11

Reassessment of the Long-term Mortality Risksof Active and Passive Smoking

1) “The Long-term Mortality Risks of Active Smoking and the Need for a Reassessment” James E. Enstrom, Ph.D., UCLA

2) “Reassessment of the Mortality Risks of Passive Smoking in the United States”Geoffrey C. Kabat, Ph.D., Einstein College of Medicine, New York

3) “Silencing of Science: The Phenomenon and Its Impact on Passive Smoking Epidemiology”Sheldon B. Ungar, Ph.D., University of Toronto

4) Additional Discussion: “Trofim Denisovich Lysenko and Pseudoscience in the Soviet Union (1927-1962)”

22

Rationale for Symposium

1) Important epidemiologic findings regarding active and passive smoking have been ignored or mischaracterized in prior assessments

2) Rigorous scientific principles require that all epidemiologic findings must be fairly and consistently assessed

3) “Silencing” of politically incorrect epidemiologic findings is ethically and scientifically wrong

4) The credibility of epidemiology is seriously damaged when ideology and politics replace rigorous scientific principles

33

Goals for Symposium

1) To present evidence that the long-term mortality risks of active smoking are greater than generally believed and the long-term mortality risks of passive smoking are less than generally believed

2) To establish the credibility of this largely ignored or mischaracterized epidemiologic evidence

3) To make the case that future research and future assessments need to be conducted objectively and transparently, free of ideology and politics

44

17 May 2003 British Medical Journal

55

Background on Enstrom

33 years of epidemiologic research at UCLA

28 years of conducting and/or analyzing prospective epidemiologic cohorts:

California MormonsCalifornia PhysiciansPrevention Magazine SubscribersAlameda County Study CohortUnited States Veterans CohortNHANES Epidemiologic Followup Study CohortCalifornia Cancer Prevention Study Cohort

Themes: low-risk subgroups and different perspectives

66

California Cancer Prevention Study

1) 1,078,000 total subjects in 25 states enrolled by American Cancer Society with late 1959 questionnaire and followed for mortality during 1960-1972 (CPS I)

2) 118,000 California subjects followed for mortality during 1960-1998 and a 1999 questionnaire survey--at UCLA with special permission from ACS (CA CPS I)

3) This is the largest epidemiologic cohort followed for at least 39 years

77

Need for Reassessment Regarding Active Smoking

1) BMJ Table 10 shows strong 39-year relationship between active smoking and lung cancer

2) 90% reduction in US tar-adjusted per capita cigarette consumption

3) Continuing high US lung cancer death rate with 160,000 deaths per year

4) Population impact of smoking cessation not fully understood or evaluated

88

BMJ Table 101960-1998 Active Smoking and Lung Cancer Deaths

Late 1959 Males Femalessmoking status RR (95% CI) RR (95% CI)

Never 1.0 1.0 Former 3.5 (2.8-4.4) 1.5 (1.1-2.0)Current

1-9 cpd 4.1 (2.9-5.8) 2.0 (1.5-2.6)10-19 7.9 (6.1-10.1) 5.1 (4.2-6.1)20 12.5 (10.0-15.6) 9.1 (7.7-10.8) 21-39 16.4 (13.0-20.8) 15.1 (12.3-18.7) 40-80 18.7 (14.5-24.0) 15.8 (11.8-21.1)

All current 11.9 (9.6-14.7) 6.2 (5.4-7.2)

99

1900-2005 U.S. Per Capita Cigarette Consumption 1900-2005 U.S. Per Capita Cigarette Consumption and Tar-Adjusted Consumptionand Tar-Adjusted Consumption

Data source: Tobacco Outlook Report, Economic Research Service, U.S. Dept. of Agriculture.

Number of cigarettes

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000

Year

Per capita

Tar adjusted

1010

1930-2005 U.S. Age-adjusted Lung Cancer Death Rates1930-2005 U.S. Age-adjusted Lung Cancer Death Rates

Data Source: NCHS Vital Statistics; Death rates are age-adjusted to 2000 US standard population.

Deaths per 100,000

0

10

20

30

40

50

60

70

1930 1940 1950 1960 1970 1980 1990 2000

Year

Total population

Never smokers

1111

Conventional Benefits of Smoking Cessation (Enstrom & Heath EPIDEMIOLOGY 1999)

CA CPS I MalesLung cancer death rate ratios by smoking status at entry

1960-1969 Late 1959 smoking status Death Rate Ratio

Current 12.3 Former Quit < 1 year (1959) 13.0 Quit 1-4 years (1955-58) 8.9 Quit 5-9 years (1950-54) 4.7 Quit 10-19 years (1940-49) 2.7 Quit 20+ years (<1939) 1.8

Never 1.0

1212

Natural Experiment of Smoking Cessation(Enstrom & Heath EPIDEMIOLOGY 1999)

Cigarette smoking prevalence among CA CPS I subjects who smoked in late 1959, based on follow-up surveys of survivors.

Sex 1959 1965 1972 1999

Males 100% 74% 51% 7%

Females 100% 86% 66% 7%

1313

Natural Experiment of Smoking Cessation(Enstrom & Heath EPIDEMIOLOGY 1999)

Relative risk of lung cancer death in CA CPS I cohort:41,000 current cigarette smokers as of late 1959 compared with 50,000 never smokers

Follow-up period (by decade)

Sex 1960-1969 1970-1979 1980-1989 1990-1997

Males 12.6 12.1 12.5 10.2 (7.9-20.2) (8.1-18.0) (8.5-18.4) (6.1-17.0)

Females 2.5 6.3 7.0 7.8 (1.7-3.8) (4.7-8.3) (5.4-9.0) (5.8-10.4)

1414

AdditionalNatural Experiments of Smoking Cessation

1) US Veterans Study: 106,000 males followed 1954-1979 (Enstrom J Clin Epi 1999)

2) NHEFS: 700 males & 1100 females followed 1971-1992(Enstrom J Clin Epi 1999)

