Tobacco Documents Online

Proposed R ar h on pa imokincr James E. Enstrom, Ph.D., M.P.H. May 22, 1996 OVERALL OBJECTIVES 1. Obtain original data for the four major U.S. case-control studies and reanalyze them in a standard way with respect to the relationship of lung cancer risk to passive smoking and determine the extent to which they are representative population-based studies. 2. Conduct survey similar to the 1986 National Mortality Followback Survey in Los Angeles County using UCLA.lung cancer patients since 1985 and recent county lung cancer deaths to establish independent results about passive smoking and lung cancer. Use national and state smoking surveys previously analyzed to construct control groups for case-control analysis. 3. Obtain new results from three major cohorts studies on the relationship of mortality from lung cancer and all causes to low levels of active smoking and to passive (spousal) smoking. 4. Establish clear statement of tobacco industry position of the health risks of active smoking to add credibility to the first three objectives.

MORTALITY PATTERNS AMONG U.S. VETERANS WHO SMOKE OCCASIONALLY: A PRELIMINARY ANALYSIS James E. Enstrom, Ph.D., M.P.H. School of Public Health University of California Los Angeles, CA 90024 January 24, 1996 ABSTRACT The relationship smoking-related mortality to five levels of occasional smoking is examined in a cohort of 245,000 U.S. veterans followed from 1954 through 1979. Proportional hazards regression analysis has been used to compare men who used tobacco occasionally with those who never used tobacco with respect to mortality from several causes of death. There does not appear to be a consistent relationship between the level of occasional smoking and mortality. This suggests that there may indeed be a threshold below which tobacco use is not related to total mortality. The nature of the relationship with lung cancer is harder to classify because of large statistical fluctuation, but there is no clear dose-response. These patterns need to be examined in other cohorts.

PASSIVE SMOKING AND MORTALITY AMONG A SAMPLE OF THE UNITED STATES POPULATION James E. Enstrom, Ph.D., M.P.H. School of Public Health and Jonsson Comprehensive Cancer Center University of California Los Angeles, CA 90024 October 24, 1995 ABSTRACT The relation between spousal cigarette smoking and mortality has been examined in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study cohort. A representative sample of 11,348 noninstitutionalized U.S. adults aged 25-74 years has been examined in detail during 1971-74 and 1982-84, including an assessment of spousal cigarette smoking. This cohort has been followed up for mortality through 1987. The relation of mortality for selected causes of death to spousal cigarette smoking in 1,047 men and 3,304 women who never smoked cigarettes has been analyzed using proportional hazards models. The relation is not significant for any cause after adjustment for age and sex, or after additional adjustment for ten potentially confounding variables (including diet, education, race, and disease history). Measurement errors in personal and spousal smoking histories are on the order of 10% based on comparing responses in 1971-74 and 1982-84. These results do not support the notion that passive smoking has a measurable impact on human mortality, but they cannot rule out small effects on individual causes of death. Keywords: passive smoking, smoking,mortality, NHEFS cohort, cancer, cardiovascular diseases, epidemiology

Draft MORTALITY TRENDS AMONG SMOKERS AND NONSMOKERS IN THE UNITED STATES: 1966-86 James E. Enstrom, Ph.D., M.P.H. School of Public Health University of California Los Angeles, CA 90024 December 1, 1995 ABSTRACT Mortality trends among smokers and nonsmokers in the United States have been analyzed using representative samples from the 1966-68 National Mortality Survey and the 1986 National Mortality Followback Survey. There have been declines of over 30% in total death rates for nonsmokers, smokers, and the total population from 1966 to 1986 with the declines somewhat greater for the nonsmokers than for smokers and somewhat greater for all cardiovascular diseases than for other causes. The declines are so large that the 1986 total death rates for U. S. white cigarette smokers who are married with 12+ years of education are about the same as the 1966-68 total death rates for U. S. whites who never smoked cigarettes. In spite of a substantial degree of smoking cessation and a large reduction in tar and nicotine levels in cigarettes during the past 30 years, there has been no decline in overall lung cancer death rate among males and there has been a large increase in the rate among women. Also, death rates for smoking-related diseases in the population as a whole are not converging toward the corresponding death rates those who have never smoked over the 1966-86 period. Indeed, the cardiovascular disease and total death rates have declined faster for never smokers than they have for current smokers, even controlling for amount smoked. The number of deaths that are 'due to' smoking and that can currently be prevented by smoking cessation may be smaller than the widely accepted estimates that rely on extrapolations from non-representative data and do not account for the large secular declines in death rates during the past 40 years.

3. obtain new results from three major cohorts studies on the relationship of mortality from lung cancer and all causes to low levels of active smoking and to passive (spousal) smoking. a. Continue analysis of the 1971-87 NHANES I Epidemiologic Follow-up Study using recently obtained followup data through 1992 for data relevant to passive smoking and lung cancer and other outcomes. b. Analyze Dorn U.S. veterans study (250,000 males) with respect to occasional smoking and lung cancer and other causes of death during 1954-79. Determine if NCI will allow extended follow-up of this cohort, which is almost entirely deceased, and conduct such follow-up using Social Security Death Index and other sources. c. Conduct analysis of California CPS I cohort (51,000 males and 67,000 females) from 1960-94 and conduct follow-up of CPS I from selected states where individual computerized death records are available (up to 200,000 and 300,000 females). Analysis will examine spousal smoking and death from lung cancer, coronary heart disease, and all causes. Also, analysis will be done of death rates among occasional smokers.

