27 Oct the basis of clinical observations.

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, 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 assigment 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

 

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.

 

 

 

PART I

 

Question 1:   In three sentences or less, what makes the first study a case-control study?

 

 

 

 

 

Question 2:   In three sentences or less, what makes the second study a cohort study?

 

 

 

 

 

Question 3:   In three sentences or less, why might hospitals have been chosen as the setting for this study?

 

 

 

 

 

The remainder of Part I deals with the case-control study.

 

 

 

Question 4:   What other sources of cases and controls might have been used?

 

 

 

 

 

Question 5:   What are the advantages of selecting controls from the same hospitals as cases?

 

 

 

 

 

Question 6:   How representative of all persons with lung cancer are hospitalized patients with lung cancer?

 

 

 

 

 

Question 7:   How representative of the general population without lung cancer are hospitalized patientswithout lung cancer?

 

 

 

Question 8:   How could these representativeness issues affect interpretation of the study’s results?

 

 

 

 

 

 

 

Over 1,700 patients with lung cancer, all under age 75, were eligible for the case-control study.

 

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 case and controls.

 

 

 

 

 

Table 1. Smoking status before onset of the present illness, lung cancer cases and matched controls with other diseases, GreatBritain, 1948-1952.          

 

Cases                      Controls

 

 

 

1,350

 

1,296

 

7

 

61

 

 

 

 

 

Cigarette smoker Non-smoker

 

 

 

Total                       1,357                         1,357

 

 

 

 

 

 

 

 

 

Question 9:      From this table, calculate the proportion of cases and controls who smoked.

 

 

 

Proportion smoked, cases: Proportion smoked,controls:

 

 

 

 

 

 

 

Question 10: What do you infer from these proportions?

 

 

 

 

 

 

 

Question 11:    Calculate the odds of smoking among the cases.

 

 

 

 

 

 

 

Question 12:   Calculate the odds of smoking among the controls.

 

 

 

 

 

Question 13:      Calculate the odds ratio between cases and controls. What do you infer from the odds ratioabout the relationship between smoking and lung cancer?

 

 

 

 

 

 

 

 

 

Table 2 shows the frequency distribution of male cases and controls by average number of cigarettes smoked perday.

 

 

 

 

 

Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer cases and matched controlswith other diseases, Great Britain, 1948-1952.                                                                                                                                                                                                                   

 

 

 

Daily numberof cigarettes

 

 

 

# Cases

 

 

 

# Controls

 

 

 

Odds Ratio

 

0

 

7

 

61

 

referent

 

1-14

 

565

 

706

 

          

 

15-24

 

445

 

408

 

          

 

25+

 

340

 

182

 

          

 

All smokers

 

1,350

 

1,296

 

          

 

Total

 

1,357

 

1,357

 

 

 

 

 

Question 14:     Compute the odds ratio by category of daily cigarette consumption on table 2, comparing each smoking category to nonsmokers.

 

 

 

 

 

Question 15:    Interpret these results.

 

 

 

 

 

 

 

 

 

 

Part 2 –  This section 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 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 female. This study was limited to the analysis of male physician respondents, 35 years of age or older.

 

 

 

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 Hillphysician cohort study, Great Britain, 1951-1961.                                                                                                                        

 

 

 

Dailynumber ofcigarettes

 

  smoked

 

 

 

Deathsfrom lungcancer

 

 

 

Person-years atrisk

 

 

 

Mortality rateper 1000person-years

 

 

 

 

 

Rate

 

 Ratio

 

 

 

0

 

3

 

42,800

 

0.07

 

referent

 

 

 

1-14

 

22

 

38,600

 

0.57

 

 

 

 

 

 

 

15-24

 

 

 

54

 

 

 

38,900

 

 

 

1.39

 

 

 

 

 

 

 

25+

 

 

 

57

 

 

 

25,100

 

 

 

2.27

 

 

 

 

 

 

 

All smokers

 

 

 

133

 

 

 

102,600

 

 

 

1.30

 

 

 

 

 

 

 

Total

 

 

 

136

 

 

 

145,400

 

 

 

0.94

 

 

 

 

 

Question 16:    Compute lung cancer mortality rate ratios, for each smoking category on Table 3 (above).  What does this measuremean?

 

 

 

 

The following table shows the relationship between smoking and lung cancer mortality in 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 ex- smokers by years sincequitting, Doll and Hill physician cohort study, Great Britain, 1951-1961.                                                                                                    

 

 

 

Lung cancer

 

Cigarette smoking status               deaths        

 

Rate per 1000

 

 person-years

 

 

 

Rate Ratio

 

Current smokers                                 133

 

1.30

 

18.5

 

For ex-smokers, years since quitting:

 

 

 

 

 

<5 years

 

5

 

0.67

 

9.6

 

5-9 years

 

7

 

0.49

 

7.0

 

10-19 years

 

3

 

0.18

 

2.6

 

20+ years

 

2

 

0.19

 

2.7

 

Nonsmokers

 

3

 

0.07

 

1.0 (ref)

 

 

 

Question 17:   What do these data imply for the practice of public health and preventive medicine?

 

 

 

 

 

 

 

 

 

Question 18:  Which type of study (cohort or case-control) would you have done first?  Why?  Why do a secondstudy?  Why do the other type of study?

 

 

 

 

 

 

 

REFERENCES

 

Doll R, Hill AB. Smoking and carcinoma of the lung. Brit Med J 1950; 2:739-748.

 

Doll R, Hill AB. A study of the aetiology of carcinoma of the lung. Brit Med J 1952; 2:1271-1286.

 

Doll R, Hill AB. The mortality of doctors in relation to their smoking habits. Brit Med J 1954; 1:1451-1455.

 

Doll R, Hill AB. Lung cancer and other causes of death in relation to smoking. Brit Med J 1956; 2:1071-1081.

 

Doll R, Hill AB. Mortality in relation to smoking: 10 years’ observation of British doctors. Brit Med J

 

1964; 1:1399-1410, 1460-1467.

 

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.

 

Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965;58:295-300.

 

Levy RA, Marimont RB. Lies, damned lies, and 400,000 smoking-related deaths. Regulation 1998; 21-29.

 

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. Adapted from the U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES