The Pragmatic Trial at 50 ICTMC 2017 May 9th Chair: Sandra Eldridge Jeremy Grimshaw Spencer Phillips Hey Cory Goldstein Charles Weijer

The Pragmatic Trial at 50: Introduction Sandra Eldridge Title Authors Centre for Primary Care & Public Health Blizard Institute Pragmatic Clinical Trials Unit

What is a pragmatic trial? Schwartz and Lellouch (J. Chron. Dis.1967;20:637-48) Pragmatic trials = to help choose between care options Explanatory trials = to test causal research hypotheses Roland and Torgerson (BMJ 1998;316:285) Pragmatic trials measure effectiveness—the benefit the treatment produces in routine clinical practice Explanatory trials generally measure efficacy—the benefit a treatment produces under ideal conditions

How pragmatic/how explanatory? EXPLANATORY PRAGMATIC How pragmatic/how explanatory?

Pragmatic Explanatory Representative participants Highly selected participants Recruited in usual care, many centres Recruited in another way, few centres Setting where results apply Different setting Intervention slotted into usual care Intervention requires additional resources Flexibility in delivery Very standardised delivery Flexibility in adherence Highly controlled adherence Follow-up exactly as would be in usual care More extensive follow up Primary outcome relevant to participants Primary outcome not relevant to participants Primary analysis intention to treat Primary analysis per protocol

When? (drug trials) Translational pathway EXPLANATORY PRAGMATIC BASIC SCIENCE EXPLANATORY PRAGMATIC “Ideal” conditions In routine practice Can this treatment work? Does this treatment work?

WAIT – Montelukast for pre-school wheeze Population Intervention Outcome Unscheduled medical attendances for wheezing Control Placebo

STOP – Smoking cessation through pharmacies Population (pharmacies) Intervention Training and support for pharmacists Outcome (customers) Control No training and support

How often? Zwarenstein & Treweek 2009 “Most trials done hitherto have adopted the explanatory approach without question; the pragmatic approach would often have been more justifiable.” Schwartz & Lellouch 1967

Vichithranie Madurasinghe Acknowledgements Gordon Forbes Kirsty Loudon Shaun Treweek Megan Clinch Steph Taylor Robert Walton Wai Yee James Sandra Jumbe Vichithranie Madurasinghe Ratna Sohanpal Carol Rivas Liz Steed Chris Griffiths Clare Rutterford Jonathan Grigg Chinedu Nwokoro Title Authors Centre for Primary Care & Public Health Blizard Institute

Pragmatic trials at 50 – Back to the future? Pragmatic RCTs and the Learning Healthcare System Precision Medicine and Pragmatic Trials: Friends or Foes? Towards ethical guidance for pragmatic randomized controlled trials