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Practicalities of Conducting Biological Assessments for Drug Use

Practicalities of Conducting Biological Assessments for Drug Use. Kenzie L. Preston, Ph.D. Chief, Clinical Pharmacology and Therapeutics Research Branch National Institute on Drug Abuse. ACTTION/ MOST Meeting, March 2015. Why Use Biological Measures?. Costly Inconvenient Unnecessary?.

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Practicalities of Conducting Biological Assessments for Drug Use

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  1. Practicalities of Conducting Biological Assessments for Drug Use Kenzie L. Preston, Ph.D.Chief, Clinical Pharmacology and Therapeutics Research BranchNational Institute on Drug Abuse ACTTION/MOST Meeting, March 2015

  2. Why Use Biological Measures? Costly Inconvenient Unnecessary? Good evidence that people under report use Adds credibility to results

  3. Ideal Drug Testing for Clinical Trials Test is: Good efficiency (sensitivity and specificity) Low cost Quick and easy Specimen is: Easily and safely collected Low risk of contamination/adulteration Easily stored/transported (if necessary) Window of detection that matches specimen collection schedule

  4. Drug Testing Workplace: public safety & reduce accidents Roadside: drugged driving Judicial: drug use & crimes Anti-doping: fair competition & promote health Military: deter drug use & ensure fitness for duty Clinical: diagnosis or postmortem Drug treatment: monitor recovery/abstinence Monitor drug use in clinical trials: evaluate treatments for efficacy Screen Confirmation ? ?

  5. Drug Testing and Addiction Urine Sweat Hair Dried Blood Spot Breath Oral Fluid

  6. Survey of Drug Testing in Biological Matrices Major analyte Detection time Detection of recent use/sensitivity to change in rate of use Collection convenient Contamination On site testing? Other Issues

  7. Survey of Drug Testing in Biological Matrices Urine Major analyte Metabolite Detection time 2-4 days Detection of recentYes/No - carry over positives can be a problem use/sensitivity towith frequent testing change in rate of use (Quantitative andfrequent testing required) Collection convenientNo - Toilet facilities and same-sex observers ContaminationUnlikely On site testing?Yes Other IssuesWell established concentration cut-offs Well established use as an outcome measure Many laboratories use the same or similar assays

  8. 90 84 78 72 66 60 54 48 42 36 30 24 500 450 400 350 300 250 200 150 100 Concentration Cutoff Affects Window of Detection N = 18 cocaine users living on a closed unit No drug administration - monitored excretion of cocaine and metabolites Sample collection - All urine voids (N=953) were collected for up to 14 days. Time to Concentration Cutoff Lower cutoff lengthen window Hours Raise cutoff shorten window Concentration Cutoff for Positive Specimen BE 300 ng/ml cutoff Preston, Epstein, Cone Wtsadik, Huestis, Moolchan, JAT 2002

  9. Clinical Trial - Contingent Reinforcement of Cocaine Abstinence Benzoylecgonine Concentration in Urine Longest Duration of Sustained (Contingent Group) ng/mL Abstinence Weeks 1000000 12 Nonresponders 100000 10 10000 8 Responders Responders 6 1000 Cutoff Nonresponders 4 100 LOD 2 10 Voucher Baseline 0 Contingent Control 1 0 5 10 15 20 25 30 35 40 45 50 Sequential Urine Specimens

  10. 1000000 1000000 100000 100000 10000 10000 1000 1000 100 100 10 10 1 1 Benzoylecgonine Concentration in Urine ng/mL ng/mL 0 5 10 15 20 25 30 35 40 45 50 0 5 10 15 20 25 30 35 40 45 50 Sequential Urine Specimens Sequential Urine Specimens Specimens were collected M, W, F for 17 weeks.

  11. 1000000 1000000 100000 100000 10000 10000 1000 1000 100 100 10 10 1 1 Benzoylecgonine Concentration in Urine SAMHSA ng/mL ng/mL Cutoff LOQ 0 5 10 15 20 25 30 35 40 45 50 0 5 10 15 20 25 30 35 40 45 50 Sequential Urine Specimens Sequential Urine Specimens 11 occasions negative Specimens were collected M, W, F for 17 weeks.

  12. 1000000 1000000 100000 100000 10000 10000 1000 1000 100 100 10 10 1 1 Benzoylecgonine Concentration in Urine Cutoff SAMHSA ng/mL ng/mL Cutoff LOQ 0 5 10 15 20 25 30 35 40 45 50 0 5 10 15 20 25 30 35 40 45 50 Sequential Urine Specimens Sequential Urine Specimens 23 occasions of negative Specimens were collected M, W, F for 17 weeks.

