New Low-Nicotine Cigarettes Are Still as Harmful:
Implications for FDA Regulation of Tobacco
University of Illinois at Chicago
Institute for Health Research and Policy
Chicago, Illinois
November 4, 2010
Andrew A. Strasser, Ph.D.
Outline
Focus: FDA Regulation and the Family Smoking Prevention and Tobacco Control Act
1) Regulatory Background
2) Smoking Topography: Measurement of Smoking Behavior, Human Smoking
Variability and Toxin Exposure
3) Research Program
a) Light cigarettes
Reliability of carbon monoxide (CO) boost
Preferred brand cigarette study
b) Quest cigarettes
Smoking topography, CO boost and filter tar stains as indices of exposure
PREP advertisement features and smokers’ beliefs
c) Marketing and labeling of low nicotine cigarettes
Novel PREP beliefs
Quest ad manipulation
Beliefs and eye-tracking
NICOTINE
1-HOP
NNAL
CO
EBC
ss 907
1. Regulatory Background
20th Century Smoking Rates in the United States
3
1
2
Standard Tar (mg)
Background of Tar Yields
24
22
20
18
16
14
12
10
8
6
4
2
0
1968
1978
1988
Year
1998
The FTC cigarette test
Basic Smoking Machine
Tar
B. Filter Vent Holes
cigar ette
35 ml pu ff
A."Syringe" Puffer takes One
2-sec Puff Per minute
C. Filter-Pad traps Tar and Nicotine
Nic
CO
How Low-tar cigarettes test low
1 ) Reduce the number of puffs by:
– decreasing the cigarette length
– increasing burn rate
– increasing paper porosity
– puffing up tobacco
2) Reduce the concentration of smoke in each puff by:
– increasing paper porosity
– adding filter ventilation holes.
Kozlowski et al., 2000 Cigarettes, Nicotine, and Health
Figure. Minimum percentage compensation C* necessary to
obtain at least as great a dosage from a cigarette of the lower
tar as the higher tar brand, per mg nicotine.
Harris JE (NTR 6(5); 2004
2. Smoking Topography: Measurement of Smoking
Behavior, Human Smoking Variability and Toxin Exposure
Measures Include:
Number of Puffs
Puff Volume
Total Puff Volume
Puff Velocity
Puff Duration
Interpuff Interval
Peak Velocity
Total Time Lit
Reliability
Puff Volume (ml)
50
Intraclass correlation coefficients: .66 - .75, p<.001
40
30
20
10
0
1
2
Day
3
4
Lee et al., Nic Tob Res 2003; Strasser et al., Pharm Bio Beh 2005
Validity
Physiological or biochemical
measure
Smoking condition
Topography
Carbon monoxide (ppm)
4.6 + 0.6
5.1 + 0.8
Plasma nicotine (mg/ml)
18.5 + 4.6
25.5 + 4.5
Time to smoke (s)
278 + 6.8
286 + 6.9
Number of puffs
11.2 + 0.8
10.3 + 0.7
Natural
COMPARISON OF SMOKING TOPOGRAPHY AND AD LIB LABORATORY SESSIONS
TOPOGRAPHY MEASURE
ICC
95% CI
p value
NUMBER OF PUFFS
.97
.95-.98
.001
INTERPUFF INTERVAL
.93
.88-.97
.002
TOTAL TIME LIT
.91
.84-.95
.008
Lee et al., Nic Tob Res. 2003; Strasser et al., Exp Clin Psych 2009
Figure. Levels of (A) total NNAL, (B) 1-HOP, and (C) total cotinine, all per mg
creatinine, in the urine of smokers of regular, light, and ultralight cigarettes (n = 175)
Hecht, SS. et al. Cancer Epidem Biomarkers Prev 2005
Bo x P lo t of NNAL/mg creatinine by cigarette type (N=113)
Levels
G r o u p in g V a r ia b le ( s ) : RL UL
6
4
PUFF VELOCITY
Total NNAL (pmol/mg Creatinine)
5
3
2
1
0
-1
1
REGULAR
N=38
2
LIGHT
N=61
3
ULTRALIGHT
N=14
Strasser et al., (under review)
Percent reduction in cigarettes per day (open bars) and total 4(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) per milligram of creatinine
(solid bars) in smokers in the reduction group during weeks 4-6, 4-12, and 4-26.
