The BLISTER Study

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

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

Treatment already known to work, but can it work in real world clinical practice? - effectiveness

Wider group of participants – co morbidity, less compliant

Maybe primary care setting

Flexible dosing, switching and rescue therapy compatible with daily practice – “policy” of a treatment pathway rather than one drug

Cost effectiveness key

Explanatory Pragmatic

Homogenous patients

Tightly defined intervention

Clearly defined control group – often placebo

Objective/surrogate outcomes

Real life patients

Flexible intervention with changes

Active comparator

Clinically important outcomes

Still have to fiercely minimise bias1.Selection - Randomisation and allocation

concealment2.Performance – similar conditions both

groups3.Detection bias – blinded outcome4.Attrition bias – collecting data on dropout

and intention to treat analysis

Is it explanatory or pragmatic? –

X wrong question

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.

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

Sent to six TMG members

Two pemphigoid experts

One clinician interested in clinical trials

Two trial statisticians

Eligibility Criteria

Flexibility of theExperimental Intervention

PrimaryAnalysis

PractitionerAdherence

ParticipantCompliance

Outcomes

Follow-upIntensity

PractitionerExpertise(Comparison)

Flexibility of theComparisonIntervention

PractitionerExpertise(Experimental)

Described explanatory and pragmatic trials

A continuum not a dichotomy

Applied PRECIS wheel to BLISTER

Pragmatic studies not an excuse for bias

Most clinical trials that change NHS practice need to be pragmatic