Post on 01-Apr-2015
11
Diagnostic versus
Classification Criteria:a continuum
Hasan YazıcıUniversity of Istanbul
I have no conflicts of interest.
3
Plan & Summary
Pre-test disease odds
Classification Diagnosis
4
Ottawa Ankle Rules
IG Stiell et al. Ann Emerg Med 1992
66
EULAR/ACR Vasculitis Criteria Group (2008)
“Perhaps the most robust criteria pertain to Behçet’s disease, where international collaboration has led to a validated proposal effective for both clinical and research purposes.”
“The challenge of producing validated diagnostic criteria for these heterogeneous diseases that are suitable for use in clinical research as a classification tool, is a formidable one. However, as the international community has exemplified with Behçet’s disease, it is achievable.”
77
International Study Group Diagnostic Criteria (Lancet, 1990)
Oral ulcers (~100%) +
Two of below:
a. Genital ulcers (80%)b. Skin lesions (80%)c. Eye lesions (50 %)d. Pathergy (50 %)
Classification
88
99
1010
11
Methods 914 unselected (366 from Iran..... 9 from France) patients with
BS from 12 centers in 7 countries 28 BS patients without OU excluded Control group: 308 patients with connective tissue diseases,
including 97 with OU only Study questionnaire based on previously published BS criteria
sets Individual disease features of a random sample (60%) were
compared with those in the control group. Sensitivities, specificities, log likelihood ratios and expected weights of evidence were calculated for each symptom or sign.
Features were added to the criteria set up to the point at which there was no further contribution to the criteria by the expected weight of evidence of a particular disease feature.
The new criteria set were further validated in the 40% sample.
1212
1313
14
Turing’s expected weight of evidence
It is the sum of the individual weights of evidence (logeLR).
It represents the weight of a question while the answers make up individual weights of evidence.
DJ Spiegelhalter Clin Gastroenterol 1985
1515
1616
17
18
Issuesapart from the – by definition- circular nature of the
exercise The initial internal validation was, in
fact, an internal check of the initial randomization.
The questionnaire did not seek for the frequency of various features of diseases that made up the control group, among the BS patients.
All work and validations were retrospective.
No attempt at confidence intervals.
1919
ACR Vasculitis Criteria*CHCC Vasculitis Criteria **
Among 198 patients (51 with vasculitis) the positive predictive value of ACR criteria ranged 17% - 29% (JK Rao et al Ann Int Med 1998)
CHCC criteria correctly identifed 8/27 patients with Wegener’s and 4/12 with MPA (SF Sorensen et al Ann Rheum Dis 2000)
2020
Hunder GG. The Use and Misuse of Classification and Diagnostic Criteria for Complex Diseases. Ann Intern Med 1998
21
ACR Classification criteria
RA SLE Sjogren Vasculitis Fibromyalgia JRA Osteoarthritis Scleroderma
22
The “circular” logic in diagnostic/classification criteria for conditions which lack a specific laboratory or a histological feature
JF Fries Arch Intern Med 1984
A perpetual motion machine, 1660Wikipedia
23
Pre-test disease odds
Classification Diagnosis
2424
Bayes theorem in c/d
post-test odds = pre-test odds x LR
LR = likelihood ratio
2525
Bayes theorem in c/d
post-test odds = pre-test odds x LR
LR = likelihood ratio
2626
Bayes theorem in c/dPre-test odds
post-test odds = pre-test odds x LR
actual disease prevalance (when c/d) or
frequency of disease manifestations in the disease studied vs. in diseases that come into the differential diagnosis (when formulating LR’s)
2727
Bayes theorem in c/d
post-test odds = pre-test odds x LR
LR = likelihood ratio
2828
Bayes theorem in c/d
post-test odds = pre-test odds x LR
LR = likelihood ratioc/d criteria
2929
Bayes theorem in c/dLikelihood ratio (LR)
post-test odds = pre-test odds x LR
+ LR = sensitivity/1-specificity or % true positives/% false positives - LR = 1-sensitivity or % true negatives/% false negatives
30
The Circular Nature
We use elements of pre-test odds (es) to estimate the LR’s.
From these LR’s we estimate the classification LR (criteria).
