Abstract
The remit of “Biopreservation and Biobanking” is to support the best practices in biobanking and facilitate the supply of biospecimens of the highest possible quality to the research community. In medical research, biospecimens are the critical link between a patient’s in vivo molecular information and the downstream diagnosis and treatment. Researchers, clinicians, and patients all need to be confident that biospecimens accurately reflect the disease being studied: the classic adage “garbage in, garbage out” applies. There is a problem, however; biospecimens deviate from their in vivo state as soon as they are removed from the body by responding biologically to the changing conditions (e.g., declines in temperature and oxygen supply) and by being modified by the physical and chemical processes involved in their collection, fixation, transportation, processing, and storage. These “preanalytical factors” can never be eliminated, so a cohort of biospecimens selected for a research project will exhibit a degree of preanalytic variability, the magnitude of which depends on the stringency by which these preanalytical factors were controlled.
Several organizations, including the International Society for Biological and Environmental Repositories (ISBER), issue guidelines defining critical preanalytical processes and promoting standardization in the way that biospecimens are processed. Adopting these guidelines facilitates the control of preanalytical variation. However, as clinical and biobanking workflows are inherently variable, the stringency by which preanalytical variables can be controlled to achieve uniform biospecimen quality varies. However, different analytical techniques have different biospecimen quality requirements, and a biospecimen considered unsuitable for one method of analysis on account of compromised quality can still be perfectly amenable to another. In addition, it is important that any assay using clinical biospecimens is validated at some point in its development using a cohort of biospecimens with variations in their preanalytics that are reflective of those in routine clinical workflows.
“Biospecimen Science” is the term used to describe the branch of science that investigates how the molecular integrity of biospecimens is effected by preanalytical factors. A milestone event in biospecimen science was the launch, in 2005, of the National Cancer Institute’s Office of Biorepositories and Biospecimen Research (later named Biorepositories and Biospecimens Research Branch, BBRB), which has become a coordinated focus of biospecimen science research activity. It published the “Best Practices for Biospecimen Resources”, which are evidence-based best practices relating to control preanalytical factors, achieved by harmonizing the protocols used in the collection, processing, storage, and distribution of biospecimens.1,2 This was followed in 2008 with the establishment of the ISBER Biospecimen Science Working Group, whose remit is to study the effects of preanalytical variables on biospecimens, develop new quality control assays to determine biospecimen fitness for purpose and to provide a consensus for minimum quality requirements for different biospecimen and different analytical assays. It is imperative that the critical preanalytical events that can bias scientific analyses are identified, limits set, and best practices written. Such guidelines are fundamental to answering questions such as “what constitutes a ‘good’ biospecimen?”, and for biospecimens potentially compromised in quality due to being collected and processed in a less research-friendly workflow, “how good is a good enough?”
Given that the quality of a biospecimen depends largely on its preanalytics, in 2009, the ISBER Biospecimen Science Working Group developed a seven-element code called the “Standard PREanalytical Code” (SPREC), that when assigned to a biospecimen, describes its most critical preanalytical and processing information. 3 The first element of the code defines the biospecimen type and the following elements report critical preanalytical factors in a defined order. For each element of the code, a range of letters is available, each with a defined meaning, so the operator can select the one that applies to the biospecimen that they are processing. The example cited in the original article was “SER-SST-A-E-N-A-G.” This equates to a biospecimen that is serum (SER), collected from the patient in a serum tube (SST), with a pre-centrifugation delay of <2 hours at room temp (A), then centrifuged at 3000 × g with braking (E), without a repeat (N), after which the serum was kept at 3–7°C for < 1 hour (A) then cryopreserved between −60°C and −85°C in straws (G). Armed with SPREC, biobanks can assign the most important preanalytical information to each biospecimen in a simple and easily searchable format that is compatible with Laboratory Information Management Systems. The standardized nature of the code means that biobanks and researchers can communicate more easily and better ensure that a cohort of biospecimens issued for a research project have similar and controlled preanalytical variables, even when individual biospecimens in the cohort may originate from different biobanks. The original version of SPREC was updated in 2012, 2018, and 2024 to accommodate additional biospecimen types, storage containers, fixatives, and processing options, with each update using additional code nomenclature so previous versions of SPREC never become obsolete.4–6
A complementary code called Biospecimen Reporting for Improved Study Quality (BRISQ) was published in 2013. 7 Issued following a symposium of interested parties with broad-ranging expertise (clinicians, pathologists, scientists, biobankers, journal editors, etc.) and hosted by the BBRB, BRISQ defines what information authors should provide in a publication to describe the pertinent preanalytical and clinical information. The variables are listed in three tiers, relating to their relative importance: “recommended to report” (e.g., organ type, clinical status of the patient, storage temperature, etc.), “beneficial to report” (e.g., patient demographic information, biospecimen ischemic time, fixation time, shipping conditions) and “additional items to report” (e.g., cause of death, type of biospecimen storage container and warm ischemic time). BRISQ provides the framework by which authors can ensure that their work contains sufficient information that it can be repeated. The application of a combination of SPREC and BRISQ should facilitate better science, better publications, and a reduction in the waste in biomedical research funding associated with unreproducible research, which, according to Moher et al. (2016), had not improved greatly since the oft-cited original estimate of 85% wastage made by Chalmers and Glasziou seven years earlier.8,9
In this issue of Biopreservation and Biobanking, Janis Jensen et al of Radboud Biobank and Radboud University Medical Centre in Nijmegen, the Netherlands, address the same topic. They present the results of a literature review they performed covering the period 2018–2023 in respect of nearly 300 publications and evaluated the extent to which critical preanalytical factors are provided in the publications. The result was disappointing in that fewer than 25% of the publications adequately described the preanalytical processes but positive in that there was near-universal reporting of the patients’ characteristics. The “missing” preanalytical information often related to the type of analyte and study, with the authors citing examples where delays to sample processing are not reported, even when it is known (at least by biobankers) that the magnitude of these delays directly influences the quality of biospecimens and therefore research results.
The Jansen et al. article is important and timely, as it illustrates that even though SPREC and BRISQ have been in existence for over a decade, the problem persists and there is still much to do. As noted by these authors, their results are very similar to those previously reported several years ago in several studies using a comparable literature review methodology.10–12
So what should be done? Although some journals have recommended BRISQ data reporting for over a decade, and some journals have also incorporated some of the SPREC variables into their reporting requirements, there is little evidence of consistent adoption of these reporting guidelines as a requirement by researchers, reviewers, and editors.13–15
And yet, previous studies have highlighted that those BRISQ elements that are typically obtained from the chart are relatively consistently reported compared to those elements that are typically only known to the biobank. SPREC elements would also fall into the latter category. This suggests that overcoming the adoption challenge may be mostly a matter for biobankers to address.
What is needed is a multi-pronged approach. Perhaps the most important aspect of this is for biobanks to convince researchers, reviewers, and editors that there is a problem. Therefore, biobank scientists need to generate and publish more evidence that failure to consider pre-analytical factors has led to problems. To stimulate biobanks a standardized BRISQ and SPREC dataset should be developed, and its capture facilitated by LIMS system design, as suggested by Jensen et al. To remind researchers of the potential importance of considering pre-analytical factors in their analysis, biobanks should routinely generate and provide pre-analytical factor data along with biospecimens and other requested data. To make it easier for researchers to comply with journal requirements, this same data should also be provided in a summary format that can be simply incorporated as a supplementary file at the time of publication. 10
Footnotes
Author Disclosure Statement
No competing financial interests exist.