IRT Archives

In an earlier blog, we presented how sponsors can minimize the amount of study drug wasted during clinical trials and reduce packing, shipping, and costs by pooling medication kits across a suite of protocols/programs. We shared a range of different approaches which enabled sponsors to pool medication effectively, discussed options with limited impact on the IRT set-up, and shared the rules to consider to achieve maximum benefit.

Here we answer common questions about medication pooling and how the RTSM experts behind Calyx IRT can help you determine if you can realize its benefits for your development program.

Is medication pooling very difficult to implement?

Not necessarily. Over the past few years, we’ve learned a lot from our clients about their pooling needs and are now helping sponsors implement what we’re calling an ‘entry-level’ pooling method, which is less complex as it only requires some small tweaks to their IRT functionality.

This simple pooling solution gives the drug supply manager full control over what they are releasing and where. It simplifies the medication release process by removing specification updates or the need to upload additional portions of a central program packaging list into the IRT system. With this simplified approach, all of this is now done in one central IRT area that can then automatically feed into all studies in the program.

This simple addition to your IRT set-up means you don’t have to interact with the individual studies to provide another portion of the packaging list or in the worst-case scenario, to upload the whole list into all the studies within the suite, which has its own risk (where the same kit could be released into multiple studies).

On-Demand Webinar

Medication Pooling: Minimizing Regulatory Risk and Realizing the Benefits.

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Are supply managers seeing the expected benefits of medication pooling?

Yes, but it depends on the method that’s being used, and keeping in mind the increased complexity of implementing something like just-in-time delivery. For example, supply managers have told us about challenges they’ve experienced related to their depots not being able to facilitate as much of the just-in-time labeling as was initially planned; this limits their ability to see the full benefit.

We’ve also heard from some clients who have tried other complicated pooling options that their expected return was not fully achieved. This does not mean that there was no benefit, it’s just that the benefits are more likely to be tied to the designs of the trials being pooled instead of solely the use of pooling functionality.

What study designs and supply chain approaches allow us to see the benefits of pooling?

We ran simulations to understand which standard study designs could achieve the 40% reduction in drug wastage that’s been reported. The scenarios which resulted in the biggest reductions were:

Trials being run in the same locations at the same time with the same medication types
A program targeting different populations of patients within the same countries
Trials using the same depots

The same style of protocol could produce a large benefit in comparison to protocols engaged in different, mutually exclusive countries that do not share local depots. As soon as you introduce different depots, you’re not sharing the depot stocks in an efficient way and the benefit is reduced.

Can your RTSM consultant team help us understand if we can benefit from medication pooling?

It’s important to note that a range of methods are available to you: pooling and JIT’s simplest form may not or may only minimally impact IRT/RTSM set-up and reduce concerns about regulatory approvals.

This is why it’s important to engage early. Calyx trial supplies consultants will help you explore pooling opportunities, review how to increase its benefits, and support just-in-time labelling.

A member of the expert RTSM team is assigned to every study and remains assigned to consult until its closure, however you don’t need to wait to engage with us. If you have been considering pooling your medication across a program of studies, we’re more than happy to discuss solutions.

If you’ve not had your labelling approved and you’re looking for other options, we’re also happy to provide further detail of what we’ve seen around just-in-time labelling.

If I’m running one study and want to pool a planned study with it, can this be done?

It would be ideal if you knew in advance, as you could set up the IRT system alongside the first study. But we know that’s not always possible. If you want to add a second study, some changes will need to be made to your ongoing study to create an overarching ‘parent study’.

Creating the parent study is not the same as a standard IRT build, as its primary function is only to hold the packaging list and facilitate the sharing of the kit list at the right time; it’s just a release facilitation tool.

Once the parent study is created, adding a third, fourth or fifth study is not an issue, because the framework is already set up.

If you are planning on pooling, you’re likely having that discussion early on so that shouldn’t impact IRT in this situation. This is another example of why early engagement is so important.

Learn more about medication pooling and other advanced RTSM designs available through Calyx IRT to reduce drug wastage and supply costs.

When considering Interactive Response Technology (IRT), many think only about its core functionality – ensuring effective randomization and trial supply management (RTSM) while maintaining the blind during clinical trials. However, today, these critical functions have become a baseline for what the industry expects of this technology.

