Value-added reporting. X. Bossuyt
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1 Value-added reporting X. Bossuyt
2 COMMUNICATING DIAGNOSTIC ACCURACY
3 Communicating diagnostic accuracy Question 1 Sensitivity: 95% Specificity: 9% Pre-test probability: 2.5% Post-test probability??? 1% 2% 5% 8% 9% Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
4 Communicating diagnostic accuracy Question 1 Sensitivity: 95% Specificity: 9% Pre-test probability: 2.5% Post-test probability??? 1% 2% 5% 8% 9% Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
5 Communicating diagnostic accuracy Question 1 Sensitivity: 95% Specificity: 9% Pre-test probability: 2.5% Post-test probability??? 1% 2% (9% of respondents) 5% 8% 9% Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
6 Communicating diagnostic accuracy Question 2 LR 1 A pos test result occurs 1 times more frequently in patients with the disease compared to patients without the disease Pre-test probability: 2.5% 1% 2% 5% 8% 9% Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
7 Communicating diagnostic accuracy Question 2 LR 1 A pos test result occurs 1 times more frequently in patients with the disease compared to patients without the disease Pre-test probability: 2.5% 1% 2% (35% of respondents) 5% 8% 9% Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
8 Communicating diagnostic accuracy Question 3 Vermeersch P, Bossuyt X. Arch Intern Med. 21;17:734-5.
9 Diagnostic task Base rate Sensitivity False-positive rate Positive predictive value Breast cancer 1% 8% 1% Rocio Garcia-Retamero, Ulrich Hoffrage Visual representation of statistical information improves diagnostic inferences in doctors and their patients Social Science & Medicine, Volume 83, 213, 27-33
10 Diagnostic task Base rate Sensitivity False-positive rate Positive predictive value Breast cancer 1% 8% 1% 1 of 1, 8 of 1 99 of 99 Rocio Garcia-Retamero, Ulrich Hoffrage Visual representation of statistical information improves diagnostic inferences in doctors and their patients Social Science & Medicine, Volume 83, 213, 27-33
11 Diagnostic task Base rate Sensitivity False-positive rate Positive predictive value Breast cancer 1% 8% 1% 7% 1 of 1, 8 of 1 99 of 99 8 of 17 Rocio Garcia-Retamero, Ulrich Hoffrage Visual representation of statistical information improves diagnostic inferences in doctors and their patients Social Science & Medicine, Volume 83, 213, 27-33
12 Fig. 1 Visual aid representing the overall number of women at risk, the number of women who have breast cancer, and the number of women who obtained a positive mammogram. Rocio Garcia-Retamero, Ulrich Hoffrage Visual representation of statistical information improves diagnostic inferences in doctors and their patients Social Science & Medicine, Volume 83, 213, 27-33
13 Fig. 2 Accuracy of diagnostic inferences across the three diagnostic tasks by numerical format, visual aid, and type of participant. Error bars indicate one standard error of the mean. Rocio Garcia-Retamero, Ulrich Hoffrage Visual representation of statistical information improves diagnostic inferences in doctors and their patients Social Science & Medicine, Volume 83, 213, 27-33
14 DIAGNOSTIC ACCURACY: BASICS
15 CD non CD ttg < 2 units/ml ttg 2 units/ml Oyaert et al. Clin Chem Lab Med. 215;53:
16 CD non CD ttg < 2 units/ml ttg 2 units/ml Likelihoods CD non CD ttg < 2 units/ml,154,988 ttg 2 units/ml,846,12 Oyaert et al. Clin Chem Lab Med. 215;53:
17 Likelihoods CD non CD ttg < 2 units/ml,154,988 ttg 2 units/ml,846,12 Sensitivity Oyaert et al. Clin Chem Lab Med. 215;53:
18 Likelihoods CD non CD ttg < 2 units/ml,154,988 ttg 2 units/ml,846,12 Specificity Sensitivity Oyaert et al. Clin Chem Lab Med. 215;53:
