This is an archived version of the Handbook. For the current version, please go to or search for this chapter here.  Determining which types of non-randomized study to include

A randomized trial is a prospective, experimental study design specifically involving random allocation of participants to interventions. Although there are variations in randomized trial design (including random allocation of individuals, clusters or body parts; multi-arm trials, factorial trials and cross-over trials) they constitute a distinctive study category. By contrast, NRS cover a number of fundamentally different designs, several of which were originally conceived in the context of aetiological epidemiology. Some of these are summarized in Box 13.1.a, although this is not an exhaustive list, and many studies combine ideas from different basic designs. As we discuss in 13.2.2 these labels are not consistently applied. The diversity of NRS designs raises two related questions. First, should all NRS designs of a particular effectiveness question be included in a review? Second, if review authors do not include all NRS designs, what criteria should be used to decide which study designs to include and which to exclude?


It is generally accepted that criteria should be set to limit the kinds of evidence included in a systematic review. The primary reason is that the risk of bias varies across studies. For this reason, many Cochrane reviews only include randomized trials (when available). For the same reason, it is argued that review authors should only include NRS that are least likely to be biased. It is not helpful to include primary studies in a review when the results of the studies are likely to be biased, even if there is no better evidence. This is because a misleading effect estimate may be more harmful to future patients than no estimate at all, particularly if the people using the evidence to make decisions are unaware of its limitations (Doll 1993, Peto 1995).


There is no agreement about the study design criteria that should be used to limit the inclusion of NRS in a Cochrane review. One strategy is to include only those study designs that will give reasonably valid effect estimates. Another strategy is to include the best available study designs which have been used to answer a question. The first strategy would mean that reviews are consistent and include the same types of NRS, but that some reviews include no studies at all. The second strategy leads to different reviews including different study designs according to what was available. For example, it might be entirely appropriate to use different criteria for inclusion when reviewing the harms, compared with the benefits, of an intervention. This approach is already evident in the Cochrane Database of Systematic Reviews (CDSR), with editors of some Cochrane Review Groups (CRGs) restricting reviews to randomized trials only and other CRG editors allowing specific types of NRS to be included in reviews (typically in healthcare areas where randomized trials are infrequent).


Whichever point of view is adopted, criteria can only be chosen with respect to a hierarchy of primary study designs, ranked in order of risk of bias according to study design features. Existing ‘evidence hierarchies’ for studies of effectiveness (Eccles 1996, National Health and Medical Research Council 1999, Oxford Centre for Evidence-based Medicine 2001) appear to have arisen largely by applying hierarchies for aetiological research questions to effectiveness questions. For example, cohort studies are conventionally regarded as providing better evidence than case-control studies. It is not clear that this is always appropriate since aetiological hierarchies place more emphasis on establishing causality (e.g. dose-response relationship, exposure preceding outcome) than on valid quantification of the effect size. Also, study designs used for studying the effects of interventions can be very much more diverse and complex (Shadish 2002) and may not be easily assimilated into existing evidence hierarchies (see the array of designs in Box 13.1.a, for example). Different designs are susceptible to different biases, and it is often unclear which biases have the greatest impact and how they vary between clinical situations.