CopLab - The Copenhagen Primary Care Laboratory Database

Click here to see the CopLab cohort profile.

Click here to see the interactive search tool: Shiny-app

The database

In the Copenhagen area (Copenhagen Municipality and the former Copenhagen County) with its approx. 1.2 million inhabitants, there was only one laboratory serving general practitioners (GPs) and other private practicing specialists from 2000 through 2015, the Copenhagen General Practitioners’ Laboratory, CGPL (Københavns Praktiserende Lægers Laboratorium, KPLL). The laboratory served doctors with a broad range of blood, urine, semen, clinical physiological, cardiac, and lung function tests. The Copenhagen Primary Care Laboratory (CopLab) Database contains all results (n=112 million) of these tests and analyses from 1.3 million different individuals.

Over-all idea and ambition

The CopLab Database possesses the strength to unravel important physiological and pathophysiological relations for a plethora of medical conditions. The large number of clinical and administrative variables are validated to create and maintain a state-of-the-art database infrastructure allowing for correct interpretation of the database content in combination with national registers and other databases.

Denmark has a long tradition for collecting information on disease incidence, use of health services, socio-economic status and other data describing its population in national registries. For research purposes more detailed data are also available in smaller clinical databases and research databases. National and research databases may be merged with the personal identification (CPR) number.

The CopLab Database consists of prospectively collected clinical data from primary care patients who were consulting their primary care doctors for health issues from 2000 through 2015. The CopLab population was sampled continuously without any restrictions as to why the analyses were requested by doctors.

Access to data from so many individuals over such a long time period enables the CopLab Database to assess both common and rare disease outcomes. Furthermore, multiple measurements over time enable longitudinal research, also across health sector boarders, and the prognostic value of the many clinical variables may be assessed for clinical outcomes, while adjusting for relevant confounders. 

Approach and concepts and methodology

This project brings together a unique partnership of institutions with a long-term dedication to translational research. The project is initiated by and rooted in the Department of Public Health, University of Copenhagen, and involves a multidisciplinary team of leading academic experts within epidemiology, basic science, nutrition, general practice, clinical medicine, clinical pharmacology, health economics, organizational research, and computer science. The commitment of this broad range of experienced partners consolidates the implementation of the database.

 

The CGPL was founded in 1922 by the GPs in the Copenhagen Municipality, but in 1994, GPs from the County of Copenhagen joined. During 2000 through 2015, CGPL served approx. 750 GPs and 300 private practicing specialists and performed tests on 1.3 million unique individuals from a dynamic population amounting to approx. 1.2 million inhabitants at a given time. When the CGPL was closed down at the end of 2015, it was one of Europe's largest laboratories, with 195 full-time employees. Besides a broad spectrum of biochemical analyses, CGPL offered a comprehensive selection of cardiac and clinical physiological tests, as well as allergological, urine and semen analyses. Blood sampling and/or testing took place at CGPL, at its 8 local branches, in doctors’ consultation rooms, and in patients’ own homes or nursing homes.

Clinical biochemistry. This was CGPL’s quantitatively largest production area with some 10 million analyses performed yearly. Fertility examinations. The CopLab Database contains results of 148,838 semen analyses from 88,625 men from 1950 through 2015, which makes it by far the largest collection of its kind in the world.

Electrocardiograms (ECGs) The ECGs were always recorded by specially trained nurses and interpreted by one of CGPL’s five cardiologists. This ensured high and uniform quality of the 1,022,842 ECGs performed.

Echocardiograms. All of the more than 35,056 echocardiograms were performed by either specially trained echo-technicians or cardiologists, who always supervised all examinations and ultimately read and described all tests.

Other relevant clinical analyses were ECG stress tests, event recordings, 24-hour ambulatory blood pressure measurements, pulmonary function tests, distal blood pressure measurements, skin and serological allergy testing, and EEGs.

Quality assurance of CGPL. As the first laboratory in Denmark, the CPGL became fully DANAK accredited in 2001. In addition, CGPL was the first laboratory in the world where cardiac, pulmonary and other analyses were fully accredited. Accreditation according to DANAK's 15189 standard (the former ISO 17025) was the highest form of quality standard and quality assurance that could be achieved. With accreditation, all aspects of information handling, patient data and data analytics, staff qualifications, procurement, IT management and staff education as well as quality goals at the CGPL were subject to strict and clearly defined criteria, and ongoing follow-up from DANAK staff ensured that CGPL constantly met the accreditation requirements.

