The choice of study designs to be included in a systematic review should be based on the type of research question being asked and should have the goal of minimizing bias (Glasziou et al., 2004; Oxman et al., 2006). Table 4-3 provides examples of research questions and the types of evidence that are the most appropriate for addressing them. RCTs can answer questions about the efficacy of screening, preventive, and therapeutic interventions. Although RCTs can best answer questions about the potential harms from interventions, observational study designs, such as cohort studies, case series, or case control studies, may be all that are available or possible for the evaluation of rare or long-term outcomes.7 In fact, because harms from interventions are often rare or occur far in the future, a systematic review of observational research may be the best approach to identifying reliable evidence on potential rare harms (or benefits).

Observational studies are generally the most appropriate for answering questions related to prognosis, diagnostic accuracy, incidence, prevalence, and etiology (Chou and Helfand, 2005; Tatsioni et al., 2005). Cohort studies and case series are useful for examining long-term outcomes because RCTs may not monitor patients beyond the primary outcome of interest or for rare outcomes because they generally have small numbers of participants. Case series are often used, for example, to identify the potential long-term harms of new types of radiotherapy. Similarly, the best evidence on potential harms related to oral contraceptive use (e.g., an increased risk of thromboembolism) may be from nonrandomized cohort studies or case-control studies (Glasziou et al., 2004).

Many systematic reviews use a best evidence approach that allows the use of broader inclusion criteria when higher-quality evidence is lacking (Atkins et al., 2005). In these cases, the systematic reviews consider observational studies because, at a minimum, noting the available evidence helps to delineate what is known and what is not known about the effectiveness of the intervention in question. By highlighting the gaps in knowledge, the review establishes the need for better quality evidence and helps to prioritize research topics.

For intervention effectiveness questions for which RCTs form the highest level of evidence, it is essential to fully document the rationale for including nonrandomized evidence in a review. Current practice does not meet this standard, however. Researchers have found, for example, that 30 of 49 EPC reports that included observational studies did not disclose the rationale for doing so (Norris and Atkins, 2005).


See Chapter 1 for the definitions of the types of experimental and observational studies.

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