Core Outcome Measures in Effectiveness Trials

Transcription

1 Core Outcome Measures in Effectiveness Trials Paula Williamson MRC North West Hub for Trials Methodology Research University of Liverpool

2 Acknowledgments Funding: MRC (MRP,) European Commission (FP7) COMET Management Group: Doug Altman, Jane Blazeby, Mike Clarke COMET project coordinator: Elizabeth Gargon FP7 collaborators: Peter Tugwell, Maarten Boers, Caroline Terwee, Holger Schunemann, Michael Rose, Sunita Vohra, Roberto D Amico, Lorenzo Moja

3 Why are outcomes important? Interventions are compared in RCTs by measuring differences in patient outcomes between the groups Selection of appropriate outcomes is crucial Clinical trials are only as credible as their outcomes (Tugwell 1993)

4 DMARD trials in RA

5 Approved application Completed (not necessarily meeting target recruitment) Stopped early Never started Interim analysis Other e.g. poor recruitment Not submitted Submitted Published Not published Not accepted Abstract only Full publication Missing outcome data Some outcomes All outcomes

6 Outcome reporting bias Selection of subset of original recorded outcomes, on the basis of the results, for inclusion in publication Fully reported: OR 2.2 to 4.7 if statistically significant (Dwan et al, PLoS ONE 2008) Reports vs protocols: 40 62% at least one primary outcome changed, newly introduced or omitted Interviews with 59 trialists: lack of clarity about importance and/or feasibility of outcomes chosen (Smyth et al, BMJ 2010)

7 Core outcome set Agreed standardised set of most important outcomes The minimum expect others to be collected Disease/condition specific All treatment types or a particular intervention Both benefits and harms COMET focus to date: effectiveness trials Relevant within routine clinical practice

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

9 The COMET Initiative WHAT to measure HOW to measure a specific outcome (validity, reliability, feasibility) COSMIN, PROMIS, TREAT-NMD

10 Zarin et al, NEJM

11 Cosmetic Outcomes Systematic Review Aspects of cosmesis assessed

12 Trials :38

13 COMET website

14 COMET website Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Cumulative Visits Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Cumulative Searches

15 Development of core outcome sets: Issues to consider (Williamson et al, Trials 2012) Scope Identifying existing knowledge Stakeholder involvement Consensus methods Achieving global consensus Regular review, feedback, updating Implementation Clear presentation

16 Appropriate outcomes Health service users seldom involved 20 studies (8 ongoing) include either patients, caregivers and/or patient support group representatives. Impact of patient involvement rheumatology (OMERACT): fatigue chronic pain (IMMPACT): expansion of previously proposed core outcome domains paediatric asthma (parents and children)

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18 Potential areas of bias Group composition Mainly researchers Patients/families seldom involved One panel or separate panels? How outcomes identified at start of process Mainly considered outcomes that were already measured in clinical trials Seldom asked open questions Attrition of participants

19 Comparison of studies (Sinha et al, Trials 2012)

20 COMET: What we are doing Development and maintenance of a publically available searchable database of projects Systematic review Survey of COS developers Guidance: Developing core outcome sets Guidance: Integrating PROs into core outcome sets COMET III

21 Mental health Database: schizophrenia (published, review of literature), forensic mental health (published, review of literature and COS), outcomes for carers for people with mental health problems (published, review of instruments and carer opinion), bipolar disorder (published, consensus conference) Non-database: offenders with mental health problems, self harm

22 Neurology Database: epilepsy (ongoing, COS), Huntington s disease (ongoing, review of outcomes), Alzheimer s disease (ongoing, COS), Parkinson s disease (ongoing, COS), children with neurodisability (ongoing, PROMS), stroke (ongoing, patient opinion), Guillain Barre syndrome (published, ICF COS), multiple sclerosis (published, ICF COS), non-epileptic seizures (published, consensus workshop), peripheral neuropathy (published, consensus workshop), West syndrome (published, COS), carpal tunnel syndrome (published, review of outcomes) Non-database: dementia, HIV dementia

23 Developmental, psychosocial and learning problems Database: neurodevelopmental delay (ongoing, review of outcomes), autism spectrum disorders (published, review of outcomes in intravenous secretin studies; ongoing, COS)

24 Tobacco, drugs, & alcohol dependence Database: smoking cessation (published, review of outcomes, recommendations made)

25 How to measure recovery COSMIN group systematic reviews of measurement properties of health status measurement instruments Burgess et al (2011) recovery measures in use in Australian mental health services Cavelti (2012) review of self-report instruments for recovery from schizophrenia

26 COSMIN criteria for evaluation of the quality of an instrument

27 Save the Date Thursday 20th and Friday 21st June 2013 COMET 2013 The Midland Hotel Manchester, UK

28 Core Outcome Measures in Effectiveness Trials