Hecht, SS. et al. J Natl Cancer Inst 2004
3. Research Program
A. Light cigarettes (addressing FDA bill ss907: Product design)
1. Reliability of carbon monoxide (CO) boost:
The effect of filter vent blocking and smoking topography on carbon
monoxide levels in smokers. Pharmacology Biochemistry and Behavior
2005; 82(2): 320-329.
2. Preferred brand cigarette study – 5 day:
Behavioral filter vent blocking on the first cigarette of the day
predicts which smokers of light cigarettes will increase smoke exposure
from blocked vents. Experimental and Clinical Psychopharmacology
2009; 17(6): 405-412.
Fig. 1. Mean CO boosts with standard errors for
both ultralight (0.1 mg nicotine, 1 mg tar, 2 mg
CO) and light (0.8 mg nicotine, 10 mg tar, 10 mg
CO) cigarettes under both blocking conditions.
Fig. 2. Mean subjective ratings of
strength/harshness with standard errors for both
ultralight (0.1 mg nicotine, 1 mg tar, 2 mg CO)
and light (0.8 mg nicotine, 10 mg tar, 10 mg CO)
cigarettes under both blocking conditions.
Fig. 3. Mean subjective ratings of heat with standard
errors for both ultralight (0.1 mg nicotine, 1 mg tar,
2 mg CO) and light (0.8 mg nicotine, 10 mg tar, 10
mg CO) cigarettes under both blocking conditions.
Kozlowski et al., 1997 Pharm. Bio. Beh.
1. Reliability of carbon monoxide (CO) boost
Fig. 1. A. Study 1. The effect of cigarette type and filter vent blocking condition on CO
boost. Significant main effects indicate blocking increased CO boost for both cigarette
types. Light cigarettes had greater CO boost than ultra-light cigarettes.
Fig.1. B. Study 1. The effect of cigarette type and filter vent blocking condition on puff
volume. Puff volume for unblocked ultra-light was significantly larger than puff volume
for the three other conditions.
Strasser et al., 2005 Pharm. Bio. Beh.
2. Preferred brand cigarette study – 5 day
25 Marlboro Light smokers only; 1 session ST, 1 session VT; ad lib smoking.
Participant Descriptive Statistics:
UNBLOCKED
BLOCKED
p value
MEAN (SD)
SEX (% FEMALE)
73%
40%
.11
AGE
47.6 (9.2)
40.0 (9.5)
.07
BODY MASS INDEX
31.0 (8.8)
27.1 (4.9)
.21
DAILY CIGARETTES
20.4 (4.8)
20.5 (2.5)
.98
NICOTINE DEPENDENCE
5.1 (1.6)
5.7 (1.8)
.42
Comparison of Smoking Behaviors between Session
ICC
95% CI
p value
NUMBER OF PUFFS
.97
.95-.98
.001
INTERPUFF INTERVAL
.93
.88-.97
.002
TOTAL TIME LIT
.91
.84-.95
.008
Filter ventilation in Light cigarettes
UNBLOCKED
BLOCKED
IRR = .88
Strasser et al., 2009 Exp Clinical Psychopharm
Strasser et al., 2009 Exp Clinical Psychopharm
3. Research Program
B. Quest cigarettes
(addressing FDA regulation of cigarette nicotine levels)
1. Smoking topography, CO boost and filter tar stains as indices of exposure
New lower nicotine cigarettes can produce compensatory smoking and
increased carbon monoxide exposure. Drug Alcohol Depend 2007; 86: 294-300.
Digital image analysis of cigarette filter stains as an indicator of compensatory
smoking. Cancer Epidemiol Biomarkers and Prevention 2006; 15(12): 2565-2569.
2. Extended PREP use, smoking behavior and exposure biomarkers
NCI R01-120594, ongoing
Descriptive Characteristics of Quest cigarettes.
