1. Occupational Drug & Alcohol Testing Conference

2. POCT Testing: The Basic Principles
Dr Genevieve Boshoff
Good afternoon ladies and gentleman. I would like to start this afternoon off by providing you with information on how Point of Care Testing kits work.

3. Principles Based on immunoassay
Reaction between an antibody and an antigen
Antigen = drug of interest
Antibody = protein produced by the immune system
POCT kits are based on immunoassay technology. Immunoassay technology (a hybrid of chemistry and biology) refers to an extremely convenient and quick analytical system that relies on specific antigen - antibody reactions for detecting analytes or compounds of interest.
The term antigen refers to any substance that when introduced into the body, stimulates the production of an antibody.
An antibody is a protein that is produced by the body in response to the antigen. For example, when your body is exposed to bacteria or viruses, it produces antibodies to these bacteria or viruses. These antibodies bind to the antigens and essentially neutralise them.

4. Antigen-Antibody Binding
Antibodies bind strongly to a compound with a specific shape
Normally only binds to compound that was used to produce the antibody
Antibody produced using single compound of interest for each test
Tests kits allow us to visualise and quantify antigen-antibody binding
The antigen and antibody bind in a number of different ways. There may be a number of weak interactions between the antigen and antibodies in the form of hydrogen bonds, ionic interactions or Van Der Waals forces. These interactions take only take place if the molecules are close enough to each other and if the molecules have complementary shapes. That means that an antibody will only bind to an antigen which has a specific shape. An antibody has a Y-shape with 2 antigen binding sites, one on each arm. The arms are made up of 4 polypeptide chains or proteins – 2 light and 2 heavy which form a Y-shape. Every member of a particular antibody family shares the same constant region but the variable region varies base on the antigen. The affinity of antibody for an antigen is governed by how well the antigen fits into the antigen binding site.
This binding is however reversible and the stability of the antibody-antigen complex is determined by affinity of the antibody for the antigen as well as the valency or charge of the molecules. For example, the complex will be much stronger when both antigen binding sites are engaged or when the antigen is more highly charged.
The antibodies are produced by injecting an antigen into the body of a mouse. The antibodies used in POCT kits are produced using a single compound of interest for each test. For example, for a
As you can imagine, the drug on its own can not elicit an immune response due to its small size. In order to produce antibodies against specific drugs, the drugs are attached to a larger protein molecule which can elicit an immune response. The drug-protein complex is then injected into the mouse, normally twice (primer and booster dose). The B-cells, which produce the antibodies are then harvested and those that produce the antibody of specific interest are identified. These are then cultured and the antibodies produced, harvested and used in the POCT kits. (monoclonal antibodies).
The POCT test kits allow us to visualise the interaction between antigens and antibodies.

5. POCT Drug Test Kits Number of different types
Dip sticks
Cassettes-testing of multiple drugs simultaneously
Cups-testing of multiple drugs simultaneously
Generally used to test urine samples
Detect use within the last week
Other test matrixes include saliva and blood
POCT kits come in a number of different forms. Some are simple single use dipsticks where the result is read off . Others comprise casettes or cups which allow you to test for multiple drugs at the same time using only one sample.
Generally speaking most POCT test kits are used to test urine samples.

6. Elements of immunoassay
3 essential components required:
Antigen that you would like to detect e.g. drug
Specific antibody to the drug
Method of quantifying the antigen
Number of immune complexes formed
Use detectable labels e.g. enzyme, dye or pigment, radioactive component
The essential components of antibody-based immunoassay systems are threefold: an antigen that we would like to detect and perhaps quantitate; a specific antibody to this antigen; and a system to measure the amount of antigen in a given sample.
The extent of the antibody-antigen bond, i.e. the number of immune complexes formed by the antibodies and immobilized analytes, is an indication
of the concentration of the analyte in the sample. However, the antibody-antigen bond is not directly accessible for analysis in most immunoassays.
This problem is solved by coupling one of the two components, either the antigen or the antibody, to an easily detectable “label”. Radioactive
components, enzymes (biocatalysts), dyes or fluorophors are examples of possible labels.

