Maximizing Extubation Outcomes Through Educational and Organizational Research: Think NIV Pilot Study
Phase: NA
Conditions: Acute Respiratory Failure
Sponsor: University of Pittsburgh

Protocol Title: METEOR: Think NIV Pilot 
 
Protocol Version 1.0 
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METEOR: Think NIV Pilot Study 
Maximizing Extubation Outcomes Through Educational and 
Organizational Research: Think NIV Pilot Study 
 
NCT04052542 
 
Timothy D Girard, MD, MSCI 
Department of Critical Care Medicine 
University of Pittsburgh School of Medicine 
 
 
 
 
 
 
 
 
 
 
Contact Details 
 
Primary Investigator  
 
Timothy D Girard, MD, MSCI 
 
 
 
 
 
Phone  
(412) 383-0582 
 
 
 
 
 
E-mail  
timothy.girard@pitt.edu 
Project Manager 
 
 
Kelsey Linstrum, MS 
 
 
 
 
 
Phone  
(412) 383-0464 
 
 
 
 
 
E-mail  
kml168@pitt.edu 
 
 
Statement of Compliance 
This investigation will be conducted in compliance with the protocol, International 
Conference on Harmonization guideline E6: Good Clinical Practice (ICH E6): 
Consolidated Guideline, and the applicable regulatory requirements from United 
States (US) Code of Federal Regulations (CFR) (Title 45 CFR Parts 46 and Title 21 
CFR including Parts 50 and 56) concerning informed consent and Institutional Review 
Board (IRB) regulations. 

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Table of Contents 
PART I: PROTOCOL SUMMARY .........................................................................3 
PART II: STUDY DESCRIPTION ........................................................................4 
1.0 
Background.............................................................................................4 
1.1 
Acute Respiratory Failure ............................................................................... 4 
1.2 
Post-Extubation Outcomes for High-Risk Patients............................................ 4 
1.3 
Efficacy of Post-Extubation Noninvasive Ventilation (NIV) ............................... 4 
1.4 
Implementation of Post-Extubation NIV .......................................................... 5 
1.5 
Existing Implementation Strategies ................................................................ 5 
1.6 
Organizational Learning ................................................................................. 6 
2.0 
Objective and Hypothesis .......................................................................7 
2.1 
Objective ...................................................................................................... 7 
2.2 
Hypothesis .................................................................................................... 7 
3.0 
Study Population and Enrollment ...........................................................7 
3.1 
Inclusion Criteria ........................................................................................... 7 
3.2 
Exclusion Criteria ........................................................................................... 7 
3.3 
Enrollment .................................................................................................... 7 
3.4 
Intervention Group Assignment ...................................................................... 8 
4.0 
Study Procedures ....................................................................................8 
4.1 
Pre-Education Survey .................................................................................... 8 
4.2 
Educational Interventions .............................................................................. 8 
4.3 
Follow-Up Interviews ..................................................................................... 9 
4.4 
Statistical Considerations ............................................................................... 9 
4.5 
Database and Case Report Forms .................................................................. 9 
5.0 
Protection of Human Participants .........................................................10 
5.1 
Potential Risks ............................................................................................. 10 
5.2 
Protection Against Risks ............................................................................... 10 
5.3 
Record Retention......................................................................................... 11 
5.4 
Data and Safety Monitoring Plan (DSMP) ...................................................... 11 
5.4.1 
Adherence Statement ............................................................................... 11 
5.4.2 
Confidentiality .......................................................................................... 12 
5.4.3 
Adverse Event Information ....................................................................... 12 
5.4.4 
Data Quality and Safety Review Plan and Monitoring ................................. 14 
5.4.5 
Informed Consent .................................................................................... 14 
5.4.6 
Reporting Changes in Study Status ........................................................... 15 
6.0 
References ............................................................................................15 
 
 
 