Quest® 1
Quest® 2
Quest® 3
Reported nicotine level (mg)
0.6
0.3
0.05
Reported tar level (mg)
10.0
10.0
10.0
Cigarette length (mm)
82.5
82.8
82.2
Cigarette diameter (mm)
7.6
7.8
7.9
Tobacco rod length (mm)
57.6
57.8
57.5
Tobacco mass (g)
0.60
0.57
0.57
Tipping paper length (mm)
30.0
30.1
30.0
Filter length (mm)
24.9
24.8
24.7
Filer length – mouth end (mm)
12.1
12.0
12.5
Filter length – rod end (mm)
8.0
7.9
7.6
Total filter mass (g)
0.23
0.22
0.24
Filter mass - mouth end (g)
0.071
0.073
0.072
Filter mass – rod end (g)
0.068
0.068
0.065
Filter carbon mass (g)
0.100
0.102
0.108
111.1 (1.1)
101.5 (1.4)
115.8 (0.9)
1.1 (0.1)
1.4 (0.1)
1.3 (0.04)
Pressure drop (mm H2O)
Ventilation (%)
Strasser et al., 2006 Cancer Epi Bio Prev
1. Smoking topography, CO boost and filter tar stains as indices of exposure
Overview of Study Design.
Time (minutes)
0
30
60
90
120
1) Informed Consent
1) Pre-cigarette CO
1) Pre-cigarette CO
1) Pre-cigarette CO
1) Pre-cigarette CO
2) Review Procedures
2) Topography:
2) Topography:
2) Topography:
2) Topography:
3) Baseline Questionnaire
Usual brand
Quest cigarette A
Quest cigarette B
Quest cigarette C
3) Post-cigarette CO
3) Post-cigarette CO
3) Post-cigarette CO
3) Post-cigarette CO
4) Subjective Ratings
4) Subjective Ratings
4) Subjective Ratings
4) Subjective Ratings
50 participants; single session; ad lib smoking.
Cigarette order of presentation was counter-balanced between subjects.
Cigarettes were color-coded and masked to double-blind researchers
and participants to nicotine level.
Outcome measures: CO boost and smoking topography
The effect of cigarette nicotine level on total puff volume [(ml; solid bars; left y-axis);
F(2, 47) = 5.73, p=.006] and mean carbon monoxide boost [(ppm; open bars; right y-axis);
F(2, 47) = 5.43, p=.01]. Data presented as mean (± 95% CI).
700
7
600
6
500
5
400
4
-15% -- 59%
-21% -- 60%
300
3
-23% -- 98%
200
2
100
1
0
COboost (ppm)
Total Puff Volume (ml)
% d-TPV
0
0.6
0.3
Quest cigarette nicotine level (mg)
0.05
Strasser et al., 2007 Drug and Alcohol Depend
Digital Imaging of Filter Tar Stains (Quest)
TPV 0.6 – TPV 0.05
0.6 mg nicotine < 0.05 mg nicotine
1024 x 768 pixel resolution images.
CIELAB color space analyses for:
L (lightness), a*(red-green), and
b*(yellow-blue).
TPV 0.6 – TPV 0.05
Strasser et al., 2006 Cancer Epi Bio Prev
Topography also refers to how people smoke over a period of time…
2. Extended PREP use, smoking behavior and exposure biomarkers
CONTROL
OWN CIGARETTES
DAY 1
USUAL
BRAND
5*
10
15*
20
QUEST 2
QUEST 2
(0.3 mg nic) (0.05 mg nic)
25 *
30
QUEST 3
USUAL
BRAND
QUEST 1
QUEST 1
(0.6 mg nic)
(0.6 mg nic)
(0.3 mg nic)
QUEST 1
QUEST 1
QUEST 2
QUEST 2
QUEST 3
(0.6 mg nic)
(0.6 mg nic)
(0.3 mg nic)
(0.3 mg nic)
(0.05 mg nic) (0.05 mg nic)
35 *
QUEST 3
(0.05 mg nic)
QUEST 3
* = denotes urine (NNAL, 1-HOP, cotinine) collection.
smoking topography, carbon monoxide boost, daily cigarettes collected at each session.
The effect of cigarette nicotine level on Total Puff Volume: Initial Exposure
800
N =62
p = .01
Total Puff Volume (ml)
700
600
500
400
300
200
100
0
Own Brand
Days 1-5
Quest 1 (0.6 mg nic)
Days 5-15
Quest 2 (0.3 mg nic)
Days 15-25
Quest 3 (0.05 mg nic)
Days 25-35
The effect of cigarette nicotine level on Total Puff Volume: Mean
800
N =62
p = .01
Total Puff Volume (ml)
700
600
500
400
300
200
100
0
Own Brand
Days 1-5
Quest 1 (0.6 mg nic)
Days 5-15
Quest 2 (0.3 mg nic)
Days 15-25
Quest 3 (0.05 mg nic)
Days 25-35
The effect of cigarette nicotine level on daily cigarettes: Own Brand
Daily Cigarette Consumption
30
N =43
r filters = .94
25
20
15
10
5
0
Days 1-5
(own)
Days 5-15
(0.6 mg)
Days 15-25
(0.3 mg)
Days 25-35
(0.05 mg)
The effect of cigarette nicotine level on daily cigarettes: Nicotine Decrease
Daily Cigarette Consumption
30
N =62
r filters = .98
25
20
15
10
5
0
Days 1-5
(own)
Days 5-15
(0.6 mg)
Days 15-25
(0.3 mg)
Days 25-35
(0.05 mg)
The effect of cigarette nicotine level on toxin exposure: Nicotine
5000
CONTROL
5000
N =43; p=. 22
NIC DEC
4000
Total Nicotine (ng per mg Creatinine)
Total Nicotine (ng per mg Creatinine)
4000
N =62; p=.001
3000
2000
1000
0
3000
2000
1000
0
DAY 5
DAY 15
DAY 25
DAY 35
DAY 5
DAY 15
DAY 25
DAY 35
The effect of cigarette nicotine level on toxin exposure: Cotinine
5000
CONTROL
5000
N =43; p= .15
NIC DEC
4000
Total Cotinine (ng per mg Creatinine)
Total Cotinine (ng per mg Creatinine)
4000
N =62; p=.001
3000
2000
1000
0
3000
2000
1000
0
DAY 5
DAY 15
DAY 25
DAY 35
DAY 5
DAY 15
DAY 25
DAY 35
The effect of cigarette nicotine level on toxin exposure: NNAL
2
N =43; p=. 28
NIC DEC
1.8
1.8
1.6
1.6
1.4
1.4
Total NNAL (ng per mg Creatinine)
Total NNAL (ng per mg Creatinine)
CONTROL
2
1.2
1
0.8
0.6
0.4
0.2
0
N =62; p=.002
1.2
1
0.8
0.6
0.4
0.2
0
DAY 5
DAY 15
DAY 25
DAY 35
DAY 5
DAY 15
DAY 25
DAY 35
The effect of cigarette nicotine level on toxin exposure: 1-HOP
2
N =43; p=. 99
NIC DEC
1.8
1.8
1.6
1.6
Total 1-HOP (pmol per mg Creatinine)
Total 1-HOP (pmol per mg Creatinine)
CONTROL
2
1.4
1.2
1
0.8
0.6
0.4
0.2
0
N =64; p=.065
1.4
1.2
1
0.8
0.6
0.4
0.2
0
DAY 5
DAY 15
DAY 25
DAY 35
DAY 5
DAY 15
DAY 25
DAY 35
The effect of cigarette nicotine level on toxin exposure: Carbon Monoxide
40
N =43; p=. 91
CONTROL
35
35
30
30
25
20
15
10
5
0
DAYS 0
N =64; p=.001
NIC DEC
Carbon Monoxide (Baseline, ppm)
Carbon Monoxide (Baseline, ppm)
40
25
20
15
10
5
0
5
10
15
20
25
30
35
DAYS 0
5
10
15
20
25
30
35
The effect of cigarette nicotine level on subjective ratings
100
N =43; p=.09
90
90
80
80
70
70
Satisfaction (mm)
Strength (mm)
100
60
50
40
60
50
40
30
30
20
20
10
10
0
0
OWN
0.6 MG
0.3 MG
0.05 MG
N =60; p=.005
OWN
0.6 MG
0.3 MG
0.05 MG
Summary of Low Nicotine (Quest) Results
Behavioral measures of Daily Cigarette Consumption and Smoking
Topography initially increase as cigarette nicotine levels decrease,
then return to approximate baseline.
