Cigarette Smoking Lung Cancer Case Study

Unformatted text preview: Centers for Disease Control and Prevention Epidemiology Program Office Case Studies in Applied Epidemiology No. 731-703 Cigarette Smoking and Lung Cancer Student's Guide Learning Objectives After completing this case study, the participant should be able to: G Discuss the elements of study design, and the advantages and disadvantages of case-control versus prospective cohort studies; G Discuss some of the biases that might have affected these studies; G Calculate a rate ratio, rate difference, odds ratio, and attributable risk percent; G Interpret each measure and describe each measure's main use; and G Review the criteria for causation. This case study is based on the classic studies by Doll and Hill that demonstrated a relationship between smoking and lung cancer. Two case studies were developed by Clark Heath, Godfrey Oakley, David Erickson, and Howard Ory in 1973. The two case studies were combined into one and substantially revised and updated by Nancy Binkin and Richard Dicker in 1990. Current version updated by Richard Dicker with input from Julie Magri and the 2003 EIS Summer Course instructors. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide A causal relationship between cigarette smoking and lung cancer was first suspected in the 1920s on the basis of clinical observations. To test this apparent association, numerous epidemiologic studies were undertaken between 1930 and 1960. Two studies were conducted by Richard Doll and Austin Bradford Hill in Great Britain. The first was a case-control study begun in 1947 comparing the smoking habits of lung cancer patients with the smoking habits of other patients. The second was a cohort study begun in 1951 recording causes of death among British physicians in relation to smoking habits. This case study deals first with the case-control study, then with the cohort study. Data for the case-control study were obtained from hospitalized patients in London and vicinity Page 2 over a 4-year period (April 1948 - February 1952). Initially, 20 hospitals, and later more, were asked to notify the investigators of all patients admitted with a new diagnosis of lung cancer. These patients were then interviewed concerning smoking habits, as were controls selected from patients with other disorders (primarily non-malignant) who were hospitalized in the same hospitals at the same time. Data for the cohort study were obtained from the population of all physicians listed in the British Medical Register who resided in England and Wales as of October 1951. Information about present and past smoking habits was obtained by questionnaire. Information about lung cancer came from death certificates and other mortality data recorded during ensuing years. Question 1: What makes the first study a case-control study? The first study is a case-control study due to the fact that Richard Doll and Austin Bradford Hill compared and studied patients with lung cancer who have, which is the “case” and smoking habits of other patients with a different diagnosis, which is the “control." Question 2: What makes the second study a cohort study? The second study is a cohort study because the data collected was fist obtained from hospitalized patients in London, as well multiple other sources. Meaning, a cohort study is when it begins with a group of people that are exposed to a disease, and when you compare them to a group that is NOT exposed. Patients in both groups are selected by the investigator or categorized from a population or cohort selected for the study. The remainder of Part I deals with the case-control study. Question 3: Why might hospitals have been chosen as the setting for this study? I believe hospitals are chosen as the setting for this particular study because of the wide variety of patients and diagnosis hospitals provide. I would think it would be easier to compare to have both groups of patients in the same setting for the identification of lung cancer can be more clear. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Page 3 Question 4: What other sources of cases and controls might have been used? Other sources of cases that could have been used are clinics, cancer centers, laboratories (for lab results), nursing homes, rehabilitation facilities, and public health centers. Other sources for controls are support groups, different patients from the same setting, and community controls. Question 5: What are the advantages of selecting controls from the same hospitals as cases? The major advantage of selecting controls from the same hospitals as cases are the convenience of the population. Information from previous cases have already been inputed in the hospital database, which makes