3) Iowa Women’s Health Study: 37,000 women 1986-1999“decline in excess lung cancer risk among former smokers is prolonged compared with other studies . . . excess lung cancer risk persisted up to 30 years”

(Ebbert, et al. J Clin Oncol 2003)

1515

Randomized Controlled Trials WithA Smoking Cessation Intervention

1) Whitehall Civil Servants Study1,445 high risk male smokers from London advised in 1970

(JECH 1978, JECH 1982, JECH 1992)

2) Multiple Risk Factor Intervention Trial (MRFIT)12,866 high risk US males enrolled in 1972

(JAMA 1982, Circulation 1996, Ann Epi 1997)

3) Lung Health Study (LHS)5,887 US/CN male and female smokers enrolled in 1986

(JAMA 1994, AJRCCM 2002, AIM 2005)

1616

Smoking cessation in three RCTs:intervention group (I) versus control group (C)

Intervention Average Cessation Study period (years) during intervention period Intervention Control

Whitehall 1 ~60% ~25%

MRFIT 6 ~45% ~20%

LHS 5 ~35% ~15%

1717

Initial RCT lung cancer deaths andrelative differences, (I-C)/C, and 95% CI (%)

Study Follow-up years Lung cancer deaths (I-C)/C & 95% CI I C (%)

Whitehall* 10.5 22 ~24* - 8.3

MRFIT 7 34 28 +21.4

LHS 5 20** 19 + 5.3

TOTAL 76 71 + 7.0 (-15.5 to +33.7)

*deaths & incident cases, which are scaled (714/731) **only “special intervention—placebo” group included

1818

Full RCT lung cancer deaths andrelative differences, (I-C)/C, and 95% CI (%)

Study Follow-up years Lung cancer deaths (I-C)/C & 95% CI I C (%)

Whitehall* 20 45 ~50* - 10.0

MRFIT 16 135 117 +15.0

LHS 14.5 77** 89 - 13.5

TOTAL 257 256 + 0.4 (-11.5 to +13.5)

*deaths & incident cases, which are scaled (714/731) **only “special intervention—placebo” group included

1919

Tobacco Smoke and Involuntary SmokingIARC Monographs on the Evaluation of

Carcinogenic Risks to Humans, Volume 83May 2004        1452   pages

Coverage of Smoking Cessation

1) Standard comparison of lung cancer rates among former smokers, current smokers, and never smokers

2) Nothing on population impact versus successful quitters

3) Nothing on “natural experiments”

4) Nothing on randomized controlled trials

2020

THE HEALTH BENEFITS OF SMOKING CESSATION

A Report of the Surgeon General 1990(628 pages)

PREFACE BY THE SURGEON GENERAL“Taken together, the evidence clearly indicates that smoking cessation has major and immediate health benefits for men and women of all ages.” MAJOR CONCLUSIONS“ the health consequences of smoking cessation for those who quit smoking in comparison with those who continue to smoke:1. Smoking cessation has major and immediate health benefits for men and women of all ages.”

2121

SUMMARY: Active Smoking & Cessation

Long-term mortality risk of lung cancer due to active smoking is greater than generally believed because it less reversible by cessation than generally believed based on evidence presented

1) The lung cancer mortality risk ratios for self-selected former smokers compared with never smokers do not accurately reflect the population impact of smoking cessation

2) Long-term “natural experiments” in cohorts within the United States do not show convergence of smoker and never smoker death rates in spite of substantial smoking cessation

3) Randomized controlled trials involving smoking cessation do not show a significant reduction in lung cancer deaths in the intervention groups relative to the control groups

2222

Factors Impeding Reassessment

1) Complex Issue: population impact of cessation versus focus on successful quitters

2) “Wrong Message”: negative findings supposedly discourage smokers from quitting

3) Uncertainty: implies lung cancer etiology and benefits of cessation are not completely understood

4) “Silencing”: ignored in major consensus reports and general information to the public

5) “Conflict of Interest”: some of the above research has been funded by the tobacco industry

2323

May 2006 EPIDEMIOLOGY

Lead Editorial: “On Conflicts of Interest”

Five Commentaries: “Kafka's Truth-seeking Dogs” “What to Declare and Why?” “He Who Pays the Piper, Calls the Tune…” “Why Focus Only on Financial Interests?” “A Conflict-of-Interest Policy for Epidemiology”

2424

Conflict of Interest & BMJ Paper

1) Because the final portion of the funding for the CA CPS I study came from the tobacco industry, attention was diverted from the substance of the BMJ paper to allegations of tobacco industry influence

2) Because the BMJ findings do not fit the anti-smoking advocacy agenda, the ACS and key anti-smoking activists have conducted an

ongoing campaign of ad hominem attack, character assassination, and “silencing” with regard to Enstrom & Kabat

3) Most troubling are the false and misleading statements made about the BMJ paper by certain powerful US epidemiologists, which will be

presented following the discussion of Lysenko & Soviet pseudoscience

4) The Enstrom & Kabat experience illustrates the difficulty of conducting “politically incorrect” tobacco epidemiology

2525

Reassessment of the Mortality Reassessment of the Mortality Risks ofRisks of

Passive Smoking in the United Passive Smoking in the United StatesStates

Geoffrey C. Kabat, Ph.D.Geoffrey C. Kabat, Ph.D.

2626

2727

BackgroundBackground

ETS contains many carcinogens and toxins ETS contains many carcinogens and toxins

exposure is widespread and involuntaryexposure is widespread and involuntary

active smoking is a major cause of active smoking is a major cause of avoidable morbidity and mortalityavoidable morbidity and mortality

2828

Environmental tobacco smokeEnvironmental tobacco smoke

ETS is a mixture of sidestream smoke from the ETS is a mixture of sidestream smoke from the burning tip of the cigarette (70-90%) and exhaled burning tip of the cigarette (70-90%) and exhaled mainstream smoke (10-30%). Over time the mainstream smoke (10-30%). Over time the mixture ages and is deposited on surfaces.mixture ages and is deposited on surfaces.

