Search tips
Search criteria 


Biopreserv Biobank. Apr 2011; 9(1): 57–70.
PMCID: PMC3142856
Biospecimen Reporting for Improved Study Quality
Helen M. Moore,1 Andrea Kelly,2 Scott D. Jewell,3 Lisa M. McShane,4 Douglas P. Clark,5 Renata Greenspan,6 Pierre Hainaut,7 Daniel F. Hayes,8 Paula Kim,9 Elizabeth Mansfield,10 Olga Potapova,11 Peter Riegman,12 Yaffa Rubinstein,13 Edward Seijo,14 Stella Somiari,15 Peter Watson,16 Heinz-Ulrich Weier,17 Claire Zhu,18 and Jim Vaughtcorresponding author1
1Office of Biorepositories and Biospecimen Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland.
2Rose Li and Associates, Inc., Brookeville, Maryland.
3Program for Biospecimen Science, Van Andel Research Institute, Grand Rapids, Michigan.
4Biometric Research Branch, National Cancer Institute, Rockville, Maryland.
5Division of Cytopathology, The Johns Hopkins Hospital, Baltimore, Maryland.
6U.S.M.C.I./Walter Reed Army Medical Center, Washington, District of Columbia.
7International Agency for Research on Cancer, World Health Organization, Lyon, France.
8Breast Oncology Program Stuart B. Padnos Professor in Breast Cancer Research, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
9TRAC-Translating Research Across Communities, Green Cove Springs, Florida.
10CDRH-Office of In Vitro Diagnostic Device Evaluation and Safety, Center for Devices and Radiological Health, Silver Spring, Maryland.
11Cureline, Inc., South San Francisco, California.
12Erasmus MC Tissue Bank, Rotterdam, The Netherlands.
13Office of Rare Diseases Research, National Institutes of Health, Rockville, Maryland.
14H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
15Windber Research Institute, Windber, Pennsylvania.
16Department of Pathology and Laboratory Medicine, University of British Columbia, Victoria, British Columbia, Canada.
17Lawrence Berkeley National Laboratory, Berkeley, California.
18Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
corresponding authorCorresponding author.
Address correspondence to: Dr. Jim Vaught, Office of Biorepositories and Biospecimen Research, National Cancer Institute, 11400 Rockville Pike, Suite 700, Rockville, MD 20852. E-mail:vaughtj/at/
Received December 27, 2010; Accepted January 11, 2011.
Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The Biospecimen Reporting for Improved Study Quality guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected.
Human biospecimens provide the basis for research leading to better understanding of human disease biology and discovery of new treatments that are tailored to individual patients with cancer or other diseases. These biological materials are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results.16 Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions vary widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner.
The purpose of this article was to make recommendations for the reporting of data elements for human biospecimens, defined as solid tissues and bodily fluids, used in biomedical studies. Cell lines and biospecimen derivatives such as nucleic acids or proteins, although crucial for biomedical research, are not intended to fall within the scope of these recommendations. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations are intended to apply to any study in which human biospecimens are used. This includes biomedical applications such as translational science, biomarker discovery, clinical trials, technology development, and diagnostic-assay and therapeutics development. The recommended data elements would be reported by an author in a journal publication, by a company in a regulatory submission, or by a biorepository distributing biospecimens. It is intended that the list and the elements within it will be interpreted, modified, and applied according to the context of the study being reported. It is also recognized that information corresponding to all data elements may not be available, but at least for some categories (described below) the known or unknown status of these elements should be documented.
The list of data elements discussed includes general information for consistent documentation of classes of biospecimens and factors that might influence the integrity, quality, and/or molecular composition of biospecimens. Reporting the details enumerated in the BRISQ list does not guarantee biospecimen quality and should not be seen as a substitute for empirical quality evaluations. The purpose of reporting these details is to supply others, from researchers to regulatory agencies, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. To maintain consistency with federal regulations on research involving human subjects, information that might enable individual identification of research participants should be withheld.
The BRISQ list has been constructed as an initial step toward defining reporting recommendations. The list will likely evolve as more is learned about the factors that influence biospecimen quality and composition and, in turn, their effects on biospecimen analysis. It is envisioned that future iterations of the BRISQ recommendations might include changes to the list of elements and the relative weight thereof in accordance with evidence-based scientific and medical findings and technological developments.
A half-day workshop, Development of Biospecimen Reporting Criteria for Publications, was held at the National Cancer Institute (NCI) 2009 Biospecimen Research Network Symposium ( to initiate a discussion on biospecimen reporting recommendations. Workshop attendees included individuals covering a broad range of expertise: laboratory scientists, clinicians, pathologists, statisticians, patient advocates, biobankers, journal editors, leaders of relevant professional societies, and other stakeholders. The attendees noted that reporting guidelines covering many aspects of biomedical studies already exist, particularly guidelines relevant to experimental design and data reporting.* It was proposed that the BRISQ recommendations apply to all studies utilizing human biospecimens and thus complement existing guidelines by filling a niche concerning reporting of biospecimen characteristics and preanalytical variables.
The attendees further proposed that the BRISQ recommendations should broadly encompass solid tissues and bodily fluids, rather than including separate lists for these biospecimen types. It was also agreed that a committee to develop biospecimen reporting recommendations should be formed to take the effort forward. Many of the individuals and disciplines participating in the workshop were included when the BRISQ committee was subsequently formed.
