The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1978-4) contains supplementary material, which is available to authorized users.

The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus.

BackgroundCore outcome sets (COS) can enhance the relevance of research by ensuring that outcomes of importance to health service users and other people making choices about health care in a particular topic area are measured routinely. Over 200 COS to date have been developed, but the clarity of these reports is suboptimal. COS studies will not achieve their goal if reports of COS are not complete and transparent.Methods and FindingsIn recognition of these issues, an international group that included experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives developed the Core Outcome Set–STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies. The developmental process consisted of an initial reporting item generation stage and a two-round Delphi survey involving nearly 200 participants representing key stakeholder groups, followed by a consensus meeting. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies. The checklist items focus on the introduction, methods, results, and discussion section of a manuscript describing the development of a particular COS. A limitation of the COS-STAR Statement is that it was developed without representative views of low- and middle-income countries. COS have equal relevance to studies conducted in these areas, and, subsequently, this guideline may need to evolve over time to encompass any additional challenges from developing COS in these areas.ConclusionsWith many ongoing COS studies underway, the COS-STAR Statement should be a helpful resource to improve the reporting of COS studies for the benefit of all COS users.

BackgroundAdverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.Methods and FindingsWe searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.ConclusionsThere is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

BackgroundA core outcome set (COS) is a standardised set of outcomes which should be measured and reported, as a minimum, in all effectiveness trials for a specific health area. This will allow results of studies to be compared, contrasted and combined as appropriate, as well as ensuring that all trials contribute usable information. The COMET (Core Outcome Measures for Effectiveness Trials) Initiative aims to support the development, reporting and adoption of COS. Central to this is a publically accessible online resource, populated with all available COS. The aim of the review we report here was to identify studies that sought to determine which outcomes or domains to measure in all clinical trials in a specific condition and to describe the methodological techniques used in these studies.MethodsWe developed a multi-faceted search strategy for electronic databases (MEDLINE, SCOPUS, and Cochrane Methodology Register). We included studies that sought to determine which outcomes/domains to measure in all clinical trials in a specific condition.ResultsA total of 250 reports relating to 198 studies were judged eligible for inclusion in the review. Studies covered various areas of health, most commonly cancer, rheumatology, neurology, heart and circulation, and dentistry and oral health. A variety of methods have been used to develop COS, including semi-structured discussion, unstructured group discussion, the Delphi Technique, Consensus Development Conference, surveys and Nominal Group Technique. The most common groups involved were clinical experts and non-clinical research experts. Thirty-one (16%) studies reported that the public had been involved in the process. The geographic locations of participants were predominantly North America (n = 164; 83%) and Europe (n = 150; 76%).ConclusionsThis systematic review identified many health areas where a COS has been developed, but also highlights important gaps. It is a further step towards a comprehensive, up-to-date database of COS. In addition, it shows the need for methodological guidance, including how to engage key stakeholder groups, particularly members of the public.