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Standardisation and improvement of generic pre-analytical tools and procedures for in vitro diagnostics

Final Report Summary - SPIDIA (Standardisation and improvement of generic pre-analytical tools and procedures for in vitro diagnostics)

Molecular in vitro diagnostics have enabled a significant progress in medicine. Further progress is expected by new technologies analysing nucleic acids, proteins, and metabolites signatures (profiles) in various human tissues and body fluids. This includes new applications for Personalized Medicine. However, the profiles of these molecules can change drastically during sample collection, transport, storage, and sample processing thus making a reliable diagnostic or biomedical research unreliable or even impossible as the subsequent analytical assay will not determine the bioanalyte profile as it was in the patient but an artificial profile generated after sample collection. A major impediment to progress in the hunt for biomarkers is therefore the lack of standardization in how specimens are collected (G. Poste. Nature 2011, Vol 469, 156-157). Also, pre-analytical errors in sample collection and handling account for 60-70% of all problems occurring in laboratory diagnostics (Lippi el al.. Clin Chem Lab Med. 2011 Jul; 49(7)).

Further progress is limited due to the lack of guidelines standardizing pre-analytical workflows and due to still missing new and improved sample preservation and handling technologies. The European project SPIDIA, a 4.5 years large-scale integrating project, aims to close this gap by providing guidelines, quality assurance schemes and innovative pre-analytical technologies and tools. SPIDIA’s results are of importance for diagnostics including patients, hospitals, doctors’ offices, and clinical diagnostic laboratories as well as for biomedical and clinical research in the pharmaceutical, biotech and diagnostic industry, for government funded research programs and biobanking.

SPIDIA was organized around three main activities. Each of these was associated with major goals.

The first activity intends to lead to pan-European quality assurance schemes and guidelines for the pre-analytical phase of in vitro diagnostics. These guidelines will be based on evidence gathered during ring trials and other studies performed in order to identify and improve problematic steps in pre-analytical workflows and procedures.

For human blood samples, SPIDIA planned and executed pan-European ring trials for three different analytes: genomic DNA from whole blood, circulating cell-free DNA from blood and plasma as well as cellular RNA from whole blood. For each analyte, two consecutive ring trials were executed and evaluated. About 320 laboratories from 29 different European countries participated in each of the two ring trials series. The findings about preanalytical impact factors on blood samples qualities derived from these different ring trials are the basis for the development of new CEN Technical Specification documents for the standardisation of the pre-analytical phase for molecular in vitro diagnostics in the European Union. These documents are currently under development by a dedicated working group within the CEN / Technical Committee 140 ("In-vitro diagnostic medical devices").

Time course studies on metabolome profile changes during pre-analytical workflows for processing human body fluids generated evidence for writing another CEN Technical Specification document on how to handle samples for metablome profile and compounds analysis.

For the standardization and validation of pre-analytical tissues collection and handling, more than 5.000 malignant and non-malignant tissue samples were collected and analysed during the project, using different tissue stabilization technologies including formalin fixation and a novel tissue fixation and stabilization technology developed within SPIDIA. The impact of pre-analytical variables like tissue fixation and ischemia times on the quality of histomorphology as well as on the quality of biomolecules like DNA, RNA, proteins and metabolites were investigated. These studies indicated that the novel tissue fixation and stabilization technology showed promising advantages compared to the classical formalin fixation with regard to the detection and analysis of proteins, phospho-proteins and nucleic acids. In addition, three cancer morphology ring trials involving 69 renowned pathologists from Europe and the US were executed, using breast, colon and prostate cancer samples in order to evaluate the applicability of the new SPIDIA tissue stabilization technology for routine pathology in comparison to the gold standard formalin. As for blood samples, all findings about pre-analytical impact factors on tissue samples qualities will be a basis for the development of new CEN Technical Specification documents.

Dr Uwe Oelmüller (project coordinator)
QIAGEN Str. 1, 40724 Hilden, Germany

A List of all beneficiaries with corresponding address and contact names can be found in the attached document Project_Final_ Report_SPIDIA GA 222916 Section 5.3: Project participants