Formulation of the recommendations was based on consideration of what biospecimen information could enable a science reviewer to fully evaluate or replicate a reported study. The preliminary list included the most commonly available data elements. The committee considered the characteristics of the biospecimens themselves as well as numerous preanalytical factors. Types of data elements include the tissue type and the pathology of the sample; patient characteristics that might influence the biospecimens, such as vital and disease states; and the collection and handling of the biospecimens, for example, the stabilization, shipping, and storage conditions.
The preliminary list of recommendations was refined by consulting the NCI Biospecimen Research Database (, an online resource compiling peer-reviewed articles that address biospecimen science. The Biospecimen Research Database's terminology for scientific literature curation that was deemed relevant was incorporated into the initial BRISQ list. This terminology served as a starting point for discussion at monthly teleconferences by the BRISQ committee.
The committee composed a list of data elements that represent factors believed to often influence biospecimen quality and thus should be considered for reporting, if known or applicable, for the particular study; for example, some list of elements will be more applicable to biospecimens collected for a disease-specific study than those collected for a population-based biospecimen resource. For clarity, these elements are organized according to the lifecycle of the biospecimen (Fig. 1), which spans the period immediately prior to removal from the patient through use in a scientific analysis.
FIG. 1.
FIG. 1.
The lifecycle of the biospecimen. The preanalytical phase of the lifecycle of the biospecimen includes each stage from patient to distribution. Preanalytical variables are addressed in the Biospecimen Reporting for Improved Study Quality list.
Many reporting elements were discussed, but only some were approved by consensus for inclusion in the guidelines. The committee was mindful that certain information, although important to report, may not have direct relevance to the biology or condition of the biospecimen and, therefore, would not be under the purview of the BRISQ recommendations. The committee attempted to carefully balance scientific interest in having access to extensive data about biospecimen collection, processing, and storage against practical challenges in obtaining such detailed information. Each reporting element included in the guidelines is backed by evidence that the factor could have an effect on the structural integrity and molecular characteristics of the biospecimen or on the ability to perform certain assays on the biospecimen and obtain reliable results. Although the committee recognizes that collection of data about biospecimens can increase the operational costs to collect and use biospecimens, cost was not factored into the exclusion of data elements that were or should be considered necessary.
The elements in the BRISQ list are prioritized into 3 tiers according to the relative importance of their being reported. The first tier, items recommended to report, includes information such as the organ(s) or the anatomical site from which the biospecimens were derived and the manner in which the biospecimens were collected, stabilized, and preserved; for quick reference, these items are summarized in Table 1. Reporting these items need not be onerous. For example, Beatty et al.7 included most BRISQ Tier 1 items in the following excerpts:
  • Fine-needle aspiration specimens were obtained from 55 surgically removed specimens of breast cancer within 1 h of resection, before tissue fixation. The aspirates were obtained using a 22- to 25-gauge needle and spread directly on slides and fixed in ethanol or formalin or placed in CytoLyt for preparation of ThinPrep slides according to the manufacturer's protocol. Corresponding formalin-fixed, paraffin-embedded tissue specimens were fixed in 10% neutral buffered formalin for 18–24 h according to routine procedures and embedded in paraffin.”
  • All fine-needle aspiration cytologic slides were air dried and stored at room temperature before fluorescence in situ hybridization analysis.”
Table 1.
Table 1.
Quick-Reference Biospecimen Reporting for Improved Study Quality Summary/Checklist: Tier 1 Items to Report if Known and Applicable
Items beneficial to report form the second tier. These are data elements an evaluator might find helpful to know but may be slightly less crucial to the scientific contribution or less likely to be annotated, such as the time from biospecimen excision/acquisition to stabilization.
Additional items to report compose the third tier. These include information about conditions that might be useful to know concerning the biospecimens but are not known to be as likely to influence research results or are unlikely to be available to researchers, such as environmental factors to which patients were exposed or the type of storage container in which the biospecimens were kept.
The full BRISQ list featured in Table 2 includes each item and its definition along with additional columns that were designed for an author or reviewer to track where the listed items are reported for a particular study. To the right of the Item descriptions is a column assigning each item a unique Roman numeral/letter/number identification code. The far right column provides space to note where each item may be found in a manuscript or application. The far left Apply to column indicates whether the BRISQ item is applicable to “all” biospecimen types or is more appropriate for solid “tissue” biospecimens or “fluid” biospecimens (such as blood, urine, or other fluids). For example, item III.b, “Type of long-term preservation,” is pertinent to all types of biospecimens; item III.b.2, “Time in fixative/preservative solution,” is more relevant to solid tissue than to fluid biospecimens; and item III.c, “Aliquot volume,” applies more often to fluid than to solid tissue biospecimens. See the Appendix for examples of prior studies, with examples of the effect of each BRISQ data element.
Table 2.
Table 2.
Biospecimen Reporting for Improved Study Quality Information on Itemsa to Consider Reporting in Publications That Employ Human Biospecimens
When reporting elements of the BRISQ list, standard operating procedures specifying many of the pertinent details, such as blood collection protocols, may be provided or referenced; any referenced documents should be publicly available. It is preferable that most Tier 1 items relevant to the biospecimen and particular scientific study be reported directly in the intended publication rather than be cited from another document. Detailed descriptions that are too lengthy to be accommodated should be made available as supplemental materials online. Whether the laboratory performing the study was operating under any formal certification or accreditation should be stated if applicable to the study being reported.
