(Snus) Research, Common Flaws, and how to critique it

Transcription

1 Tobacco Harm Reduction Scholarship programme June 13, 2018: (Snus) Research, Common Flaws, and how to critique it Karl E Lund, Ph.D. Senior Researcher

2 Agenda: Common Flaws & Misinformation examples of how bad research and misinformation have hindered the adoption of snus (and e cigs) as a THR tool The long time experience with snus in Norway and Sweden

3 Education: 1996: PhD in Sociology 2009: Professor Commissions Associate Editor: Nicotine & Tobacco Research, Tobacco Regulatory Science, Nordic Studies on Alcohol and Drugs, Tobacco Induced Diseases Int. Agency Cancer Research expert committee Lecturer on tobacco topics in several countries Executive board GFN Deputy leader of the Norwegian Council on Tobacco and Health, Professional experience: : Norwegian National Council on Tobacco and Health : University of Oslo, Inst behavioural medicine : Norwegian Cancer Society : National Institute of Pubic Health : Nor. Inst. Alcohol and Drug Research (SIRUS) 2016 > Norwegian Institute of Public Health Expert witness Four tort liability lawsuits against the tobacco industry Norwegian state vs Philip Morris inc. (tobacco display ban) New Nicotine Alliance (EU snus ban) Swedish Match vs Norwegian (plain packaging)

4 Conflict of interest: - KEL is employed by a Government entity answerable to the Ministry of Health and Care Services - KEL has no ties to pharmaceutical or tobacco industry kelu@fhi.no

5 Portion packed small sachets (75% market share and increasing) Loose snus (25% market share declining) Tobacco free snus (new nicotine product)

6 Sweden: Regulated as a food product since 1971 Norway: Regulated as a tobacco product since 1973 EU: Banned since 1992

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8 Snus very different from the unregulated African, Asian and most American smokeless tobacco as regards toxicants Maximum levels for unwanted substances (nitrosamines, benzo(a)pyrene, heavy metals, mycotoxins etc..) Levels are below those set by the WHO for smokeless tobacco products (STPs) Contradiction: Many STPs currently allowed under TPD 2014 (EU) contain much higher levels of unwanted substances than snus Inappropriate to consider STPs as a single product, still.

9 Flaws & misinformation #1: Lumping Smokeless Tobacco Products (STP) together when reviewing the health effects Authoritative systematic reviews Small focus on risk differential in authoritative systematic reviews (including IARC) until 2005 Continuum of risk between STP products now recognized by FDA, WHO, RCP and others Scandinavian snus at the lower end of the risk scale Acceptance of risk difference, still not reflected in a risk proportionate regulation/taxation Media & health information Confusing messages on risk difference (oral cancer, gum disease, tooth loss, etc.)

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11 Product: Relative risk vs non user Gutkha 8.67 (95% CI = 3.59 to 20.93) Pan tobacco/betel liquid 7.18 (95% CI = 5.48 to 9.41) Oral snuff 4.18 (50% CI = 2.37 to 7.38) Mainpuri tobacco 3.32 (95% CI = 1.32 to 8.36) Snus 0.86 (95% CI = 0.58 to 1.29)

12 Flaws & misinformation # 2 Snus is no safe alternative to cigarettes Labels on snus from 1986 in the US: This product is no safe alternative to cigarettes Interpretation by recipients: Snus is not a safer alternative to cigarettes Wackowski et al (2016), Liu et al (2015), Kozlowski (2018) if no difference, I might as well smoke

13 Framework for assessments of risk difference Toxicological studies (chemical composition) Cell studies (cytotoxicity) Clinical studies (pharmacokinetics) Epidemiological studies (long term) Strength of evidence Cigarettes Yes Yes Yes Yes Robust Snus Yes Yes Yes Yes Strong NRT Yes Yes Yes Short term Strong E cigarettes Yes Yes Yes No Moderate HnB Yes Few Few No Weak

14 Smoking cause more than one in ten deaths worldwide, killing more than 6 million people annually Approximately 2 of 3 lifelong smokers will die from a smoking related disease From what diseases do smokers die?