ETS is both different qualitatively and much more ETS is both different qualitatively and much more dilute than the smoke the active smoker inhales -- dilute than the smoke the active smoker inhales -- how much more dilute? 1/10how much more dilute? 1/10thth? 1/100? 1/100thth? ? 1/1,0001/1,000thth? ?

the effects of ETS can only be studied in never the effects of ETS can only be studied in never smokerssmokers

2929

Need for reassessment of passive Need for reassessment of passive smokingsmoking

implausible that ETS could cause a 30% increase implausible that ETS could cause a 30% increase in CHD risk given that ETS is much more dilute in CHD risk given that ETS is much more dilute than actively inhaled smoke and RR for active than actively inhaled smoke and RR for active smoking is ~1.8-2.0smoking is ~1.8-2.0

strength of association depends on which studies strength of association depends on which studies are included in meta-analysisare included in meta-analysis

issue is difficult to assess objectively because of issue is difficult to assess objectively because of enormous political stakesenormous political stakes

3030

Meta-analyses of ETS and LCMeta-analyses of ETS and LC

RRRR 95% CI95% CI

US EPA (1992) – US studiesUS EPA (1992) – US studies 1.191.19 (1.04-1.35)* (1.04-1.35)*

Hackshaw et al. Hackshaw et al. BMJBMJ (1997) (1997) 1.231.23 (1.13-1.34) (1.13-1.34)

IARC (2004) -- femalesIARC (2004) -- females 1.24 (1.14-1.34) 1.24 (1.14-1.34)

IARC (2004) – malesIARC (2004) – males 1.37 (1.02-1.83)1.37 (1.02-1.83)

*90% CI*90% CI

3131

Meta-analyses of ETS and CHDMeta-analyses of ETS and CHD

RRRR 95% CI95% CI

Law et al. Law et al. BMJBMJ (1997) (1997) 1.301.30 (1.22-1.38) (1.22-1.38)

He et al. He et al. NEJMNEJM (1999) (1999) 1.251.25 (1.17-1.32) (1.17-1.32)

Thun et al. Thun et al. EHSEHS (1999) (1999) 1.251.25 (1.17-1.33) (1.17-1.33)

3232

Estimates of US deaths due to ETSEstimates of US deaths due to ETS

Lung cancerLung cancer 3,000 -- 5,0003,000 -- 5,000

CHD CHD 35,000 – 60,000 35,000 – 60,000

3333

Follow-up of California CPS I cohortFollow-up of California CPS I cohort

followed for mortality from 1960 through 1998followed for mortality from 1960 through 1998

118,094 adults, of whom 35,561 were never-118,094 adults, of whom 35,561 were never-smokers with a spousesmokers with a spouse

ETS exposure based on smoking status of the ETS exposure based on smoking status of the spouse in 1959, 1965, & 1972spouse in 1959, 1965, & 1972

7,159 respondents to 1999 questionnaire provided 7,159 respondents to 1999 questionnaire provided assessment of their self-reported total ETS exposure assessment of their self-reported total ETS exposure

3434

3535

Deaths for analysis of active and passive Deaths for analysis of active and passive smoking – 1960-1998 smoking – 1960-1998

Total cohortTotal cohort Never Never smokerssmokers

CHDCHD 19,485 19,485 5,9325,932

Lung CancerLung Cancer 2,9702,970 156156

COPDCOPD 2,2432,243 264264

3636

Active smoking and CHD death, 1960-1998 Active smoking and CHD death, 1960-1998

MalesMalesFemalesFemales

Active smoking statusActive smoking status RR 95% CI RR 95% CI RR 95% CI RR 95% CI

Never smokedNever smoked 1.0 --- 1.0 --- 1.0 --- 1.0 --- Former smokerFormer smoker 1.2 (1.1-1.3) 1.0 (0.9-1.1) 1.2 (1.1-1.3) 1.0 (0.9-1.1) Current smokerCurrent smoker

• 1-9 cpd1-9 cpd 1.2 (1.1-1.3) 1.1 (1.0-1.2) 1.2 (1.1-1.3) 1.1 (1.0-1.2)• 10-1910-19 1.4 (1.3-1.5) 1.4 (1.3-1.5) 1.4 (1.3-1.5) 1.4 (1.3-1.5)• 20 20 1.6 (1.5-1.7) 1.8 (1.7-1.9) 1.6 (1.5-1.7) 1.8 (1.7-1.9)• 21-3921-39 1.8 (1.6-1.9) 2.0 (1.8-2.3) 1.8 (1.6-1.9) 2.0 (1.8-2.3)• 40-8040-80 1.9 (1.7-2.1) 1.9 (1.7-2.1) 2.4 (2.0-2.9) 2.4 (2.0-2.9)

All current smokersAll current smokers 1.5 (1.5-1.6) 1.5 (1.4-1.6) 1.5 (1.5-1.6) 1.5 (1.4-1.6)

3737

ETS and CHD death, 1960-1998ETS and CHD death, 1960-1998

MalesMales Females Females RR 95% CI RR 95% CIRR 95% CI RR 95% CI

All 1959 participantsAll 1959 participants followed 1960-98followed 1960-98

NeverNever 1.00 --- 1.00 --- 1.00 --- 1.00 ---FormerFormer 0.94 (0.78-1.12) 0.94 (0.78-1.12) 1.02 (0.93-1.11) 1.02 (0.93-1.11)CurrentCurrent 0.94 (0.75-2.22) 0.94 (0.75-2.22) 1.01 (0.93-1.09) 1.01 (0.93-1.09)

1-9 cpd 0.97 (0.78-1.21) 1.13 (0.97-1.33)1-9 cpd 0.97 (0.78-1.21) 1.13 (0.97-1.33) 10-1910-19 0.86 (0.70-1.05) 1.03 (0.91-1.17) 0.86 (0.70-1.05) 1.03 (0.91-1.17) 20 0.92 (0.74-1.15) 1.04 (0.92-1.16)20 0.92 (0.74-1.15) 1.04 (0.92-1.16) 21-39 1.16 (0.79-1.69) 0.95 (0.80-1.12)21-39 1.16 (0.79-1.69) 0.95 (0.80-1.12) 40+ 1.29 (0.75-2.22) 0.83 (0.65-1.06) 40+ 1.29 (0.75-2.22) 0.83 (0.65-1.06)

