Core outcome sets in randomised clinical trials

1. Core Outcomes in Clinical Trials
Declan Devane
Director, HRB-Trials Methodology Research Network
Professor of Midwifery, NUI Galway

2. The problem…
• Variety of and inconsistency in outcomes
reported in trials (and other studies);
• Differences in how outcomes are defined and
measured;
• Differences in what different stakeholders judge
to be important;
• Studies reporting positive or significant results
are more likely to be published
• Outcomes that are statistically significant are
more likely to be fully reported

3. • Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery
for obesity. Cochrane Database of Systematic
Reviews 2009, Issue 2. Art. No.: CD003641.
DOI: 10.1002/14651858.CD003641.pub3
• ‘Several different measures of weight change
were reported by the studies, namely BMI,
change in BMI, weight, weight loss, percent
weight loss, percent excess weight loss, fat mass,
fat free mass, percent ideal body weight and
proportion of ‘successes’…Quality of life was
reported by just five studies…and co-morbidities
were reported by eight studies.’

6. Fishing for effect
• The large ISIS-2 trial involved 17,000 patients
with suspected heart attack who were
randomised;
– (i) Streptokinase (ii) aspirin (iii) both active treatments
or (iv) neither.
• Substantial beneficial effect for aspirin,
comparable to the effect of streptokinase;
• Authors then do a subgroup analysis……

7. • “subdivision of the patients in ISIS-2 with respect
to their astrological birth sign appears to indicate
that for persons born under Gemini or Libra,
there was a slightly adverse effect of aspirin on
mortality (9% increase, SD 13; NS), while for
patients born under all other astrological signs
there was a striking beneficial effect (28%
reduction, SD 5; 2p <0.00001).”

8. 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

9. 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 to those making decisions about health care.