Since its inception over three decades ago, IRT has evolved to meet the ever-changing needs of the clinical development industry. Gone are the days of IRT only being considered for essential RTSM functions in large, late-phase trials. Today, IRT is frequently relied on to:

Support Phase I trials
Accommodate all trial designs, including cohort and adaptive/platform trials
Perform complex calculations and logic as per complex protocols

Clinical trial sponsors also expect more from the people behind their RTSM solutions. A reliable RTSM technology vendor should act as a partner and provide expert advice and guidance about the proper and efficient implementation of their IRT system. They should work to understand and analyze each study’s unique requirements and develop a strategy to meet the trial’s goals, identify and mitigate risks, and allow flexibility for the future.

Here, we review three different study areas and present specific examples of what an advanced IRT system and the people behind it can deliver beyond the basic expectations of RTSM.

“The ‘T’ in IRT is only part of the story; for effective and efficient clinical trials, the expertise and experience of the people behind the solution are what make the difference.”

– Candice Blackwell,
Product Director, Calyx

“We relied heavily on Calyx’s IRT expertise and followed their recommendations for overcoming our studies’ complex randomization challenges, resulting in a solution that perfectly met our RTSM needs for two complex gout trials.”

– Professional Study Lead,
LG Chem

Calyx’s IRT experts routinely design RTSM solutions that ensure the right balance between treatment arms, even in protocols with complex randomization needs.

Read the Case Study

1. Your RTSM Vendor Should Enable Effective Randomization

Using RTSM technology for randomization functionality not only helps to ensure data and study integrity by eliminating bias, but it also manages the risks of randomization imbalance.

Can your RTSM vendor tackle complex randomization?

Although blocked randomization is the methodology used for most clinical trials, IRT systems are increasingly being used to accommodate highly complex dynamic allocation methods. For example, minimization helps reduce imbalances across treatment arms while considering prognostic factors such as disease stage.

Advanced RTSM technology can be used to facilitate this and other equally complex dynamic allocation methods, such as Zelen’s, hierarchical dynamic, Urn methods, and Bayesian response. Adaptive and platform studies can also be supported. You should be able to rely on your RTSM vendor to provide expert guidance on the most appropriate methodology to meet your study’s randomization needs.

2. Your IRT Vendor Should Manage Medication

One of the most challenging aspects of global clinical trials is the management and distribution of materials between contract partners, sponsors, and logistics organizations. At a minimum, an RTSM system must:

Track study drug to the smallest unit throughout its journey from QP approval/release to patient allocation to destruction
Manage the efficient supply of drug across global sites
Ensure the right drug is sent to each site at the right time for its ongoing patients
Manage expiry to remove the risk of medication expiring in the patient’s hands

Every IRT system should be expected to manage this complexity via the setting of study parameters, including depot shipping time to sites, drug expiry dates/shelf life, patient visit schedule, and treatment regimen.

Does your IRT vendor do more than core medication management?

However, simply adding IRT to a trial does not guarantee an efficient supply chain solution.

Depending upon the complexity, the number of drug types, which country each lot of medication can be used in, regions, countries, shelf-life, and patient dosing schedules, the resulting supply chain solution may function, but questions will remain around its efficiency and cost-effectiveness.

Advanced IRT technology should be able to right-size resupply shipments, help reduce waste to support sustainability goals, and prevent site stock-outs – all while maintaining the blind. Systems designed by RTSM technology vendors who understand the protocol and the sponsor’s needs will manage this complexity and:

Automatically ensure patients can be resupplied, regardless of the complexity of the visit schedule/s & patient treatment regimen
Minimize monitoring efforts by automating site resupply, adapting to real-world changes such as recruitment rate

You should be able to rely on your IRT vendor to provide expert guidance about the optimal supply settings at the start of the trial and how best to amend those settings as the study progresses.

3. Your IRT System Should Improve Data Management

The data management side of a trial usually accounts for a substantial proportion of the total cost when procedural, site monitoring and staff time are all factored in. IRT should support data management and integrity by:

Removing duplicate data entry where practical
Enabling real-time data validation
Enabling real-time guidance for users
Allowing sites to amend authorized data themselves, e.g., data of birth…

An effective IRT will be designed in alignment with each trial protocol, tailoring it to what the site sees and guiding them to enter the exact data needed at the right time for the IRT system to make patient treatment decisions.

Does your IRT system go beyond core data management?

Data stored in IRT, whether entered directly into the system by users or provided by IRT to users, should integrate with any eClinical system the sponsor utilizes e.g., EDC, preventing the need for double data entry which is subject to additional human error.

