Research Techniques Made Simple:Pragmatic or Explanatory Trial?

The BLISTER StudyThe Bullous Pemphigoid Steroids and Tetracyclines Study

Hywel WilliamsHywel WilliamsUniversity of NottinghamUniversity of Nottingham

with help from Daniel Bratton and Andrew Nunnwith help from Daniel Bratton and Andrew NunnMRC Clinical Trials UnitMRC Clinical Trials Unit

HTA reference 06/403/51HTA reference 06/403/51ISRCTN13704604ISRCTN13704604

Pragmatic study – does it work in my clinic?

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

• Wider group of participants – more comorbidities, less compliant

• Maybe in a primary care setting

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

• Cost-effectiveness is key

Explanatory trials - can it work?

• 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

PICOT comparison

Pragmatic

• Homogenous patients

• Tightly defined intervention

• Clearly defined control group – often placebo

• Objective/surrogate outcomes

• Short-term follow-up time, e.g., 6 weeks

• Real-life patients

• Flexible intervention with changes

• Active comparator

• Clinically important outcomes

• Longer-term follow-up times, e.g., 6 months

Pragmatic does not mean “anything goes”

Still have to fiercely minimize bias

1.Selection - Randomization and allocation concealment

2.Performance – similar conditions for both groups

3.Detection bias – blinded outcome

4.Attrition bias – collecting data on dropout and intention-to-treat analysis

Back to BLISTER.....

• 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.

More about PRECIS

• The Pragmatic-Explanatory Continuum Indicator Summary

• Typically used as a tool when designing study

• Requires a judgment on key aspects of trial design

• Illustrated by a PRECIS wheel

A blank pragmatic - explanatory continuum indicator summary (PRECIS) ‘‘wheel.’’

Applied PRECIS to BLISTER

• Sent to six TMG members

• Two pemphigoid experts

• One clinician interested in clinical trials

• Two trial statisticians

Summary points• Described explanatory and pragmatic trials

• A continuum, not a dichotomy

• Applied PRECIS wheel to BLISTER

• Pragmatic studies are not an excuse for bias

• Most clinical trials that change clinical practice need to be pragmatic