The risk for a disease (or adverse event) represents the probability for the event to occur among a defined susceptible (or exposed) population. For example, the risk of a skin rash in the first week of treatment in patients receiving an antimicrobial. When risk is presented as a proportion (per 100 patients), we assume that all patients were exposed for the same length of time. In the example above, all patients were observed for 1 week. However, it is expected that the longer a patient is susceptible, or exposed, the higher is the probability for events to be observed. Incidence rates can be used to account for different lengths of times exposed when measuring risk.3
Incidence rate (or incidence density rate or patient-time incidence rate)
Is a statistic that represents a summary measure of event occurrence per population, taking into account the length of time that each member of the population was susceptible or exposed (patient-time at risk). In technical terms, incidence rate of an event in a population is the ratio of new events in a specified time period (numerator) divided by the sum of the periods of time at risk for each of the patients (denominator). For example, 1 case per 1000 patient-years exposed expresses 1 new case observed among 1000 persons during 1 year of exposure, or 1 new case observed among 500 patients during 2 years of exposure.3
Patient-time of exposure
In a study with 100 patients, 25 of whom participated for 2 years,
and the other 75 who participated for 6 years, the denominator of the
incidence rate as the total number of patient-years exposed is 500
patient-years [(25 patients x 2 years) + (75 patients x 6 years) = 50
+ 450 patient-years].
If among those 100 patients, 5 occurrences of accidental bone fracture were observed, then the risk (proportion) would have been 5/100 patients or 5%.
We assume that the risk during the remaining 4 years for the 25 patients with 2-year participation would be no different from their first 2 years or from the 6 years of participation of the other 75 patients.
However, the incidence rate of accidental bone fracture would have been 5 per 500 patient-years, or 1/100 patient-years. This means that, on average, there was 1 occurrence of accidental bone fracture per 100 patients, over the course of each 1 year of treatment.
Incidence rates are used in many epidemiological studies and statistical assessments of risk which allows researchers to reveal trends and communicate levels of risk.
Studies of new medicines can express their safety findings using incidence rates based on 100 patient-years.3
Refers to the time after a drug or biological product has been approved by FDA.4
PML that develops a few months after stopping one disease modifying therapy (DMT) and starting a different DMT. In these cases, PML could have developed without causing symptoms while the patient was still on the previous DMT, or shortly after stopping the previous DMT.5
Confounding of adverse event reporting occurs when the assessment of association between exposure to a drug and an adverse event is distorted by the effect of one or several other variables that are also risk factors for the outcome of interest.6
Porta M (Ed.) (2014) A dictionary of epidemiology (6th ed.). New York, NY: Oxford University Press. http://irea.ir/files/site1/pages/dictionary.pdf. Accessed June 2018
US Food and Drug Administration. Postmarketing Requirements and Commitments: Reports. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/ucm064436.htm. Accessed January 2018
Giovannoni G, et al. Pract Neurol. 2016; 16:389–393.
Varallo FR, et al. Clin Ther. 2017;39:686–96.