Revised and reviewed 19 May 2014
Surrogate outcomes are biomarkers intended to substitute for a clinical endpoint and expected to predict clinical benefit or harm based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence
- surrogate outcomes are not clinically important, but are used because they are thought to predict clinically important outcomes
- much of the evidence for clinical interventions is based on surrogate outcomes, rather than outcomes that actually matter to patients
- in some cases surrogate outcomes morph into actual disease entities (e.g. hypertension)
- patient-centered outcomes are those that reflect the way a patients “feels, functions and survives”
Surrogate outcomes may use biomarkers that are:
- causal factors — biomarkers that are involved directly in the chain of events leading to disease
- subclinical indicators – preclinical manifestations of organ damage
- correlated factors — bystanders not directly involved in the cause of a disease process, but correlate with the development, or regression, of disease
- easily measured and monitored
- may show larger intervention effects than clinical outcomes
- may respond to interventions more quickly that clinical outcomes
- predicted correlation with clinically important outcomes is often not found in subsequent studies nor in the real world setting
- limited by an incomplete understanding of disease pathogenesis
- treatment of the surrogate outcome may have unintended consequences (e.g. affect other disease processes, adverse effects of medications)
- can lead to over-medicalisation of pre-disease or non-disease states
- may be misused as part of a composite outcome measure, together with clinically important outcomes, to create larger intervention effects in trials (allowing smaller, faster trials to be conducted)
USE IN HEALTH POLICY
- the use of surrogate endpoints to guide health policy is hazardous as they may not reflect what is the best interests of patients
- they may lead to distraction from patient-centered outcomes and may be subject to ‘gaming’ to meet performance indicators
- e.g. 4 hour rule, readmission rates, CLABSI rates
PROBLEMS WITH PATIENT-CENTERED OUTCOMES
- can be difficult to measure
- includes a subjective component (the way patients feel)
- they are contingent (e.g. the benefit of longevity is contingent on the quality of life associated with it)
- there may be a time lag between the intervention and the benefits (e.g. increase in lifespan)
References and Links
- Yudkin JS, Lipska KJ, Montori VM. The idolatry of the surrogate. BMJ. 2011 Dec 28;343:d7995. PMID: 22205706.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.