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

Topic #3

Post-analytical

Topic #3

Summary• The laboratory plays an important role

in diagnosis.

• Laboratory resources are finite and should not be overused.

• Many factors affect laboratory results.