title: Small-study effects and time trends in diagnostic test accuracy meta-analyses: a meta-epidemiological study.
abstract: BACKGROUND
  Small-study effects and time trends have been identified in meta-analyses of randomized trials. We evaluated whether these effects are also present in meta-analyses of diagnostic test accuracy studies.
  
  
  METHODS
  A systematic search identified test accuracy meta-analyses published between May and September 2012. In each meta-analysis, the strength of the associations between estimated accuracy of the test (diagnostic odds ratio (DOR), sensitivity, and specificity) and sample size and between accuracy estimates and time since first publication were evaluated using meta-regression models. The regression coefficients over all meta-analyses were summarized using random effects meta-analysis.
  
  
  RESULTS
  Forty-six meta-analyses and their corresponding primary studies (N = 859) were included. There was a non-significant relative change in the DOR of 1.01 per 100 additional participants (95% CI 1.00 to 1.03; P = 0.07). In the subgroup of imaging studies, there was a relative increase in sensitivity of 1.13 per 100 additional diseased subjects (95% CI 1.05 to 1.22; P = 0.002). The relative change in DOR with time since first publication was 0.94 per 5 years (95% CI 0.80 to 1.10; P = 0.42). Sensitivity was lower in studies published later (relative change 0.89, 95% CI 0.80 to 0.99; P = 0.04).
  
  
  CONCLUSIONS
  Small-study effects and time trends do not seem to be as pronounced in meta-analyses of test accuracy studies as they are in meta-analyses of randomized trials. Small-study effects seem to be reversed in imaging, where larger studies tend to report higher sensitivity.
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. a.vanenst@kennisinstituut.nl.|Dutch Cochrane Centre, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. a.vanenst@kennisinstituut.nl.
authors.forename: Wynanda Annefloor
authors.initials: WA
authors.lastname: van Enst
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. c.naaktgeboren@umcutrecht.nl.
authors.forename: Christiana A
authors.initials: CA
authors.lastname: Naaktgeboren
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. eochodo@sun.ac.za.|Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, PO Box 241, Cape Town, 8000, South Africa. eochodo@sun.ac.za.
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Ochodo
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. j.degroot-17@umcutrecht.nl.
authors.forename: Joris A H
authors.initials: JA
authors.lastname: de Groot
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. m.m.leeflang@amc.uva.nl.
authors.forename: Mariska M
authors.initials: MM
authors.lastname: Leeflang
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. j.b.reitsma-2@umcutrecht.nl.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Reitsma
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. r.j.p.scholten@umcutrecht.nl.|Dutch Cochrane Centre, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. r.j.p.scholten@umcutrecht.nl.
authors.forename: Rob J P M
authors.initials: RJ
authors.lastname: Scholten
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. k.g.m.moons@umcutrecht.nl.
authors.forename: Karel G M
authors.initials: KG
authors.lastname: Moons
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. a.h.zwinderman@amc.uva.nl.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. p.m.bossuyt@amc.uva.nl.
authors.forename: Patrick M M
authors.initials: PM
authors.lastname: Bossuyt
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. l.hooft@umcutrecht.nl.|Dutch Cochrane Centre, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands. l.hooft@umcutrecht.nl.
authors.forename: Lotty
authors.initials: L
authors.lastname: Hooft
mesh_terms: D003955:Diagnostic Tests, Routine / Q000706:statistics & numerical data*; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D008297:Male; D018401:Sample Size; D012680:Sensitivity and Specificity; D013995:Time