The BRISQ committee discussed whether to request information that the biorepository and/or researcher had obtained ethical clearance to collect the biospecimens and perform the study. Clearance from an institutional review board or similar body is important to report in publications, and its reporting is generally required by journals. However, it is not immediately pertinent to the structural integrity and molecular characteristics of the biospecimen and is thus not included in the BRISQ recommendations. Similarly, accurate biospecimen-tracking mechanisms are essential to biobanking but not immediately pertinent to the condition of the biospecimen and are thus also not included in the BRISQ data elements list.
Surgical parameters, such as type of anesthesia or receipt of blood or other intraoperative infusates, were recognized to be of potential significance to the condition of the biospecimens. However, these data are often not known. When it is available, information about anesthesia and intraoperative treatments that may influence the condition of the biospecimens should be reported. These elements were not included in the BRISQ list because currently such information is rarely available or not required to be recorded as part of biospecimen collection efforts. If or when surgical parameters are determined to be critical through systematic biospecimen research studies, these elements will be integrated into future recommendations.
Several preservation parameters known to influence the condition of biospecimens and the results of analyses have been included in the list of recommendations. Researchers should state the rationale for the chosen preservation parameters. For example, if the type and temperature of the biospecimen preservative were selected to optimize stability, extraction, and analysis of a particular analyte, this should be mentioned.
The BRISQ committee recognized the need for greater specificity in the anatomic and histologic details reported concerning solid tissue biospecimens. The committee agreed that the level of detail with which pathology characteristics are reported should be enough to sufficiently address the scientific research question. These characteristics include not only the tissue site of the biospecimen and the relation of the biospecimen to the pertinent clinical diagnosis within the tissue site, but also the composition and pathology within the biospecimen where relevant.
The BRISQ committee included members of the NCI Office of Biorepositories and Biospecimen research (OBBR), participants from the OBBR Biospecimen Research Network Symposium, and members of the International Society for Biological and Environmental Repositories (ISBER) and the committees responsible for the REporting recommendations for tumor MARKer prognostic studies (REMARK)8 and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE)9 guidelines. Essential harmonization with similar efforts are underway by these groups.
An adage in the business community states, “That which is measured improves. That which is measured and reported improves exponentially.” The BRISQ reporting recommendations represent the product of extensive discussion and input from researchers with varied types of expertise and from many stakeholders, all of whom share the common goal of improving biospecimen reporting and, by extension, fields in which biospecimens are employed. The committee believes that by providing details concerning preanalytical factors that might affect assay results, investigators will further improve the quality of biomedical studies, including research for developing cancer biomarkers for screening, early detection, and treatment.
Adoption of the BRISQ recommendations is expected to help authors, reviewers, editors, and regulatory officials evaluate whether sufficient information about the biospecimens has been provided to enable assessment of the influence of preanalytical biospecimen factors on study results. If reported, this information will allow improved evaluation, interpretation, comparison, and reproduction of the results from studies that employ human biospecimens. Although items in any tier might not be available or items in Tiers 2 or 3 might not be considered significant to report, increased awareness of their potential influence on biospecimen studies might lead to improved tracking and reporting in the future.
The BRISQ recommendations may be implemented by anyone reporting on studies involving biospecimens. Reviewers, editors, and regulatory officials might also employ the list as a tool for evaluating whether sufficient biospecimen information has been included in a manuscript or application. In addition, the recommendations might be employed by investigators requesting biospecimens from a biospecimen resource: essential items on the list might be checked off to indicate that they are required annotation for the desired samples. Elements of BRISQ that document preanalytical variables for tissue biospecimens could be economically captured using a reporting system such as the Standard PREanalytical Code, or SPREC, which was recently published by the ISBER Working Group on Biospecimen Science.10
BRISQ reporting items will not be necessarily applicable to every study, and authors and reviewers are urged to use their judgment to decide which factors are essential. It is not always possible for investigators to ascertain every recommended element for every biospecimen, even for Tier 1 items, but unknown elements relevant to the study being reported should be fully acknowledged with a discussion of possible implications that the missing information might have on the study conclusions. Unknown or unreported Tier 1 data elements should not be considered a reason for automatic dismissal of a report or conditional for the award of a grant. The final decision on acceptability of missing Tier 1 information should be specific to the study context.
When consulting the BRISQ list, researchers should evaluate the importance of each item in the context of the study and adjust their reporting accordingly. An item such as “method of enrichment for relevant components,” listed here as Tier 2, might—for example, in the context of a study comparing the efficacy of various enrichment methods—be essential to report and should thus be considered Tier 1 for that study. The converse may also be true, when, for example, an item listed here as Tier 2—such as “temperature between acquisition and stabilization”—is less pertinent to the study at hand—perhaps because the time at this temperature was negligible—and should thus be considered Tier 3.
It is hoped that consideration of the BRISQ recommendations will sensitize the biobanking and research communities and their funding agencies to the importance of tracking preanalytical variables, leading to more judicious selection and handling of experimental human specimens and thus improved study quality. Anecdotally, recommendations such as REMARK seem to have had the effect of spurring researchers to consider the recommendations in advance of conducting their investigations, with the result that researchers might take greater care in the design, conduct, and analysis of their studies. The BRISQ committee envisions a similar trajectory for preanalytical biospecimen data elements. Thus, not only might overall quality of publications improve, but the quality of human biospecimen-dependent investigation in general might improve over time with the formation and adoption of publication recommendations. It is anticipated that biospecimen resources might use these recommendations to improve on their existing standard operating procedures and annotation thereof. Such improvements could include the acquisition of additional relevant biospecimen data based on the BRISQ recommendations and the release of all such data to researchers as a standard procedure. In this way, biospecimen resources might become major players in the universal application of these recommendations.
