Improving Medical Performance and Patient Diagnosis in the Clinical Laboratory
RSLM � Targu Jiu � September 2010Trefor Higgins, MSc, FCACB - Director of Clinical Chemistry,DynaLifeDx Cristina Florescu MD, MSc, EurClinChem-Country Manager, SCL
Patient/Laboratory Encounters
• 35% of Albertans had 1 encounter with the laboratory in the past year.
• 81% were satisfied with the level of service and access to testing.
Topic #1Clinical Laboratory Environment
Romania versus Canada
CANADA:• 6 provinces officially do not have private
laboratories• 4 have private laboratories• 1 is trying to purchase all private labs• 1 denies existence of private labs
Topic #1Clinical Laboratory Environment
Romania versus Canada
ROMANIA:• 2500 laboratories in total• 440 public labs• 2100 private labs
Topic #1Clinical Laboratory Environment
Romania versus CanadaCANADA:• Ownership of private laboratories is not
restricted• Must have Medical Director (MD)• Department Directors need not have MDROMANIA:• Ownership of private labs is not restricted• Must have MD, Biologist or Biochemist
degree
Topic #1Clinical Laboratory Environment
Romania versus CanadaCANADA:• All laboratories must be accredited by
provincial College of Physicians and Surgeons
ROMANIA:• Laboratories would be nice to have
accreditation of RENAR; • ISO 17025 and 15189 have been
implemented in 70% private labs and 30% public labs
Cost of Laboratory Servicesin Alberta
• 3.5 to 5% of all healthcare expenditures
• Switzerland 11.4%
• United Kingdom 5%
Cost of Medicine Healthcare in Romania
• 3.6 to 4% of all healthcare funds from PIB (2.2.billion lei)
• Laboratory costs: one of the lowest percentage
• Civilized countries:5,5-10.5%
Topic #2
The role of the clinical laboratory for clinicians and patients
Topic #2
Importance of Laboratory Services
• 60-70% of diagnoses based on laboratory tests
• 70% of objective data in a patient file is lab data
• 70 to 80% of healthcare decisions involve 1 or more laboratory investigations-NHS report
Topic #2
Purpose of Testing• Diagnosis
–Confirmation or rejection of clinical diagnosis.
• Prognosis–Information Regarding likely outcome of disease.
• Monitoring–Follow natural history or response to treatment.
• Screening–Detection of sub clinical disease.
Topic #2
The role of the clinical laboratory for clinicians and patient diagnoses:
Shift from clinical to laboratory-based diagnosis
Topic #2
Shift in Diagnosis toLaboratory
• Diabetes - glucose or HbA1c
• MI - troponin
• Thyroid - TSH
Topic #2
Shift in Expectations
• hCG: need to know pregnancy status»prior to DI»IVF
• gene testing
Topic #2
The role of the clinical laboratory for clinicians and patient diagnoses:Romania:•1997 - The Law no.145 of Health Insurance•1998-1999 - Establishment of the National
House Of Health Insurance (CNAS)
•1999 – “change” in mentality-laboratory the most flexible segment Shift from public to private system for laboratory activity•Shift from clinical to laboratory-based diagnosis•After 2000- Involvement of laboratory in clinical trials
Topic #3
Errors in Laboratory Testing
• what to avoid
• where to pay attention
Topic #3
Indiscriminate TestingTests/requisition:
urban 11.7rural 4.9
–Urinalysis is counted as one test–Complete blood count is counted as one test–Chemistry profiles cannot be ordered
Topic #3Over utilization - - Indiscriminate Testing
a) 208 mL of blood for 42 tests - Internal Medicine
b) 550 mL of blood for 125 tests - Intensive Care Unit
c) Iatrogenic pediatric anemia
d) 180 mL of blood for lab testing in 50% of patients receiving transfusion
Topic #3
Over utilization - Increased Patient Demand
Informed public due to:
a) public policy (Know your Cholesterol program)
b) special interest groups (PSA)
c) Internet access
Misunderstanding Laboratory Results
• the reference range
• the Ulysses syndrome
• Critical Difference theory
• analytical problems
Topic #3
Ca++ 2.64 H (2.10 - 2.60 mmol/L)2.5% population > 2.602.5% population < 2.10
age specific -alk phossex specific - creatinine
The Reference RangeTopic #3
The Ulysses Syndrome :
Ill effects of extensive diagnostic investigations due to a false positive or wrongful interpretation of results in the course of routine laboratory screening.
