Complexity in Clinical Trials: Overcoming Operational Challenges with RTSM/IRT Solutions
By: Libbi Rickenbacher, Senior Director, Product Strategy and Partnerships, 4G Clinical
Complexity in Clinical Trials: Overcoming Operational Challenges with RTSM/IRT Solutions
By: Libbi Rickenbacher, Senior Director, Product Strategy and Partnerships, 4G Clinical
As today’s clinical trials continue to evolve and operational complexities continue to increase, it is essential to have an experienced RTSM partner who knows how to adapt to change and serve as an extension of your clinical study team.
Clinical researchers are becoming much more creative in how they explore possible treatments. They are leveraging more adaptive trials where phases can be combined or skipped based on positive results, or where the protocol is amended to explore new treatments or disease states within the same trial. This approach allows researchers to follow the science throughout clinical development, and not waste time and resources on what is not working.
This creativity has led to an increase in clinical trial complexity, creating a cascade of considerations impacting everything from protocol design through the resulting flexible supply chain infrastructure required to support modern trials.
As trial complexity continues to increase, the technology supporting them has responded with intuitive innovative solutions, significantly reducing complex study burden.
What Makes Trials Complex?
When considering complex clinical trials, it is easy to focus on early-phase dose finding/dose escalation oncology studies. When in reality, there is complexity throughout clinical development, no matter what type of study is being conducted.
Protocol complexity arises from a multitude of factors, with one of the main drivers being uncertainty. For example, variability in the patient journey is a major source of uncertainty. This stems from demographic data values including titrations, weight groups and BSA categories, all the way to adapting the protocols to follow the science as certain treatments prove most effective.
As trials progress, complexities within the protocol design have a ripple effect on both the supply chain as well as the end- users of the RTSM. Supply complexity can be introduced as more sites engage in smaller studies, all the way to global expansion. Complexity can also come into play with kit design, not having the correct concentration or formulation for your recommended dose levels, or with your resupply strategies as you incorporate new stability data.
The technology used to support these trials, however, can help simplify the complex and help manage the uncertain. It is more important than ever to partner with an organization that has the depth of experience in complex studies and is powered by modern, flexible RTSM technology.
Operational Challenges Addressed in the RTSM/IRT
Complex clinical trials require intensive peer-level interaction and agreement between clinicians (community of investigators, clinical researchers), methodology experts (statisticians, biometricians, modeling and simulation experts) and project teams (organization, performance of trial) about the choices in scope (subjects and conditions to be included), main design features (medicinal products, arms, endpoints) and adaptations.
RTSM/IRT solutions can enable complex protocol designs by mitigating potential challenges inherent to the choice of complex design elements.
Below are 6 operational challenges that stem from complex clinical trial designs that are supported by the RTSM/IRT.
1. Amendments
Implementing new amendments due to protocol changes are very common during complex clinical trial conduct.
According to Tufts CSDD:
“Less complex protocols — those containing fewer procedures and eligibility criteria — averaged two amendments; more complex protocols averaged 3.2 amendments.”
These amendments delay studies and add incremental cost. Applying an amendment to an ongoing protocol may result in design changes, which can include dose modifications. The RTSM/IRT helps alleviate some of these challenges by enabling these changes as planned amendments within the system.
This can save time and cost for all involved. A structured training plan that instructs individual sites to apply the amendments and allows the RTSM/IRT to be updated and changed on a per site basis alleviates the possibility of amendment launch delays. For those amendments that cannot be planned, a quick turnaround, a good understanding of the protocol and a highly flexible system is required to support it.
So to summarize, to create a more stable process for amendments, sponsors should:
- Understand and address unknown variables within the protocol itself
- Build in as much flexibility into the RTSM system (advanced cohort management for example, backup arms, etc.)
- Plan for future study amendments (pre-validated test scripts)
2. Dose Finding Studies
Dose finding studies add burden on the site staff due to entering patient data and parameters into different systems, calculations, and multi-check procedures. These procedures introduce the risk of mis-dosing patients. Those errors are not uncommon occurrences, especially for IV therapy.
Modern RTSM systems can be set up to make it more difficult to commit an error in the administration process. For example, if the site is allowed to enter raw data and the RTSM calculates dosage where the investigator is empowered to make decisions, some mistakes can be prevented and therefore increases patient safety. Adding more visibility of the drug and streamlining the process with the IRT are critical for patient safety and to prevent wrong drug errors.
