Reorientation Intervention for Delirium in ICU
Phase: NA
Conditions: Delirium, Cognitive Impairment, Health, Subjective, Sleep
Sponsor: University of Miami

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Family Automated Voice Reorientation Study: 
Reorientation Intervention for Delirium in the ICU 
 
 
 
March 10, 2021, Version #1.8 
 
 
 
ClinicalTrials.gov Identifier: NCT03128671  
 
 

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1. Protocol Title 
Reorientation Intervention for Delirium in the ICU 
2. IRB Review History 
This minimal risk study received expedited review IRB approval from the University of South  
Florida IRB on September 30, 2016 and remains open following the last Continued Review on 
September 5, 2017. The contact number for the USF IRB is 813-974-5638. The USF IRB 
protocol number is Pro00027039. This study is funded by National Institutes of Health, National 
Institute of Nursing (1R01NR016702) and registered on ClinicalTrials.gov (NCT03128671). 
3. Objectives 
The primary specific aim of the proposed project is to test the effect of the Family Automated 
Voice Reorientation (FAVoR) intervention on delirium in critically ill, mechanically ventilated 
adults during hospitalization in the ICU. We hypothesize that subjects who receive FAVoR will 
have less delirium than control subjects who do not receive the intervention. 
Secondary aims of this project are to: (1) explore if the effect of FAVoR on delirium is mediated 
by sleep, (2) explore if selected biobehavioral factors may potentially moderate the effects of 
FAVoR on delirium, and (3) examine the effects of FAVoR on short term (immediately after ICU 
discharge) and long term (1 and 6 months after hospital discharge) outcomes, including cognitive 
function and patient-reported health status. 
4. Background 
Delirium is an acute disturbance in attention (reduced ability to direct, focus, sustain, and shift 
attention) and awareness (reduced orientation to the environment), with additional change in 
cognition (memory, disorientation, or language disturbance).1 Mechanically ventilated patients 
are especially at risk for cognitive dysfunction, and experience delirium at higher rates than 
patients who are not ventilated, with delirium occurring in as many as 80% of mechanically 
ventilated critically ill patients. It typically occurs within the first few days of intensive care unit 
(ICU) stay,2 and results in significant negative outcomes.2,3 A recent meta-analysis of 16 studies 
involving 6,410 patients confirmed that delirium has direct negative effects on ICU and hospital 
length of stay and mortality.4 Number of days of delirium has been identified as an independent 
predictor of mortality in ICU patients.5-7 Meta-analyses have confirmed that patients with 
delirium have longer duration of mechanical ventilation, greater incidence of complications 
including nosocomial pneumonia and higher hospital mortality than patients without delirium.4 
Sleep disturbances in the ICU have been associated with risk of delirium,3,8,9 and may also 
interact with interventions aimed at reducing delirium. A variety of other 
iatrogenic/environmental and biobehavioral factors (including environmental conditions, 
pharmacological therapies, disease severity and comorbid conditions, and demographic 
characteristics) are also theorized to affect the incidence of delirium.10,11 However, empirical 
evidence of the relationships of these factors to the development of delirium and its treatments 
is limited. 
Importantly, delirium in the ICU not only complicates the hospital course, but is also associated 
with lasting sequelae.12-15 Data suggest that 25% to 78% of patients who have delirium in the 
ICU suffer clinically significant declines in cognitive function following their ICU stay.16,17 

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Cognitive dysfunction may persist for months or be permanent,14,16,18 and is associated with 
impairments in daily function.19 In recent studies, increasing duration of delirium was an 
independent predictor of worse cognition 3 months and 12 months after ICU discharge,16,18 and 
this remained true even after adjusting for risk factors such as age, severity of illness, severe 
sepsis, and exposure to sedative medications in the ICU.16 Reducing delirium in mechanically 
ventilated ICU patients may reduce both short and long term cognitive dysfunction and 
posthospitalization disability. 
To date, the focus of delirium research has been on detection of existing delirium and on its 
pharmacologic treatment.20 In contrast, our approach focuses on prevention of delirium using a 
nonpharmacologic intervention. 
Significance 
Delirium is a common manifestation of cognitive dysfunction in critically ill patients, which is 
associated with substantial negative outcomes both during and following hospitalization. Using 
the published estimates22-24 that there are 5 million ICU admissions in the US each year, that 
approximately 40% of the critically ill require mechanical ventilation, and that delirium affects up 
to 80% of mechanically ventilated adult ICU patients, delirium likely affects an astonishing 1.6 
million critically ill, mechanically ventilated ICU patients annually. 
Delirium in critical illness is estimated to cost $4 to $16 billion annually3 Delirium increases ICU 
cost, hospital cost, complications, and mortality. A recent meta-analysis concluded that 
compared to patients without delirium, delirious patients were six times more likely to 
experience complications, had 7.22 days longer duration of mechanical ventilation, 7.32 days 
longer ICU length of stay, and 6.53 days longer hospital length of stay.4 Further, patients who 
experience delirium have problems with cognitive function and health status after hospital  
discharge, which have been documented at 3 and 12 months and may persist indefinitely.18,25,26 
Because of the extensive incidence and significant negative outcomes associated with delirium, 
identification of effective interventions to reduce delirium is critically important. The Society of 
Critical Care Medicine, in its most recent guidelines for managing pain, agitation, and delirium in 
the adult critically ill,3 recommended routine assessment for delirium in the ICU and stated that 
the study of delirium in mechanically ventilated patients may lead to important advancements in 
the treatment of critically ill patients. A primary goal for the critically ill patient is to provide 
patient comfort while maintaining a level of arousal sufficient to follow commands. As a result of 
trends toward lighter sedation, most patients are aware of the ICU surroundings and require 
consistent and frequent reorientation to all aspects of their care. 
Reorientation may enhance patients’ feelings of security and comfort, allow them to more 
accurately interpret these stimuli, and ultimately reduce delirium. However, communication with 
sedated or non-responsive critically ill patients is often not optimal27-29 and is often considered to 
be a low priority in the ICU setting.30 A review of nurse-patient communication in the ICU found 
that nurses communicate poorly with patients, despite a high level of knowledge and skill with 
respect to communication. High stress levels and preoccupation with physical care and 
technology are potential explanations.29 Although most critically ill patients are sedated and 
many appear nonresponsive, several studies have documented that patients hear, understand 
and respond emotionally to what is being said even when healthcare providers assumed they 
were not aware.31,32 In interviews 48 hours after ICU discharge, patients were not able to recall 
their nurse’s name, but did recall detailed explanations given to them by nurses.31 Automated 
messages about the ICU environment will provide consistency of information, augment the 

