Table 1.

Summary of the strengths and limitations of various pharmacoepidemiological designs

Method	Strengths	Limitations
Cohort	Exposure precedes outcomes Can explore multiple outcomes Allow rare exposures Can estimate the incidence of outcomes	Time- and resource- consuming Difficult to study rare outcomes
Case–control	Can explore multiple exposures Allow rare outcomes Quicker and cheaper (compared to cohort studies)	Difficult to study rare exposures Difficult to select proper cases and controls Cannot estimate the incidence of outcomes
Self-controlled case series (SCCS)	Eliminates time-invariant confounders Less data-intensive (compared to cohort or case–control studies) Temporal variables such as age can be accounted for by subdividing the observation period	Sensitive to time-variant confounders Cannot estimate the incidence of outcomes Not suitable when any of the following assumptions is violated  Outcome events are rare or independent of each other  Occurrence of outcome event is independent of the exposures  Occurrence of outcome event or any subsequent conditions stemming from the event should not censor the observation period
Case-crossover (CCO)	Eliminates time-invariant confounders Less data-intensive (compared to cohort or case–control studies) Exposure-trend bias can be addressed by case–time–control (CTC) or case–case–time–control (CCTC)	Sensitive to time-variant confounders Cannot estimate the incidence of outcomes Not suitable when any of the following assumptions is violated  Transient exposures and acute outcomes  Exposure has a stable trend over time CTC and CCTC may reintroduce control-selection bias if the external controls are not well-matched