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, 2017 1 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 A randomized controlled trial to inform decisions about practice & real-world effectiveness PRAGMATIC TRIALS Review Article The Changing Face of Clinical Trials No clinical trial is completely explanatory or pragmatic. Trials exist on a continuum. Efficacy Effectiveness Explanatory Trial Pragmatic Trial Can an intervention work Does the intervention work under ideal conditions? under real-world conditions? 4 PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) 1 = very explanatory 5 = very pragmatic https://crs.dundee.ac.uk/precis BMJ 2015;350:h2147 5 Case Application: Effectiveness of site-specific antibiotic treatment for periodontal disease Actisite® (tetracycline periodontal) periodontal fiber 6 7 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 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 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 1991 26(4); 361-70. J Periodontal Res 1991 26(4); 371-9. 10 Effectiveness Trial (Phase 3b study) a pragmatic clinical trial J Periodontal 1994 65(7); 685-91. 11 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? BMJ 2015;350:h2147 12 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 Setting and Recruitment: 7 private periodontal practices in the U.S. Recruited 113 periodontal maintenance patients (10-20 per practice) in 6 weeks! 14 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? BMJ 2015;350:h2147 15 Flexibility-Delivery: Standard of Care Comparison and? Source: NYC Periodontist 16 Organization: Expertise needed able to be placed by the same person who performs root planing and scaling 17 Flexibility-Adherence: Chose to be more explanatory Place fiber + glue Check fiber retention; replace if necessary 94% retention Check fiber retention 77% retention 18 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? BMJ 2015;350:h2147 19 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 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 J Periodontal 1994 65(7); 685-91. 22 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 PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) https://crs.dundee.ac.uk/precis BMJ 2015;350:h2147 24 http://www.crispebooks.org/ [email protected] THANK YOU 25.