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communication provided by nurses at the bedside, and may enhance the critically ill patient’s 
feelings of comfort. 
The scientific premise for the proposed project is that providing reorientation through scripted, 
automated, recorded messages in a family member voice familiar to the critically ill 
mechanically ventilated adult will mitigate the reduction of orientation to the environment which 
is a central feature of delirium, and reduce the occurrence of delirium. Several small studies 
have evaluated the effects of messages recorded by family on head injured comatose patients, 
although delirium was not assessed, and non-comatose patients have not been studied. Two 
small studies (12 subjects33, and 10 subjects34) evaluated physiologic risks in comatose patients 
with head injury, and found no evidence of increased ICP or other physiologic derangements 
related to a single recorded family voice message. In a recent small RCT (n=40) of comatose 
patients with acute subdural hematoma, the group who received recorded family messages of 
encouragement twice a day for 10 days had better GCS scores on day 10 compared with a 
control group (p=0.0001), although the groups had equivalent GCS scores at baseline.35 Use of 
a recorded family voice to improve orientation and reduce delirium is a novel approach which 
has not been previously described in the research literature nor considered in recent clinical 
guidelines, but our own preliminary data in a small randomized trial of 30 subjects (further 
described as preliminary study 2) supports beneficial effects of the intervention on reducing 
delirium occurrence and improving sleep in the ICU. Our own pilot work and small studies 
conducted by others support the scientific premise that scripted, automated, recorded 
messages in a family voice are not harmful, may benefit consciousness and improve cognitive 
orientation, and may reduce incidence of delirium. While promising, a more robust examination 
of the effects of this intervention, using rigorous methods in an adequately powered sample, as 
we propose, is warranted. 
The cognitive reorientation intervention we have developed and pilot tested is a simple but 
potentially powerful strategy to provide structured information in a familiar voice to patients on a 
regular basis. Because the intervention has a strong nursing care focus, it has the potential to 
affect delirium in ways that are distinct from but synergistic with medical care, which has 
focused primarily on pharmacologic management of delirium. The FAVoR intervention we 
propose in this project holds promise for reducing delirium in critically ill adults, improving sleep 
in the ICU, and secondarily benefitting cognitive function post-ICU. 
We will accomplish the objectives using a prospective, randomized, experimental design to 
achieve robust and unbiased results. Subjects (n=182) will be randomly assigned within 48 
hours of ICU admission and intubation to one of two groups. In the intervention group, scripted 
audio messages recorded by the patient’s family (FAVoR) will be played for the patient at hourly 
intervals during daytime hours. These messages will be personalized, delivered automatically, 
and provide information about the ICU environment. Subjects in the control group will not 
receive recorded audio FAVoR messages. The FAVoR intervention, a standardized protocol 
developed and tested in preliminary work, will be delivered by audio recording for 5 consecutive 
days (120 hours), or until ICU discharge if discharge occurs within the first 5 days. The number 
of episodes of delirium during ICU stay is the primary outcome measure. We will also collect 
data at 1 month and 6 months following ICU stay for secondary aim 3. A model of the study is 
presented in Figure 1. 

