Does the use of ingredients added to tobacco increase cigarette addictiveness?: A detailed analysis

Figures & data

Table 1.  List of data sets used for meta-analysis.

Study No	Author and year	Total treated/controls	Quitters treated/controls	Type of NRT	Country	Level of support	Study quality	OR (95% CI)	Time Period	Def. of Abst.*	Comments
1	Ahluwalia et al. (2006)	189/189	29/28	Gum	US	High	A	1.04 (0.59–1.81)	6 months	PP	Motivational interviewing
2	Ahluwalia (2006)	189/188	55/45	Gum	US	High	A	1.22 (0.78–1.89)	6 months	PP	Health education
3	Cinciripini (1996)	32/32	12/7	Patch	US	High	B	1.71 (0.60–4.91)	1 year	PP
4	Cooper (2005)	146/148	17/15	Gum	US	High	B	1.15 (0.55–2.39)	1 year	PP
5	Fiore (1994)	44/43	15/9	Patch	US	High	B	1.63 (0.64–4.12)	6 months	PP	Patch for 8 weeks
6	Fiore (1994)	57/55	10/4	Patch	US	High	B	2.41 (0.71–8.15)	6 months	PP	Patch for 6 weeks
7	Fortmann (1995)	260/261	55/42	Gum	US	Low	B	1.32 (0.85–2.04)	12 months	PP
8	Garvey (2000)	203/203	26/13	Gum	US	High	B	2.00 (1.00–4.00)	1 year	SA	4 mg gum
9	Garvey (2000)	202/203	27/13	Gum	US	High	B	2.08 (1.04–4.04)	1 year	SA	2 mg gum
10	Glover (2002)	120/121	22/12	Tablets	US	High	B	1.85 (0.88–3.90)	12 months	SA
11	Gross (1995)	131/46	37/6	Gum	US	High	B	2.16 (0.86–5.46)	24 weeks	SA
12	Hall (1985)	35/36	16/10	Gum	US	High	B	1.65 (0.66–4.12)	52 weeks	PP
13	Hall (1987)	35/34	12/7	Gum	US	High	B	1.66 (0.59–4.73)	52 weeks	PP
14	Hall (1987)	36/34	18/7	Gum	US	Low	B	2.43 (0.90–6.54)	52 weeks	PP
15	Harackiewicz (1988)	90/47	12/9	Gum	US	Low	B	0.70 (0.27–1.77)	52 weeks	SA
16	Hays (1999)	321/322	18/9	Patch	US	Low	B	2.01 (0.89–4.53)	24 weeks	SA
17	Hughes (1989)	210/105	31/11	Gum	US	Low	A	1.41 (0.68–2.91)	1 year	SA
18	Hughes (2003)	61/54	13/8	Patch	US	High	B	1.44 (0.55–3.73)	6 months	SA
19	Hurt (1990)	31/31	9/8	Patch	US	High	B	1.12 (0.38–3.30)	56 weeks	SA
20	Hurt (1994)	120/120	33/17	Patch	US	High	B	1.94 (1.03–3.67)	12 months	SA
21	Jorenby (1999)	244/160	40/25	Patch	US	High	B	1.07 (0.62–1.83)	12 months	PP
22	Joseph (1996)	294/290	41/32	Patch	US	High	A	1.26 (0.77–2.06)	24 weeks	PP
23	Killen (1984)	22/20	5/6	Gum	US	High	B	0.76 (0.20–2.87)	10.5 months	PP
24	Killen (1990)	301/309	57/56	Gum	US	High	B	1.04 (0.70–1.56)	12 months	PP	Ad lib gum
25	Killen (1990)	299/309	72/56	Gum	US	High	B	1.33 (0.90–1.95)	12 months	PP	Fixed gum
