Lab Manual Gaps: Sabotaging Data One Sample At A Time
By Elena Sinclair, founder and CEO, FlexPoint Bio
What is the purpose of a laboratory manual? Its life’s goal is to provide actionable instructions on how to collect, process, store, and ship biospecimens collected during a clinical trial. The reality? Laboratory manuals often become a hidden Achilles' heel, undermining the very studies they are meant to support.
Picture this scenario: despite substantial investments of time and resources, you discover that up to 70% of blood samples are hemolyzed, rendering them useless for analysis. Compounding the frustration, 20% may be rejected due to insufficient volume, 15% might be collected in incorrect containers, and another 10% may be clotted1. As you dig through this quagmire, your blood pressure goes up while the statistical significance of your study’s data goes down.
Although the poor quality of biospecimens - and consequently, data - can stem from various factors, laboratory manuals often emerge as a pivotal contributor, warranting a closer look at their inherent shortcomings.
Insufficient Emphasis On Pre-analytical Variables
Laboratory manuals often brush past the critical pre-analytical variables — those sneaky culprits that quietly sabotage data veracity before a sample even boards the courier truck. Patient preparation? Timing? Handling protocols? These foundational steps are often ignored, yet they account for a staggering 60%-70% of total laboratory errors.2
Consider this: improper blood collection techniques, such as prolonged tourniquet use, can induce pseudohyperkalemia — a fancy term for spiking potassium levels that don’t exist. Throw in hemolysis or lipemia, and you have a cocktail of pre-analytical chaos that skews biomarker measurements and undermines reproducibility.
And the consequences? Samples get rejected, entire data sets are excluded, and trial outcomes veer off course. In multicenter trials, where centralized testing magnifies the complexity, inconsistent pre-analytical procedures become a statistical minefield, introducing variability that can derail even the most robust analyses.
But the fallout doesn’t stop there. Patient safety takes a hit when errors in identification or sample labeling lead to incorrect treatment decisions. Costs spiral as sponsors shell out for repeat testing, timelines stretch painfully as errors compound, and reproducibility crumbles under the weight of shoddy pre-analytical protocols.3
Overly Complex Instructions And Lack Of Visual Aids
Laboratory manuals often present dense instructions without visual aids, creating significant challenges for site staff and patients. Technical jargon and complex formats overwhelm staff, increasing errors in specimen collection and handling and compromising data quality and patient safety. Patients, particularly those presented with intricate instructions, frequently forget essential information, while visual learners struggle without diagrams or illustrations. This leads to mistakes in critical steps, resulting in sample rejections, data set exclusions, and potential harm due to incorrect treatment decisions.
The lack of visual aids exacerbates site variability, complicating data interpretation and delaying trial progression. Longer training times and repeat collections further inflate costs. Errors and resource waste from complex instructions without adequate visual support increase costs and potentially cause delays in trial progression. It has been estimated that if 30% of participants are less than fully adherent, the number of participants needed to produce a significant data set doubles, driving the cost up.4
Ultimately, overly complex manuals without adequate visual support can undermine the entire clinical trial process, leading to misleading outcomes and compromised research integrity.
Limited Guidance On Error Prevention And Quality Control
Laboratory manuals often lack guidance on error prevention and quality control measures, leaving sites vulnerable to mistakes that can compromise data integrity. These manuals typically focus on ideal procedures but fail to address common pitfalls and strategies to avoid them.5 This lack of emphasis on error prevention can lead to increased variability in procedures across multiple trial sites, complicating data interpretation and statistical analysis.3
Furthermore, manuals may not adequately stress the importance of ongoing quality checks at the site level. This oversight can result in undetected errors until samples reach the central lab or are uncovered at the end of a study. The absence of clear quality control guidance can lead to inconsistencies in how procedures are carried out, introducing bias and reducing the study's statistical power.
Overemphasis On Routine Procedures
Laboratory manuals often provide detailed instructions for routine collections but fail to adequately address rare or complex specimens, creating risks that ripple through clinical trials. Specialized samples, such as biopsies or low-volume cerebrospinal fluid, demand meticulous handling. Yet, vague or incomplete guidance forces site staff to improvise, jeopardizing sample integrity from collection to analysis. This increases the likelihood of errors, leading to sample exclusion from pivotal analyses, delayed milestones, and compromised regulatory submissions.
Rare specimens often play a critical role in key decisions, including interim analyses, dose escalation, and treatment planning. When mishandled or omitted due to unclear protocols, these gaps distort findings and undermine trial outcomes. To address this, laboratory manuals must prioritize rare specimens with detailed step-by-step instructions, visual aids, and decision trees. By equipping site staff with clear, actionable guidance and real-time support, sponsors can protect data integrity, streamline trial timelines, and ensure no patient or sample is overlooked.
Lack Of Rationale For Procedures — When “What” Isn’t Enough
Clinical trial laboratory manuals often focus on the “what” of procedures, neglecting the critical “why.” While step-by-step instructions ensure basic compliance, they fail to foster true adherence. Without understanding the rationale behind steps, staff may unintentionally take shortcuts or improvise, leading to protocol deviations. For example, failure to explain the impact of storage temperatures on biomarker stability or the purpose of blood draw sequences can compromise sample integrity, jeopardizing scientific validity.
Diverse training levels and infrastructures magnify these challenges in multicenter trials, particularly in oncology, where deviations affect over 40% of patients. Empowering site staff with the “why” cultivates accountability, reduces errors, and fosters precision. Context-rich manuals transform compliance into collaboration, protecting data integrity and patient outcomes.
As trials grow in complexity, the flaws in contemporary lab manuals create ripple effects throughout the trial ecosystem.
However, the path forward is clear. By reimagining manuals as dynamic, accessible, and context-rich resources tailored to site-specific needs, sponsors and CROs can transform a liability into an asset.
In the next article, we’ll explore actionable solutions to modernize laboratory manuals, from leveraging digital tools to enhancing accessibility, ensuring manuals meet today’s demands and thrive in tomorrow’s landscape.
References:
- N. Nordin et al., “Preanalytical Errors in Clinical Laboratory Testing at a Glance: Source and Control Measures,” Cureus, Mar. 2024, doi: 10.7759/cureus.57243.
- A. Abdollahi, H. Saffar, and H. Saffar, “Types and frequency of errors during different phases of testing at a clinical medical laboratory of a teaching hospital in Tehran, Iran,” North Am. J. Med. Sci., vol. 6, no. 5, p. 224, 2014, doi: 10.4103/1947-2714.132941.
- G. Lippi, A. Von Meyer, J. Cadamuro, and A.-M. Simundic, “PREDICT: a checklist for preventing preanalytical diagnostic errors in clinical trials,” Clin. Chem. Lab. Med. CCLM, vol. 58, no. 4, pp. 518–526, Mar. 2020, doi: 10.1515/cclm-2019-1089.
- T. M. Shiovitz et al., “Mitigating the Effects of Nonadherence in Clinical Trials,” J. Clin. Pharmacol., vol. 56, no. 9, pp. 1151–1164, Sep. 2016, doi: 10.1002/jcph.689.
- “The Impact of Poor Sample Management · Slope Blog.” Accessed: Dec. 01, 2024. [Online]. Available: https://www.slopeclinical.com/blog/the-impact-of-poor-sample-management.
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.