1. VALIDITY OF DIFFERENT DRUG AND ALCOHOL TESTING METHODS IMHA Workshop & Seminar, Mumbai, 2006 DRUG AND ALCOHOL PREVENTION PROGRAMME – TRAINING SEMINAR VALIDITY OF DIFFERENT DRUG AND ALCOHOL TESTING METHODS IMHA Workshop & Seminar, Mumbai, 2006 DRUG AND ALCOHOL PREVENTION PROGRAMME – TRAINING SEMINAR Dr. M. Luisa Canals PhD, Specialist in Occupational Health. Master in Drug addictions and AIDS. Maritime Health MD, ISM, URV Tarragona Spain Spanish Society of Maritime Medicine (SEMM) / International Maritime Health Association (IMHA)

2. Background points of Drug and Alcohol Testing: WHAT ? -- Especial characteristics of seafarers work and vessels / Effects of drugs and alcohol … DEFINITIONS WHAT ? -- Especial characteristics of seafarers work and vessels / Effects of drugs and alcohol … DEFINITIONS WHEN ? – Reasonable suspicious / Medical Fitness Exams / Drug and alcohol test collection in situ: at random … PREVENTION WHEN ? – Reasonable suspicious / Medical Fitness Exams / Drug and alcohol test collection in situ: at random … PREVENTION HOW ? International recommendations for screening, 1993. E.g. ships that transport dangerous goods  CERTIFICATE-VALIDITY HOW ? International recommendations for screening, 1993. E.g. ships that transport dangerous goods  CERTIFICATE-VALIDITY

3. Questions related to Validity: Why to test?  What are dangerous drugs?  What drugs to test? Where? Why to test?  What are dangerous drugs?  What drugs to test? Where? Should informed consent be required?  Ethical considerations > How to keep confidentiality? What are the implications of a positive test? Should informed consent be required?  Ethical considerations > How to keep confidentiality? What are the implications of a positive test? Method of collection and transport to lab with all the circumstances, chain off custody procedures  How can we assure that the urine belongs to the patient? Method of collection and transport to lab with all the circumstances, chain off custody procedures  How can we assure that the urine belongs to the patient? Validity: How? Limitations of clinical test laboratory Validity: How? Limitations of clinical test laboratory

4. WHAT & WHY ? WHAT & WHY ?  "Dangerous drugs" – e.g. under the US Department of Transportation rules - are: marijuana, cocaine, opiates, phencyclidine (PCP), and amphetamines.  “Individual and Community Problem” - Alcohol & drugs in the workplace have a close relation to: 1. Decrease of work concentration. 2. Increased prevalence of absenteeism and social problems. 3. Increased number of injures and accidents. 4. Increased prevalence of associated diseases. 5. Increased risk of mortality and disasters…

5. Research:Research: Detection of drugs / Detection of the problem: E.g: Description of addictive substances use register though a computerised data base of seafarers’ medical records of fitness examinations to embark in Spain (ISM. 93-98, 134.219 * )  73.2 % Detection of drugs / Detection of the problem: E.g: Description of addictive substances use register though a computerised data base of seafarers’ medical records of fitness examinations to embark in Spain (ISM. 93-98, 134.219 * )  73.2 % Evidence based medicine, studies, references, international meetings. Evidence based medicine, studies, references, international meetings. (*) Registro de un factor de riesgo a través del reconocimiento médico laboral preceptivo para embarque en España: el uso de sustancias adictivas. Med Marit 1 (8): 407-416. Increased permanence in days according to the method: Blood, saliva, urine, sweat, hair.

6. Spain: Seafarers’ fitness examinations Areas that exceed the average of consumption per substances

9. Detection / Effects: Drug definition: legal occupational and medical aspects Drug definition: legal occupational and medical aspects Classification: Classification: - NCS Depression (alcohol, opiates, cannabis, barbiturates) - NCS Estimulation (cocaine, anfetamines, extasis) - Alucinations (LSD) - Volatils (solvents) Drug abuse / Addition (Consumption / substance) Withdrawal Syndrome Withdrawal Syndrome Overdose Overdose Abuse (dependence, tolerance, craving, DSM IV-TR) Abuse (dependence, tolerance, craving, DSM IV-TR) Intoxication Intoxication

10. PRE-ANALYTICAL VALIDITY Points to take into account 1. Alcohol and Drugs Detection Programme 2. Medical Review Officer (MRO) USA exam & courses “American Association of Medical Review Officers”, “American Society of Addiction Medicine”, “American College of Occupational and Environmental Medicine” accredited by the Medical Review Officer Certification Council; Europe ? Only courses “European Workplace Drug Testing Society”. 3. Specimen Collector. 4. Collection Site. 5. Collection Supplies. 6. Donor. 7. Custody and Control Form - Chain of Custody Form.

