The Hidden Work Between Protocol And Execution: Translating Requirements Into Supply Strategy
By Rachel Grabenhofer, Chief Editor, Clinical Supply Leader
A previous discussion focused on the information clinical supply teams need beyond the protocol to execute a study. Translating that information into something teams can operationalize takes it to the next level. Luis Rodriguez, who at the time of this interview was an independent RTSM-EDC integration consultant and founder of Luis Rodriguez Consulting, explained that translation layer is where much of the hidden study execution work takes place. “The protocol is intended for scientific and regulatory review. It's sufficient for those audiences, but it's not operationally sufficient,” he said.
Rodriguez is not a clinical supply strategist, but he sits at the intersection of protocol translation and operational intent, where he sees disconnects that can create downstream issues. He advised that when RTSM teams are configuring a system for clinical trial execution, core protocol contributors should be involved to clarify its intent and define the operational requirements needed for execution.
“Sometimes one or two people officially own the document, but there may be several others who really provide the operational meaning behind it,” he noted. “For example, we'll involve biostatisticians for randomization and stratification discussions. We'll also include clinical supply teams to discuss forecasting, kit types, depots, and other configurations that are not directly described in the protocol.”
Rodriguez suggested that successful study execution depends on more than the protocol itself. “The protocols, I mean, they're not wrong. It's just the translation piece of it,” he said. Before RTSM teams can configure a system, stakeholders must develop a shared understanding of how study requirements will operate in practice. Clinical supply is one of the functions that helps provide that operational context, helping teams bridge the gaps between scientific intent and operational execution.
How Protocol Requirements Become Operational Rules
“One of the gaps involves visit schedules,” said Rodriguez. “We need to understand the visit windows and what anchors them. If you have a Day 1 visit or a randomization visit, what event drives future windows? Is it anchored to randomization, Day 1, or the previous visit?” he illustrated.
He added that most protocols define Day 1, but the rules around it, such as whether windows roll forward after a delayed visit or stay fixed to the original anchor, are often left implicit. For clinical supply, that choice determines when kits can be dispensed and how demand is forecasted.
Another gap is stratification factors. “The protocol tells you what the stratification factors are, but it doesn't necessarily tell you where the source of truth comes from,” Rodriguez highlighted. “We need to know where those factors originate to build the system accurately.”
Stratification factors may include characteristics such as a person's age. These are used during randomization to ensure patients are correctly assigned per the protocol. Changes to stratification approaches can also influence randomization schemes, enrollment distributions, and ultimately the demand assumptions used by clinical supply teams. But to Rodriguez’s point, the system needs to know the source of truth for that information: is age entered directly into the RTSM or does it come from another system?
Protocol language such as continue treatment until progression creates additional ambiguity. It may be clear to a clinician, but it provides little operational guidance for an RTSM system. Supply forecasting relies on calculations working from visit schedules and projected treatment durations. Protocol language doesn't translate cleanly into operational rules. As a result, the supply team builds strategies, buffers, and forecasting assumptions to account for that uncertainty.
This is why discussions and clarifications are still necessary. According to Rodriguez, modern RTSM systems can be built quickly. It’s the interpretation, specification, review, user acceptance testing, and validation that take up most of the time. “Maybe a quarter of the timeline goes into building the system,” he explained. “The rest is spent agreeing on what should be built.”
He elaborated that sometimes stakeholders will read a single sentence and three different people will interpret it three different ways. “That's where the work happens,” Rodriguez emphasized. “We have to agree on the intended meaning and agree on how it will be operationalized before it is formalized into the specification.”
This reiterates an earlier point made by Sandra Moss, head of operations excellence at Parabilis Medicines. She emphasized that protocols are not written for clinical supply. They’re written for physicians to conduct the study and collect evidence. A protocol may outline what a study intends to do, but operations must translate that intent into something executable.
When Small Design Decisions Create Big Supply Consequences
The process of translating a protocol into execution can reveal how seemingly small decisions may have much larger consequences downstream, creating inventory, forecasting, packaging, or distribution challenges for clinical supply. “Suppose a stratification factor is added during regulatory review,” Rodriguez illustrated. “It may only be a single line in the protocol, but operationally, it has a ripple effect, requiring regenerating randomization lists, updating RTSM logic, understanding country-level impacts, and potentially changing clinical supply forecasts.”
Visit windows also create challenges, especially considering they often are intentionally broad to provide flexibility for patients and sites. This is important clinically but for supply planning, wide visit windows create forecasting uncertainty. “The broader the window, the more variability exists in drug demand,” said Rodriguez. As a result, supply teams often need larger safety buffers. Once those requirements are identified and the protocol is approved, studies typically absorb the resulting costs because changing the protocol may not be practical.
Protocol requirements can create operational challenges as well, even when they’re not outlined in the protocol. For instance, say a kit is damaged, a patient is randomized but never dosed, or a visit window becomes longer than expected. “Those situations still have to be handled operationally even though they may not appear in the protocol,” Rodriguez underscored. “If we're lucky, we identify these issues during specification review. If we're less lucky, we discover them during user acceptance testing after the system is already built.
“If we're really unlucky, the issue appears after the study is live,” Rodriguez continued. That’s when clinical operations, clinical supply, and RTSM experts must collaboratively find a workaround that preserves the study’s quality while minimizing additional cost and disruption.
Rodriguez's examples highlight another aspect of operationalization. Understanding the intent of a protocol is one thing. Recognizing its operational consequences early enough to act is another. Subsequent discussions leaned into this timing, emphasizing when consequences are identified, who identifies them, and whether there is still an opportunity to influence the outcome.
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.