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Pragmatic Trial Design Considerations: The PRECIS-2 Framework
Elaine H. Morrato, DrPH MPHAssociate Professor, Health Systems, Management and PolicyAssociate Dean for Public Health PracticeDirector, Pragmatic Trials and Dissemination-Implementation Research, Colorado Clinical & Translational Sciences Institute
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Duke Industry Statistics Symposium 2017 | Are Pragmatic Clinical Trials Ready for Prime Time? September 7, 2017
Objectives
• Review PRECIS-2, a framework for pragmatic trial design & reporting
• Apply the PRECIS-2 framework to an example of designing a Phase IIIb drug trial
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PRAGMATIC TRIALS
A randomized controlled trial to inform decisions about practice & real-world effectiveness
Review ArticleThe Changing Face of Clinical Trials
No clinical trial is completely explanatory or pragmatic. Trials exist on a continuum.
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EfficacyExplanatory TrialCan an intervention work under ideal conditions?
Effectiveness Pragmatic Trial
Does the intervention work under real-world conditions?
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BMJ 2015;350:h2147
PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2)
https://crs.dundee.ac.uk/precis
1 = very explanatory5 = very pragmatic
Case Application: Effectiveness of site-specific antibiotic treatment for periodontal disease
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Actisite® (tetracycline periodontal) periodontal fiber
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Good pragmatic trial research requires stakeholder engagement
• To produce information that is meaningful and useful in practice, we must understand priorities and needs from the perspective of patients and other stakeholders
• Patient- and stakeholder-centered research increases the likelihood for effective dissemination and implementation of the findings
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Actisite consumer and market understanding: Concept development
Who will use the product – general dentists, periodontists, both?
In what types of patients would they want to use Actisite?
What evidence do they need to see to convince them to use Actisite?
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Efficacy Trial (Phase 3 study)Multicenter evaluation of tetracycline fiber therapy
5 academic clinical centers
Adult periodontitis (N=113), with 4 non-adjacent teeth, pocket depths = 6-10 mm
4 quadrant randomization: tetracycline fiber, control fiber, scaling & root planning, untreated
Fibers were placed in the pocket and maintained with a cyanoacrylate adhesive for 10 (+/- 2 days)
Significant clinical response at 60d follow-up: pocket depth, attachment level, bleeding on probing
10J Periodontal Res 1991 26(4); 361-70. J Periodontal Res 1991 26(4); 371-9.
Effectiveness Trial (Phase 3b study)a pragmatic clinical trial
11J Periodontal 1994 65(7); 685-91.
Study population & setting
Eligibility: Who is selected to participate in the trial?
Setting: Where is the trial being done?
Recruitment: How are participants recruited into the trial?
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BMJ 2015;350:h2147
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Actisite is for adults with a
problem site, as an adjunct to root-planning and scaling
Eligibility:Mild to moderate periodontitis, 2 teeth with 5-9 mm probing depths that bled on probing
Setting and Recruitment:7 private periodontal practices in the U.S.
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Recruited 113 periodontal maintenance patients (10-20 per practice) in 6 weeks!
Real-world use
Flexibility-Delivery: How should the intervention be delivered?
Organization: What expertise and resources are needed to deliver the intervention?
Flexibility-Adherence: What measures are in place to make sure participants adhere to the intervention?
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BMJ 2015;350:h2147
Flexibility-Delivery:Standard of Care Comparison
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Source: NYC Periodontist
and?
Organization:Expertise needed
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able to be placed by the same person who performs root planing and scaling
Flexibility-Adherence:Chose to be more explanatory
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Check fiber retention; replace if necessary
Check fiber retention
Place fiber + glue
94% retention
77% retention
Research design
Outcome: How relevant is the primary outcome to participants?
Follow-Up: How closely are participants followed-up?
Analysis: To what extent is all data included in the primary analysis?
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BMJ 2015;350:h2147
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Outcomes:Clinical: Pocket depth, attachment level, and bleeding on probing
Usage: fiber retention rate
Follow-Up:Normal periodontal maintenance schedule (3 and 6 months)
Added 1 month assessment for a matching data point with the efficacy study
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Data collection:chairside “Electronic Record”
Analysis:Power: Sized to detect a pocket depth reduction of 0.5 mm or more
Analysis: intention-to-treat, including treatment-by-center interaction
22J Periodontal 1994 65(7); 685-91.
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Actisite® (tetracycline periodontal) periodontal fiber is indicated as an adjunct to scaling and root planing for reduction of pocket depth and bleeding on probing in patients with adult periodontitis.
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BMJ 2015;350:h2147
PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2)
https://crs.dundee.ac.uk/precis
