Why Execution Strategy Begins at the Business Decision: Q&A with Elizabeth Walsh, Walsh Clinical Advisory

Across 25 years in clinical development, the same pattern has repeated itself: programs struggle, and the diagnosis points to vendors and operational teams—when the conditions that created the instability were established far earlier, in planning rooms where execution expertise rarely had a seat.

On the heels of the release of her new book, Applied Clinical Trials spoke with Elizabeth Walsh, PMP, ACRP-CP, founder of Walsh Clinical Advisory and co-author of The Clinical Execution Blueprint, about why outsourcing tasks does not transfer accountability, where the most consequential capability gaps accumulate, and how inspection readiness becomes impossible to fake when it is designed in from the beginning.

ACT: What gap in how sponsors think about clinical execution prompted you to write your book?

Walsh: The book came about from watching the same pattern repeat itself across organizations and across development stages for essentially 25 years. Programs will struggle, and everyone reaches for a reason at the operational level or at the vendor level. But when you really examine it, where the conditions were established is almost never there. It very often comes from an absence of real-world execution expertise having a voice in the room during early planning decisions when they're being made.

Conversely, in response to some of that instability, what we kept seeing was more process being added, more review layers, title shifts, role changes, project management pulled in as the solution. What resulted fairly consistently was more layers, more change, more complexity—without genuinely addressing sponsor oversight, control, or the underlying solutions. And the regulations, when you go back and look at them, are not asking for that complexity. ICH E6 is asking for proportionate, risk-based oversight by qualified people making informed decisions throughout the life cycle.

When you trace all of this back to its source, the same perception kept appearing. It's quiet, it's rarely examined, and it's embedded in how organizations are structured and resourced—and it is where most of the execution instability originates. The gap is inadvertent, but it is a perception that outsourcing execution transfers the accountability and ownership along with it. You can certainly outsource tasks, but you cannot outsource accountability, and you cannot outsource ownership. That will always remain with the sponsor.

The book describes four interdependent conditions that need to coexist for sponsor oversight to be real, durable, and defensible: that execution strategy begins at the business decision; that qualified people bridge scientific intent into operational reality; that execution is facilitated rather than handed off; and that oversight emerges from design, decisions, and continuous control—because clinical execution isn't just a downstream delivery function. It brings strategic input that shapes feasibility, timelines, and capital planning from that very first decision forward.

ACT: You wrote in the book that execution strategy begins at the business decision, not at study startup. Why are most sponsors still getting this part wrong?

Walsh: I think it's inadvertent. Every industry has its blind spots. The moment a decision gets made, everyone's focus is on that asset—advance that molecule, define the regulatory pathway, hit the next milestone. The second the decision gets made, the clock is ticking and the pressure is on. And in all of that noise and effort, execution gets treated as something that just happens downstream. You take your protocol, contract your vendors, and execution is somewhat plug and play. It is anything but plug and play.

The moment you decide to develop a product, the execution assumptions that accumulate will govern everything. That is actually where quality by design is beginning. You're making assumptions about feasibility, vendor scoping, which vendor is right, timelines, how long things actually take at the site, supply requirements. These assumptions start shaping everything that follows. By the time you test them at startup, they're not assumptions anymore—they're embedded in commitments. They're in your contracts, in your timelines.

The book helps explain why compressing or deferring that work, or treating it as part of startup, doesn't save time or money. It doesn't reduce risk, and it doesn't create the continuity everyone is looking for. The work isn't eliminated. It's just pushed down to where it's more expensive and more difficult to correct. Startup is not where strategy gets implemented and refined—it's the point where the quality of your earlier decisions becomes very visible.

ACT: Where do the most consequential capability gaps accumulate when scientific intent isn't properly translated into what actually happens operationally?

Walsh: The capability gaps happen right at the beginning, in the transition from protocol to execution and into clinical trial implementation. A protocol tells you what you want to learn and the data points you're going to pursue to learn it, but it doesn't tell you if it's executable at the sites with real patients, real vendors. And it certainly doesn't tell you how to implement and operationalize that. That bridging is interpretive work. It takes judgment and capability developed through experience, pattern recognition about what assumptions hold and what assumptions fail in real programs. It is not simply administrative coordination.

Another place where gaps tend to hide is in the structure of sponsor oversight roles themselves, which too often seem to be built around relaying information—passing updates from sites to the CRO to the internal team. If you look closely, that's a communication conduit, not sponsor oversight. Sponsor oversight requires independent evaluative control over what's being done and delivered, to make sure everything is staying on track and being interpreted as intended.

And it also hides in hiring. Sponsors tend to over-index on narrow therapeutic area expertise—requiring three years of asthma experience, for example. But the risks that destabilize a clinical trial are very rarely disease specific. They come from implementation, site conduct, vendor scoping, misunderstanding, integration management, and leadership in design choices. You can have the right title in place and still have a consequential capability gap because the role was never built to carry the scope, complexity, and judgment that sponsor oversight truly requires.

ACT: How do coordination failures so often get misread as vendor performance challenges rather than handoff and oversight issues?

Walsh: They get misread because the consequences are visible where they surface, not where they originate. A site is enrolling slowly, a CRO misses a milestone, a change order arrives that nobody was expecting. Those are very visible events. And a lot of times the execution team, the CRO, the site—they absorb the accountability for conditions that were established long before they were even in the room.

Organizations are very diligent and consistent about having strong scientific, medical, and regulatory input during early planning, and that is critical. But operational execution expertise isn't always engaged with equal influence at that stage. Assumptions get developed, put on paper, and treated as settled—and commitments are made off of them that don't get challenged until someone tries to implement them. That's when the instability and the problems occur.

Clinical operations leaders very often just inherit conditions they had very little input in creating. They're handed a program in motion and asked to deliver against commitments built on assumptions they didn't make and can't easily calibrate or change. So when something goes wrong, the diagnosis points to execution. But very frequently, it's a sponsor oversight gap that was designed into the operating model much earlier.

ACT: What does inspection readiness actually look like when it's built in as an execution design condition from the outset?

Walsh: Inspection readiness from the beginning looks like a program that doesn't need to scramble before an inspection, because nothing needs to be assembled—it was accumulated. Every decision was documented at the time it was made. Risks are owned by the function best positioned to navigate them. Deviations are understood in context and fully addressed. The Trial Master File tells a coherent story because the program was coherently run.

That condition can't arrive at the end. It's the natural outcome of the four things operating simultaneously: execution strategy established at the business decision; qualified people bridging scientific intent into operational reality; active facilitation aligning across functions at the sponsor, site, and CRO level continuously throughout the life cycle; and oversight emerging through design, decisions, and continuous control—rather than through periodic review.

When those conditions are present, you don't need to prepare. There's no exercise to run before the inspection. It's just demonstrated with authenticity—how the program was authentically run, demonstrating sponsor oversight. Regulators are reconstructing what happened, and your story either holds or it doesn't. Whether it holds is determined a long time before that inspection was anticipated or announced.