Guidelines for the standardized collection of blood-based biomarkers in psychiatry: Steps for laboratory validity - a consensus of the Biomarkers Task Force from the WFSBP

Abstract

Recently, there has been a major shift in the field of psychiatry towards the exploration of complex relationships between blood-based biomarkers and the pathophysiology of psychiatric and neuropsychiatric disorders. However, issues with study reproducibility, validity and reliability have hindered progress towards the identification of clinically relevant biomarkers for psychiatry. The achievement of laboratory validity is a crucial first step for the posterior development of clinical validity. There is evidence that the variability observed in blood-based research studies may be minimised with the implementation of standardised pre-analytical methods and uniform clinical protocols (i.e., pre-venipuncture). It has been documented that errors made in the pre-analytical phase account for 46-68.2% of laboratory testing errors. Thus, standardising clinical assessment, ethical procedures and pre-analytical phase of clinical research is essential for the reproducibility, validity and reliability of blood marker assessment, and reducing the risk of invalid test results. Various other areas of research have already moved towards guidelines for the standardised collection of blood-based biomarkers. Here we aim to provide a set of guidelines that we believe would improve biomarker research: (1) pre-venipuncture information and documentation, (2) ethics of participant consent and (3) pre-analytical methods. Ultimately, we hope this will assist study planning and will improve data comparison across studies allowing for the discovery of biomarkers in psychiatry with both laboratorial and clinical validity.

Keywords: Biomarkers; guidelines; reliability; standardisation; validity.

Figure 1.

Blood Processing. (A) Total blood from EDTA whole blood. (B) Serum from silica clot activator whole blood. C) Plasma from EDTA whole blood. (D) DNA designated EDTA whole blood. (E) RNA-designated whole blood with PAXgene collection tube. (F) Ficoll-Paque + white blood cells and plasma extraction from total blood. G) Red blood cells (erythrocytes) from EDTA whole blood. (H) Platelets from EDTA whole blood. RT, room temperature; PBS, phosphate-buffered saline; EDTA, ethylenediaminetetra-acetic acid. The tube colours depicted in the figure are representative of the colours in North America, but may not be representative of appropriate tube colours across all countries and/or institutions. This figure depicts an example of blood processing methods. However, we are aware that there are other successful biobanks with different specifications for processing. This protocol has been validated by the authors of this guideline.

Figure 1.

Blood Processing. (A) Total blood from EDTA whole blood. (B) Serum from silica clot activator whole blood. C) Plasma from EDTA whole blood. (D) DNA designated EDTA whole blood. (E) RNA-designated whole blood with PAXgene collection tube. (F) Ficoll-Paque + white blood cells and plasma extraction from total blood. G) Red blood cells (erythrocytes) from EDTA whole blood. (H) Platelets from EDTA whole blood. RT, room temperature; PBS, phosphate-buffered saline; EDTA, ethylenediaminetetra-acetic acid. The tube colours depicted in the figure are representative of the colours in North America, but may not be representative of appropriate tube colours across all countries and/or institutions. This figure depicts an example of blood processing methods. However, we are aware that there are other successful biobanks with different specifications for processing. This protocol has been validated by the authors of this guideline.

Figure 2.

Summary flowchart for collection, processing and storing of blood samples in clinical studies: *participant information form (PIF), participant consent form (PFC).