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PART I: PROTOCOL SUMMARY 
 
Title: METEOR: Think NIV Pilot Study 
 
Objective: Pilot test three strategies designed to speed implementation of preventive 
post-extubation noninvasive ventilation (NIV): one control strategy (traditional online 
continuing medical education) and two novel strategies (interprofessional education and 
just-in-time education) 
Study Design: Three parallel interrupted time series studies 
Inclusion Criteria: Two study populations will be included. Learners will include [1] 
frontline care providers, including physicians, advanced practice providers, nurses, and 
respiratory therapists, [2] working in one of three participating UPMC ICUs: UPMC 
Presbyterian MICU, UPMC Mercy MSICU, and UPMC Passavant MSICU. Patients will 
include all mechanically ventilated patients treated in the participating UPMC ICUs and 
surviving to extubation. 
Exclusion Criteria: Frontline care providers will be excluded if they: 
[1] 
Have not worked in their current UPMC ICU for more than one month prior to 
the current study 
[2] 
Have not directly cared for a mechanically ventilated patient in a UPMC ICU 
during the three months preceding the current study 
Educational Strategies: 
[1] 
Traditional online continuing education 
[2] 
Interprofessional education 
[3] 
Just-in-time education 
Study Procedures: During a one-month intervention period, we will pilot test the 
educational strategies in three participating UPMC ICUs. Prior to receiving education, 
participants will be invited to complete a short online survey. Participants in the control 
group will be invited to complete a 30-minute online continuing education module, which 
will conclude with a survey. Participants in the interprofessional education group will be 
invited to attend a 90-minute, in-person, interprofessional education session that will 
occur in or near the participating ICU. A trained advance practice provider will provide 
participants in the just-in-time education group with 5-10 minutes of education in the 
ICU when the ICU team is rounding on a patient who is identified to be high risk for 
extubation failure. The just-in-time education may occur more than once per day, 
depending in the number of high-risk patients identified. All educational strategies will 
include content on the benefits of preventive post-extubation NIV, the indications and 
contraindications for preventive post-extubation NIV, and the value of working together 
as an interprofessional ICU team when implementing preventive post-extubation NIV. 
Each educational intervention will include a survey designed to determine the feasibility, 
acceptability, and preliminary impact of the educational strategies. We will also directly 
observe instances of interprofessional and just-in-time education and conduct in-person 
interviews to assess these factors in a qualitative manner. Lastly, during the intervention 
period and the 6 months before and after the intervention period, we will collect data 
from the electronic health record and analyze changes in percent of high-risk patients 
who receive preventive post-extubation NIV, reintubation rate, duration of mechanical 
ventilation, ventilator-associated pneumonia, and in-hospital mortality. 
 

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PART II: STUDY DESCRIPTION 
1.0 Background 
1.1 
Acute Respiratory Failure 
Acute respiratory failure requiring invasive mechanical ventilation affects nearly 800,000 
patients in the United States each year.1 Approximately half of these patients are >65 
years old,1 a vulnerable group at high risk for poor short- and long-term outcomes. Even 
among younger patients, mortality among mechanically ventilated ICU patients is 
extremely high, with in-hospital mortality averaging 35% for all patients and 
approaching 50% for syndromes like ARDS.1-3 Costs for these patients are also high, 
with an estimated $27 billion spent annually on their acute hospital care alone.1 
1.2 
Post-Extubation Outcomes for High-Risk Patients 
Recent improvements in the management of sepsis, ARDS, and other causes of 
respiratory failure have led to better clinical outcomes, such that 70%-80% of 
mechanically ventilated ICU patients recover to the point of extubation.2,4 The current 
evidence-based management of these patients is to extubate once the patient passes a 
spontaneous breathing trial (SBT) and is alert with adequate cough and minimal 
secretions. This SBT-based strategy, especially when paired with sedation interruption, 
greatly improves outcomes,5,6 but many patients remain at high risk for post-extubation 
respiratory failure. Multiple large cohort studies have found that 10% to 20% of patients 
recovering from acute respiratory failure require reintubation after planned extubation,2,4 
and reintubation is strongly associated with death,7-10 increased costs,11 prolonged 
hospital stays,7,11 and long-term functional disability.12 This risk is greatest in elderly 
patients4,7,10 and patients with chronic pulmonary disease.7,10 In one recent study, 24% 
of mechanically ventilated ICU patients were both >65 years old and had chronic cardiac 
or respiratory disease—these patients had a reintubation rate of 34% compared with 
9% among other patients (p<0.01).10  
1.3 
Efficacy of Post-Extubation Noninvasive Ventilation (NIV) 
When a mechanically ventilated patient with high risk characteristics passes an SBT, 
clinicians must decide whether to extubate. Continuing invasive mechanical ventilation 
exposes the patient to risk and undue burden, but extubating without providing support 
is also undesirable. Post-extubation noninvasive ventilation offers clinicians a third 
option. In a landmark randomized controlled trial, Ferrer et al.13 studied high-risk 
mechanically ventilated ICU patients and found that extubation to immediate 
noninvasive ventilation (rather than conventional oxygen treatment) reduced both post-
extubation respiratory failure (RR = 0.31, 95%CI: 0.15–0.62) and 90-day mortality (RR 
= 0.36: 95%CI: 0.15-0.85). A subsequent meta-analysis of five randomized controlled 
trials demonstrated that post-extubation noninvasive ventilation improves multiple 
outcomes, including post-extubation respiratory failure, ICU length of stay, and 
mortality.13-17 Based on this evidence, recent clinical practice guidelines on liberation 
from mechanical ventilation sponsored by the American College of Chest Physicians 
(ACCP) and the American Thoracic Society (ATS) and co-chaired by Dr. Girard (PI of this  