Besides semen analyses dating back to 1950, only data from the beginning of the millennium, when accreditation was issued, are included in the CopLab Database in order to ensure access to the highest possible quality of clinical data.

The CopPreg database is a sub-database of CopLab, that was established by merging the Danish Medical Birth Register and the CopLab database. The aim was to identify all pregnant women, their children and the fathers in CopLab to establish a new data resource, unique of its kind that contains clinical biomarker test information together with various health information provided by the Danish national registries, on the sample population.

 

 

In 2008, researchers from The Research Unit for General Practice in Copenhagen began working with CGPL data in a pilot project entitled “The Copenhagen Primary Care Differential Count (CopDiff) Database” in order to prepare for the forthcoming CopLab Database.

The research group included consultants from CGPL with great insight into data and their origin, and most of them are key members of the CopLab Steering Group (see “Organizational Structure”). The CopDiff project prepared the institution’s data managers, statisticians and researchers for the ensuing work with the much larger CopLab Database and emphasized the importance of a robust infrastructure allowing for swift and secure handling of the vast data. The experiences from the construction and analysis of the CopDiff Database are documented in 9 publications. In the history of CGPL more limited, and often un-validated data extracts from CGPL have been used in other research fields. Overall, CopLab data has until now proved its compelling properties in epidemiological research with more than 50 published peer-reviewed articles.

 

 

The CopLab Database is administered by Department of Public Health, University of Copenhagen. A Steering Group has been appointed and bylaws have been created. Steering Group responsibilities include: ensuring progress of the specific research projects; discussing vision for and structure of the database; assessing all proposed projects for scientific merit and approving access to data; approving budgets and accounts; and appointing members for the Scientific Advisory Board for consultancy.

Researchers interested in collaborating can contact Christen L. Andersen and may explore which tests are available and when with our shiny app. 

The Steering Group:

  • Christen Lykkegaard Andersen, CopLab project leader, professor, MD DMSc PhD
  • Bent Lind, Senior consultant leader, MD DMSc
  • Volkert Siersma, Head statistician, MSc PhD
  • Susanne Reventlow, professor, MD DMSc
  • Frans Waldorff, professor, MD PhD
  • Berit Heitmann, professor MD PhD
  • Theis Lange, professor, PhD

Data management

Data are stored at a server at University of Copenhagen and access to this server is limited to a few key statisticians and data managers. Researchers are not be granted direct access to the database, but are given access to data on a need to know basis. Most projects are involve merging CopLab data with national health registers which will be provided with The Public Health Database at the Department of Public Health, University of Copenhagen.

 

 

 

 

 

 

  1. Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health 2011; 39 (7 suppl):12-16.

  2. Andersen CL, Siersma VD, Karlslund W, Hasselbalch HC, Felding P, Bjerrum OW, et al. The Copenhagen Primary Care Differential Count (CopDiff) database. Clin Epidemiol 2014; 6:199-211.

  3. Andersen CL, Eskelund CW, Siersma VD, Felding P, Lind B, Palmblad J, et al. Is thrombocytosis a valid indicator of advanced stage and high mortality of gynecological cancer? Gynecol Oncol 2015; 139:312-318.

  4. Andersen CL, Lindegaard H, Vestergaard H, Siersma VD, Hasselbalch HC, de Fine Olivarius N, et al. Risk of lymphoma and solid cancer among patients with rheumatoid arthritis in a primary care setting. PLoS One 2014; 9:e99388.

  5. Andersen CL, Siersma VD, Hasselbalch HC, Lindegaard H, Vestergaard H, Felding P, et al. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death. Am J Hematol 2013; 88:843-847.

  6. Andersen CL, Siersma VD, Hasselbalch HC, Lindegaard H, Vestergaard H, Felding P, et al. Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database. Acta Oncol 2014; 53:1245-1250.

  7. Andersen CL, Siersma VD, Hasselbalch HC, Vestergaard H, Mesa R, Felding P, et al. Association of the blood eosinophil count with hematological malignancies and mortality. Am J Hematol 2015; 90:225-229.
  8. Andersen CL, Tesfa D, Siersma VD, Sandholdt H, Hasselbalch H, Bjerrum OW, et al. Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study. J Intern Med 2016.

  9. Hansen JW, Sandholdt H, Siersma V, Orskov AD, Holmberg S, Bjerrum OW, et al. Anemia is present years before myelodysplastic syndrome diagnosis: Results from the pre-diagnostic period. Am J Hematol 2017; 92:E130-E132.