This is another area of increased complexity, as the type and number of eClinical systems the IRT needs to integrate with have grown as new eClinical technologies are being used in clinical development.

Advanced IRT technology will be able to manage integrations of all types and liaise directly with third-party vendors, from requirements gathering to user acceptance testing.

For Optimized RTSM, People Make the Real Difference

What makes the real difference for a clinical trial is not just the technology. For successful trials, your RTSM technology vendor should have expert teams in study design, randomization, trial supply management, integrations, and project management. Expert support must be available to you during the life of the trial, from a team who knows the study and the study team, who can resolve issues faced during its execution effectively and efficiently, whether expected or unexpected.

The “T” in IRT is only part of the story; as usual, expertise, experience, communication & collaboration are what really make the difference.

Learn how the team of experts behind Calyx IRT repeatedly ensure the right treatment is available for the right patient at the right time. Every time.

Updated: June 25, 2024

Sometimes a clinical trial sponsor asks their RTSM/IRT provider to deliver something which conflicts with good design principles; of course, it’s being requested for a valid reason, but will have consequences. A good provider will first seek to understand that reason by asking “Why?” and provide a solution that avoids those consequences.

Even with over 30 years of industry experience under their collective belts, Calyx’s RTSM solutions designers would never make assumptions regarding the sponsor’s needs. By understanding the reason behind a request and what the study team really wants to achieve, they can find the optimal solution while mitigating or avoiding risk. Their experience from having built and managed all types of trials gives them a deep understanding of those potential risks.

Designing the Optimal IRT for Your Trial

READ THE ARTICLE

If your IRT/RTSM provider says ’yes’ to every request without understanding your needs, you could end up with a less-than-optimal, higher-risk design that:

– Isn’t right for the life of the trial
– Isn’t easy for sites
– Doesn’t avoid data reconciliation issues
– Has no flexibility to manage future amendments
– Doesn’t meet regulatory authority obligations
– Doesn’t minimize unintentional unblinding risks
– Doesn’t best manage the specific risks of the protocol and packaging plan

At Calyx, we strive to find the right RTSM solution that meets our customers’ needs throughout the life of the trial. This includes being great communicators, from understanding those needs to explaining the “Yes but…” with proposals, solutions, recommendations, and risks.

We have the same end goal – the success of your study. For the Calyx team, success means finding the optimal design that keeps the interests of your study, your data, the sites, and ultimately the patients at heart.

When it comes to IRT/RTSM design requests, it’s not a question of ‘Can we do it?’ (that answer is always,” Yes, we can!”) It’s more a question of, ‘Should we do it?’ then ‘How can we best achieve it?’

Click here to learn how Calyx IRT design experts leverage their extensive experience to design the right RTSM solution for your clinical trial.

Evolution, Acronyms & Advances in Clinical Trials

In an industry so full of acronyms, no two are more often interchanged than IRT (Interactive Response Technology) and RTSM (Randomization and Trial Supply Management). Here we look at the system behind the letters, how over time, the terms have come to be used interchangeably, and how the technology is only one component of an effective RTSM solution.

The Evolution of IRT (or Do We Mean RTSM)

In our industry, an IRT system is a central piece of clinical trial execution that enables patient randomization and real-time drug allocation. Put simply, RTSM is the role of the IRT system. But it’s had different acronyms over the decades.

Looking back, some of us remember using 3-part, NCR paper forms for CRFs and the excessive effort that was needed for double data entry. Even once the first interactive voice response systems (IVRS) were introduced in the 1980s for randomizing patients over the phone, paper CRFs were still being used into the 1990s – including a short time when it wasn’t unusual to fax completed CRFs to get the data in faster.

Since the 2000s the internet has enabled the use of web-based systems, which were initially referred to as IWRS. This led to another, often-confusing term, IxRS, which was used to describe when study users could access the system both via the phone and the web.

Today, we’ve tossed the modality aside from the acronym and simply refer to IRT as the tool, or system, for delivering RTSM in clinical trials.

IRT’s Greatest Impact

Most would agree that IRT has delivered many benefits through the decades, but one of its greatest feats was separating randomization and drug supply into two distinct processes. Prior to IRT, randomization was built into the packaging. For example, a site would randomize a patient by selecting the lowest-numbered kit in their inventory. And this kit had all the drug intended for a patient throughout the entire study, which led to wastage in many forms.

