Epidemiology of Chronic Diseases

Doll and Hill Study on Lung Cancer (1948)

During the 20th century there had been a remarkable increase in the incidence of lung cancer, both in the United Kingdom and in the US. As unbelievable as it sounds now, the cause was unknown. There was abundant speculation, but no rigorously collected data. Many people believed that the increase was associated with the increase in automobiles, roads, and factories. Richard Doll and Bradford Hill were British researchers who conducted a study to address this. They identified lung cancer patients in 20 London hospitals and enrolled a comparison group of non-cancer patients who were matched by age, gender, and hospital.

While in the hospital, all subjects were interviewed about their past smoking habits and other exposures using a 3-page questionnaire. This was a case-control study that compared subjects with lung cancer to a comparison group without cancer. Somewhat to the surprise of Doll and Hill, the study found that the one consistent difference between lung cancer patients and the non-cancer controls was that the cancer patients were more frequently smokers, and they were heavier smokers. In retrospect, the study was quite carefully done and quite convincing. Nevertheless, it initially stirred much controversy, even among the medical community. Smoking was extremely prevalent, even in physicians, and many refused to believe that it could be a cause of cancer. Other studies were conducted which corroborated these findings, and eventually the importance of the study was recognized, not only for establishing the link between smoking and lung cancer, but for establishing the role of case-control studies. At the time, case-control studies were infrequently done, and careful standards for their conduct had not been established. The study done by Doll and Hill was conducted and described very meticulously, and the discussion section of the paper earnestly addressed the potential biases that can be a problem with case-control studies.

In the video below Sir Richard Doll briefly describes the study that he and Bradford Hill conducted in 1948. (R. Doll and A. B. Hill, 'Smoking and carcinoma of the lung: preliminary report', BMJ, 1950, 2.746).

As more and more evidence accumulated indicting tobacco as the major cause of lung cancer and a number of other diseases, the tobacco industry claimed that there was no proof the tobacco was responsible for causing these diseases. Thus, the criteria for establishing that a give exposure can cause a particular outcome came into question. The battle continued for years, and Bradford Hill subsequently published a series of criteria to be considered when making a judgment of whether a given 'exposure' was truly a cause of a given disease. These are now commonly referred to as "Hill's Criteria" for causal inference.

The Framingham Heart Study

Quoted directly from the web site of the Framingham Heart Study:

"Cardiovascular disease (CVD) is the leading cause of death and serious illness in the United States. In 1948, the Framingham Heart Study - under the direction of the National Heart Institute (now known as the National Heart, Lung, and Blood Institute or NHLBI) - embarked on an ambitious project in health research. At the time, little was known about the general causes of heart disease and stroke, but the death rates for CVD had been increasing steadily since the beginning of the century and had become an American epidemic. The Framingham Heart Study became a joint project of the National Heart, Lung and Blood Institute and Boston University."

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"The objective of the Framingham Heart Study was to identify the common factors or characteristics that contribute to CVD by following its development over a long period of time in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke.

The researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, and began the first round of extensive physical examinations and lifestyle interviews that they would later analyze for common patterns related to CVD development. Since 1948, the subjects have continued to return to the study every two years for a detailed medical history, physical examination, and laboratory tests, and in 1971, the Study enrolled a second generation - 5,124 of the original participants' adult children and their spouses - to participate in similar examinations."

Click on this link to see an excellent PBS video on the history of the Framingham Heart Study and its impact on heart disease.