Nicotine and Cotinine levels decrease as cigarette nicotine levels decrease.
Toxin exposure is not uniform: 1-HOP, CO increase, but NNAL decreases.
Subjective ratings decrease as a function of cigarette nicotine levels, similar
to previous research, which may partly convey less harmfulness.
3. Research Program
C. Marketing and labeling of low nicotine cigarettes
(addressing FDA regulation of cigarette nicotine levels ss.201)
1. PREP advertisement features and smokers’ beliefs
Evaluating smokers’ reactions to advertising for new lower nicotine Quest
cigarettes. Psychology of Addictive Behaviors 2006; 20(1): 80-84.
PREP advertisement features affect smokers’ beliefs regarding potential
harm. Tobacco Control 2008; S1: 32-38.
2. Effect of explicit and implicit information on smokers’ beliefs
Robert Wood Johnson Foundation – Substance Abuse Policy Research
Program (2008-2010).
PREP advertisement features and smokers’ beliefs
Shopping mall intercept study where participants completed
demographic and smoking history questions, viewed the ad and
answered 8 items related to beliefs about Quest cigarettes.
Participants smoked an average of 16.9 cigarettes per day (SD =
10.8) and had a mean nicotine dependence score of 4.6 (SD = 2.3)
Smokers made several specific false inferences about Quest
cigarettes after exposure (i.e., lower in tar, healthier, less likely to
cause cancer).
Those lower in education, having lower nicotine dependence and
males tended to respond correctly less frequently. Need for
cognition and perceived vulnerability moderated smokers’ beliefs.
Additionally, 25% of participants reported that Quest cigarettes
would help them quit smoking, despite warnings to the contrary.
Shadel, Lerman, Strasser et al., 2006 Psych Add Beh
Advertisement Manipulation
Web-TV recruitment.
Descriptive and Smoking History.
Randomization to Ad.
8-item Quest beliefs.
NO TEXT (N=165)
ORIGINAL (N=174)
RED (N=161)
Marlboro Red King smokers
significantly preferred both the
Marlboro Ultra Light Red cigarettes
and package.
Marlboro Red King smokers viewed
the cigarettes in the Blue pack as
“too mild”, “not easy drawing”, and
“burned too fast”.
Other low tar king smokers described
the cigarettes in the Red pack as
harsher than those in the blue pack
PM docs: Bates 2047387079
2048718182
The effect of cigarette advertising on beliefs of potential harm
OR
3.5
2.0
3.0
2.5
2.1
3.3
1.5 (.1)
2.5
Strasser et al., 2008 Tobacco Control
The effect of cigarette advertising on beliefs of potential harm
OR
3.5
2.0
3.0
2.5
2.1
3.3
1.5 (.1)
2.5
Strasser et al., 2008 Tobacco Control
A
B
C
D
Figure. Ad conditions: A) accurate explicit-accurate implicit; B) accurate explicit-misleading
implicit; C) misleading explicit-accurate implicit; D) misleading explicit-misleading implicit.
ACCURATE EXPLICIT
ACCURATE IMPLICIT
Figure. Ad conditions: A) accurate explicit-accurate implicit; D) misleading explicit-misleading implicit.
Project: False Inferences from Advertising of PREPs, Lights and Cigars
RWJF: Substance Abuse Policy Research Program (2008-2010)
Regions of interest:
TIME (sec)
Explicit Correct Manipulation: Topographic Dwell Time
TIME (sec)
Figure 2. Explicit Incorrect Manipulation: Topographic Dwell Time
Quest cigarettes are lower in tar than regular cigarettes?
TIME (SECONDS)
DWELL TIME IN TAR STATEMENT (ROI)
1.2
1.1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.91
0.77
0.91
0.81
INCORRECT
CORRECT
P=.52
Quest cigarettes help people quit smoking?