26	Killen (1997)	109/108	15/11	Patch	US	Low	B	1.35 (0.59–3.08)	12 months	PP	With video
27	Killen (1997)	103/104	21/14	Patch	US	Low	B	1.52 (0.73–3.14)	12 months	PP	Without video
28	Kinnunen (2008)	279/133	56/13	Gum	US	High	B	2.05 (1.08–3.89)	12 months	SA	Non-depressed
29	Kinnunen (2008)	126/70	19/4	Gum	US	High	B	2.64 (0.86–8.06)	12 months	SA	Depressed
30	Leischow (1996)	110/110	12/6	Inhaler	US	High	B	2.00 (0.72–5.52)	12 months	SA
31	Lewis (1998)	62/62	6/4	Patch	US	Low	A	1.50 (0.40–5.58)	6 months	PP
32	Mcgovern (1992)	146/127	50/39	Gum	US	High	C	1.12 (0.69–1.80)	12 months	PP
33	Moolchan (2005)	34/40	6/2	Patch	US	High	A	3.53 (0.67–18.64)	6 months	PP
34	Moolchan (2005)	46/40	4/2	Gum	US	High	A	1.74 (0.30–10.00)	6 months	PP
35	Niaura (1999)	66/63	5/6	Gum	US	High	B	0.80 (0.23–2.74)	12 months	PP
36	Okuyemi (2007)	66/107	5/10	Gum	US	High	B	0.81 (0.26–2.48)	6 months	PP
37	Oncken (2007)	57/95	19/28	Patch	US	High	B	1.13 (0.58–2.21)	16 months	PP
38	Oncken (2008)	100/94	11/9	Gum	US	High	C	1.15 (0.46–2.90)	6 months	PP
39	Pirie (1992)	108/103	34/15	Gum	US	High	B	2.16 (1.11–4.20)	12 months	SA	Freedom from smoking program
40	Pirie (1992)	98/108	14/25	Gum	US	High	B	0.62 (0.30–1.25)	12 months	SA	Behavioral weight control program
41	Pollak (2007)	122/59	17/1	Various†	US	High	B	8.22 (1.07–63.27)	6 months	PP
42	Rennard (2006)	215/214	17/5	Inhaler	US	Low	B	3.38 (1.23–9.34)	12 months	PP
43	Sachs (1993)	113/107	28/10	Patch	US	High	B	2.65 (1.23–5.72)	12 months	SA
44	Schneider (1983)	30/30	9/6	Gum	US	High	B	1.50 (0.48–4.74)	52 weeks	SA	Clinical support
45	Schneider (1983)	13/23	2/2	Gum	US	Low	B	1.77 (0.22–14.09)	52 weeks	SA	Low support
46	Schneider (1995)	128/127	23/10	Spray	US	High	B	2.28 (1.04–4.99)	1 year	SA
47	Schneider (1996)	112/111	15/9	Inhaler	US	High	A	1.65 (0.69–3.93)	1 year	SA
48	Shiffman (2009)	819/817	43/25	Gum	US	Low	A	1.72 (1.04–2.84)	6 months	SA	2 mg gum
49	Shiffman (2009)	830/831	48/7	Gum	US	Low	A	6.86 (3.09–15.26)	6 months	SA	4 mg gum
50	TNSG (1991)	249/253	65/31	Patch	US	High	B	2.13 (1.34–3.38)	24 weeks	SA	21 mg patch
51	TNSG (1991)	254/253	46/31	Patch	US	High	B	1.48 (0.91–2.41)	24 weeks	SA	14 mg patch
52	Westman (1993)	79/80	16/2	Patch	US	High	B	8.10 (1.80–36.40)	6 months	SA
53	Wewers (2009)	147/155	13/0	Patch	US	High	B	Not calculable	12 months	PP
