5.4.1 Listing relevant outcomes

The third key component of a well-formulated question is the delineation of particular outcomes that are of interest. In some circumstances, the measurement of certain outcomes may be a criterion for including studies into a review, for example when the intervention is aimed at preventing a particular outcome. However, reporting of outcomes should rarely determine eligibility of studies for a review. In particular, studies should not be excluded because they provide no 'usable' data.

 

In general, Cochrane reviews should include all outcomes that are likely to be meaningful to clinicians, patients (consumers), the general public, administrators and policy makers, but should not include outcomes reported in included studies if they are trivial or meaningless to decision makers.  Outcomes considered to be meaningful and therefore addressed in a review will not necessarily have been reported in individual studies. For example, quality of life is an important outcome, perhaps the most important outcome, for people considering whether or not to use chemotherapy for advanced cancer, even if the available studies are found to report only survival (see Chapter 17). Including all important outcomes in a review will highlight gaps in the primary research and encourage researchers to address these gaps in future studies.

 

Outcomes may include survival (mortality), clinical events (e.g. strokes or myocardial infarction), patient-reported outcomes (e.g. symptoms, quality of life), adverse events, burdens (e.g. demands on caregivers, frequency of tests, restrictions on lifestyle) and economic outcomes (e.g. cost and resource use). It is critical that outcomes used to assess adverse effects as well as outcomes used to assess beneficial effects are among those addressed by a review (see Chapter 14). If combinations of outcomes will be considered, these need to be specified. For example, if a study fails to make a distinction between non-fatal and fatal strokes, will these data be included in a meta-analysis if the question specifically relates to stroke death?

 

Review authors should consider how outcomes may be measured, both in terms of the type of scale likely to be used and the timing of measurement. Outcomes may be measured objectively (e.g. blood pressure, number of strokes) or subjectively as rated by a clinician, patient, or carer (e.g. disability scales). It may be important to specify whether measurement scales have been published or validated. When defining the timing of outcome measurement, authors may consider whether all time frames or only selected time-points will be included in the review. One strategy is to group time-points into pre-specified intervals to represent ‘short-term’, ‘medium-term’ and ‘long-term’ outcomes and to take no more than one of each from each study for any particular outcome. It is important to give the timing of outcome measure considerable thought as it can influence the results of the review (Gøtzsche 2007).

 

As Cochrane reviews are increasingly included in Overviews of reviews (see Chapter 22), harmonization of outcomes across reviews addressing related questions will facilitate this process. It may be helpful for review authors to consider those measures used in related reviews when defining the type and timing of measurement within their own review. In addition, several clinical areas are developing agreed core sets of outcome measures for use in randomized trials, and consideration of these in defining the detail of measurement of outcomes selected for the review is likely to be helpful.

 

Various sources can be used to develop a list of relevant outcomes, including the clinical experiences of the review authors, input from consumers and advisory groups (see Chapter 2), and evidence from the literature (including qualitative research about outcomes important to those affected). Further information about the use of qualitative research to inform the formulation of review questions, including types of outcome measures, can be found in Chapter 20.

 

While all important outcomes should be included in Cochrane reviews, trivial outcomes should not be included. Authors need to avoid overwhelming and potentially misleading readers with data that are of little or no importance. In addition, indirect or surrogate outcome measures, such as laboratory results or radiologic results (e.g. loss of bone mineral content as a surrogate for fractures in hormone replacement therapy), are potentially misleading and should be avoided or interpreted with caution because they may not predict clinically important outcomes accurately. Surrogate outcomes may provide information on how a treatment might work but not whether it actually does work. Many interventions reduce the risk for a surrogate outcome but have no effect or have harmful effects on clinically relevant outcomes, and some interventions have no effect on surrogate measures but improve clinical outcomes.