practicalities of conducting biological assessments for drug use kenzie l. preston, ph.d. chief,...
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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
Why Use Biological Measures?
CostlyInconvenientUnnecessary?
Good evidence that people under report
use Adds credibility to results
Ideal Drug Testing for Clinical Trials
Specimen is:Easily and safely collectedLow risk of contamination/adulterationEasily stored/transported (if necessary)
Window of detection that matches specimen collection schedule
Test is:Good efficiency (sensitivity and
specificity)Low costQuick and easy
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
?
?
Drug Testing and Addiction
SweatHair
Oral Fluid Breath Dried Blood Spot
Urine
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
Survey of Drug Testing in Biological Matrices
Major analyte Metabolite
Detection time 2-4 days
Urine
Detection of recent Yes/No - carry over positives can be a problem use/sensitivity to with frequent testing change in rate of use (Quantitative and frequent testing required)
Collection convenient No - Toilet facilities and same-sex observers
Contamination Unlikely
On site testing? Yes
Other Issues Well established concentration cut-offs Well established use as an outcome
measure Many laboratories use the same or similar assays
Concentration Cutoff Affects Window of Detection
Preston, Epstein, Cone Wtsadik, Huestis, Moolchan, JAT 2002
N = 18 cocaine users living on a closed unitNo drug administration - monitored excretion of cocaine and metabolitesSample collection - All urine voids (N=953) were collected for up to 14 days.
500 450 400 350 300 250 200 150 10024
30
36
42
48
54
60
66
72
78
84
90
Concentration Cutoff for Positive Specimen
Ho
urs
BE 300 ng/ml cutoff
Time to Concentration Cutoff
Lower cutofflengthenwindow
Raise cutoffshortenwindow
0
2
4
6
8
10
12
Contingent Control
Longest Duration of Sustained AbstinenceWeeks
RespondersNonresponders
Clinical Trial - Contingent Reinforcement of Cocaine Abstinence
504540353025201510501
10
100
1000
10000
100000
1000000ng/mL
Baseline Voucher
Cutoff
Nonresponders
Responders
(Contingent Group)
LOD
Benzoylecgonine Concentration in Urine
Sequential Urine Specimens
Sequential Urine SpecimensSequential Urine Specimens
Benzoylecgonine Concentration in Urine
505045454040353530302525202015151010550011
1010
100100
10001000
1000010000
100000100000
10000001000000
ng/mLng/mL
Specimens were collected M, W, F for 17 weeks.
Sequential Urine SpecimensSequential Urine Specimens
Benzoylecgonine Concentration in Urine
505045454040353530302525202015151010550011
1010
100100
10001000
1000010000
100000100000
10000001000000
ng/mLng/mLCutoff
LOQ
11 occasions negative
Specimens were collected M, W, F for 17 weeks.
SAMHSA
Sequential Urine SpecimensSequential Urine Specimens
Benzoylecgonine Concentration in Urine
505045454040353530302525202015151010550011
1010
100100
10001000
1000010000
100000100000
10000001000000
ng/mLng/mL
Cutoff
LOQ
23 occasions of negative
Specimens were collected M, W, F for 17 weeks.
CutoffSAMHSA
New Use Rules
Purpose: To differentiate urine positives due to carryoverfrom positives due to recent (or new) uses of cocaine
Sequential Urine SpecimensSequential Urine Specimens
Benzoylecgonine Concentration in Urine
505045454040353530302525202015151010550011
1010
100100
10001000
1000010000
100000100000
10000001000000
ng/mLng/mL Cutoff
LOQ
28 occasions of new use28 occasions of new use12 occasions of carry-over12 occasions of carry-over11 occasions of negative11 occasions of negative
Specimens were collected M, W, F for 17 weeks.Specimens were collected M, W, F for 17 weeks.
Comparison of Urine Screen and Self-Report
Baseline Intervention Baseline Intervention
Survey of Drug Testing in Biological Matrices
Major analyte Parent>Metabolite
Detection time 1 week – months
Hair
Collection convenient Yes/No (depends of amount and style of hair
Contamination Possible
On site testing? No, must be sent to outside labOther Issues Affected by hair color & treatmentsOnly matrix with potential for replication
Detection of recent No - limited by hair growth rateuse/sensitivity to (7-10 days for hair to grow through scalp)
change in rate of use
Hair grows approximately 1 cm/mo.
Admission 1 2 3 4 5 6 7 8 9Week
Scheidweiler, Cone, Moolchan,Huestis. JPET 313, 909-915, 2005
Cocaine and metaboliteconcentrations in hair
N = 10 cocaine users
Admission to closed unit
3 week drug washoutWeek 4 - 3 administrations of 75 mg/70 kg SC cocaine on alternating daysWeek 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
Representative subject
Benzoylecgonine
Ecgonine methyl ester
Norcocaine
Cocaethylene
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%
Baseline and 3-month follow-up
Office-based vs. federally licensed narcotic treatment program
Hair testing at Baseline and 3- and 6-month follow-upsin 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.
Survey of Drug Testing in Biological Matrices
Major analyte Parent>Metabolite
Detection time 3-10 days - usually one week
Sweat
Other Issues Allergic reaction possible; patches may fall off
Not well established use as outcome measure Currently available from only one company
Collection convenient Yes/No (same-sex not needed, but patch may be visible)
Contamination Possible, especially if area not cleaned well
On site testing? No, must be sent to outside lab
Detection of recent Yes/No - carry over positives can happenuse/sensitivity to detection of change limited by lengthchange in rate of use of patch wear
BZE
11
1010
100100
1,0001,000
10,00010,000
16161414121210108866442211
1010
100100
1,0001,00010,00010,000
100,000100,000
1,000,0001,000,000
16161414121210108866442211
1010
100100
1,0001,000
10,00010,000100,000100,000
1,000,0001,000,000
11
1010
100100
1,0001,000
10,00010,000 Sweat
Cocaine
Urine
Subject CSubject C Subject DSubject D Sweat
Urine
WeeksWeeks WeeksWeeks
Cocaine
BZE
ng/mL
ELISA Sweat Patch vs. EMIT Urine Results
Sensitivity - 97.6%Specificity - 60.5%
Preston, Huestis Wong Umbricht, Goldberger, Cone. J Anal Toxicol. 1999.
Monitoring Cocaine Use in Sweat Patches
ng/mL
63 participants in a buprenorphine trial
Applied 536 patches188 (54%) properly worn, unadulterated patches
Agreement between urine and patch results cocaine – 92%opiates – 33%
Survey of Drug Testing in Biological Matrices
Major analyte Parent>Metabolite
Detection time 1-2 days (depends on cut off and analyte)
Oral Fluid
Detection of recent Yesuse/sensitivity to change in rate of use
Collection convenient Yes
Contamination Yes/No
On site testing? YesOther Issues Not established as an outcome measure
Affected by flow rate & pH
Detection of Cocaine Use in Oral Fluid
Cocaine
BZE(Cocaine
Metabolite)
Huestis et al.
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
Questions?