3838

Active smoking and lung cancer death, 1960-1998Active smoking and lung cancer death, 1960-1998

MalesMales FemalesFemalesActive smoking statusActive smoking status RR 95% CI RR 95% CI RR 95% CI RR 95% CI

Never smokedNever smoked 1.0 --- 1.0 --- 1.0 --- 1.0 --- Former smokerFormer smoker 3.5 (2.8-4.4) 1.5 (1.1-2.0) 3.5 (2.8-4.4) 1.5 (1.1-2.0) Current smokerCurrent smoker

• 1-9 cpd1-9 cpd 4.1 (2.9-5.8) 2.0 (1.5-2.6) 4.1 (2.9-5.8) 2.0 (1.5-2.6)• 10-1910-19 7.9 (6.1-10.1) 5.1 7.9 (6.1-10.1) 5.1 (4.2-6.1) (4.2-6.1)• 20 20 12.5 (10.0-15.6) 9.1 12.5 (10.0-15.6) 9.1 ( 7.7-10.8) ( 7.7-10.8) • 21-3921-39 16.4 (13.0-20.8) 15.1 (12.3-18.7) 16.4 (13.0-20.8) 15.1 (12.3-18.7)• 40-8040-80 18.7 (14.5-24.0) 18.7 (14.5-24.0) 15.8 (11.8-21.1) 15.8 (11.8-21.1)

All current smokersAll current smokers 11.9 (9.6-14.7) 6.2 (5.4-7.2) 11.9 (9.6-14.7) 6.2 (5.4-7.2)

3939

ETS and lung cancer death, 1960-1998ETS and lung cancer death, 1960-1998

MalesMales Females Females

RR 95% CI RR 95% CIRR 95% CI RR 95% CI

All 1959 participantsAll 1959 participants

followed 1960-98followed 1960-98

NeverNever 1.00 --- 1.00 --- 1.00 --- 1.00 ---

FormerFormer 0.92 (0.37-2.30) 0.92 (0.37-2.30) 1.08 (0.73-1.60) 1.08 (0.73-1.60)

CurrentCurrent 0.69 (0.34-1.39) 0.69 (0.34-1.39) 0.93 (0.65-1.33) 0.93 (0.65-1.33)

4040

Summary of BMJ resultsSummary of BMJ results

exposure to spousal smoking was not associated with exposure to spousal smoking was not associated with increased mortality from lung cancer or CHD (3 follow-up increased mortality from lung cancer or CHD (3 follow-up intervals)intervals)

exposure was weakly associated with increased mortality exposure was weakly associated with increased mortality from COPDfrom COPD

active smoking showed strong dose-response relationships active smoking showed strong dose-response relationships with lung cancer, CHD, and COPD (BMJ table 10)with lung cancer, CHD, and COPD (BMJ table 10)

4141

Conclusion of BMJ paperConclusion of BMJ paper

““The results do not support a causal relationship The results do not support a causal relationship between ETS and mortality, although they do not between ETS and mortality, although they do not rule out a small effect. The association between rule out a small effect. The association between ETS and CHD and lung cancer may be ETS and CHD and lung cancer may be considerably weaker than generally believed.”considerably weaker than generally believed.”

4242

American Cancer SocietyAmerican Cancer Society

ACS cohort studies CPS I and CPS II account for ACS cohort studies CPS I and CPS II account for the vast majority of data on ETS and CHDthe vast majority of data on ETS and CHD

ACS contends that CPS I cannot be used to ACS contends that CPS I cannot be used to address passive smoking because in 1960s address passive smoking because in 1960s everyone was exposedeveryone was exposed

4343

Response to ACS criticismsResponse to ACS criticisms

not true that everyone was exposed to ETS not true that everyone was exposed to ETS

majority of women in CA CPS I cohort were majority of women in CA CPS I cohort were “homemakers”“homemakers”

in their 1999 meta-analysis, Thun et al. saw in their 1999 meta-analysis, Thun et al. saw fit to include 2 cohort studies initiated in the fit to include 2 cohort studies initiated in the 1960’s1960’s

ACS has the ability to check our analysis for ACS has the ability to check our analysis for 1960-19721960-1972

4444

Misclassification of ETS exposureMisclassification of ETS exposure

spousal exposure may not reflect total ETS spousal exposure may not reflect total ETS exposure since there are other sources of exposureexposure since there are other sources of exposure

misclassification was lower in certain sub-groupsmisclassification was lower in certain sub-groups

1999 questionnaire showed that smoking status of 1999 questionnaire showed that smoking status of spouses was directly related to a history of total spouses was directly related to a history of total exposure to ETSexposure to ETS

misclassification was not sufficient to obscure a misclassification was not sufficient to obscure a true association between ETS & CHD, particularly true association between ETS & CHD, particularly in womenin women

4545

Spousal smoking vs. self-reported ETS exposure Spousal smoking vs. self-reported ETS exposure among CA CPS I never smokers -- femalesamong CA CPS I never smokers -- females

History of regular ETS exposure History of regular ETS exposure

as of 1999 (%)as of 1999 (%)

1959 spousal smoking1959 spousal smoking None None Light Moderate HeavyLight Moderate Heavy

NeverNever 62 24 11 3 62 24 11 3

Current 1-19 cigs/dayCurrent 1-19 cigs/day 26 26 29 29 39 39 6 6

Current 20-39 cigs/dayCurrent 20-39 cigs/day 20 20 21 21 41 18 41 18

Current 40+ cigs/dayCurrent 40+ cigs/day 16 13 48 24 16 13 48 24

Enstrom & Kabat, Enstrom & Kabat, BMJBMJ 2003 2003

4646

ETS and CHD: comparison of CA CPS I and CPS IIETS and CHD: comparison of CA CPS I and CPS II