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study), made a strong recommendation that high-risk patients who pass an SBT should 
be extubated to preventive noninvasive ventilation.18-20 A similar recommendation was 
made in guidelines published by the European Respiratory Society (ERS) and ATS, which 
were co-authored by Dr. Hess (a consultant for this study).21 
1.4 
Implementation of Post-Extubation NIV 
Despite compelling evidence of benefit, multiple international cohort studies show that 
post-extubation noninvasive ventilation is used infrequently in routine clinical practice.2,22 
One of the largest studies, for example, found that even though nearly 50% of 
invasively ventilated patients had a risk factor for failed extubation, less than 3% 
received preventative noninvasive ventilation after extubation.22 Although no studies 
have specifically examined barriers to the use of post-extubation non-invasive 
ventilation, surveys about non-invasive ventilation in general,23-26 including one led by 
our consultant Dr. Hess,25 indicate that lack of familiarity with noninvasive ventilation, 
lack of awareness of the evidence, and concerns about the time required are key 
barriers to use. Due to these barriers, and likely others in the specific context of post-
extubation use, many patients are not receiving an important evidenced-based practice. 
Based on epidemiologic data, we estimate that at least 200,000 mechanically ventilated 
patients/year in the United States are at high risk for extubation failure. If post-
extubation noninvasive ventilation leads to a 9% absolute reduction in mortality for this 
vulnerable population, as estimated in a recent meta-analysis,18-20 approximately 18,000 
deaths per year in the United States alone could be prevented by implementation of 
post-extubation noninvasive ventilation. 
1.5 
Existing Implementation Strategies 
Traditional strategies for knowledge transfer include education, guideline dissemination, 
audit and feedback of performance data, financial incentives, and automated 
reminders.27 These strategies are extremely effort intensive yet often ineffective, 
typically resulting in either no significant improvements in performance or small 
improvements that are not sustained over time.28,29 One reason for the failure of 
traditional knowledge transfer in the ICU is that these strategies do not fully account for 
the team-based nature of critical care.30 Like non-invasive ventilation, most evidence-
based practices in critical care are complex and multi-faceted, requiring ongoing 
coordination within a dynamic interprofessional care team.31 Existing strategies for 
knowledge transfer fail to account for this complexity, instead generally focusing on 
static barriers on the part of individual providers.32 33 Yet, targeting providers in isolation 
neglects the inherent role of coordination in evidence-based practice.34,35 The ICU is a 
complex adaptive system in which actors have the freedom to act in unpredictable 
ways.36 Absent a robust team, individual providers will find ways to circumvent even 
newer strategies like electronic prompts, making these interventions only modestly 
effective.37 It is essential that the next generation of implementation strategies 
acknowledge and account for this complexity so that they empower interprofessional 
teams with the skills to overcome challenges to implementation of evidence-based 
practice as they dynamically arise as well as sustain improvement after the novelty of 
the new intervention has worn off. 

