Three Months Too Late: How Late Decisions Create Clinical Supply Challenges
By Rachel Grabenhofer, Chief Editor, Clinical Supply Leader
By this point, my previous conversations had largely moved beyond protocol structure and translation. The recurring question was no longer how requirements are interpreted, but when their operational implications are recognized.
When asked what would most effectively close the gap between scientific intent and operational execution, Luis Rodriguez, who at the time of this interview was an independent RTSM-EDC integration consultant and founder of Luis Rodriguez Consulting, immediately answered: timing.
“Most of the time, we discover expensive supply or operations protocol decisions only after those decisions are locked into approved documents. At that point, the protocol is approved and the only remaining option is often to absorb the cost rather than influence the decision,” Rodriguez explained. “Almost every downstream workaround I've seen was a fix for a conversation that happened three months too late.”
When Operational Implications Are Identified Too Late
Sandra Moss, head of operations excellence at Parabilis Medicines, described the same challenge through a different lens. “Let's say I want to conduct a study in the U.S., Canada, Japan, Brazil, and South Korea. Typically, I might assume the first patient enrollment will happen in the U.S. or Canada based on historical regulatory review timelines.” But then, she learns that South Korea’s government has changed and it is accelerating its review process. “Knowing this, I would begin prioritizing South Korea alongside the U.S. and Canada,” she said. “I'm also going to prioritize the IRT setup, ECOS setup, and all the other startup activities.”
If this shift has not yet been communicated to clinical supply, however, and the label and packaging requirements for South Korea aren't ready to meet that timeline, it doesn't matter what other preparations have been made. “That information on South Korea isn't going to be in the 100-page protocol,” explained Moss. “To have that dialogue and maintain the cross-functional rhythm of operations is key.”
Ana-Zeralda Canals-Hamann, Ph.D., associate director of clinical trial supplies at Debiopharm, illustrated the issue from a clinical supply perspective. “Definitely most supply challenges are caused by communication, timing and stakeholder alignment issues,” she wrote. “For example, if clinical operations or the medical team made agile decisions without consulting supply, physical lead times could become brick walls.”
She elaborated that if clinical operations sees patient recruitment is lagging and decides to add three new countries to boost enrollment, supply may be informed too late to prepare for the change. “The existing drug supply might not have the required language translations on the labels for the new countries,” she noted. “And import licenses may not yet have been requested. In this scenario, the new sites might be activated and ready to enroll, but the drug is not yet ready to be provided to those sites.”
The examples from Rodriguez, Moss, and Canals-Hamann point to a common conclusion: execution challenges often arise not because of the protocol itself, but because its operational implications are recognized too late. The information exists. The challenge is getting it to the right stakeholders early enough to influence decisions before teams are forced to rely on workarounds.
Clinical Supply as a Strategic Partner
One way to prevent conversations from happening three months too late is to ensure the experts who can identify operational consequences are involved before decisions are fixed. This includes clinical supply. “If clinical supply is involved early, logistical traps can be flagged before they are finalized,” Canals-Hamann emphasized. For example, they might identify that changing a patient's visit window from 7 to 14 days will greatly reduce the amount of buffer stock that sites need to hold. “Or they might suggest standardizing a complex titration schedule to reduce the number of unique kit types required.”
In fact, Canals-Hamann suggested raising clinical supply’s involvement to a level above protocol design. “Instead of being treated as downstream order takers, clinical supply should be granted a seat at the table during the very early stages at program level, not just during the early protocol drafting phases,” she explained.
Why? Because small adjustments to the protocol design can save millions of dollars and months of time in the supply chain, according to Canals-Hamann. “If included at program level, clinical supply could plan for the same drug to be provided to all the studies when considerations like pooling studies and master protocols are essential to reducing waste.”
She added that supply teams could also identify countries where importation requirements, costs, or delivery timelines might significantly affect study execution. And, recommend countries where the study might be easier or harder, or more expensive, or where delivery timelines are very different. “Proactive alignment turns the supply chain into a strategic advantage rather than a bottleneck,” Canals-Hamann underscored.
