title: Challenges in diagnostic accuracy studies in primary care: the fecal calprotectin example.
abstract: BACKGROUND
  Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of our choices, using a quality assessment tool for diagnostic accuracy studies (QUADAS-2).
  
  
  METHODS
  The study investigates the diagnostic value of fecal calprotectin for detecting inflammatory bowel disease in children presenting with chronic gastrointestinal symptoms in primary care. It is a prospective cohort study including two cohorts of children: one cohort will be recruited in primary care and the other in secondary/tertiary care. Test results of fecal calprotectin will be compared to one of the two reference standards for inflammatory bowel disease: endoscopy with histopathological examination of mucosal biopsies or assessment of clinical symptoms at 1-year follow-up.
  
  
  CONCLUSIONS
  According to QUADAS-2 the use of two reference standards and the recruitment of patients in two populations may cause differential verification bias and spectrum bias, respectively. The clinical relevance of this potential bias and methods to adjust for this are presented. This study illustrates the importance of awareness of the different kinds of bias that result from choices in the design phase of a diagnostic study in a low prevalence setting. This approach is exemplary for other diagnostic research in primary care.
authors.affiliation: Department of General Practice, FA21, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD Groningen, The Netherlands. m.y.berger@umcg.nl.
authors.forename: Gea A
authors.initials: GA
authors.lastname: Holtman
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lisman-van Leeuwen
authors.forename: Boudewijn J
authors.initials: BJ
authors.lastname: Kollen
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Escher
authors.forename: Angelika
authors.initials: A
authors.lastname: Kindermann
authors.forename: Patrick F van
authors.initials: PF
authors.lastname: Rheenen
authors.forename: Marjolein Y
authors.initials: MY
authors.lastname: Berger
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D003938:Diagnostic Techniques, Digestive System / Q000592:standards*; D003967:Diarrhea / Q000209:etiology; D016145:Endoscopy, Digestive System; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D011320:Primary Health Care / Q000379:methods*; D011446:Prospective Studies; D063127:Secondary Health Care; D012680:Sensitivity and Specificity; D063128:Tertiary Health Care; D057832:Watchful Waiting
chemical_list: D039841:Leukocyte L1 Antigen Complex