11. Screening: Informed Consent in Seafarers’ Fitness Examination in Spain

12. Screening: Informed Consent Certificate (Cruise Ships)

13. Sample collection Chain of custody (Tanker Certificate)

14. DETECTION Indication (* urine, blood, sweat, saliva, hair…) Indication (* urine, blood, sweat, saliva, hair…) Validity of the test, technic drug testing (cut-off level) / *#substances: alcohol (hours), coca & opiates (2-3 days), benzodiacepines (2 w), cannabis (2-30 days) Validity of the test, technic drug testing (cut-off level) / *#substances: alcohol (hours), coca & opiates (2-3 days), benzodiacepines (2 w), cannabis (2-30 days) Informed Consent & Confidenciality Informed Consent & Confidenciality

15. Methods Urine: * high reliability (inmunoassay, cheap, 5 DOT more used for screening, minimum risk, legal backup. Urine: * high reliability (inmunoassay, GC/MS), cheap, 5 DOT more used for screening, minimum risk, legal backup. Possibility on site test (acceptable quality but legal risk). Possibility on site test (acceptable quality but legal risk).

16. Blood: high liability, expensive, many drugs but not good for cannabis. Blood: high liability, expensive, many drugs but not good for cannabis. Breath: used for alcohol (alveolar air, cheap, liability) Breath: used for alcohol (alveolar air, cheap, liability)

17. Inmunoassay, Inmunoassay, GC/MS Saliva: simple, on site, liability, few legal background Saliva: simple, on site, liability, few legal background Sweat: 2-7 days, acceptable, easy Sweat: 2-7 days, acceptable, easy Hair: long lasting, liability, few laboratories, forensic research Hair: long lasting, liability, few laboratories, forensic research

18. Drug Testing State of the question: The Initial Test : an immunoassay test that has been approved for commercial distribution as an in vitro diagnostic test by the Food and Drug Administration (FDA). A number of different immunoassay techniques are available to screen for the five drug classes [e.g., radioimmunoassay (RIA), enzyme immunoassay (EIA), kinetic interaction of microparticles in a solution (KIMS), and fluorescence polarization immunoassay (FPIA)]. The Initial Test : an immunoassay test that has been approved for commercial distribution as an in vitro diagnostic test by the Food and Drug Administration (FDA). A number of different immunoassay techniques are available to screen for the five drug classes [e.g., radioimmunoassay (RIA), enzyme immunoassay (EIA), kinetic interaction of microparticles in a solution (KIMS), and fluorescence polarization immunoassay (FPIA)]. The initial test is used to eliminate "negative" urine specimens from further consideration and to identify the presumptively positive specimens that require confirmation or further testing. A negative specimen is any specimen that contains no drug or whose apparent concentration of analyte is less than the cutoff concentration for that drug or drug class. The initial test is used to eliminate "negative" urine specimens from further consideration and to identify the presumptively positive specimens that require confirmation or further testing. A negative specimen is any specimen that contains no drug or whose apparent concentration of analyte is less than the cutoff concentration for that drug or drug class. Some laboratories may conduct a second initial test prior to gas chromatography/mass spectrometry (GC/MS) confirmation in an effort to enhance the specificity of the assay. Some laboratories may conduct a second initial test prior to gas chromatography/mass spectrometry (GC/MS) confirmation in an effort to enhance the specificity of the assay.

19. The following cutoff concentrations are used by certified laboratories to test urine specimens collected by Federal agencies and by employers regulated by the Department of Transportation : Initial Test Cutoff Concentration: Initial Test Cutoff Concentration: (nanograms/milliliter) Marijuana metabolites 50, Cocaine metabolites 300, Opiate metabolites 2000, Phencyclidine25, Amphetamines1000 Confirmatory Test Cutoff Concentration (nanograms/milliliter) Confirmatory Test Cutoff Concentration (nanograms/milliliter) Marijuana metabolite (1) 15, Cocaine metabolite (2) 50, Opiates: Morphine2000, Codeine2000, 6-Acetylmorphine (4) 10, Phencyclidine25, Amphetamines: Amphetamine500, Methamphetamine (3)500. Footnotes: (1) Delta-9-tetrahydrocannabinol-9-carboxylic acid (2) Benzoylecgonine (3) Specimen must also contain amphetamine at a concentration >= 200 nanograms/milliliter (4) Test for 6-AM when morphine concentration exceeds 2000 nanograms/milliliter (1) Delta-9-tetrahydrocannabinol-9-carboxylic acid (2) Benzoylecgonine (3) Specimen must also contain amphetamine at a concentration >= 200 nanograms/milliliter (4) Test for 6-AM when morphine concentration exceeds 2000 nanograms/milliliter

