Epidemiology terms, but used in clinical trials

Some terms often used in epidemiology fields are actually pretty commonly used in clinical trials. At least for me, I first learned these terms in epidemiology classes. Some of these terms are very close, but different.

Ratio, Proportion, Rate

• Ratio: Division of two unrelated numbers
• Proportion: Division of two related numbers; numerator is a subset of denominator
• Rate: Division of two numbers; time is always in denominator

For example, 'sex ratio' is a ratio (the number of males divided by the number of females). Rising sex-ratio imbalance is a danger in China.
In a clinical trial, there are males subjects and female subjects. We summarized the data using the percentage of male subjects among the total - this is proportion. The # of male subjects (numerator) is a subset of the total subjects (denominator).
A rate is also one number divided by another, but time is an integral part of the denominator. For example, the speed limit is a rate (65 miles per hour). In clinical trial, rate is often used to describe the incidence of adverse events.

Incidence and prevalence

• Incidence: measures the occurrence of new disease; deals with the transition from health to disease; defined as the occurrence of new cases of disease that develop in a candidate population over a specified time period
• Prevalence: measures the existence of current disease; focuses on the period of time that a person lives with a disease; measures the frequency with which new disease develops; defined as the proportion of the total population that is diseased.
  

Incidence is typically used for describing the acute disease while the prevalence is typically used for describing the chronic disease.

Both incidence and prevalence are rate, not ratio, not proportion. In practice, it comes the terms such as incidence rate and prevalence rate.

While prevalence is purely an epidemiology term, 'incidence' or 'incidence rate' is commonly used in the analysis of clinical trial data, especially the adverse event data. Clinical trial design is always prospective and can be considered as a special case of cohort study in epidemiology term.
In statistics and demography, a cohort is a group of subjects who have shared a particular experience during a particular time span. Cohorts may be tracked over extended periods of time in a cohort study. Notice that we also use the term 'cohort' in dose-escalation clinical studies where the cohort refers to a group of subjects who receive the same level of dose (this is contrary to the term 'arm' used in parallel design).

Incidence vs. Incidence Rate

In clinical trial, when we summarize the adverse event data, should we say "incidence of adverse events" or "incidence rate of adverse events"?

While both terms may be used, "incidence of adverse events" should be more accurate and is more frequently used. This can be easily seen in FDA guidance documents, for example:

• Formatting of Bioequivalence Summary Tables
• Guidance on Immune Globulin Intravenous (Human) as Replacement Therapy for Primary Humoral Immunodeficiency
• Guidance on FDA’s Transition Plan for Existing Postmarket Surveillance Protocols
  

"Incidence rate" may be more appropriate when the # of adverse events are normalized by the person year or patient year or normalized by the # of infusions, for example, the following terms may be used: "incidence rate of adverse events per infusion" "The incidence rates per 100 patients-year"