Core Outcome Measures in Effectiveness Trials

Acknowledgments COMET Management Group: Doug Altman, Jane Blazeby, Mike Clarke, Paula Williamson Funding: MRC HTMR Network, now MRC COMET project coordinator: Elizabeth Gargon

Health care research is untidy It needs to be tidied up if it is to achieve its aim of helping practitioners and patients to improve health care and health This needs initiatives such as The Cochrane Collaboration for the preparation and maintenance of systematic reviews and COMET for core outcome sets

“We sought data for rate of falls, number of people falling, and number of people sustaining a fracture. However, few studies provided fracture data.” (Preventing falls in the elderly) “No study reported relevant data on diabetes and cardiovascular related morbidity, mortality and quality of life..” (Preventing Type 2 DM) “The studies … varied greatly in intervention design, outcome measurements and methodological quality.” (Preventing childhood obesity) “Appropriate short- and long-term outcomes need to be defined for children and youth at various weight levels, rather than using conventional or adult-oriented outcomes.” ( Treating childhood obesity) “The studies were heterogeneous in terms of study design, quality, target population, theoretical underpinning, and outcome measures, making it impossible to combine study findings using statistical methods..” (Promoting activity in children) “Definitions of abstinence varied considerably... In five studies it was unclear exactly how abstinence was defined.” (Nicotine replacement therapy)

5 Systematic review of evidence on selective outcome reporting Studies reporting positive or significant results are more likely to be published Outcomes that are statistically significant are more likely to be fully reported 40–62% of publications had at least one primary outcome changed, newly introduced or omitted compared to protocol [Dwan et al, PLoS ONE 2008]

Why have core outcome sets? Several tens of thousands of research studies are underway and 500+ are published every week Working through them is overwhelming and made worse by studies of the same topic describing findings in different ways Systematic reviews might help but need to bring together and make sense of a variety of studies, using a variety of outcomes, measured in a variety of ways; and need to choose outcomes that the readers want to see We need to be able to compare, contrast and combine research to improve health care and improve health

What is a “core outcome set”? An agreed standardised set of the most important (“core”) outcomes Disease/condition specific (might cover all treatment types or a particular intervention) Includes both benefits and harms Measured and reported as the minimum (other outcomes will usually be collected) Relevant within routine clinical practice

Advantages of core outcome sets Increases consistency across trials Maximise potential for trial to contribute to systematic reviews of these key outcomes Much more likely to measure appropriate outcomes Major reduction in selective reporting 8

Trials :38

Appropriate outcomes Patient involvement Impact – rheumatology (OMERACT): fatigue – chronic pain (IMMPACT): expansion of previously proposed core outcome domains – paediatric asthma (parents and children)

COMET Initiative Facilitate and promote development and application of core outcome sets Highlighting current work on core outcome sets in over 70 clinical areas - systematic review ongoing 1 st meeting, Liverpool, UK, January 2010, 110+ attendees: trialists, systematic reviewers, health service users, clinical teams, journal editors, trial funders, policy makers, and regulators An international network

Website

Search results

Core outcome sets Should be developed scientifically – guidance Uptake should be monitored and feedback sought – to assess impact (OMERACT evaluation ongoing) – to inform possible future update 14

Development of core outcome sets: Issues to consider Scope Identifying existing knowledge Stakeholder involvement Consensus methods Achieving global consensus Regular review, feedback, updating Implementation Clear presentation Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13(1):132. doi: /

Next steps ‘What’ to measure Guidance on methods for developing core outcome sets, including patient involvement Reporting standards ‘How’ to measure (validity, reliability, feasibility) - PROMIS - COSMIN - TREAT-NMD - Musculoskeletal - Paediatrics

SPIRIT guidelines for RCT protocols Item 12: OUTCOMES Primary, secondary, and other outcomes, including the specific variable (e.g. systolic blood pressure), analysis metric (e.g. mean change; proportion of trial participants; time-to-event), and timepoint for each outcome. Explanation of the relevance of chosen outcomes is strongly recommended. [Chan et al, to appear] 18

Professor Hywel Williams, Chair of the NIHR HTA Commissioning Board: ‘Patients and professionals making decisions about health care need access to reliable evidence. The new COMET database will help researchers across the NIHR family and beyond when choosing the outcomes to include in the studies that will establish this evidence base'.

Core Outcome Measures in Effectiveness Trials

Example from outside health Choosing a route to the train station 1: “2 miles” 2: “25 minutes” 3: “very pretty” What would you prefer to have been measured? Distance, time or beauty? 1: “2 miles” 2: “4 kilometres” 3: “not too far” 1: Walking 2: In a taxi 3: On a Vespa