We use another (but related!) pre-test odds to estimate the post-test odds (c/d).
3131
Fulfilling the ISBD Criteria: What does it mean? (sensitivity = 90%; specificity =95%)
Criteria + (+LR) : 0.90/1-0.95 = 18 x pre-test odds Criteria - (-LR) :
1 - 0.90 /0.95 = 0.10 x pre-test odds
32
Sensitivity = 0.95 (0.90)Specificity = 0.95
+ LR Sensitivity/1-Specificity = 19 (18)
- LR1- Sensitivity/Specificity = 0.05 (10)
33
Sensitivity = 0.90Specificity = 0.97 (0.95)
+ LR Sensitivity/1-Specificity = 30 (18)
- LR1- Sensitivity/Specificity = 0.10 (10)
3434
90 92 94 96 980
10
20
30
40
50
60
70
80
90
100
(+) LR(-) LR
95 96 97 98 990
10
20
30
40
50
60
70
80
90
100
(+) LR
(-) LR
Sensitivity constantIncreasing specificity
Specificity constantIncreasing sensitivity
35
“Diagnostic criteria apply to individual persons rather than groups. In order to establish a correct diagnosis and to ensure that cases are not missed, such criteria should have a high sensitivity (especially for early cases of a particular disease, e.g. early ankylosing spondylitis) and will often include items that are present already early in the disease course. Such an approach will reduce specificity, which means that more false positives might be expected. Diagnostic criteria are mainly applied in clinical practice, an environment in which, at least for a limited follow-up period, a false-positive diagnosis is considered more acceptable than a false-negative rejection of a diagnosis.”
Rheumatology 4 Ed. 2008
36
Classification vs. Diagnostic Criteria ???
Classification
For groups
High specificity
Diagnosis
For individuals
High sensitivity
Rheumatology 4 Ed. 2008
37
“With this adaptation the sensitivity increased from 76% for the original New York criteria to 83% for the modified New York criteria, whereas the specificity only decreased from 99% to 98%.”
Rheumatology 4 Ed. 2008
38
LR’s and Odds of disease (assuming 1/100 frequency of AS)
Original NY criteria
Sensitivity: 76% Specificity: 99% + LR: 0.76/1-0.99= 76 (3.2:1)- LR: 1-0.76/0.99= 0.24 (500:1)
Modified NY criteria
Sensitivity: 83% Specificity: 98% + LR: 0.83/1-0.98= 42 (0.7:1)- LR: 1-0.83/0.98= 0.17 (588:1)
39
Diagnosis is classification of the individual patient.
40
What to do?
Define well your pre-test odds.
Go to well defined practices (subspecialties).
41
Ann Intern Med 1999
42
Causes of Uveitis (%) in Japan* & USA**
Japan (3060) USA (1237)
Idiopathic 38.9 34.9
B27 assoc. 1.5 10.4
Sarcoidosis 13.3 9.6
JRA 0.5 5.6
SLE 1.0 4.8
Behçet 6.2 2.5
HIV 0 2.4
* H Goto et al. Jpn J Ophtalmol 2007; ** A Rodriquez et al. Arch Ophthalmol 1996
43
Conclusions There are no separate classification or
diagnostic criteria but c/d criteria.
Classification and diagnosis are components of a continuum of which epidemiology is a most integral part.
To make a diagnosis is not an art but science backed by experience and arithmetic.
4444
A Proposal
Avoid attempts for “universal” disease criteria
and
Aim for classification/diagnostic criteria for subspecialties
H Yazici et al. Arthritis Rheum, 2008
45
Proposed Scheme of Preparing c/d Criteria in a Subspecialty Setting Retrospective tabulation of demography and
diagnoses (old & new pts.; 6 mo.) Same on new patients with checklists
(crossed) of symptoms/findings /lab./rad./hist. (6 mo.)
Estimation of clinical prediction rules and classification criteria after selecting the comparator groups
Internal and external validation of the criteria in the same and different settings (new patients; 6 mo.)
46
9/10 = 900/1000
MC Reid, MS Lachs, AR Feinstein JAMA 1995
9/10 ≠ 900/1000
Confidence Intervals