FemalesFemales

Enstrom (CA CPS I)Enstrom (CA CPS I) Steenland (CPS II)Steenland (CPS II)Spousal smokingSpousal smokingNeverNever 1.001.00 ------ 1.00 ---1.00 ---FormerFormer 1.02 (0.93-1.11)1.02 (0.93-1.11) 1.00 (0.90-1.48)1.00 (0.90-1.48)CurrentCurrent

1-19 cpd1-19 cpd 1.07 (0.96-1.19)1.07 (0.96-1.19) 1.15 (0.90-1.48)1.15 (0.90-1.48)20 cpd20 cpd 1.04 (0.92-1.16)1.04 (0.92-1.16) 1.07 (0.83-1.40)1.07 (0.83-1.40)21-39 cpd21-39 cpd 0.95 (0.80-1.12)0.95 (0.80-1.12) 0.99 (0.67-1.47)0.99 (0.67-1.47)40+40+ 0.83 (0.65-1.06)0.83 (0.65-1.06) 1.04 (0.67-1.61)1.04 (0.67-1.61)

Current – totalCurrent – total 1.01 (0.93-1.09)1.01 (0.93-1.09) 1.10 (0.96-1.27)1.10 (0.96-1.27)EverEver 1.01 (0.94-1.08)1.01 (0.94-1.08) 1.04 (0.95-1.15)1.04 (0.95-1.15)

4747

New meta-analysis US CHD studiesNew meta-analysis US CHD studies

Enstrom & Kabat, Enstrom & Kabat, Inhalation Toxicology Inhalation Toxicology ((2006)2006)..

includes published studies of CPS I and CA CPS Iincludes published studies of CPS I and CA CPS I

applies consistent criteria for inclusion of resultsapplies consistent criteria for inclusion of results

RRRRcurrent/never current/never == 1.04 (0.99-1.10)1.04 (0.99-1.10)

RRRR ever/never ever/never = 1.04 (0.99-1.10)= 1.04 (0.99-1.10)

Thun et al., Thun et al., Environ Health Perspect Environ Health Perspect (1999)(1999)

RRRRexposed/not exposed exposed/not exposed = 1.22 (1.13-1.30)= 1.22 (1.13-1.30)

4848

Meta-analysis of US lung cancer studiesMeta-analysis of US lung cancer studies

case-control & cohort studiescase-control & cohort studies includes Enstrom & Kabat, 2003includes Enstrom & Kabat, 2003

RRRRever/neverever/never = 1.10 (1.00-1.21) = 1.10 (1.00-1.21)

4949

Jenkins, “16 Cities Study”Jenkins, “16 Cities Study”(1993-94)(1993-94)

100 nonsmokers in each of 16 metro areas 100 nonsmokers in each of 16 metro areas collected 24-hr air samples both at work and collected 24-hr air samples both at work and away from work using personal monitoringaway from work using personal monitoring

participants filled out questionnaires about their participants filled out questionnaires about their exposures and gave a pre- and post- saliva exposures and gave a pre- and post- saliva samplesample

samples were analyzed for 10 markers of ETS, samples were analyzed for 10 markers of ETS, including RSP and nicotineincluding RSP and nicotine

5050

5151

Estimates of ETS exposureEstimates of ETS exposure

JenkinsJenkins (1996):(1996): mean ETS exposure ~ mean ETS exposure ~ 8 8 cigarette equivalents/yearcigarette equivalents/year

Phillips (1998)Phillips (1998):: housewives with heaviest housewives with heaviest exposure could inhale up to exposure could inhale up to 11 cigarette 11 cigarette equivalents/yearequivalents/year

5252

Richard Peto testimony before House of LordsRichard Peto testimony before House of LordsFeb. 14, 2006Feb. 14, 2006

QuestionQuestion::

““Sir Richard, I wanted to start by asking if you could give us your Sir Richard, I wanted to start by asking if you could give us your assessment of the health risks associated with passive smoking in the assessment of the health risks associated with passive smoking in the home or at work and in other public places. It would be helpful if you home or at work and in other public places. It would be helpful if you could give us an indication of both absolute and relative magnitudes could give us an indication of both absolute and relative magnitudes of the health risks and also the degree of uncertainty attached to the of the health risks and also the degree of uncertainty attached to the available statistical evidence.” available statistical evidence.”

Peto’s responsePeto’s response: :

““I am sorry, I know that is what you would like to be given, but the point I am sorry, I know that is what you would like to be given, but the point is that these risks are small and difficult to measure directly. What is is that these risks are small and difficult to measure directly. What is clear is that cigarette smoke itself is far and away the most important clear is that cigarette smoke itself is far and away the most important cause of human cancer in the world – that is, cigarette smoke taken cause of human cancer in the world – that is, cigarette smoke taken in by the smoker – and passive smoking, exposure to other people’s in by the smoker – and passive smoking, exposure to other people’s smoke, must cause some risk of death from the same diseases. smoke, must cause some risk of death from the same diseases. Measuring that risk reliably and directly is difficult.”Measuring that risk reliably and directly is difficult.”

5353

Factors impeding reassessment of Factors impeding reassessment of effects of ETS on mortalityeffects of ETS on mortality

incomplete analysis of largest available data sets (CPS incomplete analysis of largest available data sets (CPS I and CPS II)I and CPS II)

minimal research fundingminimal research funding

publication bias against null findingspublication bias against null findings

ideological and political agendasideological and political agendas

5454

ConclusionsConclusions

Estimates of the association of ETS with CHD and Estimates of the association of ETS with CHD and lung cancer appear to have been overstated.lung cancer appear to have been overstated.

From the scientific and public health viewpoints, From the scientific and public health viewpoints, the focus should be on the very large and certain the focus should be on the very large and certain effects of active smoking rather than on the very effects of active smoking rather than on the very small and highly uncertain effects of passive small and highly uncertain effects of passive smoking.smoking.