Patient contribution of biospecimens for research is a voluntary, generous action aimed at helping advance scientific discovery and progress. The research team, pathologist, and biorepository systems, as the stewards of these biospecimens, have a responsibility to be vigilant and persistent in using methods and practices that protect and preserve the highest possible quality biospecimen and associated data. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected. Researchers are further encouraged to strengthen public outreach and education around the use and potential of human biospecimens11 and the biorepository community as these are emerging and potentially misunderstood areas.
Biospecimen Reporting for Improved Study Quality Table with Example References That, When Available, Exemplify Each Data Element's Influence on Experimental Resultsa
Apply toTier no.Item descriptionItem no.Appendix References
I. Preacquisition
AllTier 1Biospecimen type. Solid tissue, whole blood, serum/plasma, isolated cells, urine, secretions, or another product derived from a human being.I.a.13
AllTier 1Anatomical or collection site. In standard terminology, organ(s) of origin or site of blood draw.I.a.1.47
AllTier 1Biospecimen disease status. From controls or individuals with the disease of interest; in the case of solid tissue, whether it is from disease site or normal adjacent (not involved but from the same anatomical site as a disease specimen in the same patient).I.a.2.8
AllTier 1Clinical characteristics of patients. In standard terminology, available medical information known or believed to be pertinent to the condition of the biospecimens.I.b.9
AllTier 1Vital state. Alive or deceased when biospecimens were obtainedI.b.110,11
AllTier 3Disease state. Patient condition relative to disease and treatment, if known (eg, during or after therapy; acute, chronic, or terminal stage).I.b.1.1.12
AllTier 3Cause of death. For postmortem biospecimens, the cause of death and other diseases present at the time of death.I.b.1.2.1315
AllTier 3Agonal state. The patients' physical condition immediately preceding death (eg, prolonged degeneration or relatively healthy)I.b.1.3.1315
AllTier 1Diagnosis. Patient diagnoses pertinent to the study being conducted, using an accepted system of standards (eg, the Systemized Nomenclature of Medicine or the International Classification of Diseases). Please note that clinical and pathologic diagnoses are not always the same.I.b.2.16
AllTier 1Clinical. Patient clinical diagnoses (determined by medical history, physical examination, and analyses of a biospecimen) pertinent to the study being conducted.I.b.2.1.9
AllTier 1Pathologic. Patient pathologic diagnoses (determined by macro and/or microscopic evaluation of a biospecimen at the time of diagnosis and/or prior to research use) pertinent to the study being conducted.I.b.2.2.17
AllTier 2Time between diagnosis and sampling. The time or range of time between disease diagnosis and sample acquisition.1.b.2.3 
AllTier 3Exposures. Neoadjuvant therapy, other current or past medical treatments or environmental factors that might influence the condition of the biospecimen (eg, chemotherapy and radiation therapy, blood thinner, smoking status).I.b.3.12,16
AllTier 3Reproductive status. The hormonal or reproductive state of the patients (eg, pregnant, prepubescent, postmenopausal).I.b.4.18
AllTier 2Patient demographic information. Demographic information that might be relevant to the condition of the biospecimens (eg, age range, gender).I.c.19
AllTier 2Accrual scheme. Whether the biospecimens were obtained for the study being conducted or for a generalized collection such as a population-based biospecimen resource (ie, retrospective or prospective procurement); whether any standard operating procedures (SOPs) were employed; and whether these SOPs are available to others upon request. Reference any clinical trials relevant to the accrual scheme.I.d.2023
AllTier 2Nature of the biobanking institution(s). The biobanking context in which the biospecimens were obtained (eg, as part of an internal collection or a biospecimen acquisition network); include name, location, and primary contact details such as email address or Web site and reference to any pertinent SOPs.I.e.20, 24
II. Acquisition
AllTier 1Collection mechanism and parameters. How the biospecimens were obtained (eg, fine-needle aspiration, preoperative blood draw).II.a.2527
TissueTier 3Time from cessation of blood flow in vivo to biospecimen excision/acquisition. The time or range of times that the biospecimens were ischemic in the body.II.b.28
AllTier 2Time from biospecimen excision/acquisition to stabilization. The time or time range between when the biospecimens were obtained (eg, blood drawn or tumor surgically removed) and when they were stabilized. For postmortem biospecimens, list the postmortem interval range (ie, the time from death to stabilization of the biospecimen).II.c.7, 2933
AllTier 2Temperature between biospecimen excision/acquisition and stabilization. The temperature or range thereof at which biospecimens were kept between when biospecimens were obtained (eg, blood drawn or tumor surgically removed) and when they were stabilized. For postmortem biospecimens, the temperature at which the cadaver was stored during the postmortem interval.II.d.30, 3335
FluidTier 2Collection container. The kind of tube into which biospecimens were captured as they left the body.II.e.3638
III. Stabilization/preservation
