Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 61

A cohort study is a basic type of epidemiologic study used in pharmacoepidemiology. This is an important concept because nearly all epidemiology designs have an underlying cohort concept. This type of study is relatively easy to grasp intuitively. Two groups of subjects are included from, for example, a database (although cohort studies may also be prospective and conducted in the field). The first group is those who took the drug in question for a certain amount of time, and the second group (the comparator “cohort”) is the group that did not take the drug. The investigator attempts to choose (“match”) a cohort that is as comparable to the drug group as possible, demographically and in other relevant aspects.

The subjects’ medical records are reviewed and the incidence rate of the AE in question is calculated for each group. These studies are prospective, as the investigator picks a point in time and studies the two groups as they move forward in time to see whether they develop the AE. This study may be done on historical data that have already been collected and stored in a database or it may be done on data that are being collected de novo and moving forward. The advantage of the cohort over the case-control study (see Table 1) is the ability to calculate the true risk ratios, excess risk, the absolute risk difference, but also incidence rates and incidence rate ratios. The excess risk is useful in determining the number needed to harm, that is, the number of patients who need be exposed to a drug to produce a specified AE.

After the data are filled in, the absolute and relative risks are calculated (Table 2).

This tells us that the drug group is more than two times at risk for this AE compared with the comparator group. If the relative risk were 1, the likelihood of getting the AE is the same in the drug group and in the cohort group. If the relative risk is less than 1 (but greater than zero — the value in this calculation is always greater than zero), then the risk of getting the AE in the drug group is less than that in the cohort group.

Table 1. Organization of Data Cells and Formula to Calculate Relative Risk and Absolute Risk.

Note: Relative risk = [a/(a + c)] ÷ [b/(b + d)] or the rate in exposed divided by the rate in the unexposed. Absolute risk = [a/(a + c)] − [b/(b + d)] or rate in exposed minus rate in unexposed.

In the example, the absolute risk indicates that there were 343 additional cases of AE per 1,000 patients exposed to the drug. Therefore, the number needed to harm is about 3; that is, every third patient on the average will develop the AE (something the clinician should keep in mind).

For an excellent discussion of risk ratios and odds ratios, their differences, when they are close to being the same (i.e., when the AEs are very rare), and other complex issues.¹ The entire Bandolier site is worth looking at for, as they put it, “evidence-based thinking about healthcare”.