Driving up the Quality and Relevance of Research Through the Use of Agreed Core Outcomes

There is a growing recognition that insufficient attention has been paid to the selection of the outcomes to measure in clinical trials and clinical audit. Outcomes need to be relevant to patients, clinicians, purchasers and policy-makers if the findings of research are to influence practice and future research. In addition, standardization of outcomes is needed to combine data from different studies to allow evidence synthesis and to compare data sets. Inconsistent choice of outcome measures means that many meta-analyses are unable to include data from all the relevant studies. For example, the five most accessed Cochrane reviews in 2009, together with the top cited review in that year, all described inconsistencies in the outcomes reported in eligible trials. A call for the standardization of outcomes is a regular conclusion of systematic reviews. Furthermore, outcome reporting bias, defined as the bias arising from selecting outcomes for publication based on the results, affects many randomized trials and ‘is an under-recognized problem that affects the conclusions in a substantial proportion of Cochrane reviews’. That bias is likely to affect systematic reviews more widely as well as affecting individual studies when considered on their own. Similar problems occur with clinical audit, highlighting the importance of establishing national audits that use and report the same outcomes for all participants. All these issues could be addressed with the development and application of agreed standardized sets of outcomes that have been termed ‘core outcome sets’. These should be measured and reported, as a minimum, in all relevant clinical trials and national clinical audits for a specific condition. Adopting a core outcome set does not imply that a particular study, review or audit should be restricted to only those outcomes. Rather, the expectation is that, as a minimum, core outcomes will always be collected and reported to allow the results of trials to be compared, contrasted and combined as appropriate. The adoption of core outcomes would have implications across all areas of research in health and health care, reduce heterogeneity between trials, and lead to research that is more likely to have measured relevant outcomes. Importantly, they would enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information. In addition, they will increase the efficiency and value of research. An important rationale for core outcome sets is that outcomes currently reported for trials do not consistently reflect endpoints that are meaningful for patients. Examples exist where trials failed to include all outcomes important to patients and where involvement of patients has identified an outcome that might not have been considered by practitioners on their own. Despite increasing recognition of the importance of incorporating patients’ opinions, their involvement has been limited. Recent regulatory guidance in the USA requires documented evidence of patient input during the development of instruments to measure patient reported outcomes (PROs). However, measurement of PROs in clinical trials is hampered by the multiplicity and heterogeneity of tools currently available. Many generic, diseaseand domain-specific instruments have been developed and validated, each containing multiple scales and items. As a result, synthesis of PRO data from trials is difficult and reviews aiming to summarize treatment effect according to PROs may fail. There is synergy between the development of core outcome sets for trials and work to select up to seven outcomes that are important to patients for inclusion in Summary of Findings tables in systematic reviews. Developed by the GRADE group (http://www.gradeworkinggroup.org), Cochrane reviews have featured such tables since 2008, and they play a key role in presenting research in guidelines, such as those produced by the World Health Organization (WHO). The development of core outcome sets needs to be accelerated and undertaken in ways that maximize efficiency. The COMET (Core Outcome Measures in Effectiveness Trials, http://www.comet-initiative.org) Initiative in the UK brings together researchers interested in the development and application of core outcome sets. These include key participants in a collaboration of researchers in rheumatology who have done the most notable work to date in this area. The COMET Initiative was launched in January 2010, with a second meeting in July 2011. Attendees included trialists, systematic reviewers, patients, clinicians, journal editors, research funders, policy-makers, people responsible for trials registries and regulators. Data on individual studies, both published and ongoing, are being included in a free, publically available internet-based resource. This will be updated periodically, to minimize the risk of duplication. Seventy-eight published or ongoing studies have already been entered into the repository. In addition, published reviews of outcomes used in clinical trials or studies examining patients’ views, will be entered.