Explanation

All randomised trials assess outcomes, for which the groups are compared. Most trials have several outcomes, some of which are of more importance than others. The primary outcome is the prespecified outcome considered to be of greatest importance to relevant stakeholders (such as patients, policy makers, clinicians, and funders) and should be the one used in the sample size calculation (item 16). The primary outcome should be explicitly indicated as such in the report of a randomised trial. Other outcomes of interest are secondary outcomes.

 

It is important to explain the rationale and clinical relevance for chosen efficacy and harm outcomes, including whether they are part of a core outcome set [217, 218]. A core outcome set is an agreed standardised set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or health care. The COMET (Core Outcome Measures in Effectiveness Trials) initiative and COMET database facilitate access to core outcome sets (https://www.comet-initiative.org/).

 

Most trials have a single primary outcome. Having several primary outcomes can incur potential problems of interpretation associated with multiplicity of analyses (items 28 and 30). There are typically multiple secondary outcomes (ie, the outcomes prespecified in the trial protocol to assess any additional effects of the intervention). Secondary outcomes can include harms that may include unintended effects of the intervention (item 27).

 

The primary and secondary outcomes reported should be consistent with the outcomes prespecified in the trial protocol and the registry. Evidence shows important discrepancies between the outcome reported in the registry or protocol and outcomes reported in final publications, frequently in favour of statistically significant results. Any change in outcome(s) specified in the protocol should be reported, with reasons (item 10) [51, 175, 176].

 

All outcomes, whether primary or secondary, should be described and completely defined. This information is typically also detailed in the trial’s protocol and the trial registry. The principle here is that the information provided should be sufficient to allow others to use the same outcomes [198]. For each outcome, it is important to detail: (1) the specific measurement variable, which corresponds to the data collected directly from trial participants (eg, Beck Depression Scale; all cause mortality) with definition where relevant (eg, major bleeding was defined as fatal bleeding or symptomatic bleeding in a critical area or organ; all cause mortality per hospital database); (2) the specific participant level analysis metric, which corresponds to the format of the outcome data that was used from each trial participant for analysis (eg, change from baseline; final value or value at a time point; time to event); (3) the method of aggregation, which refers to the summary measure format for each trial group (eg, mean; proportion of participants with score >2); and (4) the measurement time point of interest for analysis [219]. For composite outcomes, all individual components of the composite outcome should be described as secondary outcomes [21]. Only half of randomised trials published in PubMed indexed journals in 2000 and 2006 specified the primary outcome [220, 221]. In recent samples of trials published in specific fields, reporting has improved but still two thirds did not provide a complete definition [222, 223].

 

The use of previously developed and validated scales can help to enhance quality of measurement [224, 225]. For example, assessment of health related quality of life using a validated instrument is critical to the integrity and applicability of the trial [226]. Authors should report measurement properties of outcome measurement instruments to assist in interpretation and comparison with similar studies [227].

 

In most trials, information on outcomes is set to be collected as part of the trial conduct. However, some trials may use existing data collecting structures (eg, national, healthcare or administrative registries). This should be clarified in the methods. There is empirical evidence that treatment effect estimates may be different in trials where outcomes are obtained from routinely collected data [228].