15 WHEN SMOKERS DIE FROM A SMOKING RELATED DISEASE.. USA COPD/respiratory 26% CVD 35% Other cancer 8% Diabetes 2% Lung cancer 29%

16 WHEN SMOKERS DIE FROM A SMOKING RELATED DISEASE.. Not related to snus COPD/respiratory 26% CVD 35% Snus not associated with new cases Excess risk of fatal outcomes for CVD patients Other cancer 8% Inconsistent evidence for pancreas, espohagus, oral & stomach Lung cancer 29% Not related to snus Diabetes 2% Excess risk from intensive use of snus only

17 Snus has weak or no relation to those diseases that are killing 2/3 of the smokers Snus is not the cause of unique diseases beyond those affecting smokers In the few diseases affecting both smokers and snus users (eg diabetes) the risk is generally lower for snus users But what has been the message from the tobacco control community?

18 Health warning label should be replaced. This product is not riskfree, but harmful effects are considerably smaller than cigarettes Warning labels needs to be judged by its interpretation by recipients Kozlowski 2018

19 Flaws & misinformation # 3 Market entrance on of snus/e cigarettes will increase the overall tobacco/nicotine consumption Alleged mechanisms: Non smokers: Recruit users who in the absence of these products would remain nicotine free Smokers: Dual use of THR products and cigarettes Reduce quit rates for cigarette smoking Former smokers: Resumed nicotine use

20 Flaws & misinformation # 3 Market entrance on of snus/e cigarettes will increase the overall tobacco/nicotine consumption Alleged mechanisms: Non smokers: Recruit users who in the absence of these products would remain nicotine free Smokers: Dual use of THR products and cigarettes Reduce quit rates for cigarette smoking Former smokers: Resume nicotine use

21 35 Daily use of snus, men and women, years, Per cent Men Women

22 35 Daily use of snus, men and women, years, Per cent Men Women

23 gram pr capita gram pr capita

24 60 Daily smoking, men and women, years, Per cent Men Women

25 Flaws & misinformation # 4: The decline in smoking would have occurred irrespective of snus Implying: snus has only minor substitutional functions for cigarettes What does the data tell us about substitution?

26 Indications of snus as a substitute for cigarettes Snus is the most frequently used method of quitting smoking In regions where snus use is widespread smoking tend to be low In age groups where snus use is prevalent smoking is low Dual users state smoking cessation as the most frequent motive for extra snus use Quit rates for smoking is higher among smokers who uses snus than among exclusive smokers Young snus users have characteristics that predispose for smoking

27 Aids used in most recent quit attempt for smoking Norway SNUS GP/Nurse Champix/Zyban Web site Quit line

28 Indications of snus as a substitute for cigarettes Snus is the most frequently used method of quitting smoking Former smokers make up the largest segment among snus users (Lund et al 2017, Lund et al 2010, Lund & McNeill 2012, Ramström & Foulds 2006, Giljam & Galanti 2003, Norberg et al 2110, Norberg et al 2011, Stenbeck et al 2009, Rodu et al 2002, 2003, Stegmayr et al 2005, Lindström et al 2002, 2007, Furberg et al 2008) Dual users state smoking cessation as the most frequent motive for additional snus use Quit rates for smoking is higher among smokers who uses snus than among exclusive smokers (Lund et al 2010, Lund & McNeill 2012, Ramström & Foulds 2006, Giljam & Galanti 2003, Norberg et al 2110, Norberg et al 2011, Stenbeck et al 2009, Rodu et al 2002, 2003, Stegmayr et al 2005, Lindström et al 2002, 2007, Furberg et al 2008) In regions and age groups where snus use is prevalent smoking tend to be low Young snus users have many of the characteristics that predispose for smoking

29 User configuration: Ever-snus users across smoking status Current snus users, former smokers Never-smokers Former smokers Dual users Lund KE, Vedoy TF, Bauld L. (2017)

