3 Costs of Working with Poor-Quality Specimens and How to Avoid Them

According to a US survey of National Cancer Institute (NCI) funded cancer researchers, lack of quality biospecimens resulted in 60% of researchers questioning their findings and 81% limiting the scope of their work. Quoted from The National Cancer Institute:

“The reliability of molecular data derived from these new analysis platforms is dependent on the quality and consistency of the biospecimens being analyzed. As a result of the increased requirement for biospecimen quality, standardization of biospecimen resources using state-of-the-science approaches has become a pressing need across the research enterprise. The lack of standardized, high-quality biospecimens is widely recognized as a significant roadblock to cancer research.”

Biospecimens are influenced by a number of different factors during collection, storage and processing. These factors can significantly modify the molecular consistency and composition of the specimen. When these modifications occur, they may affect experimental outcomes and the ability to accurately reproduce scientific results.

Poor-quality biospecimens can cost scientists in three distinct ways: financially, time, and accuracy.

The Cost of Poor-Quality Specimens

1. Assay Failure 

According to the National Institute of Health:

“Biospecimen preanalytical variability can affect the reproducibility of clinical research. Biospecimens are the essential starting materials for the biomarker assays that will enable precision medicine. Clinical assays used for diagnosis and therapeutic decision-making are based on assessment of biological molecules (DNA, RNA, and proteins) from a patient’s biospecimen. Such assays are often based on the detection of one or more biomarkers and must be both accurate and reproducible. False positive or negative results from the evaluation of biomarkers in clinical assays can directly affect patient diagnosis, treatment, and outcomes and can lead to over-treatment, under-treatment, or incorrect treatment.”

As stated in the Fredrick National Laboratories for Cancer Research, nondiagnostic clinical assays are critical for clinical trials, often used to support important decisions during the drug development process. The accuracy of these assays is vital to advancing therapies and drug development decisions.

When a pre-analytical variable is introduced, differences in the assay readouts occur leading to failures. Failed assays resulting from poor-quality biospecimens can lead to a frustrating and unproductive research experience. Poor-quality biospecimens may have degraded RNA, insufficient DNA, or inadequate protein concentrations due to collection, processing and storage inconsistencies or poor protocols. On average, failed assays can cost between $300-700 in specimen replacement per test. 

This can be avoided by using high-quality biospecimens that are well-characterized, appropriately collected, and stored under optimal conditions. 

2. Lost Time

Biospecimens are vital to many areas of clinical research. The quality of these specimens as well as their associated data must be collected based on industry best practices to prevent faulty analytical results. These faulty results can cost precious time when it comes to getting a therapy to market.

Poor-quality biospecimens can cause significant delays in research timelines due to the need for resampling, reanalysis, or recalibrations. This can result in significant lost time that could have been utilized for other important activities and may result in further delays to collect additional biospecimens. 

The cost of lost time depends on the time that is invested. Lost time for different steps in the process may account for several days and adds up to significant costs, as listed below:

• History processing over two days can cost you up to $6K

• Assay time over the course of seven days can cost you $14K

• Reordering specimens after seven days can cost you $14K

By investing in high-quality biospecimens with effective QC, you can avoid lost time and stay on track with your research timelines. 

3. QC Implications

Control of the quality of biospecimens is a goal of biospecimen science. Despite this, there is a lack of consensus in regard to quality control (QC) tools. Ideal tools, that are most reliable, are those with a known reference range for outputs. But these are not always available for general specimen quality. Thus, accepted standardized protocols should be used for the collection, processing and storage of biospecimens. 

Biospecimen QC analysis is a crucial step in research ensuring that the biospecimens have the required attributes for the experimental assays at hand. Biospecimens with poor-quality attributes or those collected for different experimental assays, can cause inconsistencies and inaccuracies in the results and may lead to misinterpretation of data. This can be avoided by conducting QC analysis with precision and regularity. Investing in reliable QC’d biospecimens is essential to mitigate the risk of poor-quality biospecimens.

Formal QC services minimize the chances that scientific results could be adversely affected, ensure the safety of personnel, aid in operations, and ensure confidence of scientists in the quality, annotations, and quantity of the biospecimens. Independent QC services come at a cost of $25-100 for histology services and $150 an hour for diagnosis confirmation. As such, it’s important to make sure that these services are cost-effective and offer the best quality possible.

Avoid These Hidden Costs by Using a High-Quality Provider 

There are three areas that can be improved in order to help avoid these costs. Make sure, when you source your biospecimens they undergo:

Histology Quality Control

These criteria include:

• Size Criteria: <3mm tissue block depth impacts the ability to section

• Specimen Integrity Criteria: Free from air bubbles, discoloration, cracking, contamination

• Quality Score: Perform additional processing and discard/quarantine poor-quality samples

Pathology and Data Integrity Review

These criteria include:

• Pathology Confirmation: Diagnosis, tumor grade, tumor stage

• Clinical data case review

• Quarantine any biospecimen with discrepancies until resolution

 

Other Quality Control Measures

• Documented Patient Consent & IRB Approval for Broad Research Use

• External Quality Assurance through Accreditations

• Annual Auditing of Clinical Sites

• Consistent Specimen Collection SOPs

• Standardized Data Collection

Conclusion

The quality of biospecimens plays a significant role in research, and poor-quality biospecimens can lead to critical risks such as increased costs, assay failures, and lost time. These risks can be avoided by investing in high-quality biospecimens. As a researcher, it is crucial to be aware of these risks and ensure that you are working with biospecimens providers who take the necessary steps to mitigate them by adopting best practices in biospecimen collection, processing, and storage. 

Our commitment to quality, combined with our expertise and experience, make us the perfect choice when it comes to sourcing biospecimen. Contact us today and let us help you ensure the success of your research.

For additional BioiVT resources see how BioIVT can help mitigate these risks here.

References

BIOSPECIMEN ASSAYS. National Cancer Institute. (n.d.). https://frederick.cancer.gov/initiatives/scientific-standards-hub/biospecimen-assays 

Integrating Biospecimen Science Approaches into Clinical Assay Development (U01 Clinical Trial Not Allowed). Department of Health and Human Services. (2021, October 22). https://grants.nih.gov/grants/guide/pa-files/PAR-22-049.html#:~:text=Biospecimens%20are%20the%20essential%20starting,proteins 

Moore, H. M., Kelly, A., Jewell, S. D., McShane, L. M., Clark, D. P., Greenspan, R., Hainaut, P., Hayes, D. F., Kim, P., Mansfield, E., Potapova, O., Riegman, P., Rubinstein, Y., Seijo, E., Somiari, S., Watson, P., Weier, H.-U., Zhu, C., & Vaught, J. (2011, April 9). Biospecimen Reporting for Improved Study Quality. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142856/ 

National Institutes of Health. (n.d.-b). NCI Best Practices for Biospecimen Resources. National Cancer Institute. https://biospecimens.cancer.gov/bestpractices/2016-NCIBestPractices.pdf 

Paratore, V. (n.d.). BioIVT - The True Cost of Poor-Quality Specimens. https://info.bioivt.com/true-cost-of-poor-quality-specimens 

Zohouri, M., & Ghaderi, A. (2020, July 24). The Significance of Biobanking in the Sustainability of Biomedical Research: A Review. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275812/