comparison much easier. Question 6: How representative of all persons with lung cancer are hospitalized patients with lung cancer? Representatively, each patient who has been diagnosed with lung cancer has stayed in the hospital. Patients who were hospitalized at the time of the study, may have gotten more ill or had complications which made them stay in the hospital. As well as maybe being in the ending stages of lung cancer. Question 7: How representative of the general population without lung cancer are hospitalized patients without lung cancer? Patients that are hospitalized are not representative of the general population. They are more at risk. Question 8: How may these representativeness issues affect interpretation of the study's results? I believe that the severe cases of lung cancer are being assessed due to collecting data from hospitalized patients, it’s making the exposure number less than what it really is. Sort of like false diagnosis because patients could of been admitted for lung cancer for other reasons not because of smoking. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Over 1,700 patients with lung cancer, all under age 75, were eligible for the case-control study. About 15% of these persons were not interviewed because of death, discharge, severity of illness, or inability to speak English. An additional group of patients were interviewed but later excluded when initial lung cancer Page 4 diagnosis proved mistaken. The final study group included 1,465 cases (1,357 males and 108 females). The following table shows the relationship between cigarette smoking and lung cancer among male cases and controls. Table 1. Smoking status before onset of the present illness, lung cancer cases and matched controls with other diseases, Great Britain, 1948-1952. Question 9: Cases Controls Cigarette smoker 1,350 1,296 Non-smoker 7 61 Total 1,357 1,357 From this table, calculate the proportion of cases and controls who smoked. Proportion smoked, cases: 1,350/1,357 = 99.5% Proportion smoked, controls: 1,296/1,357 = 95.5% Question 10: What do you infer from these proportions? That there are other reasons for health concerns from smoking besides of just lung cancer. Question 11a: Calculate the odds of smoking among the cases. 1350/1357/7/1357= 1350/7 = 192.9 : 1 Question 11b: Calculate the odds of smoking among the controls. 1296/1357/61/1357 = 1296/61 = 21.2 : 1 Question 12: Calculate the ratio of these odds. How does this compare with the cross-product ratio? Odds - 1350/7/ (1296/61) = 192.9/21.2 = 9.1 Cross-product - (1350 x 61) / (1296 x 7) = 9.1 They are the same! CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Question 13: Page 5 What do you infer from the odds ratio about the relationship between smoking and lung cancer? The odds of smoking among case-patients was 9.1 times as high as lung cancer. Table 2 shows the frequency distribution of male cases and controls by average number of cigarettes smoked per day. Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer cases and matched controls with other diseases, Great Britain, 1948-1952. Daily number of cigarettes # Cases 0 # Controls Odds Ratio 7 61 1-14 565 706 15-24 445 408 9.5 25+ 340 182 16.3 All smokers 1,350 1,296 Total 1,357 1,357 Question 14: referent 7 9.1 Compute the odds ratio by category of daily cigarette consumption, comparing each smoking category to nonsmokers. Results are above Question 15: Interpret these results. The odds of getting lung cancer increases as the amount of daily number of cigarettes smoked increases. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Although the study demonstrates a clear association between smoking and lung cancer, Question 16: Page 6 cause-and-effect is not the only explanation. What are the other possible explanations for the apparent association? Response Bias - Patients were interviewed concerning smoking habits as well as control groups and the responses might not be accurate because they had to recall from their past smoking routines. Selection Bias - All participants including cases and controls were from the same hospital. Time Bias - The time for collecting the data was probably not enough to collect all the necessary data needed. The next section of this case study deals with the cohort study. Data for the cohort study were obtained from the population of all physicians listed in the British Medical Register who resided in England and Wales as of October 1951. Questionnaires were mailed in October 1951, to 59,600 physicians. The questionnaire asked the physicians to classify themselves into one of three categories: 1) current smoker, 2) ex-smoker, or 3) nonsmoker. Smokers and Question 17: ex-smokers were asked the amount they smoked, their method of smoking, the age they started to smoke, and, if they had stopped smoking, how long it had been since they last smoked. Nonsmokers were defined as persons who had never consistently smoked as much as one cigarette a day for as long as one year. Usable responses to the questionnaire were received from 40,637 (68%) physicians, of whom 34,445 were males and 6,192 were females. How might the response rate of 68% affect the study's results? Patients might of gave false answers. However, a response rate of 68% is helpful for evidence about smoking and how the disease developed. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Page 7 The next section of this case study is limited to the analysis of male physician respondents, 35 years of age or older. were from cytology, bronchoscopy, or X-ray alone; and only 1% were from just case history, physical examination, or death certificate. The occurrence of lung cancer in physicians responding to the questionnaire was documented over a 10-year period (November 1951 through October 1961) from death certificates filed with the Registrar General of the United Kingdom and from lists of physician deaths provided by the British Medical Association. All certificates indicating that the decedent was a physician were abstracted. For each death attributed to lung cancer, medical records were reviewed to confirm the diagnosis. Of 4,597 deaths in the cohort over the 10-year period, 157 were reported to have been caused by lung cancer; in 4 of the 157 cases this diagnosis could not be documented, leaving 153 confirmed deaths from lung cancer. Diagnoses of lung cancer were based on the best evidence available; about 70% were from biopsy, autopsy, or sputum cytology (combined with bronchoscopy or X-ray evidence); 29% The following table shows numbers of lung cancer deaths by daily number of cigarettes smoked at the time of the 1951 questionnaire (for male physicians who were nonsmokers and current smokers only). Person-years of observation ("person-years at risk") are given for each smoking category. The number of cigarettes smoked was available for 136 of the persons who died from lung cancer. Table 3. Number and rate (per 1,000 person-years) of lung cancer deaths by number of cigarettes smoked per day, Doll and Hill physician cohort study, Great Britain, 1951-1961. Daily number of cigarettes smoked Deaths from lung cancer Personyears at risk Mortality rate per 1000 person-years Rate Ratio Rate difference per 1000 person-years 0 3 42,800 0.07 referent referent 1-14 22 38,600 0.57 8.10 0.5 15-24 54 38,900 1.39 19.80 1.32 25+ 57 25,100 2.25 32.40 2.2 All smokers 133 102,600 1.30 18.60 1.23 Total 136 145,400 0.94 Question 18: Compute lung cancer mortality rates, rate ratios, and rate differences for each smoking category. What do each of these measures mean? The mortality rates increased with the number of cigarettes a person smokes daily. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Question 19: Page 8 What proportion of lung cancer deaths among all smokers can be attributed to smoking? What is this proportion called? The proportion if called an absolute risk and the proportion of lung cancer deaths among all smokers that can be attributed to smoking is 94.6% Question 20: If no one had smoked, how many deaths from lung cancer would have been averted? If no one around 126 deaths could have been averted. The cohort study also provided mortality rates for cardiovascular disease among smokers and nonsmokers. The following table presents lung cancer mortality data and comparable cardiovascular disease mortality data. Table 4. Mortality rates (per 1,000 person-years), rate ratios, and excess deaths from lung cancer and cardiovascular disease by smoking status, Doll and Hill physician cohort study, Great Britain, 1951-1961. Mortality rate per 1,000 person-years Attributable risk percent among smokers Smokers Non-smokers All Rate ratio Excess deaths per 1,000 person-years Lung cancer 1.30 0.07 0.94 18.5 1.23 95% Cardiovascular disease 9.51 7.32 8.87 1.3 2.19 23% Question 21: Which cause of death has a stronger association with smoking? Why? The smoking and lung cancer mortality rate ratio is 18.5, whereas the smoking and cardiovascular mortality rate ratio is 1.3. Clearly, someone is more likely to die from lung cancer. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide In calculating the attributable risk percent, the excess lung cancer deaths attributable to smoking is expressed as a percentage of all lung cancer mortality among all smokers. The attributable risk percent of 95% for smoking may be interpreted as the proportion of lung cancer deaths among smokers that could have been prevented if they had not smoked. A similar measure, the population attributable risk percent expresses the excess lung cancer deaths attributable to smoking as a percentage of all lung cancer mortality among the entire Page 9 population. From a prevention perspective, the population attributable risk percent for a given exposure can be interpreted as the proportion of cases in the entire population that would be prevented if the exposure had not occurred. The population attributable risk percent is often used in assessing the cost-effectiveness and costbenefit of community-based intervention programs. One formula for the population attributable risk percent is: PAR% = (Incidence in entire population ! Incidence in unexposed) / Incidence in entire population Question 22: Calculate the population attributable risk percent for lung cancer mortality and for cardiovascular disease mortality. How do they compare? How do they differ from the attributable risk percent? PAR Lung Cancer- 92.5% PAR Cardiovascular disease - 17.4% Lung cancer and cardiovascular disease mortality both attribute from smoking however more deaths are from lung cancer. Question 23: How many lung cancer deaths per 1,000 persons per year are attributable to smoking among the entire population? How many cardiovascular disease deaths? Lung Cancer - 0.87 deaths per 1,000 persons per year Cardiovascular Disease - 1.54 deaths per 1.000 persons per year CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide The following table shows the relationship between smoking and lung cancer mortality in Page 10 terms of the effects of stopping smoking. Table 5. Number and rate (per 1,000 person-years) of lung cancer deaths for current smokers and exsmokers by years since quitting, Doll and Hill physician cohort study, Great Britain, 1951-1961. Cigarette smoking status Lung cancer deaths Rate per 1000 person-years 133 1.30 18.5 5 7 3 2 0.67 0.49 0.18 0.19 9.6 7.0 2.6 2.7 3 0.07 1.0 (ref) Current smokers For ex-smokers, years since quitting: <5 years 5-9 years 10-19 years 20+ years Nonsmokers Rate Ratio Question 24: What do these data imply for the practice of public health and preventive medicine? Prevention is key and data can show the risk factors on smoking. Obviously, if you don’t smoke at all, there is no risk; in which the data shows that. Taking every prevention measure possible, is extremely necessary! The data shows that if you quit smoking for five years or less, it reduces the risk of dying from lung cancer. As noted at the beginning of this case study, Doll and Hill began their case-control study in 1947. They began their cohort study in 1951. The odds ratios and rate ratios from the two studies by numbers of cigarettes smoked are given in the table below. Table 6. Comparison of measures of association from Doll and Hill’s 1948-1952 case-control study and Doll and Hill’s 1951-1961 physician cohort study, by number of cigarettes smoked daily, Great Britain. Daily number of Cigarettes smoked 0 1-14 15-24 25+ All smokers Question 25: Rate ratio from cohort study 1.0 (ref) 8.1 19.8 32.4 18.5 Odds ratio from case-control study 1.0 (ref) 7.0 9.5 16.3 9.1 Compare the results of the two studies. Comment on the similarities and differences in the computed measures of association. The studies show that deaths are associated with smoking. By the number of cigarettes that are smoked daily, contributes to a high risk of lung cancer mortality. The difference is in comparing the odds ratio to the rate ratio. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Question 26: Page 11 What are the advantages and disadvantages of case-control vs. cohort studies? Answer 26 Case-control Sample size Costs Study time Rare disease Rare exposure Multiple exposures Multiple outcomes smaller cheaper rapid __________ advantage disadvantage advantage disadvantage ___________ Progression, spectrum of illness disadvantage Disease rates disadvantage disadvantage Recall bias Loss to follow-up advantage Selection bias disadvantage Cohort bigger expensive takes longer __________ disadvantage advantage disadvantage advantage _________ advantage advantage advantage disadvantage advantage Question 27: Which type of study (cohort or case-control) would you have done first? Why? Why do a second study? Why do the other type of study? I would have done a case control study first because is more effective and faster. Case control studies are much cheaper than a cohort study. However, if my results from the case control study needed confirmation, I would take further action. I would make sure everything is confirmed with the relationship between exposure and the disease. Question 28: Which of the following criteria for causality are met by the evidence presented from these two studies? Answer 28 YES Strong association Consistency among studies Exposure precedes disease Dose-response effect Biologic plausibility NO Strong Association - Met Consistency among studies - Met Exposure precedes disease - Met Dose-response effect - Met Biologic plausibility – Not met CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Page 12 REFERENCES 1. Doll R, Hill AB. Smoking and carcinoma of the lung. Brit Med J 1950; 2:739-748. 