Pragmatic Trial Design Considerations: The PRECIS-2 Framework€¦ · Pragmatic Trial Design Considerations: The PRECIS-2 Framework Elaine H. Morrato, DrPH MPH Associate Professor,

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

THANK [email protected]

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