Once IRT was established, the relationship between randomization and patient-specific supply packaging was severed. Kits could now be used for any patient, leading to a great reduction in wastage. This is perhaps the biggest impact IRT has had on clinical trials because it allowed for a more dynamic approach to both randomization and supply chain management, which we dig into deeper below.

Since 1993, the world’s leading biopharmaceutical companies and CROs repeatedly turn to Calyx IRT to meet their RTSM needs. That’s 30 years of experience built into the technology, processes, and people who understand what’s needed to ensure effective RTSM and reduce your trial risks.

Randomization: Putting the ‘R’ in RTSM

An IRT system ensures patients are randomized to the appropriate treatment arm and receive the correct medication throughout a clinical trial per the protocol.

Randomized clinical trials have long been considered the gold standard in clinical research. Using an IRT for randomization not only helps to eliminate bias to ensure data and study integrity, but it also manages the risks of randomization imbalance, or mis-dispensing, which can have implications for protocol compliance and patient safety.

If randomization is implemented incorrectly, the scientific integrity of the entire study could be called into question. However effective and reliable randomization requires more than just technology. Insight, expertise, and precise focus on the protocol’s needs are required to get randomization right, regardless of the protocol’s complexity.

Calyx’s wide range of fully validated randomization algorithms are configured to meet the needs of each individual study, and our proven IRT platform can be customized to any randomization algorithm, no matter how complex.

Calyx’s IRT experts routinely design RTSM solutions that ensure the right balance between treatment arms, even in protocols with complex randomization needs.

Read the Case Study

Trial Supply Management: Putting the ‘TSM’ in RTSM

IRT supports the challenging task of efficiently managing trial supplies/study drugs across global investigative sites, ensuring they have the right drug available for the right patient at the right time, every time.

At a minimum, an IRT must:

Track study drug to the smallest unit throughout its journey from QP approval/release to patient allocation to destruction
Manage the efficient supply of drugs across global sites
Manage expiry to remove the risk of medication expiring and interrupting patient treatment, which is especially challenging in oncology clinical trials
Minimize unblinding risks to drive the integrity of the trial

But an advanced IRT can do so much more than this. Coupling the expertise of our RTSM specialists with robust standard and advanced inventory management approaches, Calyx IRT helps you:

Reduce your Effort
Calyx IRT reduces the burden of monitoring site stock against patient needs, automatically adapting a site’s stock to its recruitment rate.

Improve your Carbon Footprint
Calyx IRT supports all of your drug supply management aims, from limiting overage and keeping wastage to a minimum, to reducing the number of shipments raised.

Execute Complex Trial Designs
Over the decades, Calyx IRT has successfully supported a range of increasingly complex trial designs – including adaptive trials – across all therapeutic areas and phases.

Improve Trial Efficiencies
Calyx’s in-house expert statistical design and trial supply consultants can run a Supply Simulation to help sponsors make informed decisions about the optimal quantity of medication to produce for use in clinical development.

Regardless of the acronym, an IRT system is fundamental to the success of a clinical trial. As you consider your RTSM needs, make sure your IRT provider has the right people and a robust solution to drive your trial’s success.

At Calyx, our RTSM specialists leverage their combined 92 years of IRT experience to advise how to best implement trial designs and account for planned or unplanned situations. They lean on their vast experience and a system based on 30 years of evolution to deliver an optimal IRT solution based on a comprehensive understanding of your protocol, packaging plan, recruitment rates, and ongoing study needs.

The result? An adaptable, flexible, and reliable system ready to meet your trial’s current and future RTSM challenges.

Learn more about Calyx IRT and how it helps you achieve successful RTSM and meet your clinical trial needs.

A Randomization and Trial Supply Management system (RTSM) is partly a risk mitigation tool. It is used by trial teams, monitoring teams, and investigative sites to reduce some of the risks related to clinical trial execution, including:

Risk of sites not having enough medication for patient visits

Risk of sites dispensing the wrong kit to patients

Risk of reaching recruitment targets without enough patients in some treatment arms, necessitating recruiting additional patients, extending study timelines, and delaying data analysis

Risk of accidentally revealing a patient’s treatment arm, voiding the patient’s participation in the trial

Although a lot of those risks are inherently managed by the RTSM system, no two trials are the same. Trial-specific adaptations require in-depth risk analysis to reduce the chance of something unwanted happening during trial execution. The process of risk identification, assessment, and mitigation is one of the most important steps in the RTSM system setup phase, one that cannot be overlooked.