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1.6 
Organizational Learning 
Over the last three decades a rich body of research has evolved around the area of 
organizational learning, the process by which organizations create, retain and transfer 
knowledge.38 Although individual learning underlies basic knowledge acquisition, for new 
knowledge to be useful to an organization it must embedded within a group repository 
that is accessible to other members so that it can be accessed and shared when needed. 
This is particularly true when, like in the ICU, performance is contingent upon 
coordination, since all members must be able to draw off the same knowledge 
repository for coordination to occur.39 It is also particularly true when, like in the ICU, 
team membership is dynamic. Because ICU team members rotate in and out of the 
team, unembedded knowledge is easily lost. Current theory defines the system by which 
organizations acquire and apply specialized knowledge as a transactive memory 
system.40 Colloquially, transactive memory systems are the knowledge of who knows 
what. When an organization has a robust transactive memory system, team members 
can rely each other to recall and apply key knowledge about important tasks. This 
“mutual confidence” frees up each individual team member to deepen their own 
expertise while at the same time ensuring that their knowledge remains accessible to 
others.38 Extensive empirical data now indicate that transactive memory systems 
underlie organizational learning and are tightly linked to organizational performance in a 
variety of industries ranging from service to hospitality.41 In this application, we posit 
that limitations of past implementation work can be addressed by two interventions 
designed to strengthen transactive memory systems in ICUs: interprofessional education 
and just-in-time education. 
• 
Interprofessional education: Traditional continuing education focuses on 
individuals and occurs in professional silos—physicians learning from physicians, 
nurses learning from nurses, etc. As a result, the individual professions acquire 
different mental models and lack a shared understanding of the task at hand. 
Interprofessional education, in which members of different providers learn together, 
overcomes this problem by reinforcing not only shared mental models42,43 but also 
cross-understanding, or the degree to which group members have accurate 
understandings of each other’s’ mental models.44 Interprofessional education fosters 
the development of a shared language or common set of terms, which enables 
effective coordination. Interprofessional education also helps ensure that new 
knowledge occurs in a supportive context, enabling individuals to jointly practice 
coordinated actions in a team-based setting, promoting knowledge retention through 
the development of transactive memory systems.45 
• 
Just-in-time education: Traditional continuing education occurs in classrooms or 
at home, separate from the “moment of need” and divorced from the practical 
context. Just-in-time education overcomes this problem by providing instruction at 
the bedside at the exact moment the knowledge is needed.46 Because just-in-time 
education includes demonstrations and opportunities to observe effective practice, it 
enables the transfer of tacit, difficult-to-articulate knowledge.47 Just-in-time 
education also strengthens transactive memory systems by tying knowledge 
acquisition directly to experience—instead of depending on subsequent experience 
to reinforce knowledge, knowledge acquisition and experience occur 
simultaneously.48 In addition, just-in-time education ties knowledge acquisition to a 
specific case of immediate relevance,49,50 reducing ambiguity in the learning process. 

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It also promotes coordination by directly providing individuals with the skills to 
perform their tasks within the context of a relational team.51 
2.0 Objective and Hypothesis 
2.1 
Objective 
During the METEOR: Think NIV Pilot Study, we seek to pilot test three strategies 
designed to speed implementation of post-extubation noninvasive ventilation: one 
control strategy (traditional online continuing medical education) and two novel 
strategies (interprofessional education and just-in-time education). 
2.2 
Hypothesis 
We hypothesize that interprofessional education and just-in-time education are feasible 
and acceptable to members of the interdisciplinary ICU team; and that the pilot testing 
will yield important information that will enable us to both refine the interventions and 
perform power calculations for the subsequent clinical trial. 
3.0 Study Population and Enrollment 
3.1 
Inclusion Criteria 
Two study populations will be included. 
• 
Learners will include [1] frontline care providers, including physicians, advanced 
practice providers, nurses, and respiratory therapists, [2] working in one of three 
participating UPMC ICUs: UPMC Presbyterian MICU, UPMC Mercy MSICU, and UPMC 
Passavant MSICU. 
• 
Patients will include all mechanically ventilated patients treated in the participating 
UPMC ICUs and surviving to extubation. 
3.2 
Exclusion Criteria 
Care providers will be excluded from the Learner population if they: 
[1] 
Have not worked in their current UPMC ICU for more than one month 
[2] 
Have not directly cared for a mechanically ventilated patient in a UPMC ICU 
during the three months preceding the current study 
3.3 
Enrollment 
Study personnel will provide nursing and medical managers from each participating ICU 
with an introductory script that explain the study’s methods and goals. Unit leadership 
will provide potential learners with the script, inviting them to participate and describing 
the study procedures and potential risks and benefits. Because exemptions 45 CFR 
46.101(b)(1) and 45 CFR 46.101(b)(4) apply and it will not be practicable to obtain 
informed consent, we will request a waiver to document informed consent from learners 
(whose actions will indicate their consent to participate) and a waiver to request 