DWELL TIME IN WARNING LABEL (ROI)
3
TIME (SECONDS)
2.5
2
1.5
1
0.5
1.6
2.3
2.3
1.6
0
INCORRECT
CORRECT
P=.042
Tar correct
Logistic Model Coefficients Table for tar correct
Coef Std. Error Coef/SE Chi-Square
P-Value
Exp(Coef)
95% Lower
95% Upper
1: constant
.657
.428
1.536
2.359
.1246
1.929
.834
4.462
FTND
-.129
.071
-1.824
3.328
.0681
.879
.766
1.010
explicit-acc: 1
.594
.298
1.993
3.970
.0463
1.811
1.010
3.248
implicit-acc: 1
-.164
.295
-.556
.309
.5782
.849
.476
1.512
.555
.314
1.766
3.120
.0773
1.741
.941
3.222
sex 1=M: 2
l
Log likelihood = -131.76, R2=0.04
Percent correct
.8
.7
.8
.7
.6
.7
.6
.5
.4
.3
.6
.5
.5
.4
52
68
.3
64
l
52
.2
.2
0
1
EXPLICIT
53
66
1
2
.1
0
0
.3
.2
.1
.1
.4
0
0
1
NICOTINE DEPENDENCE
SEX
Warning label correct
Logistic Model Coefficients Table for correct warning label
Coef Std. Error Coef/SE Chi-Square
1: constant
P-Value
Exp(Coef)
95% Lower
95% Upper
-.604
.425
-1.423
2.024
.1549
.547
.238
1.256
explicit-acc: 1
.108
.314
.343
.118
.7313
1.114
.602
2.060
implicit-acc: 1
-.058
.315
-.185
.034
.8530
.943
.509
1.748
FTND-di: 1
.413
.320
1.290
1.663
.1972
1.511
.807
2.832
6WarningLabelsonly
.414
.097
4.266
18.202
<.0001
1.512
1.251
1.829
-.158
.069
-2.281
5.205
.0225
.854
.745
.978
2Headline
l
Log likelihood = -119.74, R2=0.13
Percent correct
.7
.6
.6
.6
.5
.5
.4
.4
.3
.3
.5
.4
.3
.2
53
30
66
63
.2
64
37
l
52
48
.1
.1
0
1
WARNING LABEL DWELL
53
51
66
31
.1
0
0
.2
0
0
1
NICOTINE DEPENDENCE
0
1
HEADLINE DWELL
Summary of Advertising and Labeling
Embedding a correct statement (explicit accurate) in the advertisement
significantly increased participant correct response that Quest had as much tar as
a light cigarette.
However, explicit information in the warning label area did not lead to
participants correctly understanding that the product would not help them quit
smoking.
Eye-tracking data suggests overall, relatively little time was allocated to viewing
the warning labels, suggesting participant incorrect responses may be attributable
to no or little viewing time of the warning label. However, correct recall of warning
label content was positively associated with increased dwell time of warning label.
Results suggest that accurate risk information in the body of the advertisement
may increase retaining risk information more than in the warning labels.
General Concluding Statements to Apply to the FDA legislation:
Laboratory results suggest that smoking topography is an important component in
assessing smoking behavior, and is associated with constituent exposure.
-- Implementing a testing and evaluation paradigm that considers these variations is
imperative, but complex.
Conventional low nicotine cigarettes have design elasticity which permits increased
extraction of nicotine and other cigarette constituents. Blocking the filter vents on
Light cigarettes can significantly increase toxin exposure.
-- Filter vent blocking occurs in a significant proportion of smokers and ought to be banned
as a design feature that harms the public health.
Novel low nicotine cigarettes (PREPs) are less elastic in design and initially may be
smoked more intensely leading to increased toxicant exposure. Extended use
patterns suggest compensation may occur in varying ways.
-- Reducing cigarette nicotine levels may not reduce harm or improve the public’s health.
In extended examination of novel low nicotine cigarettes, nicotine (cotinine)
levels likely decrease, but all toxin exposures may not.
-- What makes a product less harmful, both at a constituent level and on a population level?
Advertising helps formulate an initial expectation of product response and risk.
-- What effect will an FDA stamp of approval have on smokers’ beliefs?
-- Is it warning labels that should be regulated?