5555

View of Major ETS ReportsView of Major ETS Reports

NAS 1986NAS 1986 Surgeon General 1986Surgeon General 1986

US EPA 1992US EPA 1992 California EPA 1986California EPA 1986

IARC 2004IARC 2004 California ARB 2005California ARB 2005

5656

5757

Additional slides—to be Additional slides—to be used during Lysenko used during Lysenko

sessionsession

5858

Silencing of Science: Silencing of Science: The Phenomenon and Its The Phenomenon and Its

Impact on Passive Smoking Impact on Passive Smoking EpidemiologyEpidemiology

Shelly UngarShelly Ungar

University of TorontoUniversity of Toronto

5959

Consider this… Consider this…

1 in 3 Americans is convinced 1 in 3 Americans is convinced

Darwinian evolution is “definitely Darwinian evolution is “definitely

false”false”

1 in 7 is convinced it’s true1 in 7 is convinced it’s true

6060

George Bush on Intelligent DesignGeorge Bush on Intelligent Design

““Teach the debate”Teach the debate”

Bumper sticker:Bumper sticker: • ““God Said It, I Believe It, and That God Said It, I Believe It, and That

Settles It.”Settles It.”

6161

Scientists as Secular ShamansScientists as Secular Shamans

Deliver the goodsDeliver the goods• Invested with authorityInvested with authority

But scientific authority is precariousBut scientific authority is precarious• No infallible sourceNo infallible source

IdeallyIdeally open to debate and revision open to debate and revision• Internal Internal disinteresteddisinterested debate debate

BUT…BUT…

6262

Vulnerable to “agenda science”Vulnerable to “agenda science”

PartisansPartisans• Not disinterested, or truth-seekingNot disinterested, or truth-seeking

unreasoned allegiance to belief or cause or unreasoned allegiance to belief or cause or $$

• aim to conscript science to own endsaim to conscript science to own ends use of a wide range of tacticsuse of a wide range of tactics

• Publication biasPublication bias Selective disclosureSelective disclosure

• silencingsilencing

6363

SilencingSilencing

efforts to prevent the making of efforts to prevent the making of specific scientific claims in arenas in specific scientific claims in arenas in which these claims are typically which these claims are typically reported.reported.

Range from gagging to Range from gagging to publication biaspublication bias• Can morph into Can morph into fraudfraud

(Note too: not all claims of silencing are valid)(Note too: not all claims of silencing are valid)

6464

State SilencingState Silencing

USSRUSSR LysenkoismLysenkoism

DenmarkDenmark Lomborg, The Skeptical EnvironmentalistLomborg, The Skeptical Environmentalist

US US Climate ScientistsClimate Scientists Reproductive issuesReproductive issues

CanadaCanada Climate ScientistsClimate Scientists

6565

Corporate SilencingCorporate Silencing

Pharmaceutical industryPharmaceutical industry VioxxVioxx PaxilPaxil

Food corporationsFood corporations aspartameaspartame

6666

Silencing by scientistsSilencing by scientists

Lomborg, Lomborg, The Skeptical EnvironmentalistThe Skeptical Environmentalist

Climate ScientistsClimate Scientists skepticsskeptics

AIDS research (?)AIDS research (?)

Tobacco researchTobacco research

6767

Silencing by advocatesSilencing by advocates

EnvironmentalistsEnvironmentalists Climate changeClimate change LomborgLomborg

Health authorities (& laypersons)Health authorities (& laypersons) Second-hand smokeSecond-hand smoke

6868

Enstrom, J., & Kabat, G. Enstrom, J., & Kabat, G.

Environmental tobacco smoke Environmental tobacco smoke and tobacco relatedand tobacco related

mortality in a prospective study of mortality in a prospective study of Californians, 1960Californians, 1960--98. 98.

British Medical Journal, British Medical Journal, 2003: 2003: 326326, 1057-1100., 1057-1100.

6969

Silencing skirmishes startSilencing skirmishes start

BMJ turns tabloid:BMJ turns tabloid:

Thanks for turning back the clock on public Thanks for turning back the clock on public health decades or more. We don’t need this health decades or more. We don’t need this kind of negligence from what used to be a kind of negligence from what used to be a professional medical publication. I seriously professional medical publication. I seriously wonder who got paid off at BMJ to publish this wonder who got paid off at BMJ to publish this utter garbage.utter garbage.Dale JackmanDale JackmanSeriously AnnoyedSeriously AnnoyedI won’t dignify this rag with my credentialsI won’t dignify this rag with my credentials

7070

0

2

4

6

8

10

12

14

16

18

# Rapid Responses

/Day

15 17 19 21 23 25 27 29 31 2 4 6 8 10 12 14 16 18 20 22 24

Dates (May 15-June 24)

Number of Rapid Responses on BMJ Web Site

7171

Level of ExpertiseEvaluation ofPublication

DecisionDecision ExpertExpert KnowledgeableKnowledgeable LaypersonLayperson**

TotalTotal

PositivePositive 55 1212 1111 2828

NegativeNegative 2020 4444 1919 8383

NeutralNeutral 66 1212 55 2323

TotalTotal 3131 6868 3535 134134

* Includes those who provide no credentials

7272

““Irresponsible Journalism”Irresponsible Journalism”

I was genuinely shocked to see this splashed across theI was genuinely shocked to see this splashed across thefront page of this week’s BMJ, tabloid-style. An industry-front page of this week’s BMJ, tabloid-style. An industry-sponsored, methodologically flawed study with inconclusive sponsored, methodologically flawed study with inconclusive results but with major potential public health implications results but with major potential public health implications especially once the press get hold of it. especially once the press get hold of it.

““Passive smoking may not kill.” How much would the Passive smoking may not kill.” How much would the tobacco industry pay for such a soundbite in a major peer-tobacco industry pay for such a soundbite in a major peer-reviewed journal? Since when did I pay my subscription reviewed journal? Since when did I pay my subscription so that you could do their dirty work for them?so that you could do their dirty work for them?