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informed consent from patients (for whom the only study procedure will be collected of 
existing data from the electronic health record). 
3.4 
Intervention Group Assignment 
Given the nature of the interventions and the dynamics of interprofessional team care in 
the ICU, randomization at the level of the individual learner would likely result in 
significant cross contamination, thereby introducing bias in the trial. A better alternative 
in this case is to assign learners to interventions in groups. We will therefore assign all 
learners in a single ICU to the same intervention group. Given the pilot nature of this 
trial, we will assign one ICU to each group. For logistical reasons, learners in the UPMC 
Mercy MSICU will be assigned to traditional online continuing education, those in the 
UPMC Passavant MSICU will be assigned to interprofessional education, and those in the 
UPMC Presbyterian MICU will be assigned to just-in-time education. 
4.0 Study Procedures 
4.1 
Pre-Education Survey 
Prior to receiving the educational interventions, learners will be asked to complete a 10-
minute survey designed to assess their baseline knowledge. 
4.2 
Educational Interventions 
During a one-month study intervention period, the following three educational 
interventions will be piloted simultaneously. 
• 
Traditional online continuing education. We will use an active control 
consisting of “best existing practice” for continuing education. Learners working in 
the ICU assigned to this arm will be offered a 30-minute, online, interactive, 
educational video describing the benefits of preventive post-extubation NIV, the 
indications and contraindications for preventive post-extubation NIV, and the value 
of working together as an interprofessional ICU team when implementing preventive 
post-extubation NIV. The video will be customized to each provider type (e.g., 
nurse, respiratory therapist, or physician). Learners will be offered provider-specific 
continuing education credits. 
• 
Interprofessional education. Learners working in the ICU assigned to this arm 
will receive, a one-time, 90-120-minute, in-person, interprofessional educational 
workshop consisting of a 30-minute didactic session and a 60-90-minute small group 
session. The workshop is designed according to modern principles of adult learning 
and interprofessional education, including provider participation in development, 
fostering authenticity, reinforcing role identity, and relating content to life 
experience. Facilitators will be trained advance practice providers with content 
expertise who can speak to all targeted professions. Research staff will observe 
educational sessions. 
• 
Just-in-time education. Learners working in the ICU assigned to this arm will 
receive, “just-in-time,” point-of-care education. Trained advanced practice providers 
will be on-hand in the study ICU, where they will deliver the just-in-time education. 

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When a patient meets criteria for preventive post-extubation NIV, the educator will 
join the interprofessional ICU team at the bedside during rounds and will briefly 
review the evidence underlying risk assessment and proper use of preventive post-
extubation NIV, providing instruction about how to provide preventive post-
extubation NIV as well as how to anticipate potential barriers and pitfalls, while also 
fostering active collaboration. The just-in-time education is designed to cause 
minimal disruptions in workflow. Research staff will observe select educational 
sessions. 
After each educational intervention, learners will be asked to complete a brief survey 
designed to determine the feasibility, acceptability, and preliminary impact of the 
educational strategies. 
4.3 
Follow-Up Interviews 
Two to six weeks after the educational interventions, trained qualitative research 
coordinators will conduct learners to invite them to participant in in-person interviews 
that will qualitatively assess the feasibility, acceptability, and preliminary impact of the 
educational strategies using open-ended questions. 
 
Lastly, during the intervention period and the 6 months before and after the intervention 
period, we will collect data from the electronic health record and analyze changes in 
percent of high-risk patients who receive preventive post-extubation NIV, reintubation 
rate, duration of mechanical ventilation, ventilator-associated pneumonia, and in-
hospital mortality. 
4.4 
Statistical Considerations 
We will use interrupted time series analysis to compare clinical outcomes measured 
during the six months before the implementation strategies with those measured during 
the six months after initiation of the strategies.52 All analyses will be adjusted for 
baseline characteristics associated with the outcomes, including age, comorbid 
conditions, and severity of illness at admission. Additionally, interaction terms will be 
used to determine whether age and chronic cardiac and/or respiratory disease modified 
the effect of the implementation strategy on outcomes. 
 
Due to the pilot nature of this study, we do not yet have preliminary data with which to 
perform power calculations or sample size analyses. The sample size will therefore be 
determined by feasibility (i.e., the number of learners who agree to participate and the 
number of eligible patients admitted to participating ICUs during the study period), and 
we will use the results of the current pilot study to determine the sample size of a 
subsequent cluster randomized trial. 
4.5 
Database and Case Report Forms 
We will collect demographics from the ICU Team including, but not limited to, UPMC 
emails (for Wolff Center use to collect detailed information), education, background and 
training, and partial social security numbers to facilitate CME credits for physician team 
members, CUE credits for nursing staff members and comparative education method for 
respiratory therapists. 