54	Abelin et al. (1989)	100/99	18/12	Patch	Switzerland	Low	B	1.48 (0.68–3.24)	12 months	SA	6, 9, and 12 months results in Müller et al., 1990
55	Blondal et al. (1989)	92/90	30/22	Gum	Iceland	High	B	1.33 (0.72–2.48)	12 months	SA
56	Blondal et al. (1997)	79/78	20/13	Spray	Iceland	High	A	1.52 (0.71–3.26)	1 year	SA
57	Dautzenberg (2007)	211/222	25/18	Lozenge	France	Low	B	1.46 (0.78–2.76)	26 weeks	SA
58	Dautzenberg (2007)	230/230	8/2	Lozenge	US	Low	B	4.00 (0.84–19.04)	26 weeks	SA
59	Ehrsam (1991)	56/56	9/3	Patch	Switzerland	High	B	3.00 (0.77–11.67)	9 months	SA
60	Fagerström (1982)	47/49	30/22	Gum	Sweden	High	B	1.42 (0.72–2.81)	6 months	SA
61	Fagerström (1984)	50/22	14/3	Gum	Sweden	High	C	2.05 (0.54–7–87)	12 months	SA	High support
62	Fagerström (1984)	46/27	10/1	Gum	Sweden	Low	C	5.87 (0.71–48.41)	12 months	SA	Low support
63	Glavas et al. (2003a)	56/56	13/9	Patch	Croatia	Low	A	1.44 (0.57–3.65)	12 months	SA
64	Glavas & Rumboldt (2003b)	40/40	15/6	Patch	Croatia	Low	A	2.50 (0.88–7.10)	6 months	SA	Patch for 3 weeks
65	Glavas & Rumboldt (2003b)	40/40	14/6	Patch	Croatia	Low	A	2.33 (0.82–6.68)	6 months	SA	Patch for 6 weeks
66	Hilberink et al. (2011)	243/148	18/5	Various‡	Netherlands	Low	B	2.19 (0.80–6.03)	12 months	PP
67	Hjalmarson (1984)	106/100	31/16	Gum	Sweden	High	B	1.83 (0.94–3.54)	12 months	SA
68	Hjalmarson et al. (1994)	125/123	34/18	Spray	Sweden	High	B	1.86 (1.00–3.47)	12 months	SA
69	Hjalmarson et al. (1997)	123/124	35/22	Inhaler	Sweden	High	A	1.60 (0.89–2.89)	12 months	SA
70	Jensen et al. (1991)	211/82	90/28	Gum	Denmark	High	B	1.40 (0.86–2.29)	6 months	SA
71	Kornitzer et al. (1995)	149/75	27/10	Patch	Belgium	High	A	1.36 (0.62–2.96)	52 weeks	SA	Active patch and gum versus placebo gum
72	Kornitzer et al. (1995)	150/75	19/10	Patch	Belgium	High	A	0.95 (0.42–2.14)	52 weeks	SA	Active patch and placebo gum versus placebo gum
73	Kralikova et al. (2009)	209/105	39/9	Inhaler	Czech Rep.	High	B	2.18 (1.02–4.66)	12 months	SA
74	Paoletti et al. (1996)	60/60	17/5	Patch	Italy	Low	B	3.40 (1.18–9.81)	52 weeks	SA
75	Puska et al. (1995)	150/150	36/26	Patch	Finland	Low	B	1.38 (0.80–2.41)	52 weeks	SA
76	Quilez Garcia et al. (1989)	37/38	13/5	Gum	Spain	High	B	2.67 (0.87–8.24)	6 months	SA
77	Salvador Llivina et al. (1988)	113/103	54/28	Gum	Spain	High	B	1.76 (1.04–2.98)	12 months	SA