30 Indications of snus as a substitute for cigarettes Snus is the most frequently used method of quitting smoking Former smokers make up the largest segment among snus users (Lund et al 2017, Lund et al 2010, Lund & McNeill 2012, Ramström & Foulds 2006, Giljam & Galanti 2003, Norberg et al 2110, Norberg et al 2011, Stenbeck et al 2009, Rodu et al 2002, 2003, Stegmayr et al 2005, Lindström et al 2002, 2007, Furberg et al 2008) Dual users state smoking cessation as the most frequent motive for additional snus use Quit rates for smoking is higher among smokers who uses snus than among exclusive smokers (Lund et al 2010, Lund & McNeill 2012, Ramström & Foulds 2006, Giljam & Galanti 2003, Norberg et al 2110, Norberg et al 2011, Stenbeck et al 2009, Rodu et al 2002, 2003, Stegmayr et al 2005, Lindström et al 2002, 2007, Furberg et al 2008) In regions and age groups where snus use is prevalent smoking tend to be low Young snus users have many of the characteristics that predispose for smoking

31 Lund I & Lund KE (2014). How has the availability of snus influenced cigarette smoking in Norway? Int. J. Environ. Res. Public Health. 2014; 11. Quit rates for smoking: Snus+cigarettes Cigarettes only

32 Indications of snus as a substitute for cigarettes Snus is the most frequently used method of quitting smoking Former smokers make up the largest segment among snus users Dual users state smoking cessation as the most frequent motive for additional snus use Quit rates for smoking is higher among smokers who uses snus than among exclusive smokers In sub populations where snus use is prevalent smoking tend to be low (and vice versa) Young snus users have many of the characteristics that predispose for smoking

33 Flaws & misinformation # 5: The low prevalence of smoking in Sweden and Norway is solely due to the robust infrastructure for tobacco control in these countries

34 The Tobacco Control Scale 2016 in Europe (Association of European Cancer Leagues)

35 Smoking prevalence Smoking prevalence (2017) vs Tobacco Control Score (2016) in Europe Eurobarometer March 2017; 458: 11 & Ass. Eur Cancer Leagues 2017 Greece Denmark Spain Poland Netherlands Sweden Finland Norway France Iceland Irland Outliers UK Tobacco Control Score (2016)

36 Flaws & misinformation # 6 Snus/e cigs will recruit users who in the absence of these products would remain nicotine free What does the data tell us about use among never smokers?

37 Flaws & misinformation # 6 Snus/e cigs will recruit users who in the absence of these products would remain nicotine free 1) What is the prevalence of snus use/vaping among never smokers? Base: all never smokers 2) What is the fraction of never smokers among vapers and snus users? Base: all users of snus/e cig

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39 Prevalence of daily snus use among never smokers Norwegian males aged years Source: SSB/NIPH

40 Prevalence of daily snus use among never smokers and ever smokers Norwegian males aged years Source: SSB/NIPH Never smokers

41 Flaws & misinformation # 6 Snus/e cigs will recruit users who in the absence of these products would remain nicotine free 1) What is the prevalence of snus use/vaping among never smokers? Base: all never smokers 2) What is the fraction of never smokers within the group of vapers/snus users? Base: all users of snus/e cig

42 User configuration: Ever-snus users across smoking status Current snus users, former smokers Never-smokers current snus users former snus user Former smokers Dual users Lund KE, Vedoy TF, Bauld L. (2017)

43 Flaws & misinformation # 7 Snus (and e cigs) serve as a gateway to cigarette smoking Examples of bad research: Submission Tobacco Control : Changes in tobacco use among Norwegian men from adolescence to young adulthood Submission BMJ Open : Use of snus during late adolescence predicts cigarette smoking in early adulthood among Finnish young men

44 Characteristics of the gateway papers : Longitudinal design, following the same adolescents over period of time Results: Snus use at baseline was associated with smoking at follow up Authors interpretation: snus causes smoking onset Authors implication: increasing snus availability will counter public health policies aiming for a smoke free society Both papers rejected by the reviewers why?