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All qualitative data collection will be performed by trained qualitative research 
coordinators. We will audiotape and transcribe all recordings. Digital voice files and 
electronic files of transcribed sessions will be stored on a password-protected server. To 
maximize participation, we will provide appropriate compensation and schedule sessions 
for a time and place that is convenient for participants. No identifiers will be collected, 
and participants will be identified by profession and a number and not by name (e.g., 
Intensivist 1, Nurse 4, etc.). Interviews will be held in private locations. 
De-identified patient data will be collected from the electronic health record and the ICU 
Registry. These data will include, but not be limited to, in-hospital mortality truncated at 
60 days from the time of intubation, ICU and hospital length of stay, post-extubation 
respiratory failure, duration of mechanical ventilation, 28-day ventilator-free days, 
ventilator-associated pneumonia, and organ failure (tracked daily using the Sequential 
Organ Failure Assessment score). 
5.0 Protection of Human Participants 
5.1 
Potential Risks 
Since the interventions being studied are educational strategies applied to care providers 
rather than to patients, we anticipate that potential risk to patient participants will be 
limited to accidental disclosure of protected health information should there be a breach 
in our data security procedures. Potential risk to learner participants includes 
psychological discomfort associated with completing the surveys, which will address 
topics related to the ICU practice environment and working relationships with 
colleagues. Given that these topics are of a non-sensitive nature, we believe 
psychological discomfort will occur infrequently. An additional risk is accidental public 
disclosure of a participant’s survey results. For this to occur, a survey must be 
accidentally misplaced and the unique key linking the participant’s survey to the ICU 
identifiers must also be misplaced, and each must be recovered by the same person, a 
series of events that is extremely unlikely. A final risk is that learner participants could 
feel pressured to participate by their employer or a researcher and worry that their 
professional relationships will be jeopardized if they refuse. For our past work, the 
University of Pittsburgh Human Research Protection Office has considered similar studies 
to be “minimal risk” under the Department of Health and Human Services Code of 
Federal Regulations because it involved social research methods (e.g., surveys) and 
because the probability and magnitude of physical and psychological harm is similar to 
that normally encountered in daily life. 
5.2 
Protection Against Risks 
We plan several steps to protect the rights of human subjects involved in this research. 
We will not record any personal information other than what is needed for a 
demographic description of the cohort (age, gender, job category, time in service); thus, 
interview participants will not be identifiable in any way. All voice recordings will be 
destroyed after transcription. All personal identifiers will be redacted by the transcriber, 
and all transcriptions will be triple-read to ensure that they contain no potential 
identifiers. We will contact all potential participants directly to give them the option of 
refusing confidentially in private and to assure them that we will not feedback 

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information regarding participation to their managers. This step will not only allow 
potential participants to refuse to participate without pressure or coercion from 
employers, but it will also ensure that information on whether or not they participated 
will not find its way back to their employer, preventing potential retaliation. We will take 
extensive precautions to guard against disclosure of protected health information and to 
maintain participant confidentially, as described in section 5.4.2. 
5.3 
Record Retention 
Informed consent documents will be source documents kept in the study coordinator’s 
locked files. Only key personnel will have access. All data will be kept for an indefinite 
amount of time at the University of Pittsburgh after the conclusion of the study. 
5.4 
Data and Safety Monitoring Plan (DSMP) 
5.4.1 Adherence Statement 
The DSMP outlined herein will adhere to the study protocol approved by the University 
of Pittsburgh IRB. The study will be conducted in compliance with the protocol, 
International Conference on Harmonization guideline E6: Good Clinical Practice (ICH 
E6): Consolidated Guideline, and the applicable regulatory requirements from United 
States (US) Code of Federal Regulations (CFR) (Title 45 CFR Parts 46 and Title 21 CFR 
including Parts 50 and 56) concerning informed consent and Institutional Review Board 
(IRB) regulations. 
5.4.2 Data and Safety Monitoring Board (DSMB) 
As described in detail in the METEOR: Think NIV Pilot Study DSMB Charter, a Data and 
Safety Monitoring Board (DSMB) will be created, consisting of three voting members 
with expertise in clinical research methodology and critical care medicine. DSMB 
responsibilities are to: 
• 
protect the safety of the study participants; 
• 
review the research protocol and plans for data and safety monitoring;  
• 
evaluate the progress of the trial, including periodic assessments of data quality 
and timeliness, recruitment, accrual and retention, participant risk versus benefit, 
performance of the trial sites, and other factors that can affect study outcome; 
• 
consider factors external to the study when relevant information becomes 
available, such as scientific or therapeutic developments that may have an 
impact on the safety of the participants or the ethics of the trial; 
• 
make recommendations to the Principal Investigator concerning continuation, 
termination or other modifications of the trial based on the observed beneficial or 
adverse effects of the treatment under study; and 
• 
ensure the confidentiality of the study data and the results of monitoring. 
The DSMB will have one planned meeting before the intervention period. Additionally, 
the DSMB Chair, the Principal Investigator, or the NHLBI may call a meeting of the 
DSMB at any time. Though unexpected given the minimal risk nature of the study, any 
serious adverse events that are suspected by the Principal Investigator to be related to 
study participation—events referred to as Serious Unexpected Suspected Adverse 
Reactions (SUSARs)—as well as any other AE report that the Principal Investigator 
believes is appropriate for DSMB review will be reviewed by the DSMB Chair. The DSMB 

