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

Transforming Healthcare, Transforming Lives USF College of Nursing c University of South Florida – College of Nursing Tampa, Florida

Transforming Healthcare, Transforming Lives USF College of Nursing c Describe challenges encountered in RCTs conducted in acute care setting with critically ill mechanically ventilated adults.

Transforming Healthcare, Transforming Lives USF College of Nursing c The exemplar The SToPP Study: Strategies To Prevent Pneumonia –Oral Care Intervention in Mechanically Ventilated Adults –NIH funded study, R01NR07652

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

Transforming Healthcare, Transforming Lives USF College of Nursing c Study design Prospective, randomized 2 2 factorial design Random assignment to one of 4 groups –Toothbrushing 3 times a day –Chlorhexidine 2 times a day –Both –Neither

Transforming Healthcare, Transforming Lives USF College of Nursing c Study design Prospective, randomized 2 2 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)

Transforming Healthcare, Transforming Lives USF College of Nursing c Study design Prospective, randomized 2 2 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)

Transforming Healthcare, Transforming Lives USF College of Nursing c Main results

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c Base for additional research SToPP-IT (In Trauma) –Peri-intubation CHX in trauma patients –DoD TSNRP MDA TS02 (Grap, PI) SToPP2 Renewal of R01NR07652 – And- multiple student research projects Oropharyngeal organisms present before intubation Decreased contamination of ET tube during intubation Chlorhexidine Intervention Decreased Risk of VAP

Transforming Healthcare, Transforming Lives USF College of Nursing c Extensive planning was effective in anticipating and reducing issues encountered, although unanticipated issues still arose.

Transforming Healthcare, Transforming Lives USF College of Nursing c Examples of issues related to Subject recruitment, enrollment, retention and attrition Data collection and integrity Intervention delivery The critical care environment

Transforming Healthcare, Transforming Lives USF College of Nursing c Recruitment Patterns tracked, data used to refine recruitment strategies.

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c Clinical practice changes affected retention and attrition Reduced time to extubation –required increase in over-enrollment to ensure adequate analysis sample size

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c Data collection was carefully planned 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 BUT...

Transforming Healthcare, Transforming Lives USF College of Nursing c Technology changed over the life of the study Trends in consumer electronics affected data collection platforms and processes

Transforming Healthcare, Transforming Lives USF College of Nursing c Technology changed over the life of the study Trends in consumer electronics affected data collection platforms and processes “Palm handhelds were Personal Digital Assistants (PDAs) which ran the Palm OS.” Wikipedia, note the past tense!Personal Digital AssistantsPDAsPalm OS

Transforming Healthcare, Transforming Lives USF College of Nursing c PDAs to Smartphones Palm launches first PDA in 1996 "PalmPilot sales 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

Transforming Healthcare, Transforming Lives USF College of Nursing c 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 $$$

Transforming Healthcare, Transforming Lives USF College of Nursing c Options Consolidate surviving Palms Find old models for sale (eBay!) Change platforms (to what??)

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

Transforming Healthcare, Transforming Lives USF College of Nursing c 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

“Always have a backup plan.” Mila Kunis

Thank You

Transforming Healthcare, Transforming Lives USF College of Nursing c Implementation Workshop