Multiple Exposure Groups: Using a Reference Group

Some cohort studies and clinical trials compare the risk of disease or other outcomes among three or more exposure groups. In this situation, results can be summarized in a table with multiple rows to accommodate the multiple exposure groups. This is a logical extension of the basic "2 x 2" table and is sometimes referred to as an "r x c" table (row and columns).

Use of a Reference Group with Risk Ratios

The table below summarizes a study examining the association between exposure to magnetic fields, e.g., from high tension wires, and the risk of leukemia. In this study there are no unexposed subjects, but we can classify them as having low, medium, and high exposure. To compute the risk ratios , it is logical to use the least exposed group as a "reference group" against which we can compare the other two exposure (or "index") groups. Note that in this example the investigators calculated and compared cumulative incidence.

 Magnetic Field Exposure Leukemia No Leukemia Total Cumulative Incidence High 30 644 674 30 / 674 = 0.0445 Medium 61 1,408 1,469 61 / 1,469 = 0.0415 Low 2,264 65,160 67,424 2,264 / 67,424 = 0.0336

The group with the lowest exposure had a cumulative incidence of 0.0336 or 33.6 per 1000 over the period of observation, while the medium exposure group had 41.5 per 1000 and the highest exposure group had 44.5 per 1000.

• The risk ratio for medium exposure compared to low exposure (the reference group) is 0.0415/0.0336 = 1.23.
• The risk ratio for high exposure compared to low exposure (the reference) is 0.0445/0.0336 = 1.33.

Interpretation:

Compared to children exposed to low magnetic field levels, those exposed to medium levels have 1.23 times the risk of leukemia (a 23% increase in risk), and those exposed to high levels have 1.33 times the risk (a 33% increase in risk).

Use of a Reference Group with Rate Ratios

When The Nurse's Health Study looked at the association between obesity & heart disease, they compared the risk of heart attacks in five categories of body mass index. They used the leanest group of women as a  reference group against which they compared each of the other four groups. Note that in the table below, the exposure groups form the rows while the columns indicate the number of outcome events, the person-years of observation, and the incidence rate for each exposure group. The last column shows the rate ratio for each group, using the leanest women as the reference group.

 Body Mass Index (BMI) Non-fatal Myocardial Infarctions Person-Years of Event-free Observation Incidence Rate per 100,000 P-Yrs Rate Ratio <21 41 177,356 23.1 - 21-23 57 194,243 29.3 1.3 23-25 56 155,717 36.0 1.6 25-29 67 148,541 45.1 2.0 >29 85 99,573 85.4 3.7

It is apparent that there is a progressive increase in risk as BMI goes up, and women in the highest BMI category had 3.7 times the rate of myocardial infarction compared to the leanest women.