7. Membrane containing test strip and control strip
Lateral Flow Assays
Sample pad-adsorbent pad to which sample is applied
Conjugate pad- contains antibodies or antigens specific to the drug of interest conjugated with pigment or colour compound
Test strip –contain antibodies/antigen
Control strip- contains antibodies to the conjugate
Wicking pad -absorbent pad to draw sample across the test strip
Sample pad
Conjugate pad
Membrane containing test strip and control strip
Wicking pad
Test Strip
Control Strip
I now want to give you an example of how one of these immunoassay systems is constructed and employed in drug testing. Most dipstick systems are based on what is called a lateral flow assay. Essentially the antibodies to the drug and the detectable labels are immobilised on a thin membrane. The test sample is introduced to one end of the membrane and migrates via capillary action laterally across the capillary, interacting with the antibody and detectable labels as it moves along. A basic test strip is composed of the following elements:
A sample pad which is made of an adsorbent material. The sample is introduced onto this pad either by dipping it into the sample or by pipetting the sample onto the pad.
A conjugate pad which contains the detectable labels conjugated to either antibodies to the drug or to the antigen itself (drug conjugate)
A test stip. This is where antibodies have been immobilised in a specific area of the strip (generally along a line)
A control strip. This is where antibodies to the detectable label conjugate are immobilised in a specific area. This control strip is devised to give an indication as too how well the test has worked.
A wicking pad which facilitates the flow of the test solution along the membrane by capillary action.

8. Assay Methods Direct Assay Competitive Assay
Positive result indicated by presence of test line
Competitive Assay
Positive result indicated by absence of a test line
Control line is present in both cases
The antibodies and detectable labels and the configuration in which they are placed on the test strip is determined by the assay method. There are 2 main assay methods:
In the direct assay method, the antigen reacts with a colour complex which then reacts with antibodies immobilised on the test strip to produce a coloured line. The presence of the analyte of interest is indicated by the appearance of a coloured line. In the competitive assay method a positive results is indicated by the absence of a coloured line.
Due to the small size of the drug molecules, the competitive assay method is normally used for drug detection.

9. Competitive Assay
Competition between free drug and immobilised drug (immobilised antigen) for limited antibodies
In presence of drug, free drug binds to the antibody conjugate, preventing it from binding to immobilised drug. No colour reaction.
If no drug present antibody complex binds to the immobilised drug to produce coloured line. 1.
Antibody conjugated to gold or pigment (conjugate) 3.
Antibodies to conjugate 2.
Immobilised Drug
Positive Result
Negative Result T C
In this assay the drug in the samples competes with immobilised drug for a limited number of antibodies. The system comprises 3 main elements:
The antibody to the drug which has been bound to a gold particle of pigment.This is called the antibody conjugate.
The drug which has been immobilised in the test strip.
Antibodies to the antibody conjugate which have been immobilised in the control area.
In the test procedure, a sample of urine is placed in the sample well of the device, and the sample is allowed to migrate upward. If any of the applicable drugs is present in the urine sample, it forms a complex with the antibody-dye conjugate specific for that drug, and the complex migrates toward the opposite end of the card, passing the specific locations on the membrane where each of the applicable drug conjugates are immobilized. The drug in the sample competes with the drug conjugate, which is immobilized on the membrane, for the limited antibodies present in the form of antibody-dye conjugate. When a sufficient amount of drug is present, the drug will saturate the antibodies, and the antibody-dye conjugate cannot bind to the drug conjugate on the membrane. Therefore, a drug-positive urine sample will not generate a line at the specific drug position in the result window, indicating a positive result from positive drug competition. Conversely, if a particular drug is absent in the urine specimen, the antibody on the antibody-dye conjugate will bind the membrane-bound drug. In this case, a drug-negative urine sample will generate a line at the specific drug position in the result window, indicating a negative result from an absence of competition  with free drug.
In addition, the test card has a procedural control built into the system, in the upper control line area. The control line is immobilized with polyclonal anti-mouse antibody; therefore, it will capture monoclonal antibody-dye conjugates that pass the region, showing a colored line in the control (validation) zone. The line works as a procedural control, confirming that proper sample volume was used and the reagent system worked. If insufficient volume is used, there may not be a control line, indicating the test is invalid.

