How Laboratory Manuals Fail Sites And Sponsors
By Elena Sinclair, founder and CEO, FlexPoint Bio
"We actually don't use those lab manuals all that much," a cheerful CRC had once said to me. “We just kinda make our own spreadsheets and follow them.”
When she finally looked at me and saw horror emanating from my eyes, she quickly added, “But we make sure to double-check everything!”
After spending several months in a non-stop battle with our central lab's project manager to get that manual out of the door, this tirade felt like Wim Hof's cold plunge. As a Biospecimen Operations lead, witnessing this site aggregating protocol deviations faster than a nut-hunting squirrel made the situation particularly bothersome.
Regrettably, I am far from alone in this quagmire. Biopharma sponsors across the clinical landscape have their own symphony of grievances to share. The punchline, however, comes from the labs themselves, the very architects of these manuals. They readily acknowledge the manuals' labyrinthine density; the Herculean struggle of drafting, error-proofing, and updating them; and the bitter irony that many sites ultimately sidestep these troves of wisdom, treating them less like guides and more like doorstops.
But are the sites really to blame?
Laboratory manuals' humble beginnings trace back to James Lind’s groundbreaking controlled trial in 1747 when he meticulously documented his methods while testing treatments for scurvy. What began as simple notetaking evolved into the elaborate, regulation-driven documents we see today, growing in complexity alongside clinical trials themselves. But these essential tools for trial success turned into unwieldy beasts somewhere along the way, burdening sites and jeopardizing efficiency.
As science and technology advanced, so did the demands of clinical trials. A study analyzing nearly 10,000 clinical trial protocols from 2001 to 2015 paints a stark picture: a 70% increase in procedures, 85% more endpoints, and an astonishing 88% growth in data points collected1. Laboratory manuals adapted organically, often by adding more pages, forms, and procedures to accommodate these complexities.
Fast forward to today, and the typical laboratory manual for a mid-complexity study can easily run 140 to 160 pages. These manuals cover everything from collection protocols to shipping logistics, and they mutate further with each protocol amendment. The result? A Frankenstein’s monster of documentation.
The consequences of this bloat are profound. Failed collections, rejected samples, and procedural missteps haunt the clinical trial landscape, echoing as desolate songs of lost time, wasted resources, and unrealized outcomes.
It’s time to ask: How did we get here, and how can we dig ourselves out? The story of laboratory manuals is more than just a cautionary tale — it’s a call to action.
Lack Of Standardization
The Achilles' heel of laboratory manuals is their glaring lack of standardization. Each laboratory seems to pride itself on crafting bespoke manual formats with terminology that rarely aligns with study protocols. For example, a protocol might vaguely request a "Clinical Laboratory Assessment," leading one lab to interpret it as “Hematology/Urinalysis/Chemistry” and another as “CBC/UA/Metabolic Profile.” This inconsistency forces site staff to navigate conflicting instructions.
Legacy systems that rely on manual data transfers between sponsors, labs, and testing facilities compound the issue, amplifying errors and inefficiencies. Site staff are burdened with reconciling differing procedures and biomarker terminology for each study, while sponsors face challenges in aggregating and analyzing data.
This lack of standardization is more than an inconvenience; it undermines biospecimen integrity, skews data quality, and disrupts uniform training and quality control efforts.
The Problem With “One-Size-Fits-All” Manuals
In clinical trials, “one-size-fits-all” laboratory manuals often fall short. These guides ignore variations in site resources, local regulations, and operational challenges, creating more issues than they resolve. For instance, a small site with minimal staff and outdated equipment cannot realistically follow the same procedures as a large state-of-the-art facility. Such mismatches lead to protocol deviations, inefficiencies, and trial delays.
Research highlights this gap: 60% of trial protocols require amendments, with a third attributable to preventable site-specific issues.2 Protocol changes cost well over $300,000 to $500,000 each. Moreover, inconsistent adherence to local regulations, as noted by the Tufts Center for the Study of Drug Development, causes delays, inflates budgets, and jeopardizes trial credibilit3
The reality is stark:
- Median protocol deviations per trial: 8.8.