20. The Validity Test Refers to testing to identify any attempt to tamper with a specimen. This includes testing to identify adulteration (e.g., putting a substance into a specimen that is designed to mask or destroy the drug or drug metabolite that the specimen may contain or to adversely affect the assay reagent) or substitution (e.g., diluting a urine specimen with a liquid to effectively decrease the concentration of a drug below the cutoff concentration, or replacing a valid urine specimen with a Drug-Free specimen). Refers to testing to identify any attempt to tamper with a specimen. This includes testing to identify adulteration (e.g., putting a substance into a specimen that is designed to mask or destroy the drug or drug metabolite that the specimen may contain or to adversely affect the assay reagent) or substitution (e.g., diluting a urine specimen with a liquid to effectively decrease the concentration of a drug below the cutoff concentration, or replacing a valid urine specimen with a Drug-Free specimen). The Mandatory Guidelines for Federal Workplace Drug Testing Programs published in the Federal Register on June 9, 1994 (59 FR 29908) and the U.S. Department of Transportation (DOT) regulations (49 CFR Part 40) applicable to DOT federally regulated programs permit laboratories to conduct additional tests to determine the validity of a urine specimen. The Mandatory Guidelines for Federal Workplace Drug Testing Programs published in the Federal Register on June 9, 1994 (59 FR 29908) and the U.S. Department of Transportation (DOT) regulations (49 CFR Part 40) applicable to DOT federally regulated programs permit laboratories to conduct additional tests to determine the validity of a urine specimen.

21. The laboratories certified under the National Laboratory Certification Program (NLCP) have reported that the number of adulterated, diluted, and substituted urine specimens has been increasing. In response, the U.S. Department of Health and Human Services (HHS) and DOT began the process, using the HHS Substance Abuse and Mental Health Services Administration’s (SAMHSA) Drug Testing Advisory Board (DTAB), to develop standards for the testing and reporting of validity test results for urine specimens tested in federally regulated programs. Urine specimens are defined in PD #35 as "dilute" if the creatinine concentration is 1.020 as the criteria to define a "substituted" specimen. (*) Urine specimens are defined in PD #35 as "dilute" if the creatinine concentration is 1.020 as the criteria to define a "substituted" specimen.

22. “Sample integrity failed” Samples with creatinine results less than or equal to 0.5 mmol/l (56 mg/l) or specific gravity results out of range are unsuitable for testing. Measurement of pH: Results within the range 4-9 are deemed to be within a normal range. Results less than 3 or greater than 11 should be considered to be adulterated. Samples falling outside this range should be reported as eg “sample integrity failed”. Nitrite test: If the nitrite concentration is determined: A nitrite level equal to or above 500 μg/ml is conclusive proof of an adulterated sample. The result should be reported as eg “sample integrity failed”. Testing for other adulterants: If other tests indicate that the sample has been adulterated, or is otherwise unsuitable for analysis then it should be reported as eg “sample integrity failed” This remark is also reported when the sample does not fall under the criteria of pH, creatinine or nitrite above, yet is still not suitable for testing. This can be due to an unidentified interferant or poor sample quality such as turbidity.

23. European Laboratory Guidelines for Legally Defensible Workplace Drug Testing (EWDTS) Objectives  The guidelines are designed to: 1 Provide a minimum set of criteria for the providers of workplace drug testing services within Europe. 2 Ensure that the processes undertaken are capable of legal scrutiny. 3 Provide safeguards to protect the specimen donors. 4 Define for laboratories common quality assurance and quality control criteria that are capable of being accredited by an external body. Scope  These guidelines consider the three key stages of the workplace drug testing process. 1 Obtaining the specimen from the donor (specimen collection). 2 Analysis of the sample for the presence of drugs (laboratory analysis). 3 Review and interpretation of the analytical results

24. When a positive result: Long-term frozen storage (-15°C or less) for any necessary retest, storage for a minimum of 1 year. Quality system ( ISO 17025 must apply) which encompasses all aspects of the testing process including but not limited to: Sample receipt. Chain of custody. Security and reporting of results. Screen and confirmation testing. Certification of calibrators and controls. Validation of analytical procedures.