10. Positive Result
Any indication of a drug above the cut-off level/threshold
Minimum concentration of the drug or metabolite that must be present in the specimen in order for the test to be reported as positive.
Vary from drug to drug and kit to kit
Negative result does not mean that the sample is drug free
A positive result provides an indication that the drug or a compound with a similar structure to the drug is present in the urine at a concentration above the cut-off or threshold of the kit that has been used. The cut-off or threshold is the minimum concentration of the drug or metabolite that must be present in the sample to provide a positive result. This values varies from drug to drug and kit to kit. In some cases it is based on regulatory requirements but this is not always the case. Each individual test is calibrated using a test calibrator. This calibrator is normally the compound that has been used to generate the antibodies.
The Rapid Exams Multi-Drug Test yields a positive result when Amphetamines in urine exceed 1,000 ng/mL. This is the suggested screening cut-off for positive
specimens set by the Substance Abuse and Mental Health Services Administration (SAMSHA).
A negative result does not mean that there is no drug present in the sample but only that it is present below the cut-off level.

11. How results from POCT kits are reported
True Positive (TP): The result of the test is positive and that drug is present in the sample at or above the threshold concentration of the test.
False Positive (FP): The result of the test is positive but the drug is not present in the sample or at concentrations below the threshold of the test.
True Negative (TN): The result of the test is negative and the drug is not present in the sample or is below the threshold concentration of the test.
False Negative (FN): The result of the test is negative but the drug is present in the sample above the threshold concentration of the test.
In a drug testing programme the main objective is to determine if a drug of abuse is present or absent. When considering how to report analytical results, there are four possible outcomes that must be considered:

12. Sensitivity Lowest concentration of analyte that can be detected
number of positive samples determined by the POCT device
number of positive samples determined by the comparison method
Comparison method normally GC-MS
Reasons for poor sensitivity:
Antibody affinity for the antigen
Amount of antibody or antigen used
Membrane use for producing dipstick
Storage conditions
Production methodology
In the next talk, you will hear a couple of terms being used. One is sensitivity and us very important when interpreting the results from a POCT kit. Sensitivity relates to the lowest concentration of the drug that can be detected by the POCT. In other words , the kits ability to detect samples that actually do contain the particular drug of abuse. As noted previously, each test kit will have different cut-off l levels below which a negative result is returned. In order to determine the sensitivity of a POCT kit it is necessary to analyse samples via a confirmatory method such as GC-MS and compare the results to those obtained by the POCT kit. The greater number of samples that the POCT identify as containing the drug of interest that actually do contain the drug of interest, the greater the sensitivity of the test kit.
Detection of a particular drug by a drug-class-specific immunoassay depends on two factors:
The structural similarity of that drug, or its metabolite(s), to the compound used for standardisation
The sample concentration of that drug / metabolite compared with the standardising compound (Yang, 2001).
The standardisation compound refers to the material used to generate the antibodies employed in the manufacturing of the devices. The greater the structural similarity, the lower the cut-off limit can be.
A PoCT device’s sensitivity is highly variable depending on the panel of drugs it is designed to detect. Also, there is variability between device manufacturers. Concerns have also been raised that there may be variability in sensitivity between batches of devices produced by the same manufacturer (Melanson et al. 2010). This makes any true estimate of sensitivity impossible
Although it is sometimes necessary to use a PoCT device to identify a single compound, most kits are used to detect a range or panel of drugs. However, due to their poor sensitivity, PoCT Immunoassays generally lack the ability to identify all drugs present in a given class (Saxon et al., 1990). For example, general opiate / opioid immunoassays are unable to detect the presence of the opioid methadone. An opiate is a drug derived from the poppy seed whilst an opioid is a synthetic or semi-synthetic compound. .

13. Specificity
The ability of the kit to detect the analyte of interest and not other compounds
Number of negative samples determined by the POCT devices
Number of negative samples determined by the comparison method
Ability to detect true positives and few false positives
Varies between drugs
e.g. opiate/opiod tests have low specificity while cocaine tests have high specificity
Another term that you will hear and is also important when interpreting the data from POCT kits, is specificity. Assay specificity refers to the ability of an antibody to produce a specific response to the analyte of interest, whilst not showing any response to other compounds. A highly specific test gives few false-positive results. Hence the results from a POCT kit with high specificity will more likely return a positive result with samples which actually contain the drug of interest. They are less likely to give a positive result which contains another compound i.e. a false positive.
The specificity of POCT kits varies between drugs. For example, For opiate / opioid immunoassays generally have a low specificity and cannot distinguish between morphine (the urinary metabolite of heroin), codeine and other opioids, including opiates from poppy seeds used in baked goods .Cocaine tests on the other hand have a high specificity.