7373

Level of Expertise

Target of NegativeEvaluations Expert (N=20)Expert (N=20) "Knowledgeable" "Knowledgeable"

(n=44)(n=44)Layperson (n=19)Layperson (n=19)

Article per seArticle per se 44 1010 55

Flaw in the articleFlaw in the article 1515 1313 55

Tobacco/AuthorsTobacco/Authors 1010 2222 1313

Journal/EditorJournal/Editor 11 2424 1111

Media/PublicMedia/Public 33 2121 88

TotalTotal 3333 9090 4242

7474

“From hero to pariah in one easy jump”Richard Smith BMJ Editor May 18, 2003

“We long ago decided that we would not have a blanket policy of refusing to publish research funded by the tobacco industry, as some journals have done. Our argument was that a ban would be antiscience, systematically distorting the scientific record. . . . Once the research has been done it should be published, and if it passes our peer review process it can be published in the BMJ. . . .

I find it distrubing that so many people and organisatons --including the BMA, our owners-- refer to the flaws in the study without specifying what they are. . . .

We judged this paper to be a useful contribution to an important debate. We may be wrong as we are with many papers. That’s science. But I remain convinced that it would have been wrong to reject the paper simply because it was funded by the tobacco industry.”

7575

Fear of Media CoverageFear of Media Coverage

““The study has already been widely The study has already been widely cited by the lay press and is being cited by the lay press and is being used by the tobacco industry to block used by the tobacco industry to block public health efforts to enact smoke-public health efforts to enact smoke-free policies.”free policies.”

7676

& Use by Tobacco Industry & Use by Tobacco Industry

““As the industry is already As the industry is already demonstrating, this ‘result’ will be demonstrating, this ‘result’ will be pumped throughout the globe in pumped throughout the globe in industry PR, in the mouths of its front industry PR, in the mouths of its front organizations, as ‘controversy’ over organizations, as ‘controversy’ over passive smoking.”passive smoking.”

7777

Multi-pronged search of Multi-pronged search of international newspaper coverageinternational newspaper coverage

Not even a “blip” of coverageNot even a “blip” of coverage• Silencing by mediaSilencing by media

About 60 articles worldwideAbout 60 articles worldwide Minor papersMinor papers

• Gwinnett Daily PostGwinnett Daily Post, Georgia., Georgia.

7878

Interactive researchInteractive research

Email: Email: ““I can tell you that I have closely I can tell you that I have closely

followed the effects of this article in followed the effects of this article in the Dutch press. It's incredible how the Dutch press. It's incredible how little newspapers have reported on little newspapers have reported on this study. Only two Dutch this study. Only two Dutch newspapers have published it… this newspapers have published it… this E&K study looks to be self-censored E&K study looks to be self-censored by the public Dutch media” by the public Dutch media” (Maessen, (Maessen, ForcesForces).).

7979

Not “balanced” coverage Not “balanced” coverage

““A new study downplaying the effects of A new study downplaying the effects of secondhand smoke on the health of secondhand smoke on the health of smokers’ spouses is being condemned smokers’ spouses is being condemned even before it has appeared in print…” even before it has appeared in print…”

[It’s a] “pretty crappy piece of science”[It’s a] “pretty crappy piece of science”

Sacramento Bee Sacramento Bee (California)(California)

8080

4 articles defend publication4 articles defend publication

““To believe that second-hand smoke To believe that second-hand smoke may not be very harmful has become a may not be very harmful has become a thought-crime almost akin to Holocaust thought-crime almost akin to Holocaust denial. Those who dare express denial. Those who dare express doubts must expect hysterical abuse doubts must expect hysterical abuse from every point of the PC compass.”from every point of the PC compass.”

National Post National Post (Toronto) (Toronto)

8181

Misuse of the Study?Misuse of the Study?

Tobacco companiesTobacco companies Not trumpet it heavilyNot trumpet it heavily

Smoker’s rights groupsSmoker’s rights groups Enshrine as proof that threat is exaggeratedEnshrine as proof that threat is exaggerated

8282

The Washington Times

Ban the bansBy Jay AmbrosePublished March 26, 2006

…nonsmokers with easily offended nostrils and who are probably mostly ignorant of the most exhaustive research project ever completed on secondhand smoke.

The study involved 118,000 Californians. It followed their health history for four decades, and was conducted by highly respected scientists and published in the highly respected British Medical Journal. Here is what it said: There is no evidence of a "causal relationship" between "exposure" to tobacco smoke in the air around you and death. A "small effect" cannot be ruled out, the scientists reported, but that's it. Period.

8383

Misunderstand scienceMisunderstand science

No single study definitiveNo single study definitive

• Especially when dealing with “small risks” Especially when dealing with “small risks” researchresearch

• Same overestimation of ‘outlier’ climate studiesSame overestimation of ‘outlier’ climate studies

8484

Mismeasure of scienceMismeasure of science

Not covered by media because…Not covered by media because…

• Changes nothingChanges nothing

““regime of truth”regime of truth” surrounding smoking surrounding smoking

• Cannot be intelligibly questionedCannot be intelligibly questioned

• Not about dueling scientistsNot about dueling scientists

8585

Smokers are deviants of choiceSmokers are deviants of choice

Secondhand smoke Secondhand smoke created a created a moral moral panicpanic• Smokers as folk Smokers as folk

devilsdevils

8686

Google Alert Secondhand…Google Alert Secondhand… Study Finds DNA Risk From Study Finds DNA Risk From SecondhandSecondhand Casino Casino SmokeSmoke

Secondhand smokeSecondhand smoke can affect pets' health can affect pets' health

Exposing infants to Exposing infants to secondhandsecondhand smokesmoke could contribute to cancer risks could contribute to cancer risks later in lifelater in life

STAT Medical News: STAT Medical News: SecondhandSecondhand SmokeSmoke Detectable in Babies Detectable in Babies

Cigarette Cigarette smokesmoke, even , even secondhandsecondhand smokesmoke, can weaken bones, can weaken bones

Stroke Prevention…avoid exposure to Stroke Prevention…avoid exposure to secondhand smokesecondhand smoke

Secondhand smokeSecondhand smoke linked to acting out [by children] linked to acting out [by children]

Small children exposed to Small children exposed to secondhandsecondhand smokesmoke are more likely to develop are more likely to develop ear infections, upper respiratory infections and asthma.ear infections, upper respiratory infections and asthma.

