Adaptive Clinical Trials: Innovation with Hidden Challenges
Clinical trials aren’t what they used to be — and that’s by design. Gone are the days when every study marched forward in a straight line, rigid from start to finish. In fields like oncology, where the pace of discovery is relentless and patient needs are urgent, researchers are trading static protocols for something far more flexible. Adaptive trial designs have started to shift the research landscape, offering real-time responsiveness and the ability to pivot as new information emerges (Woodcock & LaVange, 2017). These studies can open or close arms midstream, tailor treatments to biomarkers, and reduce the time it takes to reach meaningful results. It’s a welcome shift, especially in fast-moving therapeutic areas. But what’s often left out of the conversation is how much behind-the-scenes effort it takes to keep these complex studies running smoothly —especially for the teams on the ground who make them happen.
Adaptive trial designs come in several flavors, each offering a different kind of flexibility. In an umbrella trial, multiple targeted therapies are tested simultaneously within a single disease, with patients stratified by specific biomarkers or mutations. Basket trials, on the other hand, flip that structure: a single therapy is tested across multiple diseases that share a common molecular trait (Park et al., 2019). Platform trials go a step further, serving as open-ended frameworks where new arms can be added or removed over time, often based on interim results (Berry et al., 2015). These models are particularly well-suited for oncology, where genetic diversity across tumors makes traditional trial designs less efficient. Adaptive designs not only increase the chances of identifying effective treatments but also reduce the number of patients exposed to ineffective ones, ultimately making research more ethical and efficient (FDA, 2018).
One of the most immediate operational challenges with adaptive trials shows up in the pharmacy. Each trial arm might involve a different drug formulation, dose schedule, storage requirement, or blinding procedure—and those parameters can change mid-study. At a leading academic cancer center in Seattle, investigational drug service (IDS) pharmacists often describe these trials as managing five or six studies under a single protocol. Adjustments must be made quickly and accurately. Inventory systems must reflect real-time changes, compounding procedures must remain consistent with protocol updates, and pharmacy staff need to stay in the loop as new amendments roll in (Zarin et al., 2022). Tools like Vestigo have become essential, allowing for automated tracking, inventory alerts, and documentation standardization across active trial arms. Vestigo led to an 83% reduction in documentation time and an 80–85% decrease in physical workbook usage, highlighting its efficiency in managing complex clinical trials. (McCreadie Group, 2021).
Adaptive Trials Are Progress. Let’s Support Them
The science is faster and more focused, but to thrive, adaptive trials need strong systems and well-supported teams behind them.
Investing in tools and teams is how we make innovation sustainable.
Outside the pharmacy, adaptive trials place a heavy burden on coordination and compliance teams. Study coordinators must navigate complex eligibility criteria that shift with each new arm or amendment. They’re also responsible for re-consenting patients, adjusting visit schedules, and ensuring protocol compliance—all in a moving landscape. Regulatory teams face frequent submissions to the IRB, manage updates across multiple stakeholders, and respond to sponsor queries on tight timelines. Billing staff must continuously reassess which services are routine care versus research-only—a task that becomes increasingly difficult as new arms introduce different procedures (Rosenfeld et al., 2020). These demands require not just time but a high level of precision, flexibility, and cross-functional communication.
Even though adaptive designs are celebrated for their efficiency, they can quickly become resource-intensive if the right systems aren’t in place. Internal reviews at several NCI-designated centers have shown that platform trials, while representing only 30–40% of the trial portfolio, can consume over half of a site’s IDS staffing hours (Roberts et al., 2021). Without scalable tools and processes, sites risk activation delays, protocol deviations, and staff burnout (Kim et al., 2020). Some centers have been proactive in addressing these risks by investing in software like Vestigo, developing detailed SOPs, and improving interdepartmental coordination. But even at well-resourced centers, adaptive trials stretch existing infrastructure to its limits.
In conclusion, adaptive trial designs offer a smarter, more responsive way to conduct clinical research. They are helping researchers match the right therapy to the right patient faster than ever before. But with that flexibility comes a cost—one that’s often paid by the research sites tasked with implementing these complex protocols. If the future of clinical trials is adaptive, then the future of clinical infrastructure must be equally agile. Technology, training, and streamlined communication will all be critical. Some institutions are leading the way, but broader system-wide investment is needed to ensure these innovations can succeed without burning out the people who make them possible.
References
Berry, S. M., Carlin, B. P., Lee, J. J., & Muller, P. (2015). Bayesian adaptive methods for clinical trials. CRC Press.
FDA (2018). Adaptive Designs for Clinical Trials of Drugs and Biologics: Guidance for Industry. U.S. Food and Drug Administration. https://www.fda.gov/media/78495/download
Kim, E. S., Bruinooge, S. S., Roberts, S., et al. (2020). Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement. Journal of Clinical Oncology, 38(2), 136–144. https://doi.org/10.1200/JCO.19.01556
McCreadie Group. (2024). Case study: Transforming clinical trial management with Vestigo. https://44954812.fs1.hubspotusercontent-na1.net/hubfs/44954812/Gated%20Content/case%20study-transforming%20clinical%20trial%20management-2024.pdf
Park, J. J. H., Siden, E., Zoratti, M. J., et al. (2019). Systematic review of basket trials, umbrella trials, and platform trials: A landscape analysis of master protocols. Trials, 20(1), 572. https://doi.org/10.1186/s13063-019-3664-1
Roberts, S. A., Parmar, M. K., & Royston, P. (2021). Design issues in adaptive platform trials with multiple interventions. BMC Medicine, 19(1), 62. https://doi.org/10.1186/s12916-021-01944-3
Rosenfeld, S., Little, R. F., & Janik, J. E. (2020). Financial and logistical implications of platform trials in cancer research. The Oncologist, 25(6), 485–492. https://doi.org/10.1634/theoncologist.2020-0021
Woodcock, J., & LaVange, L. M. (2017). Master protocols to study multiple therapies, multiple diseases, or both. New England Journal of Medicine, 377(1), 62–70. https://doi.org/10.1056/NEJMra1510062
Zarin, D. A., Goodman, S. N., & Kimmelman, J. (2022). Harms from uninformative clinical trials. JAMA, 327(12), 1155–1156. https://doi.org/10.1001/jama.2022.2527
About the Author
Felecity Estrella, PharmD
PGY2 Investigational Drugs and Research Pharmacy Resident
Fred Hutchinson Cancer Center | UW Medicine
Dr. Estrella is the PGY2 Investigational Drugs and Research Pharmacy Resident at Fred Hutchinson Cancer Center in partnership with UW Medicine. In her current role, she supports investigational drug workflows, focusing on Phase 1–3 oncology clinical trials. Her responsibilities include study start-up support, clinical review of investigational therapies, protocol compliance, and contributes to protocol reviews and operational planning with the broader research team. Felecity has played an active role in process improvement initiatives, including a quality improvement project assessing the impact of early notification on oral chemotherapy dispensing wait times. She also
contributes to workflow evaluations that improve investigational drug efficiency and patient care. Felecity’s pharmacy practice interests center on investigational drug services, oncology clinical research, and the integration of pharmacists into early-phase trial teams. She has supported initiatives related to education and workflow optimization, with a focus on investigational drug safety and efficiency. She has shared her work through institutional presentations and is interested in expanding the role of pharmacists within clinical research.
Felecity earned her Doctor of Pharmacy from the University of Washington and completed her PGY1 Pharmacy Residency at Virginia Mason Franciscan Health – St. Anne Hospital. She continues to be involved in research and pharmacy-led quality improvement initiatives through her current role at Fred Hutch.