14. Cross-Reactivity Non-specific influence of substances in sample that:
Structurally resemble the analyte
Molecules have similar cross reacting epitopes or sites which bind to the antibody receptors
E.g. amphetamine assays- ephedrine/pseudoephedrine structurally similar to amphetamine
Marijuana – can produce false positives with hemp products
Leads to the production of false positives
So what causes this low specificity? Cross-reactivity.
While assay specificity refers to the ability of an antibody to produce specific response for the analyte of interest, cross – reactivity is a measurement of antibody response to substances
other than the target analyte. Cross-reactivity is the most common interference in immunoassays, but mostly in competitive assays. It is a non-specific influence of substances in a sample that structurally
resemble the analyte (carry similar or the same epitopes as the analyte) and compete for binding site on antibody, resulting in over- or underestimation of analyte concentration.
Cross-reaction is a problem in diagnostic immunoassays where endogenous molecules with a similar structure to the measured analyte exist or where metabolites of the analyte have
common cross-reacting epitopes, and where there is administration of structurally similar medications (Kroll & Elin, 1994).
Amphetamine immunoassays are among the most susceptible to analytical interference. Sympathomimetic amines like ephedrine/pseudoephedrine and phenylpropanolamine are
structurally very similar to amphetamine and are readily detected in these screening immunoassays. Ranitidine interference has been noted previously in amphetamine immunoassays.

15. Conclusions
PoCT devices offer a inexpensive screening method for drugs of abuse.
Due to the underlying method, it is always possible that a PoCT devices will report false positives or false negatives due to cross reactivity and non-specific binding.
All results should be validated using GC-MS or a similar technique.
False negative results cannot be screened i.e. just because the result is negative does not mean the drug is not present.

16. Direct Assay
At conjugate pad, sample mobilises the antibody conjugate which migrates with the analyte towards the test and control strip. As it migrates, the drug reacts with the antibody conjugate to form a drug-antibody conjugate
Drug-antibody conjugate reacts with drug antibodies in control strip-forms a coloured line – positive test
Antibody conjugate reacts with conjugate antibodies to form a coloured line
Antibodies conjugated to gold or pigment (conjugate)
Antibodies to the conjugate
Antibodies to the drug
Positive Result
Negative Result T C

18. Introduction to ‘real world’ use of PoCT devices
Dr Simon Davis

19. What to consider before using PoCT devices !
How accurate are PoCT devices?

20. Laboratory based performance of PoCT devices
Taken from data collected by the College of American
Pathologists Proficiency Testing Surveys over a 6 year period
Modified from Melanson et al.(2010)

21. How do PoCTs perform outside a clinical environment
ROADSIDE Testing Assessment Project (ROSITA 2) project was carried out between 2003 and With 2046 subjects
Observed sensitivity plots of OF PoCT devices to different classes of drug. Modified from Blencowe et al 2011.

22. Driving Under the Influence of Drugs (DRUID) project (2012)
1025 subjects
PoCT sensitivity to Cocaine and Cannabis as reported in Strano-Rossi et al Positivity criteria were based on the kit manufacturer’s recommendation (CUTTOFF KIT) and those used in the DRUID study (CUTOFF DRUID).

23. Does a PoCT device conform to your testing program criteria?
To ensure good analytical performs and reduce the risk of false positives and negatives, all testing programs have a “Threshold” of concentrations above which a positive is reported and below which a negative is reported.

24. Effect of Sample THC concentration on drug detection by a range of immunoassay techniques
A range of different immunoassay techniques were compared. These were: enzyme donor immunoassay (diamonds), colloidal metal immunoassay (Triage; squares, &), enzyme immunoassay (Diagnostics Reagents Inc; triangle), enzyme immunoassay (enzyme multiplied immunoassay technique; X-shape), fluorescent immunoassay (asterisk,), fluorescence polarization immunoassay (circle), microparticle immunoassay (kinetic interaction of microparticles in solution; plus sign.
Modified from Melanson (2010)

25. Why are Thresholds a problem for PoCT devices
Threshold concentrations for a range of PoCT Devices commonly used compared
to the SAMHSA threshold concentrations
Drug
SAMHSA EMIT (ng/ml)
Fastect® II (ng/ml)
Reditest (ng/ml)
Amphetamines
500
1000
Cocaine
150
300
Marijuana 50
Opiates
2000
300/2000
Phencyclidine 25
Substance Abuse and Mental Health Service Administration (SAMHSA)

26. Can a PoCT device reliably identify the drugs of abuse you wish to control?
There will always be a risk of false positive results with PoCT devices.
This risk can be mitigated by a process of screening and confirmation of all positive results by GC-MS or another gold standard technique.
There is also a risk of false negatives, this risk cannot be mitigated.