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Chair may distribute SUSAR reports to the other DSMB members for review. If a SUSAR 
occurs, the Principal Investigator will email a report to the DSMB Chair within 48 hours 
for review. The DSMB Chair will then indicate via email within 96 hours if additional 
information is required and whether additional action is recommended secondary to 
review of the SUSAR (e.g., DSMB teleconference). 
5.4.3 Confidentiality 
Protection of Participant Privacy: We will take extensive precautions to guard against 
disclosure of protected health information and maintain participant confidentially. All 
data management and analysis activities will take place on CRISMA’s secure, HIPAA-
compliant servers behind the UPMC firewall. Patient data will be obtained from the 
approved ICU Registry. Data in the registry is downloaded directly from the electronic 
health record (EHR) via secure FTP. No data containing any protected health information 
will ever leave the secure server. All investigators, programmers, and analysts working 
with the files will sign a confidentially agreement committing them to full privacy. We 
will also take several steps to protect the privacy of learner participants. Paper survey 
forms using during educational sessions will only include the participant’s unique study 
ID and no other identifying information. Thus, if the survey form is lost, it will not be 
directly linkable to the participant without additional information. And, we will store the 
participant study ID linkage key on our secure, password-protected, HIPAA-compliant 
server, which is maintained according to strict federal security standards. This key will 
be destroyed after data collection is complete. 
 
Database Protection: All data management and analysis activities will take place on 
CRISMA’s secure, HIPAA-compliant servers behind the UPMC firewall. No data containing 
any protected health information will ever leave the secure server. 
 
Confidentiality during Adverse Event (AE) Reporting: Adverse event reports and annual 
summaries to regulatory bodies will not include participant-or group-identifiable 
material. Each report will only include the identification code. 
5.4.4 Adverse Event Information 
Clinical Outcomes (Not Considered Adverse Events). In this study of critically ill patients 
who are at high risk for death or other adverse outcomes due to their underlying critical 
illness, clinical outcomes, including death and organ dysfunction, will be systematically 
tracked and will be included as part of the safety and effectiveness analyses for this 
study. For the purposes of reporting, death and organ dysfunction will not be recorded 
as adverse events (AEs) unless the investigator believes the event may have been 
related to study participation or is more severe or prolonged than expected given the 
underlying critical illness. This approach—considering death and organ dysfunction as 
outcomes rather than AEs and systemically tracking expected safety outcomes for 
analysis rather than solely recording individual AEs—is common during critical care trials 
because these outcomes/events occur frequently in the ICU, and this system mandates 
that data regarding death, organ dysfunction, and expected safety outcomes be tracked 
systematically for all patients and analyzed appropriately. Listed below are events that 
will be tracked as clinical outcomes and will not therefore be reported as AEs during this 

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study (unless believed to be study related and/or more severe or prolonged than 
expected given the underlying critical illness): 
• 
Death 
• 
Respiratory failure, including need for mechanical ventilation (invasive or 
noninvasive) or episodes of hypoxemia 
• 
Circulatory failure, including shock (whether requiring vasopressors or not) and 
cardiac arrhythmias, and hypertension 
• 
Hepatic failure or injury leading to increased bilirubin, AST, or ALT 
• 
Renal failure or injury leading to an increased creatinine or acute hemodialysis 
• 
Coagulation derangements leading to elevated PT/INR or PTT, DIC, 
thrombocytopenia, or thrombocytosis 
• 
Cognitive impairment that is believed to be newly acquired 
• 
Alterations in vital signs (e.g., temperature, respiratory rate, oxygen saturation) 
• 
Falls 
• 
Pressure ulcers 
• 
Thromboembolisms 
• 
ICU readmissions 
• 
Infections 
• 
Self-removal of devices and invasive tubing and/or monitoring equipment 
• 
Alterations in routine labs, including chemistries, complete blood counts, liver 
function tests, and creatine kinase 
 
