Cindy L. Munro University of South Florida Mary Jo Grap Virginia Commonwealth University

1. Lessons learned from conducting RCTs in critically ill adults Cindy L. Munro University of South Florida Mary Jo Grap Virginia Commonwealth University

2. University of South Florida – College of NursingTampa, Florida

3. Describe challenges encountered in RCTs conducted in acute care setting with critically ill mechanically ventilated adults.

4. The exemplar • The SToPP Study:Strategies To Prevent Pneumonia • Oral Care Intervention in Mechanically Ventilated Adults • NIH funded study, R01NR07652

5. The Hypothesis… Reduced Oral Organisms Reduced VAP Oral Care Interventions Two general categories of oral care interventions: Mechanical (Toothbrushing) Pharmacologic (Chlorhexidine, CHX)

6. Study design • Prospective, randomized 22 factorial design • Random assignment to one of 4 groups • Toothbrushing 3 times a day • Chlorhexidine 2 times a day • Both • Neither

7. Study design • Prospective, randomized 22 factorial design • Random assignment to one of 4 groups • Toothbrushing 3 times a day • Chlorhexidine 2 times a day • Both • Neither • Subjects remained in the study for 7 days or until extubated (whichever comes first)

8. Study design • Prospective, randomized 22 factorial design • Random assignment to one of 4 groups • Toothbrushing 3 times a day • Chlorhexidine 2 times a day • Both • Neither • Subjects remained in the study for 7 days or until extubated (whichever comes first) • Daily assessment of oral health (dental plaque index, cultures, salivary biomarkers) and VAP risk (Clinical Pulmonary Infection Score, Pugin et al., 1991)

11. Main results

12. High impact for practice • Oral care with CHX added to the Institute for HealthCare Improvement Ventilator Care Bundle in 2010 • SToPP study cited as evidence

13. Base for additional research • Chlorhexidine Intervention Oropharyngeal organisms present before intubation Decreased contamination of ET tube during intubation Decreased Risk of VAP • SToPP-IT (In Trauma) • Peri-intubation CHX in trauma patients • DoD TSNRP MDA-905-03-1-TS02 (Grap, PI) • SToPP2 • Renewal of R01NR07652 • And- multiple student research projects

14. Extensive planning was effective in anticipating and reducing issues encountered, although unanticipated issues still arose.

15. Examples of issues related to Subject recruitment, enrollment, retention and attrition Data collection and integrity Intervention delivery The critical care environment

16. Recruitment • Patterns tracked, data used to refine recruitment strategies.

17. Enrollment • Consent procedures expanded • Approval of telephone consent for distant Legally Authorized Representatives • Change in Virginia legislation expanding list of individuals who could act as LAR for research

18. Clinical practice changes affected retention and attrition • Reduced time to extubation • required increase in over-enrollment to ensure adequate analysis sample size

19. Clinical practice changes affected retention and attrition • Reduced time to extubation • required increase in over-enrollment to ensure adequate analysis sample size • original estimate based on pilot data (R15 NR04730, PI:Grap): 456 enrollments to get 300 subjects at day 3

20. Clinical practice changes affected retention and attrition • Reduced time to extubation • required increase in over-enrollment to ensure adequate analysis sample size • original estimate based on pilot data (R15 NR04730, PI:Grap): 456 enrollments to get 300 subjects at day 3 • Actual enrollment: 547

21. Data collection was carefully planned BUT... • Palm Pilot PDA • PenDragon software, running on Palm OS • Synchronized to MicroSoft Access database • Synch database on Research Nurses’ computer • Archival database on Data Manager’s computer, backed up to CDs weekly

22. Technology changed over the life of the study Trends in consumer electronics affected data collection platforms and processes

23. Technology changed over the life of the study Trends in consumer electronics affected data collection platforms and processes “Palmhandhelds were Personal Digital Assistants (PDAs) which ran the Palm OS.” Wikipedia, note the past tense!

24. PDAs to Smartphones Palm launches first PDA in 1996 "PalmPilotsales surging" on CNET News 1998 Moved away from PDAs into smartphone market (late 2000’s) Acquired by HP (2010) Moved from Palm OS to Windows OS

25. Problems with model upgrades • Incompatibilities of old and new models • Power source changed- • AAA batteries to rechargable • Synch procedures changed • Phones integral to the PDA (no PDA only option) • More integral “options” on PDA, more $$$

26. Options Consolidate surviving Palms Find old models for sale (eBay!) Change platforms (to what??)

27. Clinical practice changes affected the study • Reduced time to extubation • required increase in over-enrollment to ensure adequate analysis sample size • Increased use of oral disinfectants • influenced design of subsequent studies • Increased incorporation of head of bed elevation as standard of care • influenced rates of VAP • Focus on “Getting to Zero” • influenced provider perceptions of problem

28. Maintaining engagement • Efforts to maintain positive engagement of clinical staff and other health care disciplines with the study over 5 years • Participation in Magnet activities • Posters of research team- updated as RAs changed • Unit and Research Council updates • Inservices on related topics • Engagement with clinical facility committees

29. Final thoughts • Research in critical care settings is challenging • Occurs within the context of clinical care • Affected by provider behaviors • Recruitment and consent are complex • Good relationships with clinical staff, and negotiating with providers, is essential • Resolution of unanticipated issues is an important part of critical care research

30. “Always have a backup plan.” Mila Kunis

31. Thank You

32. Implementation Workshop