Table 1.

Biospecimen protocol and methodology reporting recommendations

Data element	Guidelines and examples
Core data element recommendations
Biological tissue sample source	CSF, serum, plasma, urine, microdialysate, saliva, etc.
Conditions included/excluded	Certain conditions may alter biomarker composition. For example: Infections of the nervous system or target organ from which samples are collected Neoplastic and paraneoplastic conditions Demyelinating conditions Inflammatory conditions such as vasculitis and nervous system involvement of systemic autoimmune disorders Renal failure Liver failure Any intrathecal or intraventricular drug administration
Baseline/time-zero specimen	If samples are collected repeatedly over time, define and collect baseline biospecimen
Site and method of sample acquisition	Blood/serum/plasma: arterial versus venous blood source, peripheral venipuncture versus central vascular access CSF: report location of acquisition (e.g., ventricular, lumbar) and method of acquisition (e.g., through external ventricular catheter or lumbar drain catheter versus via lumbar puncture) Paired sampling (simultaneous collection of biological samples from different sites, e.g., blood and CSF) may provide additional insight into biomarker distribution across different anatomical compartments
Timing of biospecimen collection	Report biospecimen collection time relative to disease/event onset
Type of collection tube	Blood collection: EDTA, Na heparin, citrate, serum collection tubes, or other Other fluid types: polystyrene vs. polypropylene vs. other collection tubes
Method of biospecimen processing	Report biospecimen processing protocol. For fluid samples such as CSF, centrifugation to separate supernatant from cellular debris and separate storage is recommended Was centrifugation used? If so, report centrifugation methods (speed, temperature, duration) Time lapse between sample collection and processing. For RNA, protein, metabolite target biomarkers, samples should be immediately processed and stored frozen
Method of biospecimen storage	Report method of storage including: Temperature of biospecimen/aliquot storage. Storage at or below − 80 °C is recommended for RNA, protein, metabolite targets Number of freeze/thaw cycles. Recommend minimization of freeze/thaw cycles
Supplemental data element recommendations
Control biospecimens	Biospecimens from comparable, non-diseased individuals should be collected to establish normal level of target biomarker
Convalescent biospecimens	Collection of convalescent biospecimens from study subjects may provide additional insight into dynamic changes in target biomarker following acute illness and recovery
Serial biospecimen collection	Serial biospecimen collection over time can provide additional information of target biomarker kinetics and dynamic biomarker change over time If serial collections acquired, recommend use consistent method of acquisition including site of acquisition to minimize variance in biospecimen and biomarker analyses
Biospecimen storage	Recommend storage in small aliquots and automated bar-code inventory system with date and time stamps to minimize errors in storage/inventory
Biomarker analysis	Report number of freeze/thaw cycles the biospecimen went through before final biomarker analyses Recommend standardized number of freeze/thaw cycles of biospecimens in a single study as additional freeze/thaw cycles may introduce variance in analyses results
Selective inhibitors use	Selective inhibitors may be used to optimize biospecimen collection for a specific target biomarker Example: protease inhibitors, RNAase inhibitors
Biospecimen transport and shipping	If biospecimens undergo transport/shipping prior to final biomarker analysis, report conditions of shipping Recommend biospecimens be shipped frozen with abundant amount of dry ice to maintain temperature at or below − 80 °C Document temperature excursions during shipping and transport
Cerebral microdialysis biospecimens	For studies involving extracellular fluid collected via cerebral microdialysis, report the following data elements: Probe placement in at risk but viable tissue. Avoid placement in hematoma or infarcted tissue Report location of probe placement and number of probes. Recommendation: use concentric configuration commercially available probes Report probe molecular weight cutoff, membrane length, manufacturer, and model Report time from ictus to monitoring and then time to sample collection. Report the composition and source of the microdialysate Recommendation: microdialysate flow rate should be 0.3 μL/min over 1 h Recommendation: First hour microdialysate after probe placement should not be used Report 4 basic essential analytes (glucose, pyruvate, lactate, and the calculated L/P ratio) in addition to any novel target analytes Recommendation: Stored samples may be assayed using the batch analysis systems. Avoid sample evaporation. If low volume samples remain in the analyzer for extended period prior to analysis, unacceptable evaporation may occur. Calibration samples should be interspersed in the batch to detect a systematic elevation in analyte levels due to evaporative loss
Emerging data element recommendations
Novel multiplex platforms	For novel multiplex platforms such as proteomics, metabolomics, lipidomics, and transcriptomics: Report if and what normalization techniques are used and any presence of batch effect Report statistical methodology to address multiple comparisons in hypothesis testing

CSF cerebrospinal fluid