diagnostic guidelines a service for clinicians and patients
TRANSCRIPT
DIAGNOSTIC GUIDELINESDIAGNOSTIC GUIDELINESA Service for Clinicians and A Service for Clinicians and
PatientsPatients
Mathias M. MüllerMathias M. Müller
LABORATORY MEDICINELABORATORY MEDICINE
OBJECTIVES• Prevention - Risk assessment• Diagnosis of conditions and diseases• Monitoring of therapy - Follow-up of patients
METHODS• Chemical, physical, biochemical,
immunological, molecular biological• Measurement procedures accurate and
precise
CLINICIANS, PATIENTS
Risk assessmentDiagnosis of diseasesMonitoring of treatmentPrognosis assessment
CLINICIANS, PATIENTS
Risk assessmentDiagnosis of diseasesMonitoring of treatmentPrognosis assessment
LABORATORIANS
Analytical proceduresTechnologies, automationStandardisationQuality assurance Quality managementLaboratory organisation
workload, workflowCertification, accreditation
LABORATORIANS
Analytical proceduresTechnologies, automationStandardisationQuality assurance Quality managementLaboratory organisation
workload, workflowCertification, accreditation
INTERESTS and EXPECTATIONSINTERESTS and EXPECTATIONS
No mutual understandingNo confidence in service
When communicating with clinicians, one must think like a clinicianR. H. Christenson 2007
INFANTINFANT
ADULTADULT
ELDERLYELDERLY
wel
lnes
s and
fitne
ss
acut
e an
d
chro
nic
dise
ases
inborn errorsgenetic
disposition
HIERARCHY OF CLINICAL DECISIONSHIERARCHY OF CLINICAL DECISIONS
Decision
Cost effectiveness
Organizational impact
Clinical impactDiagnostic
TherapeuticHealth outcome
Diagnostic performance
Technical performance
C. Price 2000
To use a test ?
GUIDELINESGUIDELINES systematic developed statements to assist practitioner systematic developed statements to assist practitioner
(clinician) and patient decisions about appropriate healthcare (clinician) and patient decisions about appropriate healthcare decisions for specific clinical circumstancesdecisions for specific clinical circumstances
Field and Lohr 1990Field and Lohr 1990
Dissemination of best practice Standardization of medical decisions
• Increased transparency• Better information of patients
Improvement of patient outcome Improve the transperancy and accountability Basis in the training of professionals Improvement in cost-effectiveness
QUESTIONS TO BE ASKEDQUESTIONS TO BE ASKED
CARO QUESTIONS
C: Case What are the patient characteristics, conditions, symptoms, demographics ?
A: Assay Which procedure or strategy is considered ?
R: Reference What is the standard procedure, the comparator ?
O: Outcome What is the interest, the diagnostic validity ? Sensitivity, specificity, predictive values, prognosis ?
R. H. CHRISTENSON 2007
GUIDELINE DEVELOPMENTGUIDELINE DEVELOPMENTTOPIC SELECTION
TARGET GROUP
MULTIDISCIPLINARY DEVELOPMENT TEAM
SCOPE OF GUIDELINE The diagnostic question
SYSTEMATIC REVIEW of LITERATURECritical Appraisal Skill Programme (CASP/NHS)
Appraisal of Guidelines Research and Evaluation (AGREE)
WRITING GUIDLINE RECOMMENDATIONSSynthesis of evidence
Consultation, consensus, peer review
GUIDELINEPresentation, dissemination, monitoring
GUIDELINE RESOURCES
US National Guideline Clearing House: http://www.guideline.gov
Finnish Medical Society:
http.//www.udate-software.com/publications/EBMG/default.html
National Academy of Clinical Biochemistry
http://www.nacb.org Clinical Guidelines from other disciplines
QUALITY of REFERENCESIa Metaanalysis of randomised trials or systematic reviews
based on consistent level Ib studies.
Ib Double blind randomised controlled clinical/diagnostic trial or outcome study of good quality.
II Diagnostic trials or outcome studies of medium quality. Insufficient number of patients, case studies.
III Non-comparative studies. Descriptive studies - case reports.
IV Statements of committees, expert opinions - reviews.