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Preliminary Studies 
1. 
Development of a reorientation intervention for critically ill adults. We conducted an 
early feasibility study to develop a reorientation intervention and test it in healthy volunteers in 
an ICU setting. A draft script of reorientation messages was developed based on published 
research by our team and others about patients’ recall of ICU experiences.38-40 The draft script 
was reviewed by 3 experts in critical care. We edited based on their feedback. The recorded 
message was then tested on 2 healthy nurse volunteers, simulating patients, in the ICU setting. 
Adjustments to message volume and length as well as location of the speaker were then made 
based on characteristics of the ICU environment (noise levels, ICU equipment placement, etc.). 
These data assisted in the development and testing of the proposed intervention in the ICU 
setting. 
2. 
Reorientation Intervention for Cognitive Dysfunction in the Critically Ill: A 
Feasibility Study. We conducted a randomized, controlled, preliminary study to explore the 
effect of a cognitive reorientation intervention on delirium in a small sample (n=30) of critically ill 
adults. Thirty adult patients admitted to Tampa General Hospital ICUs were randomized to three 
groups. The sample was 63% male, ranged in age from 19 to 97 years old (mean 59.5, SD 
17.0), and had a mean APACHE severity of illness score of 64 (SD 20.7). Using scripts 
developed in preliminary study 1, ten subjects were randomized to receive automated, scripted 
reorientation messages in a familial voice, ten subjects received the same messages in a 
nonfamilial voice (bilingual female research team member) and ten subjects did not receive a 
reorientation message. Delirium was evaluated by the Confusion Assessment Method (CAM)– 
modified ICU version. The family voice group had more delirium free days than the non-familial 
voice group, and significantly more delirium free days (Chi-Square, p= 0.0450) than the control 
group (see figure 2). During the three-day intervention period, mean days of delirium were 0.2 in 
the family voice group, 0.8 in the staff voice group, and 0.9 in the control group. Wrist actigraphy 
was recorded for a maximum of three consecutive days starting from the time of admission to 
the ICU. Actigraphy was successfully obtained in 76% (n=23) of the sample. Sleep efficiency 
was calculated from actigraphy data to evaluate sleep in the ICU. To explore the possible 
mediation effect of sleep in a longitudinal study setting, we fitted two linear mixed models: (1) 
the ICU-CAM score against the group assignment and (2) the ICU-CAM scores against the 
percent of sleep and Sobel’s test was applied. Following the reorientation intervention, sleep 
efficiency increased from baseline in both intervention groups, but decreased in the control 
group. The mean sleep efficiency in the family voice group increased from 56% to 66%, and 
sleep efficiency also increased from 45% to 52% in the non-familial voice group, both compared 
with the control group (sleep efficiency decreased from 54% to 52%). While it was not 
statistically significant, there was a trend towards improvement of the sleep efficiency as 
measured by actigraphy in the two intervention groups. Based on the results of the preliminary 
study that indicated family voice was most effective, we focused the primary aim of this proposal 
on testing the effect of family voice on delirium. 

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3. 
Oral care in mechanically ventilated adults. Over the past 2 decades, we have 
conducted research to provide definitive guidance for effective evidence-based oral care 
interventions for critically ill adults. Clinical practice recommendations for routine prescription of 
chlorhexidine (CHX) to reduce oral microbial colonization and risk of ventilator associated 
complications are based in part on the results of the first component of the program of research 
in oral care in mechanically ventilated adults (R01 NR07652)37-41. In the initial funding period, we 
examined the effects of tooth brushing three times a day and CHX twice a day, alone and in 
combination, on dental plaque and risk of VAP. We found that while CHX reduced risk, tooth 
brushing neither reduced risk nor enhanced the effect of CHX.41 In the second funding period, 
we tested the addition of a pre-intubation application of CHX, and surprisingly, found that it did 
not reduce VAP risk beyond the protection afforded by adherence to post-intubation CHX 
application guidelines.42 This was also important to clinical practice; since our data indicate that it 
is not essential to deliver the first dose of CHX prior to intubation, permitting providers to focus 
their attention on other critical pre-intubation activities. The current project will complete the 
essential evidence base for oral care delivered by nurses to critically ill patients. In the current 
funding period, we are determining optimal tooth brushing frequency, while considering 
individual-level variables that may influence both efficacy and risk of adverse events. Although 
we recognize that the proposed project addresses a different iatrogenic risk (delirium rather 
than ventilator associated complications), this series of projects is relevant to the proposed 
study because it established and refined our expertise in conducting intervention research in the 
challenging ICU environment, and demonstrates our commitment and ability to translate our 
findings to clinical practice.  
Importance of the Knowledge to be Gained 
The data obtained will provide empirical evidence that will enable us to evaluate the effect of the 
FAVoR intervention on delirium and holds promise to translate new knowledge into clinical 
decision-making about the management of delirium in the critically ill to ultimately improve 
patient outcomes, both in the ICU and as long-term survivors. We plan to publish the results of 
this study. 
5. Inclusion and Exclusion Criteria 
Since delirium in the ICU setting has a mean onset of 2.6 days (S.D.+/-1.7),45 enrolling within 48 
hours of initial intubation and ICU admission will initiate the FAVoR intervention prior to likely 
time of delirium onset. Male and female adults from all ethnic and racial backgrounds will be 
recruited.  
For inclusion, mechanically ventilated subjects must be: 
• 
at least 18 years old,  