45 Rejection based on: 1. Failing to address reverse gateway 2. Equating association with causality 3. Failing to address the Common liability theory 4. Residual uncorrected confounding 5. Failure to identify/discuss plausible causal mechanisms 6. Unclear operationalization of the variables 7. Failure to control for smoking prior to snus use 8. Small samples very few exposed to snus, even fewer making the transitions to cigarettes

46 Alcohol use Parental smoking Snus yes no R 2 Correlation Smoking Best friend smoking Baseline Follow up T I M E

47 Rejection based on: 1. Omission of the reverse gateway perspective Unilaterally examination in direction Snus > Smoking onset The researchers did not address how uptake of snus modified smoking even if data allowed such an analysis even if the transition from cigarettes to snus was greater than vice versa

48 Alcohol use Snus use Parental Smoking Smoking yes no Tobacco use outcome Dual use Smoking only Snus only Tobacco free Best friend smoking Baseline Follow up T I M E

49 Rejection based on: 1. Failing to address multiple outcomes; Unilaterally examination in direction Snus > Smoking onset Overlook the beneficial reverse gateway; Smoking > Snus > Switching product 2. Equating association with causality E.g. truancy, early sexual debut, shoplifting also associated with smoking onset But do these variables cause smoking onset? In order to claim causation, the authors must demonstrate: The snus users who subsequently start to smoke, would have remained smoke free in the absence of snus Methodologically difficult to prove We do not know if these youngsters would have started to smoke without their experience with snus

50 Rejection based on: 1. Failing to address multiple outcomes; Unilaterally examination in direction Snus > Smoking onset Overlook the beneficial reverse gateway; Smoking > Snus > Switching product 2. Equating association with causality 3. Failing to address the Common liability theory ; both snus use and smoking are determined by the same risk factors (the association is spurious)

51 Personality traits Sexual debut Common liability Alcohol use Perceived risk SES Prior smoking Snus yes no Smoking Urbanity Aspirations Best friend smoking Truancy Baseline Follow up T I M E

52 Personality traits Sexual debut Residual confounding Alcohol use Perceived risk SES Drug use Snus yes no? Smoking Urbanity Aspirations Best friend smoking Truancy Baseline Follow up T I M E

53 Rejection based on: 1. Failing to address multiple outcomes. 2. Equating association with causality 3. Failing to address the Common liability theory 4. Residual uncorrected confounding 5. Comparing different groups? Youth experimentation with snus/vaping is perceived as a type of risk taking behaviour When these kids in longitudinal studies are compared to kids who, for some reason, refrain from any experimentation with snus/e cigs, we are at risk of comparing groups who probably are different on a wide range of variables besides snus use/vaping

54 Are we comparing the good guys with the bad guys? Snus Smoking? Comparison Non Snus Smoking?

55 Rejection based on: 1. Failing to address multiple outcomes. 2. Equating association with causality 3. Failing to address the Common liability theory; 4. Comparing different groups? 5. Failure to identify plausible causal mechanisms of the association Snus Mediating links? Smoking

56 Plausible causal mechanisms: Use of snus teaches the body & brain motoric and sensory patterns that facilitate smoking? Use of snus is a ticket to communities where cigarettes are available? Indirect link Not use of the product per se Use of snus initiate an appetite for faster nicotine uptake? No difference in plasma nicotine level between smoking and snus use Use of snus may cause cigarettes to appear less risky? Larsen, Rise Lund (2012): snus did not influence cognitions known to promote smoking initiation

57 Rejection based on: 1. Failing to address multiple outcomes. 2. Equating association with causality 3. Failing to address the Common liability theory; 4. Comparing different groups? 5. Uncorrected residual confounding 6. Failure to identify/discuss plausible causal mechanisms 7. Unclear operationalization of the variables what is considered use?