Adverse Event (AE) Classifications. We define an AE as any untoward medical 
occurrence for a study participant that is not tracked as a clinical outcome, regardless of 
whether the event is considered study related or not. All AEs will be assessed as to 
whether they are (1) related to study participation, (2) serious, and/or (3) unexpected 
according to the following definitions: 
Related. AEs that an investigator suspects are related to study participation will 
be classified as Suspected Adverse Reactions (SARs). A high degree of certainty of 
relatedness is not required as long as a reasonable possibility exists that the AE is 
related to study participation. 
Serious. AEs that result in any criteria below will be considered Serious Adverse 
Events (SAEs): 
• 
Death 
• 
A life-threatening episode requiring immediate intervention 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant incapacitation or substantial disruption of the 
ability to conduct normal life functions 
• 
A congenital anomaly/birth defect 
• 
An episode that requires intervention to prevent the above and/or 
permanent impairment or damage 
Unexpected. AEs, including SARs, that are more severe or prolonged than 
expected will be considered Unexpected. 
 
All events that are related, unexpected, and serious will be reported as Serious 
Unexpected Suspected Adverse Reactions (SUSARs). Given that all known risks of 
participation in the proposed study qualify as minimal risks, we do not anticipate any 

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SUSARs. Nevertheless, we have established this system for monitoring and reporting 
should such as event occur. 
 
Unanticipated Problems (UP). Per OHRP and NHLBI regulations and guidance, any 
incident, experience, or outcome that meets all of the following criteria will be reported 
as a UP: 1) unexpected, 2) related or possibly related to participation in the research, 
and 3) suggests that the research places subjects or others at a greater risk of harm 
than was previously known or recognized. Per this definition, all SUSARs will also be 
classified as UPs, but not all UPs will be classified as SUSARs. 
 
Communication and Reporting of Adverse Events. All AEs will be reported to the 
University of Pittsburgh IRB per local policies. In addition, SUSARs and UPs will be 
reported as follows, in keeping with the NHLBI AE and UP reporting policies. 
 
Event type 
Timing of report 
Reporter 
Recipient 
Fatal or life-threatening SUSAR 
Within 7 days of initial receipt of information 
PI 
IRB, NHLBI 
Non-fatal or non-life-threatening SUSAR 
Within 15 days of initial receipt of information 
PI 
IRB, NHLBI 
UP that is not an SAE 
Within 14 days of PI becoming aware of UP 
PI 
IRB, NHLBI 
All UPs 
Within 30 days of the IRB’s receipt of the 
report of the UP from the investigator 
IRB 
OHRP 
5.4.5 Data Quality and Safety Review Plan and Monitoring 
Description of Plan for Data Quality and Management. The PI or study staff will review 
all data collection forms on an ongoing basis for data completeness and accuracy as well 
as protocol compliance. 
 
Frequency of Review. This will vary according to the data type, as follows: 
 
Data Type 
Frequency of review 
Reviewer 
Learner participant accrual (including 
compliance with protocol) 
Weekly during the one-month pilot period 
PI 
Status of all enrolled participants (patients 
and learners) 
1. End of pre-implementation period 
2. End of pilot-period 
3. End of post-implementation period 
PI 
Adherence data regarding evidence-based 
practice and implementation strategies 
1. End of pre-implementation period 
2. End of pilot-period 
3. End of post-implementation period 
PI 
5.4.6 Informed Consent 
When conducting interviews, surveys, educational sessions, and direct observation of 
the educational strategies in the ICU, we will obtain oral assent from all learner 
participants using an IRB-approved script. We will not obtain written consent for these 
activities because it is not feasible nor practicable given the sheer number and rapidity 
of these observations. Prior to each observation episode, research staff will introduce 
themselves, describe the project, and offer the opportunity for ICU staff to opt in or opt 
out. Staff wishing to opt out will be given a lapel pin to wear during the observation 
periods. Following periods of observation, we will once again give each participant the 
option to opt out if they feel uncomfortable being observed in our research. We will also 
allow any participant to later opt out after the period of observation, to the degree 
possible, thereby reducing the risk of pressure from superiors to participate in this 
research. We will seek a waiver of informed consent for inclusion of patients since the 

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research, which will be limited to collecting existing clinical data from the electronic 
health record months after the study period, involves no more than minimal risk and the 
research could not be practicably carried out without the waiver. 
5.4.7 Reporting Changes in Study Status 
Any action resulting in a temporary or permanent suspension of the study will be 
reported to the NHLBI Program Official responsible for the grant. 
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