Public Health · 1950
Doll and Hill smoking and lung cancer case-control study
Through the 1930s and into the 1940s, lung cancer mortality in Britain and the United States rose steeply. The increase was real, not a registration artifact, and it demanded explanation. Several hypotheses circulated: atmospheric pollution from coal and motor exhaust, the tarring of roads, general urban air quality, and the increasing use of tobacco. Richard Doll, then working for the Medical Research Council, and Austin Bradford Hill designed a case-control study to test these explanations against each other. They recruited patients admitted to London hospitals with confirmed lung cancer and matched them with controls admitted for other conditions during the same period.
Interviewers visited 709 lung cancer patients and 709 matched controls across 20 London hospitals between April 1948 and February 1949, gathering detailed smoking histories. The association with smoking was stronger than any of the other exposures examined. Heavy smokers, defined as those who smoked 25 or more cigarettes per day, had an odds ratio of approximately 50 for lung cancer compared with lifelong non-smokers. The study appeared in the BMJ in September 1950, alongside a parallel case-control study from Ernst Wynder and Evarts Graham in the United States that reached the same conclusion.
The response from the scientific community was mixed, and the tobacco industry's response was hostile. Critics raised methodologically legitimate concerns: case-control studies were susceptible to recall bias, and an unmeasured confounding variable could in principle explain the results. The tobacco companies funded alternative hypotheses and cast doubt on the epidemiological evidence through the 1950s and into the 1960s, a campaign later documented through internal industry documents obtained in litigation. Doll himself was a smoker at the time of the 1950 study and stopped after reviewing the data.
To address the objections, Doll and Hill launched a prospective cohort study in October 1951, enrolling British physicians who completed questionnaires about their smoking habits. That cohort was followed for 50 years. The physicians study provided dose-response data, showed that cessation reduced risk over time, and extended the causal chain to include heart disease, chronic obstructive pulmonary disease, and other conditions. It supplied the kind of longitudinal, prospective evidence that the critics of the 1950 case-control design had demanded.
The U.S. Surgeon General's Advisory Committee report of 1964 formally concluded that cigarette smoking is a cause of lung cancer and laryngeal cancer in men, drawing on the accumulated body of evidence that began with the 1950 papers. By that time the scientific consensus was not seriously in doubt among researchers, though the public policy response lagged. The case-control method Doll and Hill used in 1950, efficiently matching cases to controls to study outcomes too rare for an observational cohort of practical size, remains a standard design in chronic disease epidemiology.
Key People
- Richard Doll — Epidemiologist who designed and conducted the lung cancer case-control study
- Austin Bradford Hill — Statistician who co-designed the study and developed its methodology
- Ernst Wynder — American researcher who published a parallel U.S. case-control study in 1950
- Evarts Graham — Surgeon who co-authored the American study with Wynder
BMJ, 1950
Related landmarks
- 1954 · British Doctors Study (Doll and Hill prospective cohort) (Public Health)
- 1956 · Water Fluoridation (Grand Rapids study, 10-year results) (Public Health)
- 1961 · Framingham Heart Study: the "risk factor" concept (Public Health)
- 1964 · Surgeon General's Report on Smoking and Health (Public Health)