Oosterhuis W. P. et al 2004
STARD (Standards for reporting diagnostic accuracy) - a checklist
Introduction Diagnostic accuracy between tests or across patient groups
Probands Demographic description, inclusion and exclusion criteria, symptoms, data collection criteria.
Study design Time frame, number and group of probands, time of measurements, treatment of probands
Reference standard
Description of standard and rationale for comparison.
Test method Technical, analytical specifications (linearity, cut-off levels, uncertainty, bias, etc)
Statistical methods
Methods for reporting diagnostic validities, comparisons between groups, test reproducibility
Results Cross tabulaton of results (reference, test), analytical and diagnostic acuracy between groups of probands, ROC-curves, Box-Whiskers plot.
Conclusion Clinical application P. M. Bossuyt et al. 2003
THE DIAGNOSTIC PROCESS
PATIENT CAREPATIENT CARE
PREANALYTICS•Diagnostic strategy•Test selection/request•Patient factors•Sample collection
PREANALYTICS•Diagnostic strategy•Test selection/request•Patient factors•Sample collection
POSTANALYTICS•Laboratory report•Interpretation •Effect on patient•Clinical consultation
POSTANALYTICS•Laboratory report•Interpretation •Effect on patient•Clinical consultation
ANALYTICS•Sample preparation•Measurement•Result verification
ANALYTICS•Sample preparation•Measurement•Result verification
ESSENTIALS IN ESSENTIALS IN DIAGNOSTIC GUIDELINESDIAGNOSTIC GUIDELINES
PREANALYTICSPREANALYTICS• Prevalence of condition• Usefulness of a test
Diagnostic validities
• Diagnostic algorithm• Patient preparation
Timing / frequency of testing
Type / handling of specimen
• Biological variation
Oosterhuis W. P. et al 2004
ANALYTICS• Validated measurement procedure• Analytical characteristics
Detection limits, sensitivity, specificityInterferencesQuality assurance: bias, imprecision
• Laboratory requirementsTurnaround timeQualification, competenceCosts
ESSENTIALS IN ESSENTIALS IN DIAGNOSTIC GUIDELINESDIAGNOSTIC GUIDELINES
POSTANALYTICS• Reference ranges• Medical decision limits• Diagnostic validities
Sensitivity, specificityPredictive valuesLikelihood, ROC analysis
• Interpretation of resultsIntra-individual variationCritical limits
ESSENTIALS IN ESSENTIALS IN DIAGNOSTIC GUIDELINESDIAGNOSTIC GUIDELINES
DATABASE RESOURCES DATABASE RESOURCES for the Development / for the Development /
Appraisal of a GuidelineAppraisal of a Guideline AGREE: Appraisal of guidelines:
http://www.agreecollaboration.org AHRQ: Agency for healthcare research and quality:
http://www.ahrq.gov/ CASP/NHS: Critical appraisal skill programme of the national
health service: http://www.phru.nhs.uk/casp/casp.htm Cochrane: Methods working group on systematic review of
screening and diagnostic tests: www.cochrane.org/cochrane/sadtdoc1.htm
US National Guideline Clearing House: http://www.guideline.gov
IFCC C-EBLM: Committee on evidence based laboratory medicine database: www.ckchmb.nl/ifcc
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
RATING of GUIDELINE RECOMMENDATIONS
A Supported by one Ia level systematic review or
at least 2 level Ib studies
B Supported by at least 2 level II studies
C Not supported by sufficient level I or II studies
D Advise of experts
Oosterhuis W. P. et al 2004
MI - Which Test ?MI - Which Test ?
