Practice Misalignment
Reviewed and revised 4 December 2014
OVERVIEW
- Practice misalignment occurs in RCTs when randomization disrupts the normal relationship between clinically important characteristics and therapy titration
- This can create subgroups of patients within each study arm that receive levels of therapy that are inconsistent with current practices outside of the clinical study and may be harmful
IMPORTANCE
- Trials that can be adversely affected by practice misalignment are those that investigate routinely used interventions that are titrated based on clinical factors to maximize benefit or limit risk
- Misaligned subgroups may have worse outcomes than usual care
EXAMPLES
- ARDSNet ARMA trial (RCT of 6 mL/kg versus 12 mL/kg tidal volumes in mechanically ventilated ARDS patients)
- at the time, physicians tended to ventilate ARDS patients’ lungs with smaller tidal volumes as airway pressures increased and lung compliance decreased, not a non-titrated tidal volume of 12 mL/kg
- at the time, physicians tended to ventilate ARDS patients’ lungs with smaller tidal volumes as airway pressures increased and lung compliance decreased, not a non-titrated tidal volume of 12 mL/kg
- TRICC trial (RCT of using Hb <7 g/dl versus <10 g/dL as transfusion trigger in non-bleeding ICU patients)
- at the time clinicians decided to transfuse based on patient characteristics and risk of ischemia
- e.g. young patients with no ischemia would not have been transfused to 10 g/dL by most clinicians
HOW TO AVOID AND DETECT PRACTICE MISALIGNMENT
- thoroughly investigate usual practice before performing a trial and identify the factors that lead clinicians to titrate therapies (e.g. prospective observational studies, literature reviews)
- simulate randomisation of patients to intervention and control prior to performing the study – is there a risk of practice misalignment?
- include a true control group representing routine practice
- restricted enrollment (use more homogeneous study populations, but this limits external validity)
- a priori stratification (requires larger study numbers)
- adaptive trial designs
References and Links
Journal articles
- Deans KJ, Minneci PC, Danner RL, Eichacker PQ, Natanson C. Practice misalignments in randomized controlled trials: Identification, impact, and potential solutions. Anesth Analg. 2010 Aug;111(2):444-50. PMC2888723.
- Deans KJ, Minneci PC, Suffredini AF, Danner RL, Hoffman WD, Ciu X, Klein HG, Schechter AN, Banks SM, Eichacker PQ, Natanson C. Randomization in clinical trials of titrated therapies: unintended consequences of using fixed treatment protocols. Crit Care Med. 2007 Jun;35(6):1509-16. PMID: 17440420.
Critical Care
Compendium
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.
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