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• 
within 48 hours of initial intubation and ICU admission,  
• 
they or their legally authorized representative (LAR) must be able to provide informed 
consent in English or Spanish, and  
• 
a family member able to speak English or Spanish must be available and willing to 
audio record scripted messages.  
Exclusion criteria include:  
• 
dementia (because it complicates planned longitudinal cognitive assessments),  
• 
anticipation by the clinical provider of imminent patient death,  
• 
medical contraindication to the intervention (for example, psychiatric history of auditory 
hallucinations, or profoundly deaf), and  
• 
inability to speak either English or Spanish.  
We will use the procedure described by our consultant, Dr. Ely, and his colleagues45 to screen 
for pre-existing dementia as follows. The modified Blessed Dementia Rating scale (mBDRS)47 
will be used to screen for dementia using family interviews; it is a valid measure in ICU patients 
where direct patient assessment is not feasible.48 Similar to Ely et al.,45 we will include an 
additional family/surrogate question asking them to rate on a 5-point scale whether they believe 
the patient has dementia. We will also increase the sensitivity for detecting pre-existing 
dementia by excluding potential subjects with suspected dementia if they meet any of the 
following 3 criteria: (1) history of an expert diagnosis of dementia, (2) modified Blessed 
Dementia Rating scale score of at least 3, or (3) rating by the surrogate of at least 3 out of 5 as 
possibly having dementia.  
Because the intervention scripts have been developed, IRB approved, and pilot tested in 
English and Spanish, patients who do not speak either English or Spanish, as identified by self 
or their family, will be excluded. 
Inclusion of Adults Unable to Consent 
In our experience in conducting clinical research in the critical care areas, we have found that 
potential subjects who are mechanically ventilated are generally sedated to some degree. In 
addition, since use of mechanical ventilation primarily occurs during periods of patient instability, 
the use of sedation at these times is extensive and compromises patient’s ability to 
communicate effectively which is compounded by the presence of the endotracheal tube. As a 
result, we have always found it appropriate to contact the legally authorized representative for 
consent. However, there may be rare occurrences when potential subjects are adequately 
oriented and lucid to be able to provide informed consent. Therefore, we will use the 2-step 
procedure described by Fan et al.76 to determine the patient’s ability to provide informed consent. 
Step 1 is objective evaluation with the Richmond Agitation-Sedation Scale (RASS) and the 
Confusion Assessment Method for Intensive Care Unit (CAM-ICU). Patients who score -1, 0, +1 
on the RASS indicating drowsy, alert, or restless respectively and are not delirious (CAM-ICU =  
No) will move to Step 2. Step 2 is assessment for competency using the MacArthur 
Competence Assessment Tool for Clinical Research: MacCAT-CR that evaluates all four 
capacity domains for consent (understanding, appreciation, reasoning, expression of a choice). 
Evaluation of Step 1 requires approximately 2-3 minutes, Step 2 requires approximately 15 
minutes. Fan et al.76 found in consent evaluations of 150 ICU patients that 89% were 
sedated/delirious, and unable to provide consent; our experience in previous research is similar. 
Therefore, we expect that few potential subjects will move to Step 2 while critically ill and 
mechanically ventilated. The LAR will be contacted for those who fail Step 1 or Step 2. 

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We will evaluate the potential subject’s level of orientation and response to our discussions of 
the study on a daily basis during the hospital phase, and if the potential subject is able to 
respond in a manner that is clearly understandable, we will use the potential subject’s own 
consent to continue participation. However, in any instance where the potential subject’s ability 
to comprehend and communicate his/her desires is in question, we will seek consent for 
continued participation from the LAR and will invite the research subject to provide his/her 
assent. Verbal consent to continue participation and for post-hospital follow up will be obtained 
from the subject as soon as their medical condition permits. We will follow UM IRB, JMH, and 
UMH Policies and Procedures. 
Inclusion of Pregnant Women 
The study carries no added risk to pregnant women and the well-being of their unborn child. 
Therefore, pregnancy is not an exclusion for participation in the study.  
Inclusion of Children 
Children less than 18 years of age will not be included in this study, because delirium presents 
differently in children and is dependent upon developmental level, cognitive reorientation would 
require adjustment for developmental level, and adequate power for each pediatric 
developmental level would be prohibitive and could not be obtained during the proposed study 
period. 
Inclusion of Prisoners  
Prisoners are a vulnerable population because of the many unique conditions associated with 
confinement that compromise their ability to exercise free choice. Due to the added vulnerability 
in their ability to exercise free choice in addition to their critical illness, prisoners will not be 
recruited. 
6. Number of Subjects 
We will recruit 182 subjects in the adult intensive care units at University of Miami Hospital and 
Jackson Memorial Hospital. 
7. Study Timelines 
Duration of Intervention and Data Collection Procedures. Following consent, the duration of 
participation includes data collection over a maximum of 120 hours (5 days) of the ICU stay, 
overnight data collection at least 24 hours following ICU discharge, and overnight data 
collection during home visits at 1 and 6 months following hospital discharge.  Multiple subjects 
(up to a maximum of 4) will be actively enrolled in this study as inpatients and outpatients, using 
research equipment obtained for this study (multiple wireless speakers, Sleep Profilers, and 
actigraphy watches) to achieve the collection of key variables in Table 1.   
As of March 2020, per the updated guidance regarding research continuity from the University 
of Miami IRB and research administrations, we are complying with the COVID-19 safety 
recommendations to protect our subjects, research personnel, students, and faculty members.  
As of June 2020, we will resume new enrollments at UMH; temporary pause of enrollments at 
JMH continues. We will deliver interventions and collect face-to face data at UMH. We will not 
collect data that can only be collected face-to-face during follow up visits. We will schedule and 
conduct follow-up visits by phone or video conference calls, and we will substitute NIH PROMIS 
measures (including PROMIS Global Health, PROMIS-SD, PROMIS-SRI, PROMIS-CF,  