2 4 6 8 12 18 24 32 48 72 144
Hours after Onset
0
100
200
300
400
CK-MB, Troponin T + I
0
500
1000
1500
2000
2500
Myoglobin, CK total
CK total Activity CK-MB Activity CK-MB Mass
Myoglobin Troponin T Troponin I
2 4 6 8 12 18 24 32 48 72 144
Hours after Onset
0
100
200
300
400
CK-MB, Troponin T + I
0
500
1000
1500
2000
2500
Myoglobin, CK total
CK total Activity CK-MB Activity CK-MB Mass
Myoglobin Troponin T Troponin I
I. A. KATZ 1998
Diagnostic ValidtiesDiagnostic Validties6 hours from onset of symptomes6 hours from onset of symptomes
CK ActivityMyoglobin
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Sensitivity - %
CK ActivityMyoglobin
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Sensitivity - %
CK ActivityMyoglobin
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Specificity - %
CK ActivityMyoglobin
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Specificity - %
J. ZIMMERMAN et al. CC 1999
MyoglobinCK Activity
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120
140Sensitivity - %
MyoglobinCK Activity
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120
140Sensitivity - %
MyoglobinCK Activity
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Specificity - %
MyoglobinCK Activity
TnT TnI
CK-MB ActivityCK-MB Mass
0
20
40
60
80
100
120Specificity - %
Diagnostic ValidtiesDiagnostic Validties18 hours from onset of symptomes18 hours from onset of symptomes
J. ZIMMERMAN et al. CC 1999
Troponin I - Assay PerformanceTroponin I - Assay Performance
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
F. S. APPLE et al. AmHJ 2002
ESC - ACC - MI DIAGNOSTIC ESC - ACC - MI DIAGNOSTIC GUIDELINE (Redefinition)GUIDELINE (Redefinition)
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Ventricular DysfunctionVentricular Dysfunction Natriuretic Peptides Natriuretic Peptides
proANP proANP 1-126 proBNP proBNP 1-108
-ANP -ANP 99-12699-126active t/2 2.5 min
NTproANP NTproANP 1-98
1-30 31-67 79-98
NTproBNP NTproBNP 1-76t/2 60-120 min
BNP BNP 77-108active t/2 20 min
Volume overloadVolume overloadMyocardial wall tensionMyocardial wall tension
Natriuresis - DiuresisNatriuresis - DiuresisVasodilatation Vasodilatation
Hammerer-Lercher et al. 2001 CCA
LVEF < 55% LVEF < 40 %
Natriuretic PeptidesNatriuretic PeptidesLeft Ventricular DysfunctionLeft Ventricular Dysfunction
NATRIURETIC PEPTIDESNATRIURETIC PEPTIDESin heart function assessmentin heart function assessment
• Assessment of cardiac conditions• Screening of NYHAN I patients• Diagnosis of left ventricular dysfunction• Diagnosis of heart failure• Diagnosis of ventricular hypertrophy• Prognosis of myocardial infarction• Diagnosis of essential hypertension
C. J. BURDBURY et al HSQ Scotland 2005S. K. JAMES et al. Circulaton 2003
ÖGLMKC: DIAGNOSTIC GUIDELINE ÖGLMKC: DIAGNOSTIC GUIDELINE OF THYREOD FUNCTIONOF THYREOD FUNCTION
Investigation ofo Newborn (screening)o Asymptomatic adults > 50 a
family history of thyreoidea dysfunctionpatients in hospitalsbefore exposure to Jodide
o Symptomatic adults Hypothyreosis ?Hyperthyreosis ?Autoimmun disease ?InfertilityPost PartumDepression, demenzia Abnormal lipids
1st Diagnostic test: TSH> TSH within reference range - euthyreosis> TSH > 3.0 mU/L - hypothyreosis> TSH < 3.0 mU/L - hyperthyreosis
C. BIEGLMAYER et al. 2007
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
1
Clinical Diagnosis
2 Control after 3 months
Control after2 months
Clinical Diagnosis
3
1 - medication 2 - T3/T4 medication 3 - Initial phase of thyreostatic therapy 4 - sec. Hyperthyreosis, hormone resistance
Thyroid function tests: Reference ranges for adults
Elecsys/ Modular (Roche)
Advia Centaur (Bayer)
Immulite 2000
(DPC) Architect (Abbott)
Axsym (Abbott)
IMX (Abbott)
Dimension (Dade
Behring)
Erwachsene von bis von bis von bis von bis von bis von bis von bis MW von MW bis CV von CV bis
TSH mU/L 0,27 4,20 0,35 4,50 0,40 4,00 0,35 4,94 0,47 4,64 0,47 5,01 0,34 4,82 0,38 ± 0,07 4,59 ± 0,38 19% 8%
TT3 nmol/L 1,27 3,07 0,92 2,79 1,26 2,76 0,89 2,45 1,22 2,29 0,79 2,54 1,34 2,57 1,10 ± 0,22 2,64 ± 0,26 20% 10%
TT4 nmol/L 59 154 58 148 67 161 63 151 58 154 58 154 60 171 60 ± 3 156 ± 8 6% 5%
FT3 pmol/L 3,95 6,80 3,08 6,47 2,77 6,47 2,63 5,71 2,23 5,36 2,59 5,45 2,88 ± 0,59 6,04 ± 0,61 21% 10%
FT4 pmol/L 12,0 22,0 10,3 21,9 10,3 24,5 9,0 19,0 9,1 23,8 9,1 23,8 7,6 15,1 9,6 ± 1,4 21,4 ± 3,3 14% 16%
Alter TSH mU/L
FT4 pmol/L
Frühgeborene - – 4. T ag
0,8 – 6,9
5,15 - 36
Neugebo rene 3. Tag
1,3 - 16
25,74 – 51,48
Kinder 1 – 12 Monate
0,9 – 7.7
11,58 – 33,46
Kinder prä pube rtär
0,6 – 5,5
10,3 – 28,31
Kinder Pubert är
0,5 – 4,8
10,3 – 29,6
Age
Thyroid function tests: Reference ranges for children
ÖGLMKC: WG: Laboratorians, Clinicians (endocrinology,
internal medicine, nuclear medicine, practitionare).