19 CD non CD LR ttg < 2 units/ml,154,988,15 ttg 2 units/ml,846,12 69 Oyaert et al. Clin Chem Lab Med. 215;53:
20 CD non CD LR ttg < 2 units/ml,154,988,15 ttg 2 units/ml,846,12 69 LR 1 no clinical value >1 <.1 clinically important difference modest, but substantial difference small difference that may be relevant
21 Celiac Disease Control PPV NPV Tissue transglutaminase antibodies < 2 units/ml ,976 Tissue transglutaminase antibodies 2 units/ml , prevalence celiac disease,14 Celiac Disease Control PPV NPV Tissue transglutaminase antibodies < 2 units/ml ,988 Tissue transglutaminase antibodies 2 units/ml 66 12, prevalence celiac disease,7 Celiac Disease Control PPV NPV Tissue transglutaminase antibodies < 2 units/ml 2 966,998 Tissue transglutaminase antibodies 2 units/ml 9 12, prevalence celiac disease,1
22 RHEUMATOID ARTHRITIS
23 Anti-CCP 298 patients RA patients (n=85) 45 early RA 4 established RA Diseased controls (n=165), including: Psoriatic arthritis Connective tissue disease Organ-specific autoimmune disease Consecutive patients (n=48) 16 RA Anti-CCP: Phadia (7Units/mL) RF: nephelometry, Immage, Beckman-Coulter (2 IU/mL) Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
24 Likelihoods Likelihood ratio 1,,96 3,8 25,6 2, Controls RA LR,2 5,,2,3 CCP < 7 Units/mL CCP 7-25 Units/mL CCP > 25 Units/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
25 Likelihoods Likelihood ratio 1, 3,8 25,71 2,6, Controls RA LR,23,2 5,7, CCP < 7 Units/mL CCP 7-25 Units/mL CCP > 25 Units/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
26 Likelihoods Likelihood ratio 1,,96 3,8 25,71 2,6, Controls RA LR,23,2,,7,2,3 CCP < 7 Units/mL CCP 7-25 Units/mL CCP > 25 Units/mL 5 Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
27 Likelihoods Likelihood ratio 1,,96 27,7 3,8 25,71 2,6, Controls RA LR,23,2, 4,5,7,2,2,3 CCP < 7 Units/mL CCP 7-25 Units/mL CCP > 25 Units/mL 5 Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
28 LR 1 no clinical value >1 <.1 clinically important difference modest, but substantial difference small difference that may be relevant
29 Likelihoods Likelihood ratio 1 27,7 3,8 25,6 2, Controls RA LR,2 4,5 5,2 CCP < 7 Units/mL CCP 7-25 Units/mL CCP > 25 Units/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
30 probability odds Post-test odds = Pre-test odds x LR.2.2 / (1.2).25 odds probability 4 4 / (1 + 4).8
31 Post-test probability RA 1,8,6 CCP <7 Units/mL,4 CCP 7-25 Units/mL CCP > 25 Units/mL,2,2,4,6,8 1 Pre-test probability RA Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
32 Likelihood Likelihood ratio 1, 6,8,77 4,6,4 Controls RA LR 2,2,11,7,5, RF <2 IU/mL RF 2-1 IU/mL RF 11-3 IU/mL RF >3 IU/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
33 Likelihood Likelihood ratio 1, 6,8 4,6 Controls RA,4 LR,32 2,2,23,21,25, RF <2 IU/mL RF 2-1 IU/mL RF 11-3 IU/mL RF >3 IU/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
34 Likelihood Likelihood ratio 1, 6,8,77 4,6 Controls RA,4 LR,32 2,2,23,21,25,11,7,5, RF <2 IU/mL RF 2-1 IU/mL RF 11-3 IU/mL RF >3 IU/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
35 Likelihood Likelihood ratio 1, 6,8,77 4,8 4,6 2,9 Controls RA,4,32 2, 2 LR,2,23,21,25,4,11,7,5, RF <2 IU/mL RF 2-1 IU/mL RF 11-3 IU/mL RF >3 IU/mL Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
36 Post-test probability RA 1,8,6 RF <2 IU/mL RF 21-1 IU/mL,4 RF 11-3 IU/mL RF >3 IU/mL,2,2,4,6,8 1 Pre-test probability RA Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
37 Post-test probability RA Post-test probability RA 1,8,6 CCP <7 Units/mL,4 CCP 7-25 Units/mL CCP > 25 Units/mL,2,2,4,6,8 1 Pre-test probability RA 1,8,6,4,2 RF <2 IU/mL RF 21-1 IU/mL RF 11-3 IU/mL RF >3 IU/mL,2,4,6,8 1 Pre-test probability RA Bossuyt X. et al. Ann Rheum Dis. 29;68:287-9.
