The Role of Pragmatic Clinical Trials in the CQIs
Sachin Kheterpal MD MBA
Kevin K Tremper Professor of Anesthesiology
University of Michigan Medical School
Disclosures
• I have no personal financial, consulting, contractual relationships with any vendor
• I am PI or co-I on funded projects
– PCORI re: RCT of general anesthesia technique
– NIH re: T32 training program, surgical outcomes, wearables and depression
– NIH re: Phenylephrine vs Norepinephrine to prevent postoperative AKI
– BCBSM re: anesthesiology QI
– Merck re: Neuromuscular Blockade Monitoring and Reversal
– Edwards Life Sciences re: Intraoperative hypotension epidemiology and outcomes
– Becton Dickinson re: Medication Error Epidemiology and costs
– Apple re: trajectories of health detected by digital phenotyping
A preview
•
The need for evidence in perioperative medicine
• Past success may predict future performance
• Pragmatic, cluster randomized trial feasibility scorecard
• Potential clinical controversies ready for science
• Barriers & facilitators
Evidence gaps
• Wide variation in practice continues
• Surveys demonstrate lack of compelling evidence
• Lack of generalizability in many RCTs
• Assumptions regarding ideal clinical state
• “efficacy” vs “effectiveness”
“If you want me to provide evidence-based practice, start building practice-based evidence”
The opportunity in Michigan
• Move beyond observational data analyses
• Take advantage of practice variation
• Minimize / eliminate “research” infrastructure needs
• Answer questions that matter to clinicians and patients
• Use settings where we practice every day
• Population: 117 general surgery residency programs
• Intervention & Comparator: “Flexible” work hours vs “Standard policy”
• Outcome: NSQIP: 30 day patient outcomes & resident dissatisfaction, well being
• Result: 138,691 patients, 9.1% vs 9.0% complications, 11% vs 10.7% resident
dissatisfaction
• Population: 25 US & Canada hospitals performing extremity fracture fixation
• Intervention & Comparator: 0.7% iodine/alcohol vs 2% chlorhexidine/alcohol
• Outcome: superficial surgical site infection within 30 days or deep within 90 days
• Result: 6,785 closed fractures, 1,700 open fractures
– Closed:2.4% iodine vs 3.3% chlorhexidine
– Open: 6.5% iodine vs 7.3% chlorhexidine
• Population: US hospital, patients undergoing cardiac, thoracic, or vascular surgery
• Intervention & Comparator: videolaryngoscopy vs direct laryngoscopy for 1
st
attempt
• Outcome: >= 2 intubation attempts, intubation failure (switching device)
• Result: 8,429 intubations:
– >= 2 attempts: 1.7% video vs 7.6% direct laryngoscopy
– failure: 0.27% video vs 4.0% direct laryngoscopy
Common features across these studies
• IRB approved waiver of patient consent
• Patients not involved in clinical decision
• No new data collection
• Both options already in routine use
• Both options are safe (according to some people)
• Strong clinician preference maintained (>90% compliance needed)
• Opinions without compelling evidence (equipoise)
• Clinicians interested in answering the question
• Amenable to hospital level “policy”
Traditional RCT’s:
Patient Approached
and Eligibility
Confirmed
Patient
Randomized
Treatment 1
Treatment 2
Outcomes
Ascertained
Credit: Douglas Colquhoun
Traditional vs Cluster Randomized Trials:
Trial
Credit: Douglas Colquhoun
Cluster Randomized Crossover Examples:
Cluster
Month 1
Month 2
Month 3
Month 4
Month 5
Month 6
Hospital 1
Hospital 2
Hospital 3
Hospital 4
Hospital 5
Hospital 6
Cluster
Month 1
Month 2
Month 3
Month 4
Month 5
Month 6
Hospital 1
Hospital 2
Hospital 3
Hospital 4
Hospital 5
Cluster Multiple Crossover Design
Stepped Wedge Cluster Crossover
Credit: Douglas Colquhoun
Upcoming studies
• VEGA-2: Phenylephrine vs dilute Norepinephrine in non cardiac to prevent AKI
• IntraopOx: Different FiO2 levels to prevent AKI, MI, and mortality
• TRACTION: Tranexamic acid to prevent transfusion in unstudied populations
Wanderer JP and Rathmell JP (2017) Anesthesiology
• Norepinephrine
improves renal blood flow
& outcomes in septic shock
• No RCTs directly
comparing these in non-
cardiac, non-obstetric
surgery
Norepinephrine vs. Phenylephrine
Credit: Allison Janda
DEPARTMENT OF ANESTHESIOLOGY
*Unpublished,
unadjusted data
from MPOG
DataDirect
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2015 2016 2017 2018 2019 2020 2021 2022
Percentage of Vasopressor Use by Case
Year
University of Michigan Vasopressor Use by Year
Phenylephrine Norepinephrine Ephedrine Vasopressin
Credit: Allison Janda
First-line Monthly Assigned Vasopressor:
For
Infusions AND Boluses
2025
April May June July August Sept Oct Nov Dec
Phenylephrine
Norepinephrine
2026
Jan Feb March April May
Phenylephrine
Norepinephrine
General recommendation: Keep MAP ≥ 65 mmHg -or- BP within 20% of baseline (unless specific MAP
goal)!
Official
Schedule
Monthly emails at time of vasopressor change
Emails on the 1
st
Monday of each month for vacations the prior week
Morning page the day of the vasopressor change
Badge cards
Posters (ORs, lounges, tech rooms, pharmacy and pharmacy anteroom)
MiChart reminders in the side panel
Reminder cards in OR anesthesia cart clear bins
Reminder cards on the Pyxis
Bin of the “vasopressor-of-the-month” on the pharmacy window ledge
Anesthesia monitor displays
Reminder treats!
VEGA-2 Trial Reminders
Credit: Allison Janda
EHR Sidebar Reminders
Credit: Allison Janda
Pragmatic, cluster randomized scorecard
• Maintain patient autonomy
• Use existing CQI data collection for intervention & outcome
• Data demonstrates practice variation & safety
• MOST people at SOME hospitals willing to be flexible
• A passion for turning belief into evidence into best practice
Barriers that we can address
• Regulatory approval –> single IRB approval and review
• Research coordinators –> existing non research staff placing signage or coordinating center
team?
• Data collection –> none!
• Clinical champions --> only ask questions that matter to clinicians
• Topics -> many QI efforts need systematic evaluation
Next steps
• Controversies you care about
• Barriers we don’t realize
Questions?