78	Segnan et al. (1991)	294/275	22/15	Gum	Italy	High	A	1.37 (0.70–2.70)	1 year	SA
79	Tonnesen et al. (1988)	60/53	23/12	Gum	Denmark	High	A	1.69 (0.77–3.73)	12 months	SA
80	Tonnesen et al. (1991)	145/144	25/6	Patch	Denmark	High	A	4.14 (1.65–10.39)	12 months	SA
81	Tonnesen et al. (1993)	145/141	22/7	Inhaler	Denmark	High	A	3.06 (1.27–7.38)	12 months	SA
82	Tonnesen et al. (2006)	95/88	13/4	Tablet	Denmark	Low	B	3.01 (0.95–9.58)	12 months	SA
83	Tonnesen et al. (2006)	90/97	13/6	Tablet	Denmark	High	B	2.34 (0.85–6.40)	12 months	SA
84	Wallstrom et al. (2000)	123/124	28/19	Tablet	Sweden	High	A	1.49 (0.79–2.80)	12 months	SA
85	Binnie et al (2007)	59/57	4/2	Various¶	UK	High§	C	1.93 (0.34–10.97)	12 months	PP
86	BTS (1983)	400/402	40/56	Gum	UK	Low	B	0.72 (0.47–1.10)	12 months	PP
87	Campbell et al. (1987)	424/412	13/9	Gum	UK	Low	B	1.40 (0.59–3.32)	12 months	SA
88	Campbell et al. (1991)	107/105	21/21	Gum	UK	High	B	0.98 (0.51–1.90)	12 months	SA
89	Campbell et al. (1996)	115/119	24/17	Patch	UK	High	B	1.56 (0.75–2.86)	12 months	SA
90	Gilbert et al. (1989)	112/111	7/8	Gum	Canada	Low	B	0.87 (0.30–2.47)	12 months	SA
91	Gourlay et al. (1995)	315/314	5/4	Patch	Australia	Low	B	1.25 (0.33–4.68)	6 months	SA
92	Hand et al. (2002)	136/109	20/15	Various∥	UK	High	C	1.07 (0.52–2.18)	1 year	SA
93	ICRF (1994)	842/844	76/53	Patch	UK	High	A	1.44 (1.00–2.07)	12 months	SA
94	Jamrozik et al. (1984)	101/99	10/8	Gum	UK	Low	A	1.22 (0.46–3.23)	6 months	PP
95	Jarvis et al. (1982)	58/58	18/8	Gum	UK	High	B	2.25 (0.91–5.58)	12 months	SA
96	Malcolm et al. (1980)	73/63	17/3	Gum	UK	High	B	4.89 (1.37–17.46)	6 months	SA
97	Molyneux et al. (2003)	91/91	10/4	Various#	UK	Low	B	2.50 (0.76–8.26)	12 months	SA
98	Prapavessis et al. (2007)	26/27	4/4	Patch	New Zealand	High	B	1.04 (0.24–4.60)	52 weeks	SA	Cognitive therapy
99	Prapavessis et al. (2007)	33/35	9/3	Patch	New Zealand	High	B	3.18 (0.79–12.78)	52 weeks	SA	Exercise
100	Richmond et al. (1993)	200/150	17/14	Gum	Australia	High	C	0.91 (0.44–1.91)	6 months	SA
101	Richmond et al. (1994)	156/157	39/19	Patch	Australia	High	A	2.07 (1.14–3.73)	6 months	SA
102	Russell et al. (1983)	679/675	60/28	Gum	UK	Low	C	2.13 (1.34–3.38)	1 year	SA
103	Stapleton et al. (1995)	800/400	77/19	Patch	UK	High	A	2.03 (1.21–3.40)	52 weeks	SA
104	Sutherland et al. (1992)	116/111	30/11	Spray	UK	High	B	2.61 (1.25–5.46)	12 months	SA