- 80% of trials miss enrollment timelines due to procedural misalignment.
- Inconsistent procedures across sites erode data integrity and comparability.
- Frustration and inefficiency among site staff lower performance metrics.
- Regulatory missteps risk trial interruptions or termination.
The verdict? Generic manuals don’t simplify trials, they sabotage them.
The Manual Is Delivered — Now What? The Manual Implementation Gap
A laboratory manual without clear, actionable guidance is as unhelpful as an IKEA manual without diagrams. Trial sites are left to navigate dense, 160+ page documents while juggling patient care and operations. Initial training often consists of uninspiring PowerPoint presentations, leaving staff ill-prepared. When inevitable errors arise, CRAs provide retraining, frequently struggling to interpret the manual themselves, perpetuating confusion.
This lack of alignment between manual content and site implementation is a fundamental flaw. Ambiguous instructions hinder staff from accurately applying study protocols, leading to missteps such as overlooking critical links between eligibility criteria and sample collection or misinterpreting visit schedules.
The impact is significant:
- Oncology trials see 30% more deviations than other areas, particularly in CRO-managed studies.2
- Misinterpreted procedures jeopardize data integrity, risking regulatory rejection.
- Misunderstood criteria lead to unnecessary patient exclusions, slowing enrollment.
- Errors demand costly corrections and retraining, draining resources and demoralizing staff.
These issues are amplified in complex trials, such as oncology or cell and gene therapies, where precision is essential. Yet, many manuals remain static and disconnected from the practical realities of trial execution.
Limited Accessibility — Static Manuals In A Dynamic World
Static PDFs and paper manuals are outdated tools in today’s fast-paced clinical trials, creating inefficiencies and accessibility challenges. Their rigid layouts make navigation on mobile devices cumbersome, forcing site staff to rely on memory or improvisation instead of consulting the manual. The lack of real-time updates leaves sites working with outdated instructions, increasing the risk of errors and inefficiencies.
The accessibility issue is particularly concerning. Manuals often cater exclusively to English speakers, excluding non-native speakers and limiting trial diversity — an essential component of generalizable results. Even for English speakers, dense jargon and unclear formatting create barriers, leading to misinterpretation and preventable mistakes.
These issues have wide-reaching effects: missed steps, compromised data integrity, increased patient burden due to repeat visits, and delayed trial timelines.
Bloated documentation, inconsistent usage, and inadequate site training highlight a pressing need for a fresh approach. In our follow-up article, we’ll take a closer look at the procedural quirks of laboratory manuals that add yet another layer of complexity to an already tangled problem.
References:
- K. A. Getz and R. A. Campo, “Trends in clinical trial design complexity,” Nat. Rev. Drug Discov., vol. 16, no. 5, pp. 307–307, May 2017, doi: 10.1038/nrd.2017.65.
- K. Getz, Z. Smith, A. Jain, and R. Krauss, “Benchmarking Protocol Deviations and Their Variation by Major Disease Categories,” Ther. Innov. Regul. Sci., vol. 56, no. 4, pp. 632–636, Jul. 2022, doi: 10.1007/s43441-022-00401-4.
- “Examination of Clinical Trial Costs and Barriers for Drug Development | ASPE.” Accessed: Dec. 01, 2024. [Online]. Available: https://aspe.hhs.gov/reports/examination-clinical-trial-costs-barriers-drug-development-0
About The Author:
Elena "Ella" Sinclair is the founder and CEO of FlexPoint Bio, a consulting firm specializing in biomarker and biospecimen strategy, logistics, and clinical outsourcing. With over 20 years of experience spanning bench research, site-level operations, and sponsor-side clinical trials, Ella brings a holistic perspective to clinical development. Passionate about ethical and innovative AI implementation, she drives lean, technology-driven clinical trials that aim to deliver treatments to patients faster, safer, and more reliably. FlexPoint Bio embodies this mission, offering tailored solutions to advance the success of every clinical program it supports.