A link exists between A link exists between secondhand smokesecondhand smoke and type 2 diabetes. and type 2 diabetes.

8787

Eurobarometer poll, 2005Eurobarometer poll, 2005

95% said smoking in the presence of a 95% said smoking in the presence of a pregnant woman could harm the baby pregnant woman could harm the baby

75% said they would not smoke in the 75% said they would not smoke in the presence of a child presence of a child

75% said they were aware smoke could be 75% said they were aware smoke could be dangerous for non-smokers dangerous for non-smokers

53% of people aged 15 to 24 were worried 53% of people aged 15 to 24 were worried about second-hand smokingabout second-hand smoking

8888

Eurobarometer poll, 2005Eurobarometer poll, 2005

SUPPORT FOR BANS SUPPORT FOR BANS • Office/indoor workplace: Office/indoor workplace: 86% 86% • Any indoor public space: Any indoor public space: 84% 84% • Restaurants: Restaurants: 77% 77% • Bars or pubs: Bars or pubs: 61%61%

8989

9090

Ministers accused of exaggerating risks of passive smoking

By JANE MERRICK, Daily Mail 08:50am 7th June 2006

Peers said the ban was not justified by the relatively low risks of passive smoking

Ministers exaggerated the risk of passive smoking to force through a blanket ban on lighting up in public, a report has claimed.

The Government ignored scientific research on the effects of secondhand smoke in enclosed public places, according to the report from the Lords economic affairs committee.

It says that the smoking ban, which comes into effect in all pubs, clubs and workplaces next summer, was a political decision by Labour's nanny state tendency - and not justified by the relatively low risk of passive smoking.

9191

Not long ago I was something of a hero of the antitobacco movement-- because I resigned my professorship at Nottingham University when it

accepted money from British American Tobacco. I felt somewhat embarrassed by the whole episode. I was no hero. But now I'm a pariah for publishing a piece of research funded by the tobacco industry. Because of some sort of personality defect that is common among editors I'm more

attracted to being a pariah than a hero, but I don't think that I deserve to be a pariah.

We long ago decided that we would not have a blanket policy of refusing to publish research funded by the tobacco industry, as some journals have

done. (1) Our argument was that a ban would be antiscience, systematically distorting the scientific record.

I would try to dissuade anybody from accepting tobacco company money, and I resigned from Nottingham because it did so. Isn't it thus hypocritical to

publish research funded by the industry? To my mind it isn't. With some difficulty, I'm setting the ethic that all science should be published above the

ethic that you shouldn't take money from the tobacco industry. Once the research has been done it should be published, and if it passes our peer

review process it can be published in the BMJ. Our way of making decision on research papers is first to ask if we are

interested in the question. We are certainly interested in the question of whether passive soming kills, and it's clear to us that the question has not

been definitively answered. Indeed, it may well never be answered definitively. It's a hard question,and our methods are inadequate. We then peer review the study. Two top epidemiologists-- including George Davey-

Smith--reviewed the paper. Then the paper went to our hanging committee, which always includes a statistician as well as practising doctors and some of

us. Everybody reads every word of every paper. We asked for extensive changes to the paper, and the paper we published was different from the

paper submitted--which is usually the case. We are planning to post on our website all the comments of the reviewers,

our statistician, and the hanging committee. I hope that they will be up soon after the weekend.

Of course the paper has flaws --all papers do-- but it also has considerable strengths-- long follow up, large sample size, and more complete follow up

than many such studies. I find it distrubring that so many people and organisatons --including the BMA, our owners-- refer to the flaws in the study

without specifying what they are. We judged this paper to be a useful contribution to an important debate. We may be wrong, as we are are with many papers. That's science. But I remain convinced that it would have been wrong to reject the study simply because

it was funded by the tobacco industry. Richard Smith Editor, BMJ

9292

Trofim Denisovich Lysenko & Pseudoscience in the Soviet Union

(1927-1962)

9393

Trofim Denisovich Lysenko was a self-promoting Soviet agronomist who invented a procedure called vernalization, which he claimed would lead to dramatically increased crop yields.

Lysenko's claims violated Mendelian genetics and never faced a rigorous test. However, Joseph Stalin was impressed because Lysenko promised improved agricultural output unbounded by hereditary constraints.

Lysenko was portrayed as a genius and rose rapidly in power and prestige with the backing of Stalin and the media. He was especially skillful at denouncing geneticists who disagreed with him as enemies of the state. The result was purges that sent hundreds of dissenting Soviet scientists to the gulags or killed.

9494

Lysenko and his theories dominated Soviet biology for over thirty years. However, vernalization never increased crop yields and there were two major famines that killed millions. Current Russian biology still has not entirely recovered from the Lysenko era.

This episode dramatizes the dangers of political ideology influencing science and of uncritical media promoting false concepts. A crude analogy can be made with certain aspects of tobacco epidemiology. With the goal of reducing smoking, activists exaggerate the dangers of passive smoking and attack scientists want to do objective work in this area. In this climate attention is diverted from the real dangers of active smoking and from a complete understanding of lung cancer etiology. And the lung cancer epidemic continues.

9595

Statement of Major Points of Symposium

1) all epidemiologic findings must be evaluated in a fair and consistent manner in order to obtain an accurate assessment of the mortality risks of active and passive smoking

2) epidemiologic findings must be judged on their merits and not on extraneous factors

3) additional epidemiologic research in this area needs to be conducted free of partisanship.