3. Staffing and Resources
To manage a complex trial, experienced personnel on the site and the CRO are required. Within the current landscape, staff shortages and retention challenges in combination with a reduction in average years of experience is adding complexity to the management of clinical trials. Selecting sites with the needed expertise and working with CROs that have resources to support these trials is increasingly difficult.
4. Decentralized Clinical Trials (DCT)
COVID-19 has been a catalyst for the development of contingency plans globally and the running of DCT trials. There are several layers of complexity running a DCT trial. For sites, it means supporting two processes including traditional visits at sites and remote visits and allowing those DCT elements virtually, such as ePRO reporting, Direct to Patient shipment, etc.
In order to allow those processes, one of the main areas of focus today is how to handle the Patient Health Information (PHI) and be compliant with GDPR and HIPPA requirements. PHI handling is complex due to the differing regulatory status per country that is difficult to ascertain.
Sites struggle today with the burden it brings because they must collect the data from patients and must pass it to the right vendor each time, while complying with regulations and focusing on the patient’s safety. There are many challenges along the way including technological issues and frequent communication to keep everything on track.
Using an RTSM/IRT to store this information centrally in an encrypted manner can meet local requirements and allow for more efficiencies by eliminating the need to enter the data per each shipment to the patient home and using manual forms that can be passed between key stakeholders. Instead, only the relevant people receive the data when needed.
5. Study Operational Queries
By speaking with CRAs and Sponsor site support teams, we’ve uncovered a high correlation between an increase in queries due to complexity, which eventually requires more Sponsor and CRA support for site users. Adding more training and guidelines during the process, and tracking who received training in the IRT can help determine gaps in real time, remove burden from sites and sponsors in managing that and documenting the training records and also meet current regulatory requirements.
6. Data Integrity
The amount of data collected throughout complex clinical trials is growing. As this happens, data integrity becomes even more crucial for the success of the trial. Challenges arise when determining the source of truth, viewing the trial holistically and defining the right integration flow (CRF, RTSM, EDC, etc.). Alignment must be reached between data managers and the clinical staff to incorporate the site journey into those decisions. Using modern integration technology requires less time due to streamlining processes and less reliance on entering the same data into multiple systems.
Leaders in Complex Trials
Oftentimes technology has limited what is possible in clinical trials. 4G Clinical’s Prancer RTSM® has changed that. With a dedicated focus on complex studies since inception, Prancer RTSM® continues to support even the most intricate study designs.
The core functionality within Prancer RTSM® has enormous flexibility to support even the most radical patient flow. Combine that with the ability to add bespoke features and you can be as creative as you need to be in the design and execution of your trials. If bespoke requirements are needed to support future trials, we can incorporate them into the core product as a dedicated feature. This way, Prancer RTSM® continuously evolves to support complex trial needs.to support even the most intricate study designs.
Beyond the feature set, Prancer RTSM® supports complex studies through our iterative design process. Our goal is to make building a complex system as simple to review as possible, giving you the opportunity to visualize your protocol in our system and adjust prior to spec signature.
While the system design can be complex, the build experience should be straightforward - and you get to iterate on the design to make sure the system is intuitive for your sites. The design can also support many self-service capabilities, removing the burden of contacting support for simple, routine changes as well as more advanced changes including cohort or dose modifications.
As today’s complex trials evolve, it is essential to have a partner who knows how to adapt to change, and how to update the study for optimal outcomes. 4G Clinical’s team brings hundreds of years of cumulative experience in clinical trial development to the table, across all therapeutic areas and indications, always keeping the patient at the forefront of our work.
4G Clinical’s thought leaders and clinical study experts remain a steadfast resource throughout the clinical trial, providing sound advice for every aspect of your study, no matter where the science leads, or where your patients reside.
ABOUT Libbi Rickenbacher
Libbi Rickenbacher, Senior Director of Product Strategy and Partnerships at 4G Clinical, has more than 15 years of experience in the field of life science, and is an e-clinical RTSM solutions subject matter expert. Her expertise lies at identifying trends and opportunities considering operational business processes, product opportunities and managing partnerships with market leading solutions to drive strategic initiatives. Libbi is an enthusiastic team player passionate about creating opportunities and innovative direction to improve the clinical trial experience for end user stakeholders and patients. Libbi holds a BA in both Neuroscience and Psychology and a Doctorate (PhD) in Neuroscience.