AllTier 1Mechanism of stabilization. The initial process by which biospecimens were stabilized during collection [eg, snap or controlled-rate freezing, fixation, additive (heparin, citrate, or ethylenediaminetetraacetic acid), none].III.a.3941
AllTier 1Type of long-term preservation. The process by which the biospecimens were sustained after collection (eg, freezing and at which temperature; formalin fixation, paraffin embedding; additive; none). Please note that this might or might not differ from the mechanism of stabilization.III.b.4244
AllTier 1Constitution and concentration of fixative/preservation solution. The make-up of any formulation employed to maintain the biospecimens in a nonreactive state (eg, 10% neutral-buffered formalin or 10 United States Pharmacopeia heparin units/mL).III.b.1.45, 46
TissueTier 2Time in fixative/preservation solution. The time or range thereof that biospecimens were exposed to the preservation medium.III.b.2.47, 48
TissueTier 2Temperature during time in preservation solution. The temperature of the medium during the preservation process.III.b.3.31
FluidTier 2Aliquot volume. The amount in each liquid biospecimen sample.III.c.46
TissueTier 2Specimen size. The approximate size or weight of solid biospecimen samples processed (eg, cubes approximately 0.5 cm on a side, 0.5 g).III.d.49
IV. Storage/transport
  Storage parameters. The conditions under which the biospecimens were maintained until analysis. 29, 50, 51
AllTier 1Storage temperature. The temperature or range thereof at which the biospecimens were maintained until distribution or analysis.IV.a.129, 5053
AllTier 1Storage duration. The time or range thereof between biospecimen acquisition and distribution or analysis.IV.a.2.29, 49, 50, 52, 55, 56
AllTier 2Storage details. Other conditions under which specimens were maintained during storage (eg., to minimize oxidation).IV.a.3.29, 49
AllTier 3Type of storage container. The vessel in which biospecimens were kept.IV.a.438, 45, 56
AllTier 3Type of slide. The microscope slides to which biospecimens were affixed.IV.a.557
  Shipping parameters. The conditions to which biospecimens were exposed during each shipment or inventory management. 29, 58
AllTier 1Shipping temperature(s). The temperature or range thereof at which biospecimens were maintained during each shipment or relocation.IV.b.1.58, 59
AllTier 2Shipping duration. The time, estimate, or range thereof that the biospecimens spent in shipment each time they were transported.IV.b.2.58, 59
AllTier 3Type of transport container. The type of vessel (eg, premanufactured shipping container, polystyrene box) and the packing material in which the biospecimens were transported.IV.b.3. 
AllTier 3Shipping parameters. Other conditions under which the biospecimens were transported (eg, vacuum sealing, desiccant, packing material). Please note any deviations from standard operating procedures that might influence the condition of the biospecimens (eg, shipping anomalies that exposed paraffin blocks to high temperatures).IV.b.4. 
  Freeze–thaw parameters. The conditions to which biospecimens were subjected during any thaw events. 29
FluidTier 2Number of freeze–thaw cycles. The number, estimate, or range thereof of thaw–refreeze events to which biospecimens were subjected prior to analysis.IV.c.1.56, 60, 61
FluidTier 3Duration of thaw events. The amount of time or range thereof the biospecimens spent thawed prior to the final thaw before processing.IV.c.2.62
FluidTier 3Time from last thaw to processing. The time or range of times between unfreezing and analysis.IV.c.3. 
AllTier 3Temperature between last thaw and processing. The temperature at which biospecimens were kept between unfreezing and analysis.IV.c.4.63
V. Quality assurance measures relevant to the extracted product and processing prior to analyte extraction and evaluation
AllTier 1Composition assessment and selection. Any parameters that were used to evaluate and/or choose biospecimens for inclusion in the study.V.a.64
AllTier 2Gross and microscopic review. The anatomical characteristics of the biospecimens in the study and the relevant qualifications of the individual performing the review (eg, anatomist, pathologist, hematologist, microbiologist, or researcher).V.a.1. 
TissueTier 2Proximity to primary pathology of interest. Whether the biospecimen was taken from a region adjacent to or distal from another region of interest, such as a tumor or area of necrosis. Give approximate distances if known.V.a.2.65, 66
AllTier 2Method of enrichment for relevant component(s). The method by which pertinent portions of the biospecimen were separated from the rest of the biospecimen (eg, laser-capture microdissection of tissue, block selection for region of lesion, centrifugation of blood).V.a.367, 68
AllTier 2Details of enrichment for relevant component(s). The parameters used to separate pertinent portions of the biospecimen from the rest of the biospecimen, if applicable (eg, centrifugation speed and temperature).V.a.469
TissueTier 3Embedding reagent/medium. Any formulation used to enclose the biospecimens (eg, paraffin).V.b.70
AllTier 2Quality assurance measures. Any methods used to assess the quality of the biospecimens relevant to the biomolecular analyte, when these methods were employed (eg, prior to long-term storage or immediately before experimental analysis), and the results (eg, RNA integrity number, hemolysis assessment).V.c16, 71
Bold text: Tier 1—recommended to report; plain text: Tier 2—beneficial to report; italic text: Tier 3—additional items to report.
aThis is not intended to be an exhaustive list.
