Pragmatic Trial Design Considerations: The PRECIS-2 Framework

Transcription

1 Pragmatic Trial Design Considerations: The PRECIS-2 Framework Elaine H. Morrato, DrPH MPH Associate Professor, Health Systems, Management and Policy Associate Dean for Public Health Practice Director, Pragmatic Trials and Dissemination-Implementation Research, Colorado Clinical & Translational Sciences Institute Duke Industry Statistics Symposium 2017 Are Pragmatic Clinical Trials Ready for Prime Time? September 7,

2 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 2

3 A randomized controlled trial to inform decisions about practice & real-world effectiveness PRAGMATIC TRIALS Review Article The Changing Face of Clinical Trials

4 No clinical trial is completely explanatory or pragmatic. Trials exist on a continuum. Efficacy Explanatory Trial Can an intervention work under ideal conditions? Effectiveness Pragmatic Trial Does the intervention work under real-world conditions? 4

5 PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) 1 = very explanatory 5 = very pragmatic BMJ 2015;350:h2147 5

6 Case Application: Effectiveness of site-specific antibiotic treatment for periodontal disease Actisite (tetracycline periodontal) periodontal fiber 6

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8 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 8

9 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? 9

10 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 J Periodontal Res (4); J Periodontal Res (4);

11 Effectiveness Trial (Phase 3b study) a pragmatic clinical trial J Periodontal (7);

12 Study population & setting Eligibility: Setting: Recruitment: Who is selected to participate in the trial? Where is the trial being done? How are participants recruited into the trial? BMJ 2015;350:h

13 Eligibility: Mild to moderate periodontitis, 2 teeth with 5-9 mm probing depths that bled on probing Actisite is for adults with a problem site, as an adjunct to root-planning and scaling 13

14 Setting and Recruitment: 7 private periodontal practices in the U.S. Recruited 113 periodontal maintenance patients (10-20 per practice) in 6 weeks! 14

15 Real-world use Flexibility-Delivery: Organization: How should the intervention be delivered? 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? BMJ 2015;350:h

16 Flexibility-Delivery: Standard of Care Comparison and? Source: NYC Periodontist 16

17 Organization: Expertise needed able to be placed by the same person who performs root planing and scaling 17

18 Flexibility-Adherence: Chose to be more explanatory Place fiber + glue Check fiber retention; replace if necessary 94% retention Check fiber retention 77% retention 18

19 Research design Outcome: Follow-Up: Analysis: How relevant is the primary outcome to participants? How closely are participants followed-up? To what extent is all data included in the primary analysis? BMJ 2015;350:h

20 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 20

21 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 21

22 J Periodontal (7);

23 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. 23

24 PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) BMJ 2015;350:h

25 THANK YOU 25