Introduction to the design of diagnostic criteria Joop P van de Merwe Dept. of Immunology & Internal...

introduction to the design of diagnostic criteria

Joop P van de MerweDept. of Immunology

& Internal MedicineErasmus MC Rotterdam

[email protected]

ESSIC Meeting Baden 16-18 June 2005

2 * Fries JF et al. Arthritis Rheum 1994;37:454-62

Types and purposes of criteria*

Type Purpose

Classification criteria To separate those with a specific disease from those without the disease

Subclassification criteria To separate diseases or subsets within a disease cluster

Prognostic criteria To separate subjects with good or potentially favorable outcomes from those with bad outcomes

Status indexes To assess present disease activity or accumulated damage from the disease

Activity indexes (implies reversibility)

To estimate current disease activity status

Damage indexes (implies irreversibility)

To estimate accumulated damage from the disease

Outcome criteria To measure the overall impact of a disease and to serve as dependent variables for clinical studies

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* Fries JF et al. Arthritis Rheum 1994;37:454-62 (modified)

CLASSIFICATION CRITERIA*

Classification criteria separate patients with the disease from the general population and from patients with potentially confusable conditions

Persons with Diseases

Persons with ConfusableDiseases

All Persons

Persons with Target

Disease

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overlapping features

example: systemic autoimmune diseases

the problem

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systemic autoimmune diseases (1)

• rheumatoïd arthritis• Sjögren's syndrome• systemic lupus erythematosus (SLE)• antiphospholipid syndrome (APS)• mixed connective tissue disease (MCTD)• systemic sclerosis (scleroderma, CREST-syndrome) • polymyositis / dermatomyositis• relapsing polychondritis

examples

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possible features

clinical

• arthritis / arthralgia• vasculitis• fever• Raynaud's phenomenon• fatigue• various renal diseases

laboratory

• increased ESR, CRP• anaemia • leukopenia• rheumatoid factor• ANA• trombopenia


not specific

for

one single disease

not specific

for

one single disease

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possible accompaning organspecific autoimmune diseases

• atrophic gastritis - pernicious anaemia• Hashimoto's disease• keratoconjunctivitis sicca • lymfocytic interstitial pneumonitis • myositis • pericarditis, pleuritis • peripheral neuropathy • uveitis (iritis, iridocyclitis)• scleritis • interstitial cystitis


no combination is specific

for one single disease

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how do you recognize them ?


9

people


each person

has a face

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people


none of the

parts of the

face is unique,

but the

combination is

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people


none of the

parts of the

code is unique,

but the

combination is

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each autoimmune disease

has its own "face"



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characteristic feature

specific way it affects the lacrimal and salivary glandsspecific way it affects the joints specific way it affects the skin specific way it affects the skin

combination of clinical symptoms and anti-RNP specific way it affects the skin combination of symptoms

disease

Sjögren's syndrome

rheumatoid arthritissystemic lupus erythematosus subacute cutaneous lupus erythematosus mixed connective tissue disease (MCTD)systemic sclerosis (scleroderma) CREST syndrome

characteristic features

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what are the characteristic features of IC ?

• what is the consequence of the PBS/IC concept ?

ICS definition of PBS/IC

PBS: "suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and nighttime frequency in the absence of infection or other pathology"

IC: above with "typical cystoscopic and histological features"

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what are the "typical cystoscopic and histological features of IC" ?

what has happened to urgency ?

ICS definition of IC may be written as:

suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and nighttime frequency with typical cystoscopic and histological features in the absence of infection or other pathology

what are the characteristic features of IC ?

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what are the "typical cystoscopic and histological features of IC" ?

Cysto features: Hunner's ulcer or low capacity

epithelial denudation, submucosal inflammation, granulation tissue, edema, congestion, haemorrhage; detrusor fibrosis (and myopathy)

increased mast cell number & activation and neuronal staining

from: Hanno P, Burks D. Painful bladder syndrome / interstitialcystitis. Course 93 IC, AUA 2005 Annual Meeting, San Antonio, TX, May 21-26,2005

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Cysto features: Hunner's ulcer or low capacity

epithelial denudation, submucosal inflammation, granulation tissue, edema, congestion, haemorrhage; detrusor fibrosis (and myopathy)

increased mast cell number & activation and neuronal staining

from: Hanno P, Burks D. Painful bladder syndrome / interstitialcystitis. Course 93 IC, AUA 2005 Annual Meeting, San Antonio, TX, May 21-26,2005

does this matter as long as the combination is unique ?

but these are not unique for IC !

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PBS / IC concept

PBS

IC

PBS

orIC

IC has "typical" cystoscopic and histological features of IC in addition tosuprapubic pain and frequency

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gold standard

gold standard = diagnosis by experts

why ?- the diagnosis by experts is the best standard we have as long as the cause of a disease is unknown

advantage- non-experts can diagnose a disease as if they were experts (skill level)- diagnoses are made on the same basis by experts and non-experts (uniformity)- rules are based on information from many experts (acceptance and support)

20 Arthritis Rheum 1990;33:1137-44

classification methods (1)

classification tree

the classification tree is constructed by repeated splits of groups into 2 descendant subgroups


classification tree

pro

• items may be polychotomous or continuous

• nonparametric: no reference to a model for the

relationship between classification items and disease

status

• high information content - classified groups of subjects in

studies may be referred to the exact classifying subgroup

of the tree

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"number of criteria present rule"

Ann Rheum Dis 2002;61:554-8


classification methods (2)

con• simple definitions (+/-): - all items are given equal weight - all items must be dichotomous (+/-)

little insight into the characteristics of a classified patient group

pro• simple definitions (+/-): easy application

"number of items present rule"

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1. collect what information (symptoms and signs*) is used

by experts to diagnose IC and

differentiate IC from confusable diseases

for both men and women

suggested approach in a multicentre study

* requires definitions and decisions on data format

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2. collection of data from

patients with IC and

patients with confusable diseases

to define classification criteria for IC

(training phase)

sensitivity specificity


calculate an optimal combinationon the basis of how many false negative and false positivediagnoses we accept

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3. validation with new patient groups


the same database can be used to create

number of items present rule

for clinical diagnoses and a

classification tree

for scientific studies

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data may be

- continuous

avoid entry of cut-off points for continuous data

but have the statistical analysis decide

- categorical

data format

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tests to be evaluated for their diagnostic value

should be done in all patients with IC and confusable

diseases

1. antiproliferative factor

2. ................................

3. ................................

to be evaluated ….

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1. decision on broad definition of IC

PBS + "typical" cystoscopy and/or histology

2. select diseases with which IC can be confused

(confusable diseases, CD)

list to be discussed this morning

3. what information is needed to distinguish IC from CD:

follows from (2) but needs discussion and decision

4. decision on what percentage of false negative and

false positive diagnoses we accept

summary & conclusions (1)

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5. decision on gold standard for the diagnosis IC

diagnosis by experts

6. decision on methods of classification

classification tree and

"number of items present rule"

7. decision to perform a small pilot to test procedures

8. decision on tests to be evaluated

APF test

summary & conclusions (2)

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consensus on IC

Introduction to the design of diagnostic criteria Joop P van de Merwe Dept. of Immunology & Internal...

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