Appendix References
1. Di Nunno N. Costantinides F. Cina SJ, et al. What is the best sample for determining the early postmortem period by on-the-spot flow cytometry analysis? Am J Forensic Med Pathol. 2002;23:173–180. [PubMed]
2. Humphreys-Beher MG. King FK. Bunnel B, et al. Isolation of biologically active RNA from human autopsy for the study of cystic fibrosis. Biotechnol Appl Biochem. 1986;8:392–403. [PubMed]
3. Barton RH. Nicholson JK. Elliott P, et al. High-throughput 1H NMR-based metabolic analysis of human serum and urine for large-scale epidemiological studies: validation study. Int J Epidemiol. 2008;37(Suppl 1):i31–i40. [PubMed]
4. Centeno BA. Enkemann SA. Coppola D, et al. Classification of human tumors using gene expression profiles obtained after microarray analysis of fine-needle aspiration biopsy samples. Cancer. 2005;105:101–109. [PubMed]
5. Hoff-Olsen P. Jacobsen S. Mevåg B, et al. Microsatellite stability in human post-mortem tissues. Forensic Sci Int. 2001;119:273–278. [PubMed]
6. Yang ZW. Yang SH. Chen L, et al. Comparison of blood counts in venous, fingertip and arterial blood and their measurement variation. Clin Lab Haematol. 2001;23:155–159. [PubMed]
7. Heinrich M. Matt K. Lutz-Bonengel S, et al. Successful RNA extraction from various human postmortem tissues. Int J Legal Med. 2007;121:136–142. [PubMed]
8. Weis S. Llenos IC. Dulay JR, et al. Quality control for microarray analysis of human brain samples: the impact of postmortem factors, RNA characteristics, and histopathology. J Neurosci Methods. 2007;165:198–209. [PubMed]
9. Tantipaiboonwong P. Sinchaikul S. Sriyam S, et al. Different techniques for urinary protein analysis of normal and lung cancer patients. Proteomics. 2005;5:1140–1149. [PubMed]
10. He S. Wang Q. He J, et al. Proteomic analysis and comparison of the biopsy and autopsy specimen of human brain temporal lobe. Proteomics. 2006;6:4987–4996. [PubMed]
11. Jones RF. Sunheimer R. Friedman H, et al. Comparison of ante- and post-mortem PSA levels for epidemiological studies. Anticancer Res. 2005;25(2B):1263–1267. [PubMed]
12. Pinder SE. Provenzano E. Earl H. Ellis IO. Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy. Histopathology. 2007;50:409–417. [PubMed]
13. Tomita H. Vawter MP. Walsh DM, et al. Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol Psychiatry. 2004;55:346–352. [PMC free article] [PubMed]
14. Preece P. Virley DJ. Costandi M, et al. An optimistic view for quantifying mRNA in post-mortem human brain. Brain Res Mol Brain Res. 2003;116:7–16. [PubMed]
15. Johnston NL. Cervenak J. Shore AD, et al. Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR. Stanley Neuropathology Consortium. J Neurosci Methods. 1997;77:83–92. [PubMed]
16. Webster MJ. Tissue preparation and banking. Prog Brain Res. 2006;158:3–14. [PubMed]
17. Ellis M. Davis N. Coop A, et al. Development and validation of a method for using breast core needle biopsies for gene expression microarray analyses. Clin Cancer Res. 2002;8:1155–1166. [PubMed]
18. Reyna R. Traynor KD. Hines G, et al. Repeated freezing and thawing does not generally alter assay results for several commonly studied reproductive hormones. Fertil Steril. 2001;76:823–825. [PubMed]
19. Papale M. Pedicillo MC. Thatcher BJ, et al. Urine profiling by SELDI-TOF/MS: monitoring of the critical steps in sample collection, handling and analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;856:205–213. [PubMed]
20. Barnes RO. Parisien M. Murphy LC, et al. Influence of evolution in tumor biobanking on the interpretation of translational research. Cancer Epidemiol Biomarkers Prev. 2008;17:3344–3350. [PubMed]
21. McIntosh M. Anderson G. Drescher C, et al. Ovarian cancer early detection claims are biased. Clin Cancer Res. 2008;14:7574. [PubMed]
22. Sidiropoulos N. Dumont LJ. Golding AC, et al. Quality improvement by standardization of procurement and processing of thyroid fine-needle aspirates in the absence of on-site cytological evaluation. Thyroid. 2009;19:1049–1052. [PubMed]
23. Thorpe JD. Duan X. Forrest R, et al. Effects of blood collection conditions on ovarian cancer serum markers. PLoS One. 2007;2:e1281. [PMC free article] [PubMed]
24. Karsan A. Eigl BJ. Flibotte S, et al. Analytical and preanalytical biases in serum proteomic pattern analysis for breast cancer diagnosis. Clin Chem. 2005;51:1525–1528. [PubMed]
25. Sung MT. Lin H. Koch MO, et al. Radial distance of extraprostatic extension measured by ocular micrometer is an independent predictor of prostate-specific antigen recurrence: a new proposal for the substaging of pT3a prostate cancer. Am J Surg Pathol. 2007;31:311–318. [PubMed]
26. Morrison C. Palatini J. Riggenbach J, et al. Fine-needle aspiration biopsy of non-Hodgkin lymphoma for use in expression microarray analysis. Cancer. 2006;108:311–318. [PubMed]
27. Schaub S. Wilkins J. Weiler T, et al. Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int. 2004;65:323–332. [PubMed]
28. Smith JL. Pillay SP. de Jersey J, et al. Effect of ischaemia on the activities of human hepatic acyl-CoA:cholesterol acyltransferase and other microsomal enzymes. Clin Chim Acta. 1989;184:259–268. [PubMed]
29. Visvikis S. Schlenck A. Maurice M. DNA extraction and stability for epidemiological studies. Clin Chem Lab Med. 1998;36:551–555. [PubMed]