1. Clinical practice guidelines, laboratory diagnosis and monitoring of hypothyroidism in adults. http://www.anaes.fr
2. Clinical practice guidelines, laborartory diagnosis and monitoring of hyperthyroidism in adults. htttp://www.sante.fr
3. Guidelines for in vivo and in vitro procedures for thyroid disease – version 2. 4. Laboratory medicine practice guidelines, laboratory support for the diagnosis and
monitoring of thyroid disease. http://www.nacb.org 5. American association of c linical endocrinologists, medical guidelines for clinical
practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. http://www.aace.com/pub/guidelines/
6. Medical/surgical guidelines for clinical practice: management of thyroid carcinoma. http://www.aace.com/pub/guidelines/
7. National guidelines clearinghouse, guidelines for detect ion of thyroid dysfunction. http://www,guidelines.gov/summary/summary.aspx?doc_id=2362
8. Leitlinien zur Schilddrüsendiagnostik. http://www.nuklearmedizin.de/publikationen/leitlinien/schild_diagn.php
9. Protocol for the use of thyroid function tests in the diagnosis and monitoring of patients with thyroid disease. http://www.hlth.gov.bc.ca/msp/protoguides/gps/thyroid.html
10. Laboratiory testing guidelines for investigation of thyroid dysfunction (adults). http://www.albertdoctors.org
11. Prodigy guidance – hyperthyroidism. http://www.prodigy.nhs.uk/guidance.asp? 12. Key recommendations and overview for the management of thyroid cancer
(differentiated and medullary). http://www.rcplondon.ac.uk/pubs/wp_thyroidcancer_summarysummary.htm
Databases:
References: 1. - 35 - 1990 - 2004
Thyroid function tests in serious diseasesThyroid function tests in serious diseases
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
DISEASED RECOVERY
DEMERS AND SPENCER NACB 2002
Thyroid function tests during medicationThyroid function tests during medication
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
CLINICSThyreostatics
Intermediatephase
Intermediatephase
NormalTSH/FT4
Equilibrium
Diagnostic Test
Referencerange
Months
DEMERS AND SPENCER NACB 2002
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
SCREENING forSCREENING forDIAGNOSIS of DIAGNOSIS of DYSLIPIDAEMIADYSLIPIDAEMIACardiovascular Risk Cardiovascular Risk PopulationPopulation(Family History CVD, smoker, (Family History CVD, smoker, hypertension, diabetes, hypertension, diabetes, obese obese
FLP: Fasting lipids(TG, Chol, HDL-Chol)
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
SCREENING forSCREENING forDIAGNOSIS of DIAGNOSIS of DYSLIPIDAEMIADYSLIPIDAEMIANot Cardiovascular Risk Not Cardiovascular Risk PopulationPopulation
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
WHAT IS A GOOD GUIDELINE ?WHAT IS A GOOD GUIDELINE ?
A good guideline is one that leads to improved outcomes in patients.
Needs to be based on evidence
Needs to be used(implemented)
Needs to be regularly assessed,and updated
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
A lot of work !A lot of work !