27. Sample Collection
Can operatives with minimal training be used to carry out PoCT tests and interpret and record the
results?
Operatives must understand and be able to identify false positives due to cross reactivity.
Operatives must be able to review a subjects medical, pharmaceutical, dietary and behavioural characteristics to identify false positives and false negatives.
Operatives must be able to identify individuals claiming to be taking a legal substance with cross reactivity to an illegal substance in an attempt to mask drug abuse.

28. Sample Collection
“It is well known that in clinical settings immunoassay tests are more accurate when the results are interpreted by clinicians rather than non-technical staff (Melanson et al., 2010).

29. Can a PoCT Device Have a Legally Defensible Chain of Custody?
What is a Chain of Custody?
US government regulations:
“[a]ll urine specimens must be collected using chain of custody procedures to document the integrity and security of the specimen…” (Bush, 2008).
The World Anti-Doping Agency (WADA) considers CoC to have been appropriately conducted when:
“[t]he external record is initiated at the collection site and ensures that the Samples and the results generated by the Laboratory can be unequivocally linked to the [donor].” (WADA TD2009LCOC).
The EWDTS provides similar language requiring that:
“…the results reported relate beyond a doubt to that specimen.” (EWDTS (2011)).

30. Can a PoCT Device Have a Legally Defensible Chain of Custody?
Results from PoCT devices only remain visible as long as the sample remains aqueous.
ISO requires a laboratory to:
“retain records of original observations, derived data and sufficient information to establish an audit trail…” (ISO ).

31. Are you confident that a PoCT devices will provide a consistent analytical performance?
PoCT devices are not covered by any formal accreditation.
There are no regulations monitoring the manufacture, use or distribution of PoCTs within the UK or Europe.
No ISO accreditation exists for occupational testing.
Most Devices are not CE marked.
Quality, performance and accuracy vary between different providers and even between batches of devices from the same manufacturer.
Don’t forget about Thresholds!

32. Conclusions
PoCT devices can only be used as a screening method and require confirmation by a gold standard method such as GC-MS.
The use of PoCT devices will always run the risk of false negatives, even if used as part of a screening program. Therefore, PoCT devices should never be used in safety critical environments.
Positivity criteria (thresholds) are fixed in PoCT devices, if your positivity criteria is different to that of the PoCT, you cannot use the PoCT device.
The lack of accreditation means you cannot be confident of the quality of the devices you purchase. Detection limits may vary causing doubt over threshold levels.
PoCTs should only be used by trained operatives.
A full chain of custody is not possible with PoCT devices.

34. Case Study
Michalakis Michael – LGC Ltd
April 2013

35. LGC history
Origins dating back to 1842 as customs laboratory protecting excise duty payable on tobacco importation into the UK
Company established in 1996 on privatisation from government agency
Grown organically and through strategic acquisitions
Organised in to divisions – Health Sciences, Genomics, Forensics, Standards, Science and Technology 35

36. LGC locations FINLAND N. IRELAND RUSSIA SWEDEN UK IRELAND POLAND CHINA
Borås
FINLAND
Turku
Berlin
Luckenwalde
Almere
Wesel
Cologne
Lomianki
Brno
Szentendre
Cluj-Napoca
Molsheim
GERMANY
CZECH REPUBLIC
POLAND
HUNGARY
ROMANIA
ITALY
FRANCE
BULGARIA
Sofia
Milan
Barcelona
SPAIN
NETHERLANDS
RUSSIA
St Petersburg
CHINA
Beijing
Shanghai
TURKEY
Istanbul
Dubai
INDIA
UAE
Delhi
Ahmadabad
Mumbai
Goa
Bangalore
Hyderabad
Edinburgh
Wakefield
Leeds
Bury
Runcorn
Risley
Tamworth UK
Culham
Exeter
Sandwich
Hoddesdon
St Neots
Belfast
N. IRELAND
IRELAND
Fordham
Twickenham
Teddington
Beverly
USA
Lexington
Denver
Manchester
Sao Paulo
SOUTH AMERICA
Johannesburg
SOUTH AFRICA 36