ENVIRONMENTAL TOBACCO SMOKE AND LUNG CANCER IN NONSMOKING WOMEN: A REANALYSIS James E. Enstrom, Ph.D., M.P.H. School of Public Health and Jonsson Comprehensive Cancer Center University of California Los Angeles, CA 90024-1772 April 25, 1996 ABSTRACT This reanalysis points out several serious problems with the largest case-control study of environmental tobacco smoke (ETS) and lung cancer, a supposedly well-designed population-based study. About 50% of the expected lung cancer cases among women who never smoked are missing based on reasonable assumptions, including past research by these same authors and independent case ascertainment. Cases are missing in all five geographic areas and all age groups. It appears that the deficit is due to the misclassification of never smokers as smokers because only about 5% of the otherwise eligible lung cancer cases were among never smokers. This percentage is far lower than that found in other concurrent studies and in an independent examination of medical records for lung cancer patients seen at a major hospital in the ascertainment area of the study. It is highly unlikely that their identification of cases is complete and accurate because this would imply that the lung cancer incidence rate among female never smokers had declined by 50% in the last decade, a finding that is contradicted by other evidence that this rate has remained stable. Furthermore, it appears the never smoker cases are nonrepresentative because there are too few small cell and squamous cell carcinoma cases and too many acinar cell cases when compared with expected histology distribution. Analysis of the authors' publications and grant application discloses further anomalies. The key finding of their five year study, that tobacco use by spouses is associated with a 30% excess risk of lung cancer, is actually a 90% excess risk during the first year and only a 10% excess risk during the last four years using the population controls. There is no excess risk over five years using the colon cancer controls. In addition, there is a very unusual pattern of excluded cases and controls throughout that could have a substantial effect on several of the results. All of these issues lead to conclusions about ETS and lung cancer that are different than those of the authors. They point to the need for independent confirmation, analysis, and interpretation of the original data collected for this study.

GENERAL PROCEDURES FOR EACH SPECIFIC AIM 1. Develop plan and methods for completion of specific aim. 2. Obtain human subjects approval, if necessary. 3. Obtain necessary data set(s) and documentation if they already exist. 4. Collect data according to plan if it does not already exist. 5. Analyze data according to plan and carefully assess quality of data and results. 6. Prepare results in the form of a scientific paper: Introduction, Methods, Results, Discussion. 7. Prepare documentation and summary data set that can be used by designated others for reanalysis and prepare summary of results that can be used for presentation.

4. Establish clear statement of tobacco industry position of the health risks of active smoking to add credibility to the first three objectives. a. Previous tobacco industry statements on cigarette smoking "A Frank Statement to Cigarette Smoker" January 1954 ad in 448 newspapers "A Scientific Perspective on the Cigarette Controversy" April 1954 booklet: 205,000 copies distributed to doctors "Antismoking Theories Not Based on Complete Scientific Knowledge" June 1955 research booklet: 135,000 copies LCF Blackman, "The Controversy on Smoking and Health: Some Facts and Anomalies" 1984 position paper referred to in JAMA 1995:274:240 Broin vs. Philip Morris Deposition of James W. Johnston May 26, 1994 statements on smoking/health (pages 102-105) b. Mortality Trends Among Smokers and Nonsmokers in the United States: 1966-86 c. Excess Mortality among Cigarette Smokers: Changes in a 20- year Period d. The Effect of Cigarette Smoking on Coronary Heart Disease from 1983 Surgeon Generals Report

SPECIFIC AIMS 1. Obtain original data for the four major U.S. case-control studies and reanalyze them in a standard way with respect to the relationship of lung cancer risk to passive smoking and determine the extent to which they are representative population-based studies. a. To the extent possible, obtain and analyze grant applications, thesis, and original data files for the four largest U.S. case-control studies: Janerich, Stockwell, Brownson, and Fontham. Varela (Janerich) thesis, Brownson original data, and Correa (Fontham) grant application have already been obtained. 1. Freedom of Information Act 2. PHS Policy relating to Distribution of Unique Research Resources Produced with PHS Funding 3. DHHS Office of Research Integrity 4. Federal False Claims Act b. Estimate lung cancer case selection and distribution for Janerich, Stockwell, Brownson studies similar to estimates made for Fontham study, order to determine accuracy, completeness, and representativeness of lung cancer cases in these studies c. Conduct a standardized analysis of passive smoking and lung cancer risk for the individual and combined studies, which include about 1500 never smoker cases (about 80% of all U.S. cases from case-control studies). Several such analyses have already been done using Brownson data.

2. Conduct survey similar to the 1986 National Mortality Followback Survey in Los Angeles County using UCLA female lung cancer patients since 1985 and recent county female lung cancer deaths to establish independent results about passive smoking and lung cancer. Use national and state smoking surveys previously analyzed to construct control groups for case-control analysis. a. Interview survivors of 1985-94 UCLA female lung cancer patients who never smoked according to their medical records regarding smoking history of patient and spouse. Use simplified questionnaire with basic questions on spousal smoking and exposure to passive smoke. b. Use "Development, Methods, and Response Characteristics of the 1986 National Mortality Followback Survey" in order to plan and undertake a similar survey in Los Angeles County of recent lung cancer deaths with regard to passive smoking and related variables (see enclosed letter to Los Angeles County Department of Health Services). About 1,000 lung cancer and 500 colon cancer deaths per year among Los Angeles County women can be investigated, yielding about 100 lung cancer deaths and over 100 colon cancer deaths per year among women who never smoked. This has the potential of becoming a large case-control study. Prepare detailed "Methods of Procedure" similar to above document for NMFS. c. Use smoking data for women and their spouses from national and state smoking surveys to establish baseline control groups for comparison with lung cancer cases. Among the surveys that can be used are: 1988-91 NHANES III Survey 1990 and 1992 California Tobacco Surveys 1992 and 1993 Current Population Survey, Tobacco Use Supplement