30. Micke P. Ohshima M. Tahmasebpoor S, et al. Biobanking of fresh frozen tissue: RNA is stable in nonfixed surgical specimens. Lab Invest. 2006;86:202–211. [PubMed]
31. Burke WJ. O'Malley KL. Chung HD, et al. Effect of pre- and postmortem variables on specific mRNA levels in human brain. Brain Res Mol Brain Res. 1991;11:37. [PubMed]
32. Spruessel A. Steimann G. Jung M, et al. Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision. Biotechniques. 2004;36:1030–1037. [PubMed]
33. Espina V. Edmiston KH. Heiby M, et al. A portrait of tissue phosphoprotein stability in the clinical tissue procurement process. Mol Cell Proteomics. 2008;7:1998–2018. [PubMed]
34. van Maldegem F. de Wit M. Morsink F, et al. Effects of processing delay, formalin fixation, and immunohistochemistry on RNA Recovery From Formalin-fixed Paraffin-embedded Tissue Sections. Diagn Mol Pathol. 2008;17:51–58. [PubMed]
35. Langebrake C. Günther K. Lauber J, et al. Preanalytical mRNA stabilization of whole bone marrow samples. Clin Chem. 2007;53:587–593. [PubMed]
36. Yucel A. Karakus R. Cemalettin A. Effect of blood collection tube types on the measurement of human epidermal growth factor. J Immunoassay Immunochem. 2007;28:47–60. [PubMed]
37. Drake SK. Bowen RA. Remaley AT, et al. Potential interferences from blood collection tubes in mass spectrometric analyses of serum polypeptides. Clin Chem. 2004;50:2398–2401. [PubMed]
38. Preissner CM. Reilly WM. Cyr RC, et al. Plastic versus glass tubes: effects on analytical performance of selected serum and plasma hormone assays. Clin Chem. 2004;50:1245–1247. [PubMed]
39. Frank M. Döring C. Metzler D, et al. Global gene expression profiling of formalin-fixed paraffin-embedded tumor samples: a comparison to snap-frozen material using oligonucleotide microarrays. Virchows Arch. 2007;450:699–711. [PubMed]
40. Scicchitano MS. Dalmas DA. Bertiaux MA, et al. Preliminary comparison of quantity, quality, and microarray performance of RNA extracted from formalin-fixed, paraffin-embedded, and unfixed frozen tissue samples. J Histochem Cytochem. 2006;54:1229–1237. [PubMed]
41. Narayanan S. Considerations in the application of selected molecular biology techniques in the clinical laboratory: preanalytical and analytical issues. Rinsho Byori. 1996;(Suppl 103):262–270. [PubMed]
42. Greer CE. Lund JK. Manos MM. PCR amplification from paraffin-embedded tissues: recommendations on fixatives for long-term storage and prospective studies. PCR Methods Appl. 1991;1:46–50. [PubMed]
43. Beatty BG. Bryant R. Wang W, et al. HER-2/neu detection in fine-needle aspirates of breast cancer: fluorescence in situ hybridization and immunocytochemical analysis. Am J Clin Pathol. 2004;122:246–255. [PubMed]
44. Kouri T. Malminiemi O. Penders J. Limits of preservation of samples for urine strip tests and particle counting. Clin Chem Lab Med. 2008;46:703–713. [PubMed]
45. Zsikla V. Baumann M. Cathomas G. Effect of buffered formalin on amplification of DNA from paraffin wax embedded small biopsies using real-time PCR. J Clin Pathol. 2004;57:654–656. [PMC free article] [PubMed]
46. Ferry JD. Collins S. Sykes E. Effect of serum volume and time of exposure to gel barrier tubes on results for progesterone by Roche Diagnostics Elecsys 2010. Clin Chem. 1999;45:1574–1575. [PubMed]
47. Macabeo-Ong M. Ginzinger DG. Dekker N, et al. Effect of duration of fixation on quantitative reverse transcription polymerase chain reaction analyses. Mod Pathol. 2002;15:979–987. [PubMed]
48. Miething F. Hering S. Hanschke B, et al. Effect of fixation to the degradation of nuclear and mitochondrial DNA in different tissues. J Histochem Cytochem. 2006;54:371–374. [PubMed]
49. Gillio-Tos A. De Marco L. Fiano V, et al. Efficient DNA extraction from 25-year-old paraffin-embedded tissues: study of 365 samples. Pathology. 2007;39:345–348. [PubMed]
50. Sigurdson AJ. Ha M. Cosentino M, et al. Long-term storage and recovery of buccal cell DNA from treated cards. Cancer Epidemiol Biomarkers Prev. 2006;15:385–388. [PubMed]
51. Atkins D. Reiffen KA. Tegtmeier CL, et al. Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem. 2004;52:893–901. [PubMed]
52. Zhou H. Yuen PS. Pisitkun T, et al. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int. 2006;69:1471–1476. [PMC free article] [PubMed]
53. Ahmad S. Sundaramoorthy E. Arora R, et al. Progressive degradation of serum samples limits proteomic biomarker discovery. Anal Biochem. 2009;394:237–242. [PubMed]
54. Isaksson HS. Nilsson TK. Preanalytical aspects of quantitative TaqMan real-time RT-PCR: applications for TF and VEGF mRNA quantification. Clin Biochem. 2006;39:373–377. [PubMed]
55. Kauppinen T. Martikainen P. Alafuzoff I. Human postmortem brain tissue and 2-mm tissue microarrays. Appl Immunohistochem Mol Morphol. 2006;14:353–359. [PubMed]
56. Rosenling T. Slim CL. Christin C, et al. The effect of preanalytical factors on stability of the proteome and selected metabolites in cerebrospinal fluid (CSF) J Proteome Res. 2009;8:5511–5522. [PubMed]
57. Paik S. Kim CY. Song YK. Kim WS. Technology insight: application of molecular techniques to formalin-fixed paraffin-embedded tissues from breast cancer. Nat Clin Pract Oncol. 2005;2:246–254. [PubMed]