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PROMIS-CFA) for the Sleep Profiler and Actigraphy measures, until it is safe to resume face-
toface interactions with subjects at follow-up.   
Please refer to the updated Table 1 for a detailed list of which data will be collected remotely via 
the electronic medical record and from the subject over the phone or via video conference.  
 
We plan to review approximately 350 medical records in order to achieve our sample size of 
182 enrollments during the 4-year study. The data collection schedule is shown in Table 2.  

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Table 2. Study Timeline  
 
8. Study Endpoints 
Primary Endpoint.  To test the effect of the Family Automated Voice Reorientation (FAVoR) 
intervention on delirium in critically ill, mechanically ventilated adults during hospitalization in the 
ICU, we plan for 95% power respectively to detect an effect size (W) of 0.35 using a 2 degrees 
of freedom Chi-Square Test with a significance level (alpha) of 0.05.  
Secondary Endpoint. The recently completed BRAIN-ICU descriptive study of ICU survivors 
reported a 43% attrition from the inpatient sample to a 12 month follow up time point.18 Given 
that a secondary aim of the proposed project plans 1month and 6 months post-hospital 
discharge follow up, we conservatively planned for a 40% attrition rate, which is a sample size 
of 182 total (91 in each group). 
Primary and Secondary Safety Endpoints. The FAVoR intervention will be interspersed with 
the care team’s activities, and at no time will the study personnel delay or interfere with critical 
care procedures; if the needs and activities of providers are such that the study personnel are 
unable to access the subject to provide audio reorientation, the subject will be withdrawn from 
the study. At all times, we will place the subject’s need for medical treatment, and avoidance 
with interference with treatment, foremost. 
To reduce skin irritation from applied devices, the Sleep Profiler and ActiWatch will not be 
placed on skin that is not intact or damaged in any way. The Sleep Profiler and ActiWatch will 
be removed as soon as data collection is complete (up to 120 hours) and skin assessments will 
be conducted daily. If the skin shows any signs of irritation, the sleep monitoring devices will be 
discontinued. 
If a 20% or larger fluctuation in vital signs (heart rate and blood pressure) during the recorded 
message occur, research staff will turn off the recorded message. The clinical nurse assigned to 
the subject will be immediately notified, and the clinical medical provided will be notified as well. 
The message will be restarted when the critical care nurse or physician indicates the patient is 
stable. If the 20% or larger fluctuation in vital signs re-occurs, the intervention will be 
discontinued and the in-hospital data only up to that point will be included in the study. 
Prior to beginning the NIH Toolbox Cognition Battery testing and questionnaires, the subject will 
be told if they feel excessively frustrated or anxious during the test, they may stop. There is no 
alternative therapy. However, subjects may elect not to participate and may withdraw from the 
study at any time without affecting the care they receive. 

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9. 
Procedures Involved 
Research Design 
We will use a prospective, randomized, experimental design to accomplish the specific aims. 
Subjects (n=182) will be randomly assigned within 48 hours of intubation and ICU admission to 
one of two groups. The intervention group will receive the FAVoR intervention over a 5-day 
period (120 hours) or until discharge from the ICU, if discharged within 5 days. The control 
group will receive standard ICU care, but will not receive the FAVoR intervention. All subjects 
will receive standard clinical care for mechanically ventilated patients, as per clinical guidelines 
and clinical agency guidelines. Standard clinical care includes all components of the IHI 
ventilator care bundle.37 
Sample. Because delirium occurs with a greater frequency in those who are mechanically 
ventilated,43 this study will focus on subjects who are mechanically ventilated. The sample of 182 
subjects will be drawn from all patients over the age of 18 years admitted to the Intensive Care 
Units at University of Miami Hospital (UMH) and Jackson Memorial Hospital (JMH) who are 
newly intubated (within 48 hours of initial intubation at time of study recruitment) and have a 
family member available to record the scripted intervention message. Subjects will be 
randomized to group according to a permuted block design44 developed by Dr. Ji such that after 
every k subjects, balance will be maintained between the groups. In order to fully enroll the 
study during the requested 4-year funding period, we will target enrollment of 7 subjects per 
month. 
Group Assignment. The Project Director and Research Assistants will recruit, enroll, and 
assign subjects to groups. Subjects will be randomly assigned to one of two study groups 
(FAVoR intervention or control) using randomization processes described in the Sample section 
above.  
1) Intervention Group: Subjects in the intervention group will receive personalized digitally 
recorded reorientation messages administered for up to 2 minutes every hour over an 
8hour daytime period (beginning at 9 am daily) recorded in the voice of a family 
member. Subjects in the intervention group will continue to receive the intervention for 
up to a total of 5 days (120 hours), or until ICU discharge if ICU discharge occurs within 
the first 5 days. Since in the ICU setting delirium has a mean onset of 2.6 days (S.D.+/-
1.7), and a mean duration of 3.4+/-1.9 days,49 a 5-day period for the study intervention is 
appropriate and includes the period prior to delirium onset as well as when delirium has 
been shown to occur most frequently.  
2) Control Group: The control group will consist of usual care, and will not receive audio 
reorientation messages. Subjects will remain in the study for five days or until ICU 
discharge if discharged before five days. 
Subjects in both groups will be reoriented by care providers as part of usual care practices. Data 
will be collected from the medical record daily. Both groups (intervention and control) will 
undergo longitudinal cognitive and patient-reported health status evaluations concurrently with 
24-hour sleep profiler-polysomnography and actigraphy at three different points in time. The first 
time point is inpatient, at least 24 hours after ICU discharge, then outpatient with two home visit 
data collection events at 1 month and 6 months post hospital discharge. 
Description of Intervention. The FAVoR intervention includes a set of 8 recorded messages 
which were developed in preliminary study 1, and were tested and refined in preliminary study 
2. Based on the feasibility data (preliminary study 2) each message is scripted, is no longer than  

