proven solution which supports medication pooling and just-in-time labelling across multiple studies in their program. Calyx IRT medication pooling enables study drug to be shared across multiple protocols, enabling trial sponsors to reduce the impact of excessive drug wastage typically incurred during drug development.

“In addition to reducing drug wastage, medication pooling delivers an effective solution for addressing scarcity concerns and other restrictions which affect the supply of medication during clinical trials,” said Malcolm Morrissey, Head of Statistical Design and Trial Supplies at Calyx.

Medication pooling is possible when a suite of studies or programs use the same medication. The Top 10 pharma company implemented IRT medication pooling for a suite of five studies involving nearly 500 sites using 20 depots across 30 countries. In the first year of the program, Calyx has managed 1.5 million packs of a dozen medication types.

This latest innovation around pooled medication has already been deployed in 80 trials to date across North America, Europe, and Asia. IRT medication pooling is one of Calyx’s many advanced inventory management strategies that could help trial sponsors reduce drug wastage by up to 50%.

Click here for more information on how Calyx IRT self-service tools and other advanced functionality drives clinical trial success.

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

Contact:

Christine Tobin | [email protected] | +1 412-628-8598