Topic #3
Pre-analytical variables :PATIENT:
age (alk phos)sex (hemoglobin)medications (coumadin & INR)
SAMPLE:quality, labeling, transport, tempproper collection technique
tube, hemolysis (K+), dilution (CBC)
Topic #3
Pre-analytical variables :
1. diurnal: cortisol/Fe high am, low pm2. posture: calcium higher on standing3. sample type: K+ lower in plasma than serum4. time of year: trig. high in spring/HbA1c
higher in winter5. pregnancy: electrolytes
Topic #3
Case Study72 y male has serum K+ collected at 0830 at PCC. K+
is 6.2 mmol/L. Physician phones and tells patient to go to Emergency Room. On a sample collected at 1630, K+ result from hospital lab is 4.2 mmol/L on plasma.
Case Study Conclusion:• One lab cannot perform K+ tests with any accuracy
or• Thromboctyopenia
or• Interference – ACE inhibitors increase serum K.
Topic #3
Critical Difference Theory : When a result is clinically different than previous result.
Critical difference =C = Z x √2 x √Cbiological2 + Canalytical2
Topic #3
Calculated Critical Differences for Some Chemistry Parameters
TEST BIOLOGICALCV
ANALYTICALCV
CD AS %
Glucose 4.7 1.9 9.9Cholesterol 5.8 2.0 17.0Uric Acid 8.6 3.0 25.2Urea 10.3 1.6 28.9Total Protein 2.6 3.1 11.2Albumin 2.6 3.1 11.2Calcium 1.6 1.5 6.1In Phosphorus 4.8 1.3 13.8T. Bilirubin 16.5 4.7 47.5Alk Phosphate 6.5 3.6 37.1 LD 12.9 1.5 35.0 AST 8.2 5.7 27.7
Topic #3
Case Study
57 y female has a TSH ordered as part of a yearly physical. The result is 6.62 mU/L (reference range 0.2 – 4.0 mU/L). Before commencing therapy with Synthyroid, the physician orders another TSH. This time the result is 3.1 mU/L.
To treat or not to treat
Topic #3
TSH analytical variation 10%TSH biological variation 19%
Total variation (critical difference) 62%
First TSH result CD = 6.62 x 0.62 = 4.1
∴ 2nd result of 3.1 is within critical difference (6.62 – 4.1) of first result
Topic #3
TSH
< 0.2 mIU/L 0.2 - 6.1 mIU/L 6.1 - 18.0 mIU/Lno further testing
fT4fT4
abnormal normal
no further testing fT 3
Thyroid Algorithm Topic #3
Requesting all Thyroid Tests
• 2% of all thyroid test requisitions request every available test.
• 2000 patients’ thyroid results where all tests were ordered were reviewed.
• 1 potentially useful result not provided by algorithm.
Topic #3
Pitfalls in analysis:
what you get is not what it is
Topic #3
HAMA• heterophile anti-mouse antibody• especially in rural populations
Lab A Lab B
TSH mIU/L 27.6 0.04
fT4 pmol/L 34.8 34.8
Topic #3
Jury Awards $16.2M in Diagnosis Case
Topic #3
Problems withJennifer Rufer Case
• Inappropriate use of test
• No confirmation of test
• No clinical support
Topic #3
Residual tissue can produce same hCG pattern as heterophile antibody.
Topic #3
Ascorbic acid can lower/raise:cholesterolglucoseurate
Topic #3
M- protein , especially IgM, caninterfere with assay results: •Glucose •Electrolytes•Bilirubin•GGT•Ferritin
Topic #3
Pre-analytical in laboratory services for clinical trials:•Too much blood required by study protocols for laboratory tests(e.g.7 ml blood for CBC versus 2ml needed, 10 ml blood for safety chemistry versus 4 ml needed)•Missing/incomplete data on RF•Sometimes, investigators do not protect the patient confidentiality
Topic #3
• Patient enrolled
for CT no. X, SCR visit, identified by barcode, but investigator sent RF where revealed the identity of the patient
Topic #3
Case study
•Patient has to collect urine samples for 6 weeks, inconsecutively days, store them at study site and send them to laboratory for testing urinary pregnandiolLaboratory provided RF + SK , designed visit specificThe samples were collected using wrong sampling kitPatient mixed up the collection weeks, and alsowithin a week, the dates of collection
Topic #3
Case study
Post-analytical
1) Report.Correct information on correct patient to correct physician in a timely manner.
2) Interpretation of result.
Topic #3
Post-analytical
Reporting errors - when using IT communication channels to send the results.
This usually affect TAT for reporting lab parameters and sometimes may influence the investigator’s decision regarding which step to follow in the patient treatment with the study medication
Topic #3
Post-analytical
Topic #3
Post-analytical
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Post-analytical
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Summary• The laboratory plays an important role
in diagnosis.
• Laboratory resources are finite and should not be overused.
• Many factors affect laboratory results.