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2 minutes long, is a personal message using the subject’s name, uses simple terms, and is 
written at a 5th grade reading level. Messages include information about the critical care 
environment, the visual and auditory stimuli to be expected, and the availability of providers and 
family. The messages call the patient by name (preferred name as recommended by the 
patient’s family); we believe the use of the patient’s name may create greater attention to the 
message. 
Each message indicates that it is daytime (to provide general time orientation), states that the 
message is a recorded message, and tells the subject that he/she will hear messages 
frequently throughout the day to help him/her understand that he/she is in the ICU. Other than 
the patient’s name, the recorded message is generic in nature, and not specific to any one 
patient condition, procedure, or family situation. Topics for message scripts were developed in 
response to patients’ recollections of the ICU experience.38-40 The 8 recorded messages will vary 
randomly in order each day, reducing message repetition, which may eventually annoy or be 
ignored by the subject. 
The messages will be recorded by a family member of the family’s choice using a standardized 
script, in either English or Spanish, based on the family member’s decision regarding which 
language would be most meaningful to the subject. Family members are not human subjects in 
this project; no data will be collected about the family members. The messages will be digitally 
recorded using audacity software and stored on the study computer’s hard drive as a standard 
Microsoft wave files. The wave files are loaded onto a small, wireless, digital audio player with a 
wireless speaker, protected inside a disposable plastic bag, placed near the subject’s ear, and 
set to shuffle play. Shuffle play is a mode of audio playback in which messages are played in a 
randomized order that is decided upon for all tracks at once and prevents repeated tracks, 
which makes it distinct from random playback. Shuffle play randomly selects the order of the 
messages to be played in the patient’s room every hour for 8 hours during the daytime, 
beginning at 9:00 am. The digitally recorded messages will continue at the predetermined 
daytime intervals each day for a total of 5 days (120 hours), or until ICU discharge if ICU 
discharge occurs prior to 5 days. All intervention “doses” will be administered during the hours 
of 9:00 am and 4:00 pm for each of the 5 days, with intervention beginning at the earliest 
available time following completion of family recording. The research personnel will document 
the time and number of recordings each day so that a message “dose” can be documented. 
Research personnel will monitor the subject and the recorded messages regularly to document 
if the subject was not in the unit (for procedures off the unit etc.) so that those off-unit times can 
be included in the dose calculation. 
The timeframe chosen for intervention delivery coincides with usual waking hours; no message 
will be played outside of this timeframe so as not to disturb sleep or interrupt family visits in the 
evening hours. Further, early morning hours are typically times of patient care intensity and 
additional stimulation at that time may not be appropriate. Based on our preliminary studies we 
found that by placing the speaker near the patient’s ear, the recorded message is able to be 
heard at a volume that is loud enough for the patient but not so loud as to be noxious or 
interfere with care providing activities; the message will be loud enough for the patient to hear 
comfortably but not loud enough to be excessively stimulating or irritating to the normal listener. 
Although the use of earphones to deliver the message might focus the subject’s attention on the 
message, we chose not to use earphones as these would also block out other stimuli and 
potentially result in greater disorientation. In addition, earphones could impair understanding of 
communication to the subjects from providers or family. 