  13. New Use Rules Purpose: To differentiate urine positives due to carryover from positives due to recent (or new) uses of cocaine

  14. 1000000 1000000 100000 100000 10000 10000 1000 1000 100 100 10 10 1 1 Benzoylecgonine Concentration in Urine ng/mL ng/mL Cutoff LOQ 0 5 10 15 20 25 30 35 40 45 50 0 5 10 15 20 25 30 35 40 45 50 Sequential Urine Specimens Sequential Urine Specimens 28 occasions of new use 28 occasions of new use Specimens were collected M, W, F for 17 weeks. Specimens were collected M, W, F for 17 weeks. 12 occasions of carry-over 12 occasions of carry-over 11 occasions of negative 11 occasions of negative

  15. Comparison of Urine Screen and Self-Report Baseline Intervention Baseline Intervention

  16. Survey of Drug Testing in Biological Matrices Hair Major analyte Parent>Metabolite Detection time 1 week – months Detection of recentNo - limited by hair growth rate use/sensitivity to(7-10 days for hair to grow through scalp) change in rate of use Collection convenientYes/No (depends of amount and style of hair ContaminationPossible On site testing?No, must be sent to outside lab Other IssuesAffected by hair color & treatments Only matrix with potential for replication Hair grows approximately 1 cm/mo.

  17. Cocaine and metabolite concentrations in hair Representative subject N = 10 cocaine users Admission to closed unit 3 week drug washout Week 4 - 3 administrations of 75 mg/70 kg SC cocaine on alternating days Week 7 - 3 administrations of 150 mg/70 kg SC cocaine on alternating days Sample collection - electric razor Head hair shaved on admission Weekly collection of shavings Analysis Liquid chromatography tandem mass spectrometry Benzoylecgonine Ecgonine methyl ester Norcocaine Cocaethylene Admission 1 2 3 4 5 6 7 8 9 Scheidweiler, Cone, Moolchan, Huestis. JPET 313, 909-915, 2005 Week

  18. Cocaine - Concordance between hair testing and self-report – 86% Specificity >90%, Sensitivity 65 % Amphetamine - Concordance between hair testing and self-report – 86% Specificity >90%, Sensitivity 24%

  19. Baseline and 3-month follow-up

  20. Office-based vs. federally licensed narcotic treatment program Hair testing at Baseline and 3- and 6-month follow-ups in addition to self-report and urine toxicology No difference between groups Hair testing identified two additional participants in each group who had used illicit drugs. Positive hair test predicted drug use during the trial.

  21. Survey of Drug Testing in Biological Matrices Sweat Major analyte Parent>Metabolite Detection time 3-10 days - usually one week Detection of recentYes/No - carry over positives can happen use/sensitivity todetection of change limited by length change in rate of useof patch wear Collection convenientYes/No (same-sex not needed, but patch may be visible) ContaminationPossible, especially if area not cleaned well On site testing?No, must be sent to outside lab Other IssuesAllergic reaction possible; patches may fall off Not well established use as outcome measure Currently available from only one company

  22. Monitoring Cocaine Use in Sweat Patches Sweat Sweat Subject C Subject D Subject C Subject D 10,000 10,000 10,000 10,000 Cocaine 1,000 1,000 1,000 1,000 100 100 100 ng/mL 100 10 10 10 10 1 1 1 1 Urine Urine 1,000,000 1,000,000 1,000,000 1,000,000 100,000 Cocaine 100,000 100,000 100,000 BZE BZE 10,000 10,000 10,000 10,000 ng/mL 1,000 1,000 1,000 1,000 100 100 100 100 10 10 10 10 1 1 1 1 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 Weeks Weeks Weeks Weeks ELISA Sweat Patch vs. EMIT Urine Results Sensitivity - 97.6% Specificity - 60.5% Preston, Huestis Wong Umbricht, Goldberger, Cone. J Anal Toxicol. 1999.

  23. 63 participants in a buprenorphine trial Applied 536 patches 188 (54%) properly worn, unadulterated patches Agreement between urine and patch results cocaine – 92% opiates – 33%

  24. Survey of Drug Testing in Biological Matrices Oral Fluid Major analyte Parent>Metabolite Detection time 1-2 days (depends on cut off and analyte) Detection of recentYes use/sensitivity to change in rate of use Collection convenientYes ContaminationYes/No On site testing?Yes Other IssuesNot established as an outcome measure Affected by flow rate & pH

  25. Detection of Cocaine Use in Oral Fluid Cocaine BZE (Cocaine Metabolite) Huestis et al.

  26. Potential Areas of Research Optimize concentration cut-offs/detection windows Combine different biological matrices to optimize windows of drug detection Investigate methods to improve adherence to specimen collection Investigate methods to improve remote collection of specimens

  27. Questions?

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