Navigating Complex Clinical Trials with a Flexible and Scalable RTSM Approach

This blog was written by Sheri Lillis, RTSM Solution Services Principal at Medidata.

Clinical trials continue to rapidly grow in complexity, largely driven by increasingly sophisticated protocols, both from scientific and operational perspectives.

As sponsors adopt more diverse designs, their randomization and trial supply management (RTSM) systems (sometimes referred to as interactive response technology [IRT]) must be flexible and scalable so that they can implement complex mid-study changes—both unplanned (protocol amendments) and planned (adaptive trial designs)—to alter treatments and randomization scenarios quickly and seamlessly with limited or no downtime for systems, sites, or users.

“Medidata has solved the difficulties of implementing an IRT system separate from the trial EDC. Medidata’s RTSM solution is an integrated IRT system that provides our sponsor partners with the assurance that the reconciliation of the IRT with the EDC is programmatic and validated. This is especially important for studies with complex randomization plans. Medidata RTSM streamlines workflow at the study site, saving staff time and avoiding randomization and supply errors.”

– Kathy Zheng, MPH, Director, Project Management and Clinical Innovations, PROMETRIKA

The following three areas are contributing to the rapid increase in trial complexity.

1) Unplanned Protocol Amendments

Recent years have seen a considerable rise in the number of unplanned protocol amendments. A study by the Tufts Center for the Study of Drug Development indicates that protocols across all study phases had a higher average number of substantial amendments¹ in 2018–2020 compared to 2013–2015. It was observed that 78% of phase II protocols and 69% of phase III protocols averaged 2.7 and 3.3 amendments per protocol, respectively.

This trend is especially apparent in trials with more complex designs, such as oncology and rare diseases. In oncology, Phase II protocols were found to have approximately twice the average number of substantial amendments compared to non-oncology protocols. Phase II protocols require an average of 4.3 significant amendments for rare diseases—almost 65% higher than the average for non-rare diseases.

“... the Medidata products are very innovative, and we use them to support our complex oncology studies...”

– Vijay Chundru, Senior Director, EDC Programming Team, Global Clinical Data Operations, Jazz Pharmaceuticals

2) Planned Protocol Amendments

There has been increased adoption of adaptive trial designs², such as late-phase, multi-arm, multi-stage platform trials³. Adaptive designs allow for valid and compliant preplanned mid-study changes⁴ that can maximize outcomes and efficacy with fewer trials and minimize patient safety impacts. But they require rapid responses to changes in dosing levels, formulations, and trial arms.

Our white paper, Adaptive Trial Designs Save Time and Money, and two blog posts (Revolutionizing Clinical Studies with Adaptive Trial Designs and Medidata Rave EDC Provides Proven Flexibility and Scalability) explain how adaptive designs differ from traditional, fixed-sample designs. 

3) Operational Complexities

Growing protocol complexities and unforeseen events, such as pandemics and geopolitical changes, can rapidly strain trial operations; this includes patient recruitment and retention, as well as supply chains. Modern trials must consider many scenarios that can disrupt supply chains, such as temporary product shortages due to manufacturing problems or natural disasters⁵ and the impact of trial site location on product handling and storage. This concern is elevated as the complexity and cost of clinical supplies increase, particularly with antibody-based drugs and cellular and gene therapy products.

It's critical to monitor geopolitical conditions and have contingency plans across geographical regions. For instance, when Ukraine was invaded early in 2022, this led to both direct and indirect delays in clinical trials⁶. Such delays can have detrimental consequences since modern late-phase studies are often part of a global clinical trial network, and they may end up being underpowered due to lost data and patients lost to follow-up.

“Medidata has made a tremendous impact on how MyMD Pharmaceuticals has been able to conduct its clinical research. Medidata’s comprehensive suite of services has simplified multiple aspects of the clinical trial process, from randomization [with RTSM] to data collection and analysis. Through the platform’s intuitive interface, our research teams can confidently navigate the complexities of the trial to ensure all data elements are captured efficiently. Medidata has also helped reduce the administrative burden of data collection, allowing the research teams to focus on patient outcomes. I look forward to our continued work with Medidata and their professional services team.”

– Jenna Brager PhD, RN, Executive VP, Drug Development

Medidata’s long history of navigating complex trials ensures that these complexities can be effectively overcome by working closely with experts with extensive expertise in and industry knowledge of RTSM/IRT. Our experts have a deep understanding of randomization algorithms, complex dosing, titration schemes, and supply strategies, ensuring that your study design and RTSM processes are optimized to provide the best opportunity for your study to achieve its objectives.

“Medidata’s RTSM solution gives PROMETRIKA a competitive advantage to support our sponsors' highly complex clinical trials. The integration of IRT and EDC shortens trial implementation and validation timelines. PROMETRIKA is proud to be an accredited Medidata RTSM CRO partner.”

– Miganush Stepanians, PhD, President and CEO, PROMETRIKA

Summary

With the increasing complexity of clinical trials and the growing challenges in their execution, the need for a flexible and scalable RTSM system has never been greater. These RTSM systems can alter treatments and randomization scenarios quickly and seamlessly in response to shifting needs.

Medidata Rave RTSM, which was ranked the #1 “Most Preferred IRT Provider” in the 2022 Industry Standard Research IRT Report, provides a flexible and configurable randomization system capable of creating both traditional and modern randomization algorithms and uploading custom-designed schedules. As it is fully integrated with the Rave EDC platform, it minimizes the potential for unblinding or data errors. Medidata professional consulting services are available to aid in adopting Rave RTSM as an easy-to-use, self-service platform and meeting out-of-the-ordinary randomization requirements.

Download a copy of our white paper to learn more about how Medidata RTSM supports complex clinical trials:

References

1 Doubling Down on Protocol Amendments and Deviations, https://www.pharmoutsourcing.com/Featured-Articles/584137-Doubling-Down-on-Protocol-Amendments-and-Deviations/

2 Adaptive Design Clinical Trials: a Review of the Literature and ClinicalTrials.gov, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829673/

3 Uptake of the Multi-arm Multi-stage (MAMS) Adaptive Platform Approach: a Trial-registry Review of Late-phase Randomized Clinical Trials, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915371/

4 Adaptive Design Clinical Trials: a Review of the Literature and ClinicalTrials.gov, https://pubmed.ncbi.nlm.nih.gov/29440155/

5 Report | Drug Shortages: Root Causes and Potential Solutions, https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causes-and-potential-solutions

6 The Impact of the 2022 Ukraine/Russian Conflict on Cancer Clinical Trials, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751167/