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Sources of Materials 
Data will be obtained both inpatient and outpatient from the patient’s medical record, 
noninvasive physiologic monitoring, cognitive testing (delirium assessment and NIH Toolbox 
Cognition Battery), and observation. Data will include patient’s gender, age, race, ethnic 
background, reason for admission to the ICU, pharmacological therapies affecting cognition and 
sleep, laboratory data to calculate the APACHE III, SBM and SOFA, wrist actigraphy, sleep 
profiler-polysomnography, cognitive testing (delirium and NIH Toolbox Cognition Battery) scores 
and PROMIS global health scores. Only study personnel who are responsible for enrolment and 
data collection will have access to individually identifiable information. Each subject will be 
assigned an arbitrary study identification number, and no individually identifiable private 
information will be entered into the study database. 
Key Variables and Their Measurement 
Please refer to Table 1 for a detailed list of which data can only be collected in person. To 
protect human subjects, we are closely following the COVID-19 safety recommendations. 
Therefore, we will pause data collection for the following 4 measures at JMH until enrollment 
resumes, and during followup visits:  
1. CAM-ICU (substituted by CAM) 
2. Actigraphy  
3. SP-PSG (substituted by PROMIS-SD and PROMIS-SRI) 
4. NIH Toolbox Cognition Battery (substituted by PROMIS-CF and PROMIS-CFA) 
Delirium. The primary outcome measure for this project is delirium free days. We will quantify 
delirium using the Confusion Assessment Method for the ICU (CAM-ICU).45 CAM-ICU scores for 
each subject will be obtained by study personnel twice daily at 9 am and 4 pm (coinciding with 
the schedule for initiation and conclusion of messages each day in the FAVoR intervention 
group, and at identical times for the control group). CAM-ICU scores will also be recorded at the 
same times for two days following the completion of the intervention period. The Confusion 
Assessment Method (CAM) will be used during study visits after transfer from the ICU (post 
ICU, 1 month, and 6 month follow up periods) for comparison. 
We will also collect documentation by providers in the medical record of episodes of delirium 
occurring outside of the CAM-ICU data collection conducted by research personnel. Only days 
without any instances of delirium will be counted as delirium free days. The CAM-ICU is 
recognized in the Clinical Practice Guidelines for the Management of Pain, Agitation, and 
Delirium in Adult Patients in the Intensive Care Unit as a valid, reliable, and feasible tool to 
detect delirium in ICU patients3 with pooled sensitivity of 75.5% and specificity of 95.8%.50 
Sleep/Activity. Sleep patterns in the critically ill are highly disorganized, with fragmentation, a 
predominance of light sleep, and reduction in deep sleep and rapid eye movements.8 We will 
use the FDA approved Sleep Profiler system (Advanced Brain Monitoring, Carlsbad, CA) to 
obtain continuous polysomnography data (SPPSG). The Sleep Profiler has been successfully 
utilized in mechanically ventilated and sedated patients and provides three frontopolar 
electroencephalographic (EEG) signals (AF7/AF8, AF7/Fpz and AF8/Fpz).51-54  
A wrist actigraph (ActiWatch Spectrum, Philips Respironics, Bend, OR) will be placed on the 
wrist to measure patient activity and ambient light levels. We have extensive experience with 

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the use of actigraphy. In our previously published work55-57 and the preliminary study, we used 
actigraphy as a surrogate measure of sleep, as have other ICU researchers58. Wrist actigraphy 
also has been found by our research team to be a reliable method of assessing activity and 
agitation in the ICU.55-57,59 
Iatrogenic/Environmental and Biobehavioral Factors. Critical illness and its treatment 
predispose patients to delirium through several mechanisms which are poorly understood. 
Factors may include patient characteristics, predisposing conditions, and 
iatrogenic/environmental factors. 
Ambient light. Although the FAVoR intervention does not involve manipulation of ambient light 
levels, environmental conditions have been hypothesized to influence risk of delirium and may 
affect sleep in the ICU. 
Pharmacological Therapies Affecting Cognition and Sleep. We will collect data regarding 
specific pharmacologic therapies. For sedatives and narcotics, we will determine equivalent 
doses to facilitate analysis. To provide sedative and analgesic dose equivalents for analysis, 
doses will be converted as described in Cammarano et al.60  
Disease Severity and Comorbid Conditions 
Acute Physiology and Chronic Health Evaluation (APACHE) IV. There is strong 
evidence that severity of illness on admission to the ICU, assessed by APACHE score 61-65, is  
a risk factor for delirium.4,11  
Sequential Organ Failure Score (SOFA). To determine daily severity of illness we will use 
the SOFA66, which was developed to quantify severity of illness based on the degree of 
organ dysfunction, serially over time. The SOFA score has good reliability and accuracy,67 
accurately reflects the daily severity of organ dysfunction, predicts prognosis68 and is able to 
predict ICU mortality.69 
STOP-Bang Model (SBM) Assessment. Obstructive sleep apnea (OSA) underlies numerous 
co-morbidities and is linked with cardiovascular and neurovascular diseases, metabolic 
disorders, and impaired neurocognitive function.70-72 The STOP-Bang Model (SBM) questionnaire 
will be used as an OSA screening tool for baseline data collection.  
Subject Demographics. Subject characteristics that may affect the development of delirium will 
be collected at admission to the study, including age, race, ethnicity and gender.11  
Additional Subject Descriptive Data. In order to completely describe the study population, we 
will also collect the type of ICU (reflecting type of critical illness and population; i.e. surgical, 
medical ICU). In addition, because visual or auditory deficits may affect measurements and/or 
delirium, information about these will be recorded including if patients wore corrective lenses 
(glasses, bifocals, or contacts) or hearing aids prior to ICU admission. Families or significant 
others will also be asked if the patient had any documented impairment in vision or hearing. 
Patient-Reported Health Status. The Patient-Reported Outcomes Measurement Information 
System (PROMIS) global health instrument will be used to document subjects’ perceptions of  
their health status.73,74.The PROMIS Sleep Disturbance (PROMIS-SD) and Sleep Related 
Impairment (PROMIS-SRI) instruments will be used to document subjects’ perception of their 
sleep quality following transfer out of the ICU and during 1 month and 6 month visits. Both  

