An RTSM, or Randomization and Trial Supply Management system, is responsible for enabling critical functions of a clinical trial, from randomizing patients (who gets the active drug vs. the placebo), dispensing drug (ensuring patients receive the correct dose) and site resupply (controls the flow of drug from the manufacturer to the depot to the clinical site).
From inception, the RTSM system has gone through many iterations. Early randomization practices were performed manually. Patient-numbered kit labels were shipped to all sites in (generally) full blocks corresponding to the full course of treatments for a study. This method resulted in enormous amount of wasted supply.
Then in the 1990’s and 2000’s, IVRS (Interactive Voice Response Systems), IWRS (Interactive Web Response Systems) and IxRS (a term coined for either IVRS or IXRS with the x being a variable) were developed to randomize patients over the phone, and later, over the web. For the first time, all patient kits could be interchangeable for any other equivalent kit.
Today, the most widely used term in the industry today for our systems is IRT. IRT (Interactive Response Technologies) is considered more of an umbrella term that encompasses all modalities (voice, web and even mobile).
Historically, IRT systems were used primarily for randomization and getting drug to the site. Over time, it became apparent that supply management was just as critical as randomization and the combined action of them together elevated the functionality of the system.
Enter the modern, 100% configurable RTSM. There is a treasure-trove of data housed in RTSM systems that can be used to streamline and accelerate clinical trials – both operationally and to enable supply chain optimization.
In order to reap the full benefits of an RTSM, you must take the following guidelines into considerations.
When it comes to the management of RTSM systems no industry standard exists. Many organizations have internal RTSM standards, but across organizations they are managed very differently. Here are 7 steps to help you reap the full benefits of a modern RTSM.
1. Develop RTSM Strategy in Tandem with Draft Protocol
In parallel with drafting the study protocol, the operations group should begin thinking about what they need the RTSM system to do. Fundamentally, the core functions of the RTSM are randomization and trial supply management. From the study manager’s point of view, the RTSM is responsible for patient tracking, medication dispensation, cohort management as well as site activation, enrollment and maintaining the study blind. From the supply manager’s point of view, the RTSM is responsible for inventory management, drug accountability and reconciliation.
2. Create a Data Strategy – Inputs, Outputs and Systems Integrations
A key to success is beginning with the end in mind and working backwards. What study data will be needed from the RTSM once the study is completed? By whom and for what purpose? Who should have access to the information? What reports do you need? What is your audit preparedness strategy? What data will you need on an ongoing basis to support interim analyses? Daily study oversight? The answers to these questions inform your RTSM reporting requirements.
3. Align Supply Strategy
Before designing the RTSM, there are several core supply decisions that need to be made. How will supply release information be entered in the RTSM; lot management features or a data integration? Resupply parameters? Answers to these questions directly impact the RTSM design and can be very challenging to add to the system after the fact, depending on the flexibility of your RTSM. The next step is to conduct an internal assessment on forecasting capabilities. What forecasting tools are available to support your trial? Is this tool built into the RTSM itself or separate systems?
4. Qualify Your Vendors
The bio/pharmaceutical industry is a heavily regulated industry. RTSM systems must be validated for their intended use according to an established protocol. Any changes to the system must be validated and the results documented. While vendors must build and validate the system, sponsors must be able to show proper oversight and quality controls over their clinical trial operations.
5. Assign an Internal RTSM SME
In many sponsor organizations, there may not be a clear strategy for the RTSM after system go-live. In addition, as many clinical trial teams change the RTSM knowledge may be lost through transition. To combat this, an internal RTSM SME should be designated as part of the study start-up plan. This person can also focus on standardizing systems across studies and programs where applicable.
6. Simplify the Specification Process for Your Study Team
Traditionally, the IRT system design process is cumbersome and complex. A 200+ page specification document is drafted from the final protocol and clinical study team members must review and sign-off on complex technical information they may not fully understand.
As technology evolves, the 4th generation of RTSM using agile software development methodologies and natural language processing (NLP) is being applied to disrupt this process. Today, study teams no longer need to approve 200+ page specification documents – they approve the actual system. The fully deployable system is delivered before the specs are even signed, and in some cases, in a demo state before seeing the actual spec for the first time.
7. Understand What Level of UAT is Necessary
While the vendor is responsible to ensure the system is properly validated to perform to requirements, sponsors need to accept the system for use. This process called UAT, involves having the trial sponsor interact with the system and signing-off that it works as intended - or is fit-for-purpose.
"'How much validation is enough?' is a question that all sponsors struggle with. By focusing on those areas that introduce the highest risk to the study; particularly those that are not sufficiently covered by the vendor – should help sponsors hone in to exactly what they need to do to complete the validation of their RTSM."
Drive Operational Efficiencies in Phase 1 Clinical Trials
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. With the increasing complexity of today’s trials, scale is no longer the determining factor when choosing to implement an RTSM. With the trend towards 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.
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.
Leverage an RTSM for Investigator Sponsored Trials (IST) Supply Chain Optimization
Although not traditional, using a modern, flexible RTSM for ISTs provides the sponsor with several key benefits. Manual management of the IST supply is not scalable, so with an increasing number of ISTs, automation of this process is critical. Other key benefits include avoiding waste, pooling supply across all ISTs in that program, transparency of IST status and maintaining a record of shipments to facilitate sunshine reporting. Most importantly, an RTSM system helps sponsors track and project demand for all manufacturer sponsored studies and ISTs, accounting for the use of both commercial and clinical drug product.
The caveat? For this approach to work, sponsors must work collaboratively with sites to ensure the system is used properly. There needs to be a clear communication strategy, and possibly retraining, with the sites on this new approach.
Learn More: IST Supply Chain Optimization
Enable Creativity in Early-Phase Oncology Trials
Depending on where the science leads, Oncology trials often experience several protocol amendments throughout the duration of the study to adapt to new information (dose titration, adding combination therapies, new dosing schedules, etc.) In order to enable innovations in study designs and adjust to changes in your protocol based on what is working, your RTSM must include flexible cohort management functionality.
A modern, 100% configurable RTSM system should not only off the ability to support creative designs, it should provide real-time updates, enrollment and supply management, flexibility built into the system and full transparency into changes with robust audit trail capabilities.
"The challenge is that most clinical systems are not flexible enough to adapt to mid-study changes without trial disruption. To address these challenges, it is crucial for sponsors to have a robust RTSM and specifically cohort management functionality in place.”
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