37. LGC Health Sciences Nutritional Composition Fatty acids Vitamins
Workplace Drug Testing
Pre-employment, random, incident & for-cause
Urine, hair, oral fluid
Banned Substance Testing
Doping control
Drug surveillance
Bioanalysis
Small Molecule
Biologicals
Residue analysis
ILVs
QuEChERS/bespoke
Sports supplement assurance schemes
Informed-Sport TM
Informed-Choice TM
Materials Science
Particle Characterisation
Physical properties
Food contaminants
Heavy metals
Vet drugs & pesticides
Product Safety
E&L
Nitrosamines
Pharmaceutical Impurities
Contamination testing
Foreign particulates
Genotoxic
Health & Wellbeing
Nutritional biomarkers
Fitness Screening 37 37

38. Drug Testing Dedicated laboratory established for over 16 years
Urine, oral fluid, and hair
Controlled, prescribed, and ‘legal high’ drugs
Steroids and supplements
Legal, clinical, employment sectors
Experienced team
Broader scientific network within LGC

39. Case Study Customer background Employ over 50,000 people
2000 pre-employment interviews per annum
Professional workforce
High specification training
Pre-employment drug testing
Random drug testing
For-cause/Incident drug testing
Total cost to recruit, train, staff downtime = £25,000 per successful candidate

40. Historic Testing Approach
Previously used a combination test approach (even spread)
urine testing (random)
urine point of care testing (pre-employment/random)
oral fluid (pre-employment)
oral fluid point of care testing (pre-employment)
Instant result
Quick
Easy
Cheap

41. Customer Review Customer requirements Legally defendable
Effective Programme
Simple
Cost efficient
Reliable service
Good support
Meet policy requirements

42. Oral Fluid Detection Advantages Disadvantages
No specific facility (i.e. toilet) required
Observed sample
Low to moderate sample cost
Disadvantages
Short window of detection (12-24hrs)
Collection devices are all different (not universally supported)
Inconsistent approach between labs
True A and B samples questionable
Contested samples can be problematic

43. Urine Detection Advantages Disadvantages Industry standard
Low initial sample cost
Robust and proven procedures
No shortage of sample
Disadvantages
Requires specific collection facilities (toilet)
Not observed sample
Longer collection time if ‘shy bladder’

44. Hair Detection Advantages Disadvantages Easy to collect
Quick to collect
Observed sample
Easy to store and send
Long timeframe available (up to 3 months)
Disadvantages
Initial costs are high
Not suitable for ‘for-cause’

45. Point Of Care Test (POCT)
Advantages
Generally low cost device
Initial test result available in few minutes
Decision can be taken based on screen result
Disadvantages
No detailed guidelines for performance criteria
Huge variation in performance between test devices
Less analytical flexibility (i.e. harder to change cut offs)

46. Detection Times

47. Trial Period Hair Testing Urine Testing Oral Fluid POCT
Best for pre employment testing (longest window)
Policy easier to change as it’s pre-employment
More expensive initial outlay but expecting to be ‘cost efficient’
Urine Testing
Random and for-cause (reasonable window)
Policy easy to appease as industry standard
Cost efficient
Oral Fluid
Historically used but dropped in favour of urine and hair
POCT

48. Trial Results 3 month trial Findings Comparison to previous methods
Both hair an urine run side by side for pre-employment
Findings
2.5% positive rate in urine (overlap with hair)
5% positive rate in hair
Comparison to previous methods
Prior methods (POCT and Oral Fluid) found 0.5% over the previous 3 year period
Similar (some the same) sample population and conditions to historic populous

49. Finance Background Overall costs at 100% selection
Average of £25,000 to recruit and train
2,000 pre-employment interviews
Hair = £90 per test
Urine = £30 per test
Oral Fluid = £30 per test
POCT = £20 per test
Overall costs at 100% selection
Hair (at 5%) = 2000*90 = £180,000
Potential of 100 donors being recruited and £2.5M ‘lost’ (+£2.32M)
Urine (at 2.5%) = 2000*30 = £60,000
Potential of 50 donors being recruited and £1.25M ‘lost’ (+£1.19M)
POCT (at 0.5%) = 2000*20 = £40,000
Potential of 10 donors being recruited and £250K ‘lost’ (+£210K)
Figures are not actual but representative of cost