58. Guder WG. Preanalytical factors and their influence on analytical quality specifications. Scand J Clin Lab Invest. 1999;59:545–549. [PubMed]
59. Timms JF. Arslan-Low E. Gentry-Maharaj A, et al. Preanalytic influence of sample handling on SELDI-TOF serum protein profiles. Clin Chem. 2007;53:645–656. [PubMed]
60. Chan KC. Yeung SW. Lui WB, et al. Effects of preanalytical factors on the molecular size of cell-free DNA in blood. Clin Chem. 2005;51:781–784. [PubMed]
61. Fiedler GM. Baumann S. Leichtle A, et al. Standardized peptidome profiling of human urine by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Clin Chem. 2007;53:421–428. [PubMed]
62. Kirk MJ. Hayward RM. Sproull M. Non-patient related variables affecting levels of vascular endothelial growth factor in urine biospecimens. J Cell Mol Med. 2008;12:1250–1255. [PubMed]
63. Kueltzo LA. Wang W. Randolph TW, et al. Effects of solution conditions, processing parameters, and container materials on aggregation of a monoclonal antibody during freeze-thawing. J Pharm Sci. 2008;97:1801–1812. [PubMed]
64. Ginocchio CC. Wang XP. Kaplan MH, et al. Effects of specimen collection, processing, and storage conditions on stability of human immunodeficiency virus type 1 RNA levels in plasma. J Clin Microbiol. 1997;35:2886–2893. [PMC free article] [PubMed]
65. Braakhuis BJM. Tabor MP. Kummer JA, et al. A genetic explanation of slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727–1730. [PubMed]
66. Deng G. Lu Y. Zlotnikov G, et al. Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science. 1996;274:2057–2059. [PubMed]
67. Mojica WD. Stein L. Hawthorn L. An exfoliation and enrichment strategy results in improved transcriptional profiles when compared to matched formalin fixed samples. BMC Clin Pathol. 2007;7:7. [PMC free article] [PubMed]
68. Umar A. Dalebout JC. Timmermans AM, et al. Method optimisation for peptide profiling of microdissected breast carcinoma tissue by matrix-assisted laser desorption/ionisation-time of flight and matrix-assisted laser desorption/ionisation-time of flight/time of flight-mass spectrometry. Proteomics. 2005;5:2680–2688. [PubMed]
69. Breit S. Nees M. Schaefer U, et al. Impact of pre-analytical handling on bone marrow mRNA gene expression. Br J Haematol. 2004;126:231–243. [PubMed]
70. Coudry RA. Meireles SI. Stoyanova R, et al. Successful application of microarray technology to microdissected formalin-fixed, paraffin-embedded tissue. J Mol Diagn. 2007;9:70–79. [PubMed]
71. Sanchez-Carbayo M. Saint F. Lozano JJ, et al. Comparison of gene expression profiles in laser-microdissected, nonembedded, and OCT-embedded tumor samples by oligonucleotide microarray analysis. Clin Chem. 2003;49:2096–2100. [PubMed]
*The EQUATOR project ( provides an extensive listing of guidelines for health research.
This project has been funded in whole or in part with Federal Funds from the NCI, National Institutes of Health, under contract no. HHSN261200800001E and by NIH grant CA136685 (HUW) carried out at the Lawrence Berkeley National Laboratory under contract DE-AC002-05CH11231. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.
Author Disclosure Statement
No competing financial interests exist.
1. Srinivasan M. Sedmak D. Jewell S. Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol. 2002;161:1961–1971. [PubMed]
2. Moore HM. Compton CC. Lim MD, et al. Biospecimen Research Network Symposium: Advancing Cancer Research through Biospecimen Science. Cancer Res. 2009;69:6770–6772. [PMC free article] [PubMed]
3. Apweiler R. Aslanidis C. Deufel T, et al. Approaching clinical proteomics: current state and future fields of application in cellular proteomics. Cytometry A. 2009;75:816–832. [PubMed]
4. Apweiler R. Aslanidis C. Deufel T, et al. Approaching clinical proteomics: current state and future fields of application in fluid proteomics. Clin Chem Lab Med. 2009;47:724–744. [PubMed]
5. Espina V. Muelle C. Edmiston K, et al. Tissue is alive: new technologies are needed to address the problems of protein biomarker pre-analytical variability. Proteomics Clin Appl. 2009;3:874–882. [PMC free article] [PubMed]
6. Ransohoff DF. Gourlay ML. Sources of bias in specimens for research about molecular markers for cancer. J Clin Oncol. 2010;28:698–704. [PMC free article] [PubMed]
7. Beatty BG. Bryant R. Wang W, et al. HER-2/neu detection in fine-needle aspirates of breast cancer: fluorescence in situ hybridization and immunocytochemical analysis. Am J Clin Pathol. 2004;122:246–255. [PubMed]
8. McShane LM. Altman DG. Sauerbrei W, et al. Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics. Reporting recommendations for tumor marker prognostic studies (REMARK) J Natl Cancer Inst. 2005;97:1180–1184. [PubMed]
9. von Elm E. Altman DG. Egger M, et al. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–349. [PubMed]
10. Betsou F. Lehmann S. Ashton G, et al. Standard preanalytical coding for biospecimens: defining the sample PREanalytical code. Cancer Epidemiol Biomarkers Prev. 2010;19:1004–1011. [PubMed]
11. Secko DM. Preto N. Niemeyer S, et al. Informed consent in biobank research: a deliberative approach to the debate. Soc Sci Med. 2009;68:781–789. [PubMed]
Articles from Biopreservation and Biobanking are provided here courtesy of
Mary Ann Liebert, Inc.