Pharmacoepidemiology for nephrologists (part 1): concept, applications and considerations for study design

FIGURE 1. Steps in the process of drug use and interplay between different players (i.e. healthcare, society and patients).

FIGURE 2. Assessment of drug persistence/discontinuation based on the refill-gap method. In this example there is a treatment discontinuation during follow-up because the third prescription of the treatment occurred after the pill supply + time gap period from the second prescription.

FIGURE 3. Assessment of persistence/discontinuation based on the treatment anniversary method. In this example there is a treatment discontinuation during follow-up because the third prescription of the treatment occurred after the predefined ‘anniversary’ (including also a time gap).

FIGURE 4. Schematic representation of a hypothetical case–control design investigating the association between NSAIDs and AKI. Cases are selected at the time of AKI. Controls are selected from the remaining population of individuals who did not experience AKI at the same point in time. Exposure to NSAIDs is compared between cases and controls.

FIGURE 5. Schematic representation of a hypothetical case-crossover design investigating the association between NSAIDs and AKI. Cases are selected at the time of AKI. The exposure to NSAIDs in the period right before the AKI is compared with a similar period earlier in time.

FIGURE 6. Schematic representation of a hypothetical self-controlled case-series design investigating the association between NSAIDs and AKI. The self-controlled case-series design consists of three steps: (i) cases are selected at the time of AKI, (ii) a particular observation period is selected (in this case the study period from NSAIDs dispensed to end of study) and (iii) the entire exposure history inside this observation period is classified as exposed or unexposed periods. The periods of exposure to NSAIDs are compared with all available control periods within the observation period.

FIGURE 7. Schematic representation of a hypothetical cohort design investigating the association between NSAIDs and AKI. NSAID users are selected when they start therapy. A group of controls is selected at the same point in time among those who were not using the drug or were using another drug (active comparator). Both users and non-users are followed until the AKI event or end of follow-up.