50. Finance 2 (NOT ACTUALS)
100% selection not realistic therefore based on 10% selection
Hair (at 5%) = 2000*90 = £180,000
Potential of 10 donors being recruited and £250,00 ‘lost’ (+£70K)
Urine (at 2.5%) = 2000*30 = £60,000
Potential of 5 donors being recruited and £125,000 ‘lost’ (+65K)
POCT (at 0.5%) = 2000*20 = £40,000
Potential of 1 donor being recruited and £25,000 ‘lost’(-£15K)
Recruitment and Training figures do not include loss due to
Absenteeism
Theft
Related accidents
Loss of productivity
Disciplinary actions
Dismissal

51. Case Conclusion (Historic)
POCT/Oral fluid combination
Oral fluid gave too short detection time for pre-employment
POCT and oral fluid gave a very low (confirmed) positive rate
POCT random testing was viewed as unsuitable due to questions over the integrity of test result and on-site POCT result not essential
POCT did not offer the flexibility of laboratory testing
Often slow collections when dealing with larger numbers of people
Cost
Cheapest initial cost and met budgetary requirements but…
After considering all costs easy to show that it works out as the most expensive option (on recruitment and training alone)

52. Customer Conclusion (New)
Hair - pre-employment
Excellent window of detection
Excellent ‘positive return’ (5%)
Quick and easy to collect, store, and send
Most expensive initial cost but excellent overall value (based on recruitment and training costs alone)
Urine – random and for-cause and incident
Suitable window of detection
Industry standard
Good ‘positive return’ (2.5%)
Good value initial outlay and good overall value
Requires specific collection facilities (i.e. toilet)
Successful programme
More efficient, cheaper overall
More effective, people aware programme is more effective with higher calibre recruitment

53. Questions? Teddington, UK Teddington, UK mdm@lgc.co.uk Lexington, USA
Wesel, Germany
Bury, UK
Teddington, UK
Beijing, China
Bangalore, India
Kyalami, South Africa
Luckenwalde, Germany
Teddington, UK 53

55. Point of Collection Testing – the Legal Issues
Peter Feldschreiber
Four New Square, Lincolns Inn

56. Relevant technical issues
Do the validity, reproducibility, precision sensitivity and specificity of the point of collection (POCT) diagnostic tests for drugs provide the degree of accuracy that such testing for both screening and diagnostic purposes requires in order to satisfy the statutory health and safety legislation ?

57. Potential for false positive and false negative test results
Potential for false positive and false negative test results. This implies very wide confidence intervals for the statistical values of the point of collection evaluations of urine tests. Such wide confidence intervals would amplify the risk of false results in random testing.
Technology of POCT analysis for drugs could enhance the risk of contamination and interaction of chemical analytes with potential for spurious results with different drugs.

58. Harm from false positive and from false negative tests (1)
Examples of indirect harm include
 misdiagnosis,
 delayed diagnosis,
 delayed treatment,
 inappropriate treatment,
 absence of treatment,
 transfusion of inappropriate materials.
Indirect harm may be caused by
 imprecise results,
 inadequate quality controls,
 inadequate calibration,
 false positive or
 false negative results

59. Harm from false positive and from false negative tests
Employers could be liable in negligence for taking action regarding employment of examinees on the basis of both false negative and false positive tests.
False positive test resulting in a prospective employee being refused employment on the grounds of alcohol or drug misuse, employer liable in negligence.
False negative screening test; subsequently operates machinery under the influence and causes injury or death leading to action for substantial damages, and potentially prosecution e.g. corporate manslaughter.

60. Insurance
Validity of insurance contract depends on compliance with statutory health and safety legislation. Potential for failure to mitigate against the risk of unreliable and inaccurate testing. If a test result, originally evaluated as negative, is subsequently found to be unreliable or incorrect and the employee causes injury or death and/or damage in the course of his job, questions as to the applicability and validity of the insurance policies, regarding negligence and possibly product liability may arise.

61. Insurance (2)
Validity of indemnity insurance for negligence when decisions on employment of persons who subsequently cause loss and/or damage are found to have been employed on the basis of false negative tests. Reliance on technologically flawed tests without due care or process to ensure their accuracy could result in void contracts of insurance. This could result from false negative tests, when an employee was subsequently found to be under the influence of drugs and/or alcohol and also from false positive results if an applicant claimed discrimination if not appointed.