2. Doll R, Hill AB. A study of the aetiology of carcinoma of the lung. Brit Med J 1952; 2:1271-1286. 3. Doll R, Hill AB. The mortality of doctors in relation to their smoking habits. Brit Med J 1954; 1:1451-1455. 4. Doll R, Hill AB. Lung cancer and other causes of death in relation to smoking. Brit Med J 1956; 2:1071-1081. 5. Doll R, Hill AB. Mortality in relation to smoking: 10 years' observation of British doctors. Brit Med J 1964; 1:1399-1410, 1460-1467. 6. U. S. Public Health Service. Smoking and health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. US Department of Health, Education, and Welfare, PHS, CDC. PHS Publication No. 1103, 1964. 7. Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965;58:295-300. 8. Levy RA, Marimont RB. Lies, damned lies, and 400,000 smoking-related deaths. Regulation 1998; 21-29. ...
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Unformatted text preview: Centers for Disease Control and Prevention Epidemiology Program Office Case Studies in Applied Epidemiology No. 731-703 Cigarette Smoking and Lung Cancer Student's Guide Learning Objectives After completing this case study, the participant should be able to: G Discuss the elements of study design, and the advantages and disadvantages of case-control versus prospective cohort studies; G Discuss some of the biases that might have affected these studies; G Calculate a rate ratio, rate difference, odds ratio, and attributable risk percent; G Interpret each measure and describe each measure's main use; and G Review the criteria for causation. This case study is based on the classic studies by Doll and Hill that demonstrated a relationship between smoking and lung cancer. Two case studies were developed by Clark Heath, Godfrey Oakley, David Erickson, and Howard Ory in 1973. The two case studies were combined into one and substantially revised and updated by Nancy Binkin and Richard Dicker in 1990. Current version updated by Richard Dicker with input from Julie Magri and the 2003 EIS Summer Course instructors. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide A causal relationship between cigarette smoking and lung cancer was first suspected in the 1920s on the basis of clinical observations. To test this apparent association, numerous epidemiologic studies were undertaken between 1930 and 1960. Two studies were conducted by Richard Doll and Austin Bradford Hill in Great Britain. The first was a case-control study begun in 1947 comparing the smoking habits of lung cancer patients with the smoking habits of other patients. The second was a cohort study begun in 1951 recording causes of death among British physicians in relation to smoking habits. This case study deals first with the case-control study, then with the cohort study. Data for the case-control study were obtained from hospitalized patients in London and vicinity Page 2 over a 4-year period (April 1948 - February 1952). Initially, 20 hospitals, and later more, were asked to notify the investigators of all patients admitted with a new diagnosis of lung cancer. These patients were then interviewed concerning smoking habits, as were controls selected from patients with other disorders (primarily non-malignant) who were hospitalized in the same hospitals at the same time. Data for the cohort study were obtained from the population of all physicians listed in the British Medical Register who resided in England and Wales as of October 1951. Information about present and past smoking habits was obtained by questionnaire. Information about lung cancer came from death certificates and other mortality data recorded during ensuing years. Question 1: What makes the first study a case-control study? In a case-control study, the participants are selected and divided on the basis of presence of disease and it examines the relation of an exposure to a certain disease. The first study is a case-control study because it investigated the patients with a new diagnosis of lung cancer (case) and patients with other disorders(control) and determined the proportion of cases and controls exposed to lung cancer . Question 2: What makes the second study a cohort study? In a cohort study, the participants are selected and divided based on presences of exposure.The second study collected the information about the present and past smoking habits(exposure) from records from records, and compare incidence of outcome between exposed group and unexposed group during ensuing years. The remainder of Part I deals with the case-control study. Question 3: Why might hospitals have been chosen as the setting for this study? Medical record is accessible and easy to obtain from the hospitals and lung cancer may be a rare disease in 1950 and hospitals are good for finding rare disease. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Page 3 Question 4: What other sources of cases and controls might have been used? sources for cases: cancer registries, physician practices, insurance records, sources for controls: door-to-door recruiting; telephone recruiting; other sources(school enrollment lists, insurance company lists,selective service registry) ;special control groups(friends, spouses,siblings and decreased individuals) Question 5: What are the advantages of selecting controls from the same hospitals as cases? The cases and controls come from the same geographic area; less subject to recall bias; the medical records are easy to access and the patients are more likely to enroll. Question 6: How representative of all persons with lung cancer are hospitalized patients with lung cancer? It is not very representative. Cancer is a disease with many stage and usually people need hospitalization only when they are in late stage of cancer. Thus, it would miss out those in the early stage of cancer, making the sample less representative. Question 7: How representative of the general population without lung cancer are hospitalized patients without lung cancer? It is also not representative. Patients generally have poorer health conditions compare to those of the general population. They are more vulnerable to the exposure. Or they may be better protected from the exposure. Question 8: How may these representativeness issues affect interpretation of the study's results? These representativeness issues would cause selection bias. Since the smoking in the hospitalized population is greater than that found in general population, the real risk might be underestimated. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Over 1,700 patients with lung cancer, all under age 75, were eligible for the case-control study. About 15% of these persons were not interviewed because of death, discharge, severity of illness, or inability to speak English. An additional group of patients were interviewed but later excluded when initial lung cancer Page 4 diagnosis proved mistaken. The final study group included 1,465 cases (1,357 males and 108 females). The following table shows the relationship between cigarette smoking and lung cancer among male cases and controls. Table 1. Smoking status before onset of the present illness, lung cancer cases and matched controls with other diseases, Great Britain, 1948-1952. Cases Cigarette smoker 1,350 1,296 Non-smoker 7 61 Total Question 9: Controls 1,357 1,357 From this table, calculate the proportion of cases and controls who smoked. Proportion smoked, cases: (1350/1357 )*100%=99.5% Proportion smoked, controls: (1296/1357)*100%=95.5% Question 10: What do you infer from these proportions? The proportion of cases and controls who smoked are 99.5% and 95.5%, respectively. So smoking is a common behavior in both cases and controls. Question 11a: Calculate the odds of smoking among the cases. odds of smoking among the cases = a/c = 1350/7=192.9 Question 11b: Calculate the odds of smoking among the controls. odds of smoking among the controls=b/d=1296/61=21.2 Question 12: Calculate the ratio of these odds. How does this compare with the cross-product ratio? OR=192.9/21.2=9.1 cross-product ratio = ad/bc= 1350*61/1296*7= 9.1 They are the same. CDC / EIS Summer Course 2003: Smoking and Lung Ca - Student's Guide Question 13: Page 5 What do you infer from the odds ratio about the relationship between smoking and lung cancer? people who are smoking has 9.1 times the risk of developing lung cancer as those non-smokers. Table 2 shows the frequency distribution of male cases and controls by average number of cigarettes smoked per day. Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer cases and matched controls with other diseases, Great Britain, 1948-1952. Daily number of cigarettes # Cases 0 # Controls Odds Ratio 7 61 referent 1-14 565 706 15-24 445 408 9.5 25+ 340 182 16.3 All smokers 1,350 1,296 Total 1,357 1,357 7.0 9.1 Question 14: Compute the odds ratio by category of daily cigarette consumption, comparing each smoking category to nonsmokers. Question 15: Interpret these results. The possibility of developing lung cancer is increased with the number of cigarettes a person smoked daily. However, correlation is not causation. ...
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