Transcript Preston presentation

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?
Good evidence that
people under report use
Adds credibility to results
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
Drug Testing
Screen Confirmation
• 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
Drug Testing and Addiction
Urine
Hair
Sweat
Oral Fluid
Breath
Dried Blood Spot
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
Urine
Major analyte
Metabolite
Detection time
2-4 days
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
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.
90
Time to Concentration Cutoff
84
78
66
60
Hours
Lower cutoff
lengthen
window
72
54
48
42
Raise cutoff
shorten
window
36
30
24
500 450 400 350 300 250 200 150
Concentration Cutoff for Positive Specimen
100
BE
300 ng/ml cutoff
Preston, Epstein, Cone Wtsadik, Huestis, Moolchan, JAT 2002
Clinical Trial - Contingent Reinforcement of Cocaine Abstinence
Longest Duration of Sustained
Abstinence
Weeks
Benzoylecgonine Concentration in Urine
12
ng/mL
1000000
10
100000
8
10000
6
Responders
Nonresponders
4
Nonresponders
Responders
1000
100
2
0
(Contingent Group)
Cutoff
LOD
10
Contingent
Control
Voucher
Baseline
1
0
5
10
15
20
25
30
35
40
Sequential Urine Specimens
45
50
Benzoylecgonine Concentration in Urine
1000000
1000000
100000
100000
10000
10000
1000
1000
ng/mL
ng/mL
100
100
10
10
11
00
55
10
10
15
15 20
20 25
25 30
30 35
35 40
40
Sequential
Sequential Urine
Urine Specimens
Specimens
45
45
Specimens were collected M, W, F for 17 weeks.
50
50
Benzoylecgonine Concentration in Urine
1000000
1000000
100000
100000
10000
10000
1000
1000
ng/mL
ng/mL
SAMHSA
Cutoff
100
100
LOQ
10
10
11
00
55
10
10
15
15 20
20 25
25 30
30 35
35 40
40
Sequential
Sequential Urine
Urine Specimens
Specimens
45
45
50
50
11 occasions negative
Specimens were collected M, W, F for 17 weeks.
Benzoylecgonine Concentration in Urine
1000000
1000000
100000
100000
10000
10000
Cutoff
1000
1000
ng/mL
ng/mL
SAMHSA
Cutoff
100
100
LOQ
10
10
11
00
55
10
10
15
15 20
20 25
25 30
30 35
35 40
40
Sequential
Sequential Urine
Urine Specimens
Specimens
45
45
50
50
23 occasions of negative
Specimens were collected M, W, F for 17 weeks.
New Use Rules
Purpose: To differentiate urine positives due to carryover
from positives due to recent (or new) uses of cocaine
Benzoylecgonine Concentration in Urine
1000000
1000000
100000
100000
10000
10000
1000
1000
ng/mL
ng/mL
Cutoff
100
100
LOQ
10
10
11
00
55
10
10
28
28 occasions
occasions of
of new
new use
use
12
12 occasions
occasions of
of carry-over
carry-over
11
11 occasions
occasions of
of negative
negative
15
35
15 20
20 25
25 30
30
35 40
40
Sequential
Sequential Urine
Urine Specimens
Specimens
45
45
50
50
Specimens
Specimens were
were collected
collected M,
M, W,
W, FF for
for 17
17 weeks.
weeks.
Comparison of Urine Screen and Self-Report
Baseline Intervention
Baseline Intervention
Survey of Drug Testing in Biological Matrices
Hair
Major analyte
Parent>Metabolite
Detection time
1 week – months
Detection of recent
No - limited by hair growth rate
use/sensitivity to
(7-10 days for hair to grow through scalp)
change in rate of use
Collection convenient
Yes/No (depends of amount and style of hair
Contamination
Possible
On site testing?
No, must be sent to outside lab
Other Issues
Affected by hair color & treatments
Only matrix with potential for replication
Hair grows approximately 1 cm/mo.
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
Benzoylecgonine
Analysis
Liquid chromatography tandem
mass spectrometry
Ecgonine
methyl ester
Norcocaine
Cocaethylene
Scheidweiler, Cone, Moolchan,
Huestis. JPET 313, 909-915, 2005
Admission 1
2
3
4
5
Week
6
7
8
9
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-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.
Survey of Drug Testing in Biological Matrices
Sweat
Major analyte
Parent>Metabolite
Detection time
3-10 days - usually one week
Detection of recent
Yes/No - carry over positives can happen
use/sensitivity to
detection of change limited by length
change in rate of use
of patch wear
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
Other Issues
Allergic reaction possible; patches may fall off
Not well established use as outcome measure
Currently available from only one company
Monitoring Cocaine Use in Sweat Patches
Sweat
Subject
Subject C
C
10,000
10,000
ng/mL
Cocaine
1,000
1,000
1,000
1,000
100
100
100
100
10
10
10
10
11
11
Urine
1,000,000
1,000,000
ng/mL
100,000
100,000
10,000
10,000
100,000
100,000
10,000
10,000
1,000
1,000
1,000
1,000
100
100
100
100
10
10
11
10
10
11
44
66
88
10
10 12
12 14
14
Weeks
Weeks
Urine
1,000,000
1,000,000
Cocaine
BZE
BZE
22
Sweat
Subject
Subject D
D
10,000
10,000
16
16
22
44
66
88
10
10 12
12 14
14
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.
16
16
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%
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 recent
Yes
use/sensitivity to
change in rate of use
Collection convenient Yes
Contamination
Yes/No
On site testing?
Other Issues
Yes
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?