What Protocol Standardization Can and Cannot Solve
It is worth noting that throughout my discussions, none of the experts described a dynamic where teams were working from conflicting protocol versions or relying on uncontrolled documents. Most organizations have internal processes, templates, and governance mechanisms in place to maintain a common source of truth. The challenges discussed tended to emerge after that starting point.
Still, it made me wonder what protocol standardization could potentially solve for clinical supply. Rodriguez sees a practical advantage. "One benefit is simply locating information," he said. "If everybody understands the protocol structure, reviewers know where to find what they need."
Another potential gain is reducing manual transcription and re-entry work. “M11 includes guidelines, templates, and technical specifications,” Rodriguez explained. “The technical specifications are particularly exciting because they're machine-readable.” This means information such as visit schedules could potentially be extracted and translated more efficiently into RTSM specifications. “It removes an entire class of manual transcription errors,” he added.
Perhaps the greatest value of M11 to clinical supply, however, is making protocol amendments easier to evaluate. "One of the biggest benefits for supply teams is amendment impact assessment," Rodriguez highlighted. For example, if a new stratification factor is added or visit windows change, supply needs to know as early as possible because that could affect forecasting and inventory. “A structured M11 protocol makes it easier to identify where changes occurred and understand their potential impact. That helps supply teams adapt faster,” Rodriguez summarized.
Yet Rodriguez is careful not to overstate what standardization alone can achieve. "You gain conformance, but not necessarily correctness. Judgement and clarification are still required." A standardized protocol may help ensure information is organized consistently and exchanged more efficiently, but it cannot determine whether a study is operationally feasible, whether important assumptions are realistic, or whether stakeholders recognize downstream implications early enough to act on them.
Viewed through this lens, M11 and similar initiatives address an important piece of the study execution puzzle. Making protocol information easier to locate, exchange, and reuse may reduce friction across the clinical trial ecosystem and help teams respond more efficiently to protocol changes. But as my interviews suggest, that successful execution ultimately depends on more than the protocol itself.
Beyond The Trial Protocol
When I started down this rabbit hole, I expected conversations would reveal the benefits of standardizing protocol information. Instead, experts described the pain points of operationalizing it.
M11 may make protocol information easier to locate, exchange, and assess, but the challenges described by Moss, Rodriguez, and Canals-Hamann largely emerged after that information was already available – when protocol design met operational reality, scientific intent required translating, and critical conversations happened too late.
The protocol may be the starting point, but execution determines a trial's success. That requires understanding the downstream implications of upstream decisions and recognizing them early enough to correct the course.
Rodriguez captured the latter succinctly: "Almost every downstream workaround I've seen was a fix for a conversation that happened three months too late."
About The Experts
Sandra Moss is head of operations excellence at Parabilis Medicines, where she leads systems design, processes, and operational frameworks for the organization. She previously spent more than a decade in leadership roles at Amgen, including as global head of strategic procurement for development, and regional head of clinical trial site management for North and South America.
Ana-Zeralda Canals Hamann, Ph.D., is Associate Director of Clinical Trial Supplies at Debiopharm. She has more than a decade in sponsor-side pharmaceutical clinical operations, CMC, supply chain management, regulatory, IP, project management, and preclinical services. Her experience includes various roles at Sanifit Therapeutics, where she managed clinical trials between Phase I and III, as well as the supply chain. Canals Hamann earned her M.Sc. in clinical research administration and a Ph.D. in molecular medicine from the University of Oxford.
Luis Rodriguez, MBA, specializes in RTSM/IRT and the integrations that connect it to EDC, eCOA and drug supply forecasting. He spent nearly five years at Suvoda, finishing as Project Manager II, Delivery Lead. He led a team that delivered more than 100 RTSM-EDC integrations across oncology, CNS and rare disease studies, facilitating efforts to improve specification templates and delivery processes, which cut delivery times in half. At the time of this interview, he was an independent consultant focused on RTSM-EDC integrations and AI adoption for clinical data teams.