38 Post-test probability RA 1,8,6 CCP <7 Units/mL,4 CCP 7-25 Units/mL CCP > 25 Units/mL,2,2,4,6,8 1 Pre-test probability RA Female, 5 years old Recent onset undifferentiated arthritis Intermittent asymmetric tender and swollen small joints of the hands (n=5) CRP: 1 mg/l A.H. van der Helm-van Mil, S. le Cessie, H. van Dongen, F.C. Breedveld, R.E. Toes, T.W. Huizinga A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: how to guide individual treatment decisions Arthritis Rheum, 56 (27), pp
39 Post-test probability RA 1,8,6 CCP <7 Units/mL,4 CCP 7-25 Units/mL CCP > 25 Units/mL,2,2,4,6,8 1 Pre-test probability RA Female, 5 years old Symmetric arthritis of upper and lower extremities Tender and swollen small joints (n=12) CRP: 7 mg/l Bossuyt X. Autoimmun Rev. 29;8:543-8.
40 CELIAC DISEASE
41 IGG anti-dgp (U/mL) Thermo Fisher EliA 1 A 1 1 CD CD (IgA Def) non-cd (IgA def) non-cd 1 x ULN 3 x ULN 1 x ULN IgA anti-ttg (U/mL) CD (n=156) Diseased controls (n=974) Oyaert et al. Clin Chem Lab Med. 215;53:
42 Likelihood Likelihood ratio 1, IgA anti-ttg 8, ,6 5,4 4 3 non-cd CD LR,2 2 1,,16 8,8 16 <2 CU 2-6 CU >6-2 CU >2 CU Oyaert et al. Clin Chem Lab Med. 215;53:
43 Post-test probability 1 IgA anti-ttg,8,6,4 <2 CU 2-6 CU >6-2 CU >2 CU,2,2,4,6,8 1 Pre-test probability Oyaert et al. Clin Chem Lab Med. 215;53:
44 Likelihood Likelihood ratio 1, IgG DGP 3,8 2,6,4 non-cd CD LR 1 1,2, 9,12 neg 2-6 >6-2 >2 Oyaert et al. Clin Chem Lab Med. 215;53:
45 Post-test probability IgG DGP 1,8,6,4,2,1,2,3,4,5,6,7,8,9 1 Pre-test probability <2 CU 2-6 CU >6-2 CU >2 CU Oyaert et al. Clin Chem Lab Med. 215;53:
46 Post-test probability The pretest probability of celiac disease in the general population: 1%. in patients suspected of celiac disease who underwent intestinal biopsy: 7%. In patients with a Marsh class I lesion: 2%. In patients with gastrointestinal complaints: 6% In patients with weight loss, failure to thrive, or small stature: 14% in patients with anemia or iron deficiency: 14% in patients with malabsorption: 9%. 1 IgA anti-ttg,8,6,4,2,2,4,6,8 1 Pre-test probability <2 CU 2-6 CU >6-2 CU >2 CU Vermeersch et al. Defining thresholds of antibody levels improves diagnosis of celiac disease. Clin Gastroenterol Hepatol. 213;11:398-43
47 SYSTEMIC RHEUMATIC DISEASES
48
49 Study Population n M(%)/F(%) Median age (range) Blood donors 18 51/49 45 (19-65) Chronic Fatigue 15 19/81 41 (16-75) Syndrome Diseased Controls /75 45 (17-81) 392 Systemic Lupus 85 12/88 35,5 (15-72) Erythematosus Sjögren s Syndrome 36 14/86 56 (21-75) Systemic Sclerosis 76 34/66 53 (18-8) Polymyositis / Dermatomyositis Mixed Connective Tissue Disease 32 44/56 5 (24-77) 16 6/94 31,5 (16-66) 245 Schouwers et al. Clin Chem Lab Med. 214;52:547-51
50
51 NOVA View 35 Outlier Boxplot 3 Percentiles (95% of Distribution) 25 Outliers > 1.5 and < 3 IQR L I U 2 15 Outliers > 3 IQR 1 5 HC CVS DC SLE SS SSc PM/DM MCTD Schouwers et al. Clin Chem Lab Med. 214;52:547-51
52 Prevalence Likelihood ratio NOVA View,6 4,5 33 3,4,3 2 controls SRD,2 1 1 LR,1,9,25,85 < >2 Nuclear Index Schouwers et al. Clin Chem Lab Med. 214;52:547-51
53 NOVA View LR LIU Controls SLE SS SSc PM/DM MCTD SARD Prevalence <49,56,6,3,3,13, ,26,5,6,5,19, ,13,11,3,9,34, ,4,46,61,34,25,6,39 >2,1,33,28,49,9,94,38 LR <49,11,5,5,23, ,18,21,2,73, ,79,21,69 2,57, ,2 15, 8,4 6,1 1,5 9,6 >2 29,1 24,5 42,9 8,3 82,7 33,5 Schouwers et al. Clin Chem Lab Med. 214;52:547-51