*PP, point prevalence; SA, sustained abstinence.

†Gum, patch, or tablet.

‡NRT type cannot be specified, since subjects were responsible for choosing and purchasing their own treatment.

¶Gum or patch.

§High support for the treated group, low support for controls.

□Patch or inhaler.

#Gum, patch, inhaler, tablet, or spray.

Table 2.  List of additional or excluded treatment and control data sets.

Study no.	Author and year	Number of participants	Number of quitters	Type of NRT	Country	Level of support	Study quality	Time period	Def. of Abst. *	Comments
List of additional treatment data sets used for the multiple regression analysis
12a	Hall (1985)	42	15	Gum	US	Low	B	52 weeks	PP	Low support plus gum
16a	Hays (1999)	315	34	Patch	US	Low	B	24 weeks	SA	Open label with pay
76a	Quilez Garcia (1989)	31	8	Gum	Spain	High	B	6 months	SA	Follow-up individually with physician
79a	Tonnesen (1988)	60	16	Gum	Denmark	High	A	12 months	SA	Two additional treatment groups with 4 mg gum (27) and 2 mg gum (33)
100a	Richmond (1993)	100	12	Gum	Australia	Low	C	6 months	SA	GP advice plus nicotine gum
List of treatment data sets excluded from the multiple regression analysis
74	Paoletti (1996)	60		Patch	Italy	Low	B	52 weeks	SA	Data not appropriate for multiple regression analysis
List of additional control data sets used for the multiple regression analysis
15a	Harackiewicz (1988)	38	3		US	Low	B	52 weeks	SA	Short booklet distributed with tips to stop smoking
31a	Lewis (1998)	61	3		US	Low	A	6 months	PP	Minimal counseling
78a	Segnan (1991)	62	3		Italy	Low	A	1 year	SA	Minimal intervention
78b	Segnan (1991)	292	19		Italy	High	A	1 year	SA	Repeated counseling with spirometry
86a	BTS (1983)	377	41(2)		UK	Low	B	12 months	SA	Verbal advice from physician, stop smoking booklet
86b	BTS (1983)	371	41(3)		UK	Low	B	12 months	SA	Verbal advice from physician
87a	Campbell et al (1987)	149	2		UK	Low	B	12 months	SA	Additional control group
96a	Malcolm (1980)	74	10		UK	High	B	6 months	SA	Additional control group
97a	Molyneux (2003)	92	7		UK	Low	B	12 months	SA	Usual care
102a	Russell (1983)	584	23		UK	Low	C	1 year	SA	No contact with physician
List of control data sets excluded from the multiple regression analysis
9	Garvey (2000)	203	13		US	High	B	1 year	SA	Same control group as used for data set 8
34	Moolchan (2005)	40	2		US	High	A	6 months	PP	Same control group as used for data set 33
51	TSNG (1991)	253	31		US	High	B	24 weeks	SA	Same control group as used for data set 50
72	Kornitzer (1995)	75	10		Belgium	High	A	52 weeks	SA	Same control group as used for data set 71
74	Paoletti (1996)	60	5		Italy	Low	B	52 weeks	SA	Data not appropriate for multiple regression analysis
75	Puska (1995)	0	0		Finland	Low	B	52 weeks	SA	Both the treatment group (patch) and the control group were encouraged to use gum. Therefore, the entire sample was considered as a treatment group.

*PP, point prevalence; SA, sustained abstinence.

Table 3.  Estimates of treatment effects on cessation rates, overall as well as stratified by type of NRT, type of cigarette, study duration, type of abstinence, level of support, study decade, study size, study quality, as well as combined strata, regarding type of cigarette and type of abstinence.

