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

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 Nursingc

University of South Florida – College of NursingTampa, Florida


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


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)


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


Study design



• Subjects remained in the study for 7 days or until extubated (whichever comes first)


Study design



• 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)


Main results


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


Base for additional research

• 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

Oropharyngeal organisms present before intubation

Decreasedcontamination of ET tube during

intubation

Chlorhexidine Intervention

Decreased Risk of VAP


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


Examples of issues related to

• Subject recruitment, enrollment, retention and attrition• Data collection and integrity• Intervention delivery• The critical care environment


Recruitment

• Patterns tracked, data used to refine recruitment strategies.


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


Clinical practice changes affected retention and attrition

• Reduced time to extubation– required increase in over-enrollment to ensure adequate

analysis sample size




analysis sample size– original estimate based on pilot data (R15 NR04730, PI:Grap):

456 enrollments to get 300 subjects at day 3




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


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...


Technology changed over the life of the study

• Trends in consumer electronics affected data collection platforms and processes


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!

http://en.wikipedia.org/wiki/Personal_Digital_Assistant

http://en.wikipedia.org/wiki/Personal_Digital_Assistant

http://en.wikipedia.org/wiki/Palm_OS


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


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 $$$


Options

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


Clinical practice changes affected the study


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


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


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


Implementation Workshop

Documents

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