INTEGRATED PROJECT

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INTEGRATED PROJECT
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LABORATORY 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

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• IFCC AIMS
• Forum for standardisation
• Dissemination of information of best practice
  in diagnostics, technology, and economics
• Promotion of an integrated vision of Clinical
  Chemistry and Laboratory Medicine beyond
  traditional narrow perceptions
• Projects with an impact on clinical Medicine
• IFCC OBJECTIVES
• To advance the theory and practice of clinical
  laboratory science
• To establish Laboratory Medicine in health
  services as an integrated discipline
• To provide service to individuals, professional
  national societies, diagnostic industries and
  governmental and non-governmental organisations

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• STRATEGY and SCOPE of INTEGRATED IFCC PROJECTS
• Diagnostic laboratories have a responsibility for
  the individual patient by applying the correct
  strategy for diagnosis, patient reports give the
  results of measurements and the interpretation of
  these results based on pathophysiological and
  evidence based medicine knowledge.
• Standardization, research and educational
  activities must be more focused on patient care
  and the health of the individual.
• IFCC will establish working parties (EB, SD, EMD,
  CPD) to improve and maintain the
  multidisciplinary and international leadership
  in standardisation activities (reference systems,
  traceability).
• Standardisation will harmonise patient results.
  Linking these projects to evidence-based medicine
  and to clinical guidelines is very important for
  the acceptability of IFCCs status among medical
  organisations.
• Several projects reflect the multidisciplinary
  character and orientation towards the patient
  (cardiac markers, HbA1c, GFR).

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• ACTIONS
• General Considerations
• National Societies and Corporate Members should
  be asked at least every 2nd year to name three
  projects in which they believe the Scientific
  Division or the Education and Management Division
  should be involved and which are relevant for
  clinical medicine.
• The TF for integrated IFCC projects should
  evaluate and prioritize these proposals. The EB
  in collaboration with SD and EMD will decide
  which projects will be conducted, taking the
  clinical impact into account (grading 1-5). The
  basis of these decisions is a project plan
  describing the intentions, the resources and the
  time frame.
• Each year the SD and EMD reports at the budget
  meeting to the EB about the congruence between
  the Divisions activities for integrated projects
  and the originally stated expectations of the
  membership.
• The Annual reports highlights specifically the
  accomplishments of integrated projects reflecting
  the expectations of the proposing members.

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QUESTIONNAIRE

• The following new integrated projects should be
  developed by the IFCC (please, give not more than
  3)

2) Currently the IFCC Scientific Division and its
working parties are active in the following
standardisation projects. Please, indicate
whether you consider it pertinent that in
addition to the analytical aspects also clinical
and diagnostic aspects should be integrated in
these projects.
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19 Members 4 Corporates
Questionnaire
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INTEGRATED PROJECT
Pharmacogenetics Brains storming meeting Milano
2008 02 Screening for chronic kidney
disease Bergmeyer Conference Eibsee 208 03
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Pharmacogenetics

• Genetic polymorphisms influence
• rate of metabolism
• transporter proteins
• Interest in
• Oxidative CYP3A enzymes and drug efflux pump
  P-glycoprotein (P-gp) in enterocytes
• Multiple drug resistance gene-1 (MDR-1)
• Impact on dosage requirements
• Impact on pharmacodynamics
• Ethnic differences in distribution

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MDR-1 Gene SNPs in NTX Tacrolimus dose
requirements for blood trough concentration of 10
15 ng/ml (mean 11.8 2.8 ng/ml)
Dany Anglicheau et al 2003
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Cytochrome P450 CYP3A5 Genotype in NTX
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Pharmacogenetics BackgroundR. H. N. Van Schaik

• Effectiveness of drugs in 25-60 of patients
• US 100.000 fatalities 100 Billion US

Rationale

• Interindividual variation of drugs
• Rationale application of drugs
• Individualized medication
• Polymorphism of Cytochrome P450

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Cytochrome P450 genetics

• Cytochrome P450 80 oxidative metabolism of
  drugs
• Genetic polymorphisms of CYP1A2, CYP2D6, CYP2C9,
  CYP2C19, CYP3A4 and CYP3A5
• CYP2D6 Deficiency in 5 10 Caucasians
• Immunosuppressive drugs
• Beta-blockers
• Statins
• warfarin

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BRAIN STORMING OUTCOME
1.) Pharmacogenetics of tamoxifen CYP2D6 In
particular, the number of SNPs measured varies
between laboratories at present, in part
determined by economic considerations. Quality
assurance of this type of testing is also an
important issue in view of the major clinical
consequences of the test result and the fact that
is a once only test (analogy with blood group
testing). Repeating the genotyping in a
different laboratory or to confirm the result, or
at least genotyping at least twice in a single
laboratory? This should be a joint initiative
with the European Organisation for Research and
Treatment of Cancer
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2.) Pharmacogenetics of azathioprine and
6-mercaptopurine TPMT was also identified as
an important area of work (although not a
cytochrome gene). This is a relatively mature
area and a guideline could be generated rapidly.
Jointly with relevant clinical societies in
Oncology, Gastroenterology and Dermatology.
3.) Pharmacogenetics of coumarols CYP2CP9 and
VKORC1 both influence coumarin/warfarin
prescribing. A joint initiative with the
International Society for Thrombosis and
Hemostasis.
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Working PartyMembers

• IFCC
• Scientific Division (2)
• Education Management Division (2)
• Clinician Organisation (?) (2)

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Working PartyTasks Term of References

• Define relevant polymorphisms
• Define clinical indications for genetic testing
• Make recommendations on laboratory methodology,
  including which technique should be used and the
  quality specifications
• Describe interpretation of test results,
  including relation between genotype and phenotype
• Provide guidelines for specific drugs to include
  the following
• advice / information for clinicians and
  patients (pre- test and post-test)
• dosage / blood concentrations / risk of
  adverse events
• 6. Dissemination of guidelines