25. Interpretation results An analytical positive result may be due to medication (prescribed or over-the-counter) or to dietary causes. An essential part of the drug testing process is the final review of positive analytical results. The interpretation is best carried out by a qualified medical practitioner (Medical Review Officer) who can consult with the laboratory toxicologist, the donor, and the donor's medical practitioner. A toxicologist must be available to advise the customer and/or Medical Review Officer regarding queries with results. The toxicologist cannot issue a negative report for a positive analytical result even if the test result is likely to be due to the use of declared medication.

27. Medical Review (a) The Medical Review Officer (MRO) is a medical physician with responsibility for interpreting laboratory results. (b) A medical physician will have greater access to medical records than a toxicologist and may therefore be in a better position to provide interpretation of positive analytical results. (c) The MRO must have specialist knowledge of and training in · Specimen collection procedures. · Analytical procedures. · Chain of Custody. · Alternative explanations for positive analytical results. (d) The MRO can issue a negative report for a positive analytical result if the test result is likely to be due to the use of declared medication, or a valid alternative explanation has been found. (e) The service provider may provide access to an independent medical review service.

28. How to interpret a positive result For how long the sample is positive after drug consumption? E.g. cocaine 250 mg (8-48 h) For how long the sample is positive after drug consumption? E.g. cocaine 250 mg (8-48 h) Is the seafarer a drug addict or a casual consumer? Repeat controls in intervals, it depens on the substance, use hair E.g. Cannabis once a week (7-30 days, every day (6-80 days) Is the seafarer a drug addict or a casual consumer? Repeat controls in intervals, it depens on the substance, use hair E.g. Cannabis once a week (7-30 days, every day (6-80 days) In the time of urine collection, was the seafarer under drug effects? Saliva-blood-breath are better correlated. E.g. Heroine 10 mg IV (1-4 days), morfine IV (>72 h.), metadone 38mg (8-56 h.) In the time of urine collection, was the seafarer under drug effects? Saliva-blood-breath are better correlated. E.g. Heroine 10 mg IV (1-4 days), morfine IV (>72 h.), metadone 38mg (8-56 h.) Is it reliable? Yes about consumption not about addiction and legal considerations. What way of administration? Can it be by accident? Opiates & poop seeds, thé? & cocaine. By contamination? Hair & cannabis oil, Because of prescribed or self-administrated medicines? Cocaine no, cannabis? Marinol®, look for metabolite in Opiates… Is it reliable? Yes about consumption not about addiction and legal considerations. What way of administration? Can it be by accident? Opiates & poop seeds, thé? & cocaine. By contamination? Hair & cannabis oil, Because of prescribed or self-administrated medicines? Cocaine no, cannabis? Marinol®, look for metabolite in Opiates…

29. International Recomendations Identify drug & alcohol problems (Research...). Identify drug & alcohol problems (Research...). Policy of control: 1993 procedures for ‘screening’ (tankers, urine test…). Policy of control: 1993 procedures for ‘screening’ (tankers, urine test…). Prevention campaigns: information, education...). Prevention campaigns: information, education...).

30. Research in seafarers Research in seafarers WJ Inzhong (1991) seafarers with HT 80 % smokers & 85,3 % drinkers. WJ Inzhong (1991) seafarers with HT 80 % smokers & 85,3 % drinkers. S. Balanza (1996) 72,3 % seafarers smokers, 88 % drinkers (Cartagena - Spain). S. Balanza (1996) 72,3 % seafarers smokers, 88 % drinkers (Cartagena - Spain). M. Villanueva (1997, tesis) 51,1 % smokers & 50,3 % drinkers (País Vasco - Spain). M. Villanueva (1997, tesis) 51,1 % smokers & 50,3 % drinkers (País Vasco - Spain). Alcohol: F. Mestre (1997) 85 % smokers in coastal fishing (Castellón-Spain) & J. Montoya (1991) 83 % in injured ones (Almería-Spain). MJ. Loira (1987) in deep sea fishing 54,5 % drink more at home that on board. Alcohol: F. Mestre (1997) 85 % smokers in coastal fishing (Castellón-Spain) & J. Montoya (1991) 83 % in injured ones (Almería-Spain). MJ. Loira (1987) in deep sea fishing 54,5 % drink more at home that on board.

31. Alcohol