62. Obligations of Confidentiality
Disclosure of confidential and private information regarding the health and welfare status of the examinee could breach employer’s and relevant medical staff’s obligation of confidentiality.
Current legal position is that the obligation of confidence applies where a doctor or medical professional receives information other than in connection with a professional relationship, e.g. medical screening in respect of employment.
May have implications for training and qualifications of staff undertaking screening.

63. Statutory Obligations
Type of testing, sample collection and security of the sample from contamination are specifically referred to in the European Workplace Drug Testing Society Guidelines: ‘1.1 Legally defensible workplace drug testing is a three stage process. The specimen has to be collected, analysed and finally the analytical result has to be correctly interpreted. This all has to be done in the context of ‘Chain of Custody’.
1.3 If any one of these three stages has flaws, then the whole process may be invalid.’
1.4 Where immediate test results are required, Point of Collection Tests (POCT) can be utilised, but the principles and procedures for specimen collection outlined in these guidelines still apply.’
BUT : note the appendix referred to was never drafted!

64. POCT testing is explicitly approved, with the caveat that privacy and security is ensured at the specimen collecting site, there is proper identification of the examinee, appropriate steps are taken to protect against tampering and adulteration, there is evidence of written informed consent of the individual and that disclosure of recent medication or evidence that the individual was advised of the significance of recent medication is confirmed. .

65. Practical Questions (1)
POCT test fails to spot a positive and the person is then involved in an incident. If they are then tested by laboratory analysis and found positive (and if, for example there is serious injury or death on a construction site) what legal sanctions could be taken against the contractor and his Occupational Health Company?

66. False negatives – negligence and potential criminal issues
If employee operates machinery under the influence drugs/alcohol and causes injury, action for substantial damages. Employer could face potential liability for gross negligence manslaughter. Employer owed duty of care, was in breach of that duty and the breach of duty must have caused the death of the victim. The nature of the breach of duty must have been so bad as to amount to gross negligence with criminal consequences. Jury question. In a foreseeably false negative test missing a dangerous drug level the jury would have to consider whether the extent to which employer’s conduct (in failing to ensure that their testing policy was followed) departed from the proper standard of care incumbent upon them, involving a risk of death, was such that it should be judged criminal. Similarly there is a real possibility of prosecution for corporate manslaughter.

67. What would be the legal implications where an employee gives a false positive test via POCT and is suspended pending laboratory confirmatory testing?
Could be action in breach of confidence
Although suspension is a neutral act, the reputational damage suffered by ‘an employee could cause him to feel that there had been a breakdown in trust and confidence in his relationship with his employer, leaving him no choice but to resign – constructive dismissal

68. As regards the duty of confidentiality of the company towards employees in relation to drug testing results, what would be the legal situation whereby contractors designate potentially untrained administrative staff to conduct POCT testing?
Current operating system contravenes the EWDTS guidelines. Audit trail for chain of custody sampling demands a robust administrative procedure and mechanisms to ensure privacy and security of the collection site, identification of both the individual and the samples, protection against tampering and adulteration, evidence of informed consent and disclosure of recent medication or evidence that the examinee was advised of the significance of recent medication. In the absence of a qualified, trained and competent individual to collect the test sample, analyse and interpret the results and then have a robust administrative system to handle the test sample(s) appropriately, testing process invalid and potentially legally indefensible in actions in negligence and breach of confidence.

69. Point of Collection vs Chain of Custody
Immediacy of the result and subsequent lack of a tamper proof and auditable ‘chain of custody’ procedure in POCT testing considerably reduces the protection from disclosure of medical information that is inherent in the conventional sampling and laboratory testing.
Inadvertent disclosure of confidential information without the written express consent of the examinee may constitute negligent disclosure

70. PoC tests as medical devices
Regulated under the In Vitro Devices Directive
Must comply with essential requirements as specified by appropriate Notified Body
Obligations to report incidents of defective performance
Both false and negative test results constitute ‘incidents’ and may cause indirect harm; must be reported to Notified Body and potentially to competent authority such as MHRA

71. CORPORATE GOVERNANCE accurate and reliable results are paramount
If company fails to apply sufficiently vigorous governance to regime of testing Board of Directors may be held to be negligent

72. CONCLUSIONS
False positives and false negatives, coupled with unqualified staff reading tests and making employment and/or operating decisions could render employer liable in negligence.
Potential insurance issues
Potential criminal liability
Serious doubts over use of PoC tests as employment screening tools

74. Thank you for attending our conference