While questions should be posed in the protocol before initiating the full review, these questions should not become a straitjacket that prevents exploration of unexpected issues (Khan 2001). Reviews are analyses of existing data that are constrained by previously chosen study populations, settings, intervention formulations, outcome measures and study designs. It is generally not possible to formulate an answerable question for a review without knowing some of the studies relevant to the question, and it may become clear that the questions a review addresses need to be modified in light of evidence accumulated in the process of conducting the review.
Although a certain fluidity and refinement of questions is to be expected in reviews as a fuller understanding of the evidence is gained, it is important to guard against bias in modifying questions. Data-driven questions can generate false conclusions based on spurious results. Any changes to the protocol that result from revising the question for the review should be documented in the section ‘Differences between the protocol and the review’. Sensitivity analyses may be used to assess the impact of changes on the review findings (see Chapter 9, Section 9.7).When refining questions it is useful to ask the following questions:
What is the motivation for the refinement?
Could the refinement have been influenced by results from any of the included studies?
Are search strategies appropriate for the refined question (especially any that have already been undertaken)?
Are data collection methods appropriate to the refined question?