title: Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.
abstract: BACKGROUND
  The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components.
  
  
  OBJECTIVE
  In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014.
  
  
  METHODS
  Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed.
  
  
  RESULTS
  In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials.
  
  
  CONCLUSIONS
  The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.
authors.affiliation: Helmholtz Zentrum Muenchen-German Research Center for Environmental Health (GmbH), Institute of Epidemiology I, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kühn
authors.forename: A
authors.initials: A
authors.lastname: Nieters
authors.forename: A
authors.initials: A
authors.lastname: Köttgen
authors.forename: O N
authors.initials: ON
authors.lastname: Goek
authors.forename: K
authors.initials: K
authors.lastname: Michels
authors.forename: U
authors.initials: U
authors.lastname: Nöthlings
authors.forename: G
authors.initials: G
authors.lastname: Jacobs
authors.forename: C
authors.initials: C
authors.lastname: Meisinger
authors.forename: F
authors.initials: F
authors.lastname: Pessler
authors.forename: M F
authors.initials: MF
authors.lastname: Akmatov
authors.forename: J
authors.initials: J
authors.lastname: Kühnisch
authors.forename: S
authors.initials: S
authors.lastname: Moebus
authors.forename: E
authors.initials: E
authors.lastname: Glocker
authors.forename: S
authors.initials: S
authors.lastname: Naus
authors.forename: M
authors.initials: M
authors.lastname: Keimling
authors.forename: M
authors.initials: M
authors.lastname: Leitzmann
authors.forename: J
authors.initials: J
authors.lastname: Linseisen
authors.forename: H
authors.initials: H
authors.lastname: Sarioglu
authors.forename: C
authors.initials: C
authors.lastname: von Toerne
authors.forename: S M
authors.initials: SM
authors.lastname: Hauck
authors.forename: H
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: H E
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D002908:Chronic Disease / Q000453:epidemiology* / Q000517:prevention & control; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods*; D011785:Quality Assurance, Health Care / Q000706:statistics & numerical data*; D013048:Specimen Handling / Q000592:standards* / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D015415:Biomarkers