54 Post-test probability 1,8,6,4 < >2 >2,2,,2,4,6,8 1, Pre-test probability Pre-test probability Post-test probability < >2 1%: a young women with hair loss and polyarthralgia.7%,5% 5% 25% Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. J Immunol Res. 214;214:
55 Post-test probability 1,8,6,4 < >2 >2,2,,2,4,6,8 1, Pre-test probability Pre-test probability Post-test probability < >2 1%: a young women wit photosensitivity and mild leucopenia (3-35/mm 3 ),7% 5,5% 36% 79% Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. J Immunol Res. 214;214:
56 Post-test probability 1,8,6,4 < >2 >2,2,,2,4,6,8 1, Pre-test probability Pre-test probability Post-test probability < >2 5%: a young women with photosensitivity, malar rash and symmetrical polyarthritis 6,5% 35% 83% 97% Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. J Immunol Res. 214;214:
57 ALLERGY TESTING
58
59 Clinical history Skin prick testing Grass pollen Birch pollen allergic possible allergy sensitization Non-allergic Van Hoeyveld et al. Clin Chim Acta. 215;45:46-5
60 Likelihood Likelihood ratio Likelihood Likelihood ratio Likelihood Likelihood ratio Likelihood Likelihood ratio Birch pollen t3 Grass pollen mixture gx3 1, 2 1, 4,8,8,6,4,2,,,1 <,1,1 -,35 4,2,35 -,7 6,3,7-3,5 3,5-17,5 17, >1 1 Contr Pat LR,6,4,2,,,2 1,2 <,1,1 -,35,35 -,7,7-3,5 3,5-17,5 17, >1 2 Contr Pat LR rbet v1 rphl p1,5 1, 2 1, 2,8,8,6,4,2,,3 <,1,1 -,35 1,4 1,4,35 -,7,7-3,5 3,5-17,5 17, >1 1 Contr Pat LR,6,4,2,,2,4 <,1,1 -,35 3,6,35 -,7,7-3,5 3,5-17,5 17, >1 1 Contr Pat LR
61 Allergen sige (ku/l) < > grass pollen mixture (.7-.75).4 ( ) rphl p 1,5.2 (.4-.6) birch pollen..1 rbet v 1.3 (.1-.8) (.1-.75) 1.41 ( ) ( ) 3.6 ( ) 4.22 ( ) 1.41 ( ) 6.33 ( ) Van Hoeyveld et al. Clin Chim Acta. 215;45:46-5
62 Post-test probability Post-test probability Post-test probability Post-test probability Birch pollen t3 Grass pollen mixture gx3 1 1,8,8,6,4,2 <,1 ku/l,1 -,35 ku/l,35 -,7 ku/l,7-3,5 ku/l >3,5,6,4,2 <,1 ku/l,1 -,35 ku/l,35 -,7 ku/l >,7 ku/ml,2,4,6,8 1,2,4,6,8 1 Pre-test probability Pre-test probability rbet v1 r Phl p1,5 1 1,8,8,6 <,1 ku/l,6 <,1 ku/l,4,1 -,35 ku/l,35 -,7 ku/l,4,1 -,35 ku/l,35 -,7 ku/l,2 >,7 ku/l,2 >,7 ku/l,2,4,6,8 1,2,4,6,8 1 Pre-test probability Pre-test probability
63 Pre-test Probability Allergen Post-test probability <.1 ku/l ku/l ku/l ku/l >3.5 ku/l Grass pollen allergy 17.6% GP % 5% 2% 1% 1% rphl p 1,5.3% 8% 43% 1% 1% 44% GP % 15% 48% 1% 1% rphl p 1,5 1% 24% 74% 1% 1% Birch pollen allergy 9.7% BP % 1% 31% 4% 1% rbet v 1.3% 13% 13% 1% 1% 4% BP % 6% 74% 81% 1% rbet v 1 1.6% 48% 48% 1% 1% Van Hoeyveld et al. Clin Chim Acta. 215;45:46-5
64 Conclusions We illustrated how likelihood ratios depend on antibody level for a number of immune-mediated diseases Such knowledge may help with the interpretation of a specific test result Clinical laboratories might consider to provide likelihoods ratios or probability data for autoantibody test result intervals
65 Acknowledgements Department of General Internal Medicine Dr Blockmans Department of Rheumatology Dr Verschueren Dr Westhovens Department of Gastroenterlogy Dr Hiele Department of Immunology and Allergy Dr J. Ceuppens Department of Pediatrics Dr I. Hoffman Department of Laboratory Medicine Dr Van Hoeyveld Dr Vermeersch Dr Mariën M. Oyeart S. Schouwers
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