  10. Andersen CL. Eosinophilia and The Copenhagen Primary Care Differential Count (CopDiff) Database - from cells to cohorts. Doctoral Dissertation - University of Copenhagen 2017.

  11. Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 2012; 97:2644-2652.

  12. Jensen TK, Jacobsen R, Christensen K, Nielsen NC, Bostofte E. Good semen quality and life expectancy: a cohort study of 43,277 men. Am J Epidemiol 2009; 170:559-565.

  13.  Nielsen JB, Graff C, Pietersen A, Lind B, Struijk JJ, Olesen MS, et al. J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study. J Am Coll Cardiol 2013; 61:2557-2564.

  14. Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab 2014; 99:2372-2382.

  15. Grann AF, Erichsen R, Nielsen AG, Froslev T, Thomsen RW. Existing data sources for clinical epidemiology: The clinical laboratory information system (LABKA) research database at Aarhus University, Denmark. Clinical epidemiology 2011; 3:133-138.

  16. Haneuse S, Daniels M. A General Framework for Considering Selection Bias in EHR-Based Studies: What Data Are Observed and Why? EGEMS (Wash DC) 2016; 4:1203.

  17. Influence of educational level on test and treatment for incident hypothyroidism. Møllehave LT, Jacobsen RK…Andersen CL et al. Clin Endocrinol (Oxf). 2021 Jan 29.

  18. Anemia – Diagnostic Workup in Western Primary Health Care. Pojskic E and Andersen CL. J Fam Med. IN PRESS 2021

  19. Egholm GJ, Andersen MA, Andersen CL, Frederiksen H, Bjerrum OW, Niemann CU. Abnormal eosinophil count at CLL diagnosis correlates with shorter treatment free survival. Br J Haematol. Br J Haematol. 2021 Feb;192(3):e81-e84.

  20. Engell AE, Svendsen ALO, Lind BS, Andersen CL, Andersen JS, Willadsen TG, Persson F, Pottegard A. Drug-drug interaction between warfarin and statins: A Danish cohort study. Br J Clin Pharmacol. 2020.

  21. Janbek J, Kriegbaum M, Grand MK, Specht IO, Lind BS, Andersen CL, Heitmann BL. The Copenhagen Primary Care Laboratory Pregnancy (CopPreg) database. BMJ Open. 2020;10(5):e034318.

  22. Palmblad J, Siersma V, Lind B, Bjerrum OW, Hasselbalch H, Andersen CL. Age-related prevalence and clinical significance of neutropenia - isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals. Am J Hematol. 2020;95(5):521-8.

  23. Agius R, Brieghel C, Andersen MA, Pearson AT, Ledergerber B, Cozzi-Lepri A, Louzoun Y, Andersen CL, Bergstedt J, von Stemann JH, Jorgensen M, Tang ME, Fontes M, Bahlo J, Herling CD, Hallek M, Lundgren J, MacPherson CR, Larsen J, Niemann CU. Machine learning can identify newly diagnosed patients with CLL at high risk of infection. Nat Commun. 2020;11(1):363.

  24. Bjerrum OW, Siersma V, Hasselbalch HC, Lind B, Andersen CL. Association of the blood eosinophil count with end-organ symptoms. Ann Med Surg (Lond). 2019;45:11-8.

  25. Hejl JL, Grand MK, Siersma V, Goetze JP, de Fine Olivarius N, Andersen CL, Lind B. In Reply - Brain Natriuretic Peptide in Plasma as Predictor of All-Cause Mortality in a Large Danish Primary Health Care Population Suspected of Heart Failure. Clin Chem. 2019;65(6):812-3.

  26. Medici BB, Nygaard B, la Cour JL, Grand MK, Siersma V, Nicolaisdottir DR, Lind B, Olivarius NF, Andersen CL. Changes in Prescription Routines for Treating Hypothyroidism Between 2001 and 2015: An Observational Study of 929,684 Primary Care Patients in Copenhagen. Thyroid. 2019;29(7):910-9.

  27. Hejl JL, Grand MK, Siersma V, Goetze JP, de Fine Olivarius N, Andersen CL, Lind B. Brain Natriuretic Peptide in Plasma as Predictor of All-Cause Mortality in a Large Danish Primary Health Care Population Suspected of Heart Failure. Clin Chem. 2018;64(12):1723-31.