Should risk analysis start from a blank piece of paper for each trial?

No, this would be a recipe for disaster. Starting the RTSM risk analysis from scratch every time would put too much reliance on the RTSM vendor’s team. They could easily miss trial risks that may not be obvious, which could lead to complications further down the line.

What the RTSM vendor should have is a list of potential risks that can be assessed by the system which the sponsor team can review to confirm if they apply to the trial. I always think that you can measure an RTSM vendor’s experience based on the length of the list of potential risks. This list will have been developed based on what the vendor has seen in previous trials. Hence, the more trials they have delivered, the more complete the list of potential risks.

Calyx IRT project teams follow a structured process when performing trial-specific risk analysis:

1. Review the list of pre-defined risks; for each risk, define the likelihood of it occurring and the severity of the impact on the trial.

2. Assess any risks that are driven directly by the trial design and environment that are not already in the pre-defined list.

3. For any risk that has a high likelihood/severity score, identify the most efficient mitigating actions. As an IRT vendor, our mitigating actions are mainly focus on reducing risks through system design. However, some mitigating actions may be owned by the study team as well.

4. Present the high risks and corresponding mitigating actions to the client team.

5. Track the completion of mitigating actions

This process is followed every time a change in the system and/or trial environment occurs, to control any impact on the IRT-related risks.

Why does expertise matter

IRT teams who have delivered RTSM systems time and time again know instinctively how to mitigate some of the trial-specific risks. Complex trials often lead to complex risks, and not all risks have been seen before. IRT experts will know how to tackle risks, even ones they have not seen before, as they know the RTSM system’s capabilities and they have access to in-house subject matter experts who will apply their knowledge to contribute to risk mitigation.

What about protocol amendments?

Changing a system during trial execution introduces new risks. You should have confidence in the experience of the IRT vendor, their established processes, and how they control change. You should also expect the vendor to review the risks logbook, refresh their risk analysis, and complete the mitigation cycle as necessary.

Risk analysis is an ongoing task, not a one-off.

Click here to learn how Calyx IRT mitigates risks throughout the entire clinical trial lifecycle to keep your development program on track.

Clinical Trial Managers have a lot to orchestrate during the study start-up phase. One of the most overwhelming aspects is setting up all the different systems that will be used to conduct the trial. Depending on the trial, the team may need up to 20 different systems, most of which will require some level of study-specific configuration.

Study teams rely on experts to help them set up each system to meet their protocol needs. Calyx IRT teams offer their expertise to CROs and sponsors, making recommendations on how the system should be set up to align with the protocol design. They know that words do not suffice when configuring a system though. Study teams, especially those who aren’t used to setting up an IRT, need to see the end result to be confident it matches their expectations.

Traditional IRT systems that rely on programmable implementation do not offer the ability to show the system as it is being built. With configurable systems like Calyx IRT, however, the team can show the system as it is being configured. The system itself becomes the center of specification discussions, instead of focusing on theoretical concepts that often do not mean much to trial teams.
With the right underlying architecture, the IRT vendor can even give the study team access to the system during the setup phase. Study teams can look around the system in their own time, allowing them to anticipate the alignment of system functionalities with end-user workflows, system understanding by non-expert users, and appropriate language usage.

Study teams experience the following benefits when seeing and interacting with the IRT system during setup:

Minimized sponsor effort during specification: We see a reduction in the number of questions asked during the specification phase when the study team can see the system as it is being configured. It helps with their understanding of the impact of the decisions they make and helps them picture what the product will look like.

Confidence that the system is as expected: Viewing and using the system early in the IRT setup process increases the study team’s confidence that the system will meet protocol requirements. Considering how stressful a trial start-up is, having confidence that a part of the start-up is covered helps study teams focus on other aspects that require their attention.

Reduction in last-minute changes: Seeing the system reduces miscommunication or misunderstanding during the specification phase, which has a knock-on effect on the UAT phase. With traditional technology, the system is first discovered during UAT, by which time there is little time left to make extensive changes to the IRT. Seeing it upfront results in smoother UAT and reduces the number of change requests raised late in the setup process.

Streamlined UAT: getting access to the system during setup allows study teams to write their UAT scripts knowing what the system looks like. It reduces the number of script errors that are traditionally discovered during UAT execution.

Visit CALYX.AI/IRT for more information on how Calyx IRT simplifies randomization and trial supply management at every step during the clinical trial lifecycle.