Most Cochrane reviews focus on randomized trials, which provide the most reliable estimates of effect. However, rare adverse events or long-term adverse effects are unlikely to be observed in clinical trials, and a thorough investigation may require the inclusion of cohort studies, case-control studies and even case reports or case series. In particular, the strategies outlined in Sections 14.2.2 and 14.2.3 are likely to be chosen specifically so that different study designs are included to address adverse effects. For more detailed discussion of issues in the inclusion of non-randomized studies (including case-control and cohort studies) in a Cochrane review, see Chapter 13 (Section 13.2). Some issues to consider in the inclusion of case reports appear in Section 14.6.3.