  28. Borg R, Persson F, Siersma V, Lind B, de Fine Olivarius N, Andersen CL. Interpretation of HbA1c in primary care and potential influence of anaemia and chronic kidney disease: an analysis from the Copenhagen Primary Care Laboratory (CopLab) Database. Diabet Med. 2018;35(12):1700-6.

  29. Bjerrum OW, Fassi DE, Madsen G, Stentoft J, Vestergaard H, Rønnow-Jessen D, Pedersen PT, Pulczynski S, Overgaard UM, Andersen CL. Eosinofili. Ugeskrift for Laeger. 2018;180:1052-7.

  30. Hansen JW, Sandholdt H, Siersma V, Orskov AD, Holmberg S, Bjerrum OW, Hasselbalch HC, Olivarius NF, Gronbaek K, Andersen CL. Anemia is present years before myelodysplastic syndrome diagnosis: Results from the pre-diagnostic period. Am J Hematol. 2017;92(7):E130-E2.

  31. Andersen CL, Tesfa D, Siersma VD, Sandholdt H, Hasselbalch H, Bjerrum OW, Felding P, Lind B, Olivarius Nde F, Palmblad J. Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study. J Intern Med. 2016;279(6):566-75.

  32. Haneuse S, Daniels M. A General Framework for Considering Selection Bias in EHR-Based Studies: What Data Are Observed and Why? EGEMS (Wash DC). 2016;4(1):1203.

  33. Andersen CL, Eskelund CW, Siersma VD, Felding P, Lind B, Palmblad J, Bjerrum OW, Friis S, Hasselbalch HC, de Fine Olivarius N. Is thrombocytosis a valid indicator of advanced stage and high mortality of gynecological cancer? Gynecol Oncol. 2015;139(2):312-8.

  34. Andersen CL, Siersma VD, Hasselbalch HC, Vestergaard H, Mesa R, Felding P, Olivarius ND, Bjerrum OW. Association of the blood eosinophil count with hematological malignancies and mortality. Am J Hematol. 2015;90(3):225-9.

  35. Andersen CL, Lindegaard H, Vestergaard H, Siersma VD, Hasselbalch HC, de Fine Olivarius N, Bjerrum OW, Junker P. Risk of lymphoma and solid cancer among patients with rheumatoid arthritis in a primary care setting. PLoS One. 2014;9(6):e99388.

  36. Andersen CL, Siersma VD, Karlslund W, Hasselbalch HC, Felding P, Bjerrum OW, de Fine Olivarius N. The Copenhagen Primary Care Differential Count (CopDiff) database. Clin Epidemiol. 2014;6:199-211.

  37. Andersen CL, Siersma VD, Hasselbalch HC, Lindegaard H, Vestergaard H, Felding P, de Fine Olivarius N, Bjerrum OW. Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database. Acta Oncol. 2014;53(9):1245-50.

  38. Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, Pedersen OD, Faber J, Torp-Pedersen C, Gislason GH. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab. 2014;99(7):2372-82.

  39. Andersen CL, Siersma VD, Hasselbalch HC, Lindegaard H, Vestergaard H, Felding P, de Fine Olivarius N, Bjerrum OW. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death. Am J Hematol. 2013;88(10):843-7.

  40. Nielsen JB, Graff C, Pietersen A, Lind B, Struijk JJ, Olesen MS, Haunso S, Gerds TA, Svendsen JH, Kober L, Holst AG. J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study. J Am Coll Cardiol. 2013;61(25):2557-64.

  41. Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab. 2012;97(8):2644-52.

  42. Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health. 2011;39(7 Suppl):12-6.

  43. Grann AF, Erichsen R, Nielsen AG, Froslev T, Thomsen RW. Existing data sources for clinical epidemiology: The clinical laboratory information system (LABKA) research database at Aarhus University, Denmark. Clin Epidemiol. 2011;3:133-8.

  44. Andersen CL, Vestergaard H, Felding P, Pallisgaard N, Rasmussen IH, Hasselbalch HC, Bjerrum OW, Larsen PN. Eosinofili--patogenese, klassifikation og behandling. Ugeskrift for Laeger. 2009;171:3256-62.

  45. Jensen TK, Jacobsen R, Christensen K, Nielsen NC, Bostofte E. Good semen quality and life expectancy: a cohort study of 43,277 men. Am J Epidemiol. 2009;170(5):559-65.