58 Snus Experimentation Weekly use Regular use Smoking Experimentation? Weekly use? Daily use? Baseline Follow up T I M E

59 Rejection based on: 1. Failing to address multiple outcomes. 2. Equating association with causality 3. Failing to address the Common liability theory; 4. Uncorrected residual confounding 5. Comparing different groups? 6. Failure to identify/discuss plausible causal mechanisms 7. Unclear operationalization of the variables 8. Failure to control for smoking prior to snus use

60 Relapse to smoking Smoking history Snus To quit smoking? Smoking Baseline Follow up T I M E

61 Rejection based on: 1. Failing to address multiple outcomes. 2. Equating association with causality 3. Failing to address the Common liability theory; 4. Uncorrected residual confounding 5. Comparing different groups? 6. Failure to identify/discuss plausible causal mechanisms 7. Unclear operationalization of the variables 8. Failure to control for smoking prior to snus use 9. Small samples very few exposed to snus, even fewer making the transitions to cigarettes. (miss match between empirical basis and political implication)

62 Public Health England (2015): «we strongly suggest that use of the gateway terminology be abandoned until it is clear how the theory can be tested in this field»

63 Let s look at it this way. If there is a meaningful impact from a gateway effect, then we would expect that the increase in snus use/vaping would increase smoking among adolescents (or curb the decline). But has it.? No, the opposite has been the case

64 Use of snus and cigarettes (daily + occasionally) in the age-group years Males (Two-yearly moving average) Females Cigarettes Snus Cigarettes Snus

65 Flaws & misinformation What the data suggest Comment Lumping all SLT together Huge risk difference between SLT Snus on the lower end of the risk scale products Snus is no safe alternative to cigarettes Interpreted as no risk difference Huge difference. Warnings cementing existing misperceptions THR products will increase the overall tobacco/nicotine consumption THR products will recruit never smokers On the contrary E cig: no Snus: to some degree Snus & e cig have several substitutional functions The share of never smokers among users must be irrationally high to tip the public health effect to negative THR products are a gateway to smoking Association but causation? Gateway concept should be abandoned THR products will result in widespread poly product use of nicotine THR products will reduce quit rates for cigarette smoking Decline in smoking is mainly caused by tobacco control measures Snus: Dual use is small E cig: Dual use is widespread Snus: on the contrary E cig: no Scandinavia: snus clearly contributes to the decline Dual use a transient or stable phenomenon? Lower cigarette consumption among dual users Randomised Controlled Trials unfit when studying effect of recreational nicotine products in smoking cessation

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68 Flaws & misinformation # 8 Dual use will increase the overall tobacco consumption Mechanisms: 1) The prevalence of dual use will increase over time 2) Dual users will consume more tobacco than smokers who exclusively smoke cigarettes

69 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Dual use of snus and cigarettes Male Norwegians, aged 16-74, Tobacco free Snus only Cigarettes only Dual use

70 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Dual use of snus and cigarettes Female Norwegians, aged 16-74, Tobacco free Snus only Dual use Cigarettes only

71 Smoking intensity Cigarettes per week: Only cigarettes 81 (95% CI 78-84) Cigarettes and snus 57 (95% CI 52-63) Compared to dual users, exclusive cigarette smokers consume 42% more cigarettes Lund, Bauld & Vedøy 2017 Consistent with Hatsukami et al 2004, Tomar 2002, Gilljam & Galanti 2003, Lund et al 2010, Ramström & Foulds 2006, Carpenter & Gray 2010, Rae Olmsted 2011

72 What determine the quit smoking effectiveness of snus/e cigs in the real world? Effectiveness = Use * Efficacy

73 Flaws & misinformation What the data suggest Comment Lumping all SLT together Huge risk difference between SLT Snus on the lower end of the risk scale products Snus is no safe alternative to cigarettes Interpreted as no risk difference Huge difference. Warnings cementing existing misperceptions THR products will increase the overall tobacco/nicotine consumption THR products will recruit never smokers On the contrary E cig: no Snus: to some degree Snus & e cig have several substitutional functions The share of never smokers among users must be irrationally high to tip the public health effect to negative THR products are a gateway to smoking Association but causation? Gateway concept should be abandoned THR products will result in widespread poly product use of nicotine THR products will reduce quit rates for cigarette smoking Decline in smoking is mainly caused by tobacco control measures Snus: Dual use is small E cig: Dual use is widespread Snus: on the contrary E cig: no Scandinavia: snus clearly contributes to the decline Dual use a transient or stable phenomenon? Lower cigarette consumption among dual users Randomised Controlled Trials unfit when studying effect of recreational nicotine products in smoking cessation