Protocol Pitfalls Part 2: More Mistakes That Cost Science (and Sanity)

In the first part of this series, I highlighted three common mistakes in protocol design that make clinical trials more confusing than they need to be — especially for the people tasked with executing them. If you missed it, you can catch up here: Avoid These 3 Protocol Pitfalls in Clinical Research.  

Since publishing that post, I’ve heard from dozens of CRCs, PMs, and other research pros who offered additional examples (and a few battle scars) of navigating protocol complexity. The themes were clear: the challenges are systemic and they’re costing us time, money, and good science. 

So, let’s continue this conversation. Here are three more protocol mistakes that deserve a spotlight. 

Mistake 4: The “Choose Your Own Adventure” Eligibility Criteria 

Some protocols are written like mystery novels. You start reading an inclusion criterion, then jump to an exclusion note, which leads you to a footnote, which refers to an appendix. By the time you’ve assembled the full eligibility puzzle, the screening window is over — or worse, a patient was enrolled incorrectly. Queue your favorite protocol deviation soundtrack. 

Clear eligibility criteria aren’t just a nice-to-have — they’re essential for reducing expensive screen failures and avoiding protocol deviations. When criteria are scattered, missing, ambiguous, or contradictory, sites are forced to interpret, guess, or delay enrollment. Each of those paths wastes time and increases risk for site and patients alike. 

What's interesting is that at first glance, what might look like a recruitment issue is actually a more complicated screening, enrollment, and conduct issue. Sites will deprioritize your protocol if it’s more complex than others enrolling at their site. 

Mistake 5: Vague Timing Windows 

There’s a big difference between “Day 1” and “within 7 days of Day 1.” And yet, protocols often toss around these phrases without enough context or consistency. This creates confusion around visit windows, lab timing, dose administration, and more. 

A coordinator shouldn’t need to build a Gantt chart to schedule a patient visit. Precision in protocol language matters. Every visit and procedure should have a clearly defined window — and if flexibility is allowed, it should be explicitly stated with examples, not buried in the third-degree footnote.  

I’ll share an example I saw first-hand recently. Screening activities could be completed as late as 10 pm on the day of screening, but because of lab work processing times, Day 2 should have been 24 hours after Day 1 activities completed— but that wasn’t noted explicitly in the protocol. This created an enormous amount of guesswork and 22 unnecessary emails among the entire study team.  

This lack of clarity and examples introduces needless risk that could jeopardize the science and, more importantly, the safety of the patient. 

Mistake 6: Layered Protocol and Supporting Document Versions That Don’t Talk to Each Other 

Let’s say you’re working with version 6.0 of a protocol. You assume the SOA reflects that version...but the lab manual? That’s still referencing version 5.2. The ICF was updated, but only in version 5.9. Suddenly, you’re running three timelines, ending up in dead ends and creating a web of references among your study documents.  

This is more than an annoyance. Layered, non-synced versions create real deviation risk. One CRC told me she didn’t know a procedure had been removed in an amendment because the site training hadn’t caught up. The result? A completely unnecessary procedure and an unhappy patient. 

It’s 2025. Cars self-drive and TVs now double as picture frames, yet the clinical trial industry still struggles with version control. But it doesn’t have to be that way. Tools like ProofPilot’s Site Hub make it easy to centralize and manage all study documents, with version control, update notifications, and intelligent search capability. Furthermore, Visit Overviews can be updated rapidly to ensure detailed workflows are always accurate. 

Protocols are our playbook. But if the playbook keeps changing, contradicts itself, or buries the rules, even the best players are set up to fail. CRCs, study nurses, investigators — they all deserve better. 

We don't need perfect protocols. But we do need cleaner, simpler, and better-connected ones. Because the cost of getting it wrong isn’t just a busted workflow — it’s a delay in getting effective treatments to patients who need them, introducing enormous financial risk, and needlessly risking patient safety. 

Let’s do better. (And yes, Part 3 is probably coming.)