Surrogate outcomes

Revised and reviewed 19 May 2014

OVERVIEW

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”

TYPES

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

ADVANTAGES

  • cheap
  • available
  • easily measured and monitored
  • may show larger intervention effects than clinical outcomes
  • may respond to interventions more quickly that clinical outcomes

DISADVANTAGES

  • 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

Journal articles

  • Yudkin JS, Lipska KJ, Montori VM. The idolatry of the surrogate. BMJ. 2011 Dec 28;343:d7995. PMID: 22205706.

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Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the  Clinician Educator Incubator programme, and a CICM First Part Examiner.

He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.

His one great achievement is being the father of three amazing children.

On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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