Description	No. of studies	Fixed effects pooled OR (95% CI)	Random effects pooled OR (95% CI)	I^2	Degrees of freedom	p
All studies	104	1.70 (1.58–1.82)	1.76 (1.61−1.93)	0.28	103.00	0.006
Nicotine gum	47	1.52 (1.38–1.69)	1.61 (1.39−1.86)	0.44	46.00	0.001
Nicotine patch	36	1.80 (1.59−2.04)	1.81 (1.59−2.06)	0.05	35.00	0.383
Nicotine tablets/lozenge	6	1.95 (1.39−2.74)	1.95 (1.39−2.74)	0.00	5.00	0.722
Nicotine inhaler	6	2.30 (1.65−3.21)	2.30 (1.65−3.21)	0.00	5.00	0.784
Nicotine spray	4	2.34 (1.62−3.34)	2.34 (1.62−3.34)	0.00	3.00	0.789
Blended countries	84	1.75 (1.61−1.90)	1.80 (1.63−1.98)	0.20	83.00	0.066
Flue-cured countries	20	1.53 (1.31−1.79)	1.61 (1.27−2.04)	0.50	19.00	0.007
1-year cessation data	73	1.66 (1.52−1.80)	1.71 (1.54−1.90)	0.24	72.00	0.037
6-month cessation data	31	1.81 (1.58−2.08)	1.91 (1.59−2.30)	0.36	30.00	0.025
Sustained abstinence	72	1.94 (1.78−2.12)	1.96 (1.78−2.16)	0.14	71.00	0.16
Point prevalence	32	1.30 (1.15−1.48)	1.32 (1.15−1.51)	0.09	31.00	0.322
High support	73	1.69 (1.55−1.84)	1.73 (1.57−1.91)	0.22	72.00	0.051
Low support	30	1.72 (1.49−1.98)	1.88 (1.53−2.30)	0.42	29.00	0.009
Studies, 1980–1989	24	1.70 (1.44−2.02)	1.82 (1.45−2.28)	0.37	23.00	0.037
Studies, 1990–1999	46	1.64 (1.48−1.80)	1.68 (1.49−1.90)	0.30	45.00	0.029
Studies, 2000–2010	34	1.83 (1.59−2.12)	1.88 (1.60−2.22)	0.18	33.00	0.183
>300 subjects	32	1.57 (1.42−1.74)	1.64 (1.42−1.89)	0.47	31.00	0.002
<300 subjects	72	1.84 (1.66−2.05)	1.86 (1.67−2.08)	0.11	71.00	0.227
Quality A	26	1.73 (1.52−1.98)	1.79 (1.52−2.11)	0.28	25.00	0.091
Quality B	70	1.71 (1.56−1.88)	1.80 (1.60−2.02)	0.31	69.00	0.009
Quality C	8	1.51 (1.18−1.94)	1.51 (1.17−1.95)	0.03	7.00	0.403
Blended and SA	55	2.03 (1.82−2.25)	2.04 (1.82−2.27)	0.08	54.00	0.315
Blended and PP	29	1.38 (1.21−1.57)	1.38 (1.21−1.57)	0.00	28.00	0.647
Flue cured and SA	17	1.74 (1.47−2.06)	1.75 (1.42−2.16)	0.27	16.00	0.145
Flue cured and PP	3	0.79 (0.54−1.17)	0.85 (0.52−1.38)	0.15	2.00	0.308

Table 4.  Effect estimates and 95% CI based on the main effects model in control and treatment group data. Effect estimates of the interaction model are given for the control group data on the right half, indicating the scope of applications of estimates (population restrictions), according to the interaction structure of the model. In the effect column, the exposure category is mentioned.

Main effects model			Interaction model
Effect	OR	95% CI	Effect	Population restrictions	OR	95% CI
Data: Control groups			Data: Control groups
Blended cigarettes	1.32	1.14–1.53	Blended cigarettes	Low support and 1980–1989	3.47	2.20–5.45
Sustained abstinence	0.49	0.44–0.55	Blended cigarettes	Low support and 1990–1999	1.52	0.95–2.42
High support	2.38	2.06–2.75	Blended cigarettes	Low support and 2000–2010	1.05	0.39–2.82
1990–1999	0.58	0.50–0.69	Blended cigarettes	High support and 1980–1989	2.12	1.41–3.20
2000–2010	0.42	0.35–0.50	Large study	Point prevalence and 1980–1989	2.19	1.39–3.44
Large study	0.71	0.63–0.80	Large study	Point prevalence and 1990–1999	1.04	0.84–1.30
Data: Treatment groups			Large study	Point prevalence and 2000–2010	1.26	0.96–1.65
Blended cigarettes	1.90	1.70–2.13	Large study	Sustained abstinence and 1980–1989	0.97	0.62–1.52
Sustained abstinence	0.89	0.81–0.98	High support	Flue-cured cigarettes	3.22	2.12–4.88
High support	2.02	1.82–2.25	1990−1999	Flue-cured cigarettes and small study	1.18	0.77–1.80
1990–1999	0.62	0.55–0.70	2000–2010	Flue-cured cigarettes and small study	1.16	0.71–1.87
2000–2010	0.45	0.39–0.51	Sustained abstinence	Small study	0.70	0.58–0.83
Large study	0.73	0.66–0.80

Figure 1.  In small studies (left panel), studies with high support resulted in increased levels of smoking cessation as compared to studies with low support in decade 1. The difference in smoking cessation rates as a function of support declined in the 1990s (decade 2) and 2000s (decade 3). In large studies (right panel), there was a significant effect of high support in studies conducted in the 2000s but not in studies conducted in the 1990s.

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