Transcript Talk given by Hywel Williams - "Pragmatic versus Explanatory trials"

The BLISTER Study
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Introduce explanatory and pragmatic designs
The concept of a continuum rather than
dichotomy
Use of the PRECIS wheel in BLISTER
Clinical implications of internal versus
external validity
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Conducted under “ideal” conditions
Highly selected and homogeneous participants
Usually tertiary care
Good compliance
Likely to remain in study
Only one medical condition
Strict dosing schedules
Monitored closely
To “explain” if a treatment works - efficacy
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Treatment already known to work, but can it work in real
world clinical practice? - effectiveness
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Wider group of participants – co morbidity, less compliant
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Maybe primary care setting
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Flexible dosing, switching and rescue therapy compatible
with daily practice – “policy” of a treatment pathway rather
than one drug
Cost effectiveness key
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Homogenous patients
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Tightly defined
intervention
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Clearly defined control
group – often placebo
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Objective/surrogate
outcomes
Explanatory
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Real life patients
Flexible intervention
with changes
Active comparator
Clinically important
outcomes
Pragmatic
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Still have to fiercely minimise bias
1. Selection
- Randomisation and allocation
concealment
2. Performance – similar conditions both groups
3. Detection bias – blinded outcome
4. Attrition bias – collecting data on dropout
and intention to treat analysis
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Is it explanatory or pragmatic? –
X wrong question
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To what extent is it explanatory or pragmatic? –
right question
Thorpe KE et al: A pragmatic–explanatory continuum
indicator summary (PRECIS): a tool to help trial designers.
Journal of Clinical Epidemiology 2009, 62:464-475.
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The Pragmatic-Explanatory Continuum
Indicator Summary
Typically used as a tool when designing study
Requires a judgement on key aspects of trial
design
Illustrated by a PRECIS wheel
A blank pragmatic - explanatory continuum indicator summary (PRECIS) ‘‘wheel.’’
PRECIS summary of a randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsia
(Collaborative Low dose Aspirin Study in Pregnancy [CLASP])
PRECIS summary of a randomized trial of low-dose aspirin for the prevention of
pre-eclampsia in women at high risk
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Sent to six TMG members
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Two pemphigoid experts
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One clinician interested in clinical trials
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Two trial statisticians
Flexibility of the
Comparison
Intervention
Practitioner
Expertise
(Experimental)
Practitioner
Expertise
(Comparison)
Flexibility of the
Experimental
Intervention
Follow-up
Intensity
Eligibility
Criteria
Primary
Analysis
Outcomes
Participant
Compliance
Practitioner
Adherence
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Described explanatory and pragmatic trials
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A continuum not a dichotomy
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Applied PRECIS wheel to BLISTER
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Pragmatic studies not an excuse for bias
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Most clinical trials that change NHS practice
need to be pragmatic