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PROMIS measures are validated and available in English and Spanish on the NIH website.  
Cognitive Function. The NIH Toolbox Cognition Battery75 testing will be used to measure 
cognitive function after transferring out of the ICU and at 1 month and 6 months following 
hospital discharge.  
The PROMIS Cognitive Function (PROMIS-CF) and PROMIS Cognitive Function Abilities 
(PROMIS-CFA) instruments will be used to document subjects’ perception of their cognitive 
function following transfer out of the ICU and during 1 month and 6 month visits. Both of these 
assessments can be completed remotely, over the phone or by video conference. Both 
PROMIS measures are validated and available  in English and Spanish on the NIH website.  
Inpatient. Once consent is obtained and the subject is enrolled, baseline data will be collected 
from medical records. In randomized assignment to the intervention group, the family member 
selected by the family to record scripted FAVoR messages will be contacted, and taken to a 
quiet area to complete the recording on the assigned computer. FAVoR will be delivered 
through a wireless speaker, which will be placed near the patient’s head. Delivery of the 
intervention to subjects randomized to receive it will begin as soon as possible during 9 am and 
4 pm; if the FAVoR messages cannot be recorded before 4 pm, the intervention will begin on 
the following morning at 9 am. Data recording devices (SP-PSG and ActiWatch) will be applied 
to the subjects receiving the intervention immediately prior to the onset of the FAVoR 
intervention, and to control subjects as soon as feasible following consent. Actigraphy and 
SPPSG will continue throughout the 120-hour period beginning with the intervention delivery 
and continuing until the same time 5 days (120 hours) later. Data collection will resume and 
continue after at least 24 hours of ICU discharge. The subject will complete the NIH Toolbox- 
Cognition Battery, and the PROMIS Global Health instrument, and actigraphy and SP-PSG will 
be obtained. 
We will follow University of Miami Hospital and Jackson Memorial Hospital infection control 
policies and procedures for cleaning portable equipment before and between patients, which 
include appropriate germicidal or bleach agents and single use disposable equipment covers. 
As of June 2020, we will resume data collection at UMH for the following measures: CAM-ICU, 
Actigraphy, SP-PSG, and the NIH Toolbox Cognition Battery. Data collection remains paused 
for these measures at JMH. 
  
Outpatient. There will be two outpatient data collection events at 1 month and 6 months 
posthospital discharge. During the 1 month home visit, research staff will travel to the subject’s 
home (or other location agreed upon) to administer the NIH Toolbox-Cognition Battery testing 
and the PROMIS Global Health assessment, PROMIS-SD, PROMIS-SRI, PROMIS-CF,   
PROMIS-CFA questionnaires. While face-to-face interaction is not permitted, the subjects will 
not be asked to wear the SP-PSG and ActiWatch (for acquisition of sleep and activity data) 
overnight. Identical data collection processes will be used at the 6 month visit.  
Procedures for telephone or video conference:  
Per protocol, research staff will collect data on subjects’ hospital discharge dates. There 
are two outpatient data collection time points: 1 month post-hospital discharge, and 6 
posthospital discharge. Research staff will call the phone number that the subject or subject’s 
LAR provided for outpatient follow-up visits.  
During this phone call, we will verbally notify the subject that we have modified 
procedures to enable remote visits to protect all enrolled subjects and our research personnel. 

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The subject will be asked to complete the visit entirely by phone or by Zoom-enabled video 
conference. If the subject agrees to a Zoom-enabled video visit, then we will provide two options 
for accessing the Zoom video link: 1) email address as provided by the subject and/or the 
subject’s LAR, or 2) text message to a phone number as provided by the subject and/or the 
subject’s LAR. If the subject does not have access to video capability, or does not wish to 
conduct the visit by video, then the visit will be conducted entirely by phone.  
The CAM, STOP-BANG, PROMIS Global Health, PROMIS-SD, PROMIS-SRI, 
PROMISCF, and PROMIS-CFA can all be completed over the phone or by video call; each 
instrument will be administered by the research staff. Subjects may choose not to complete any 
measure if unwilling, and may end the call at any time.  
Compensation 
Upon the hospital discharge date, a gift card in the amount of $25, along with a note of thanks 
to the participant and their family, will be mailed to the home address of the participant. A 
second gift card valued in the amount of $25 will be hand delivered if the visit is face-to-face 
during the second (and final) home visit, approximately 6-months after the hospital discharge 
date. If the visit is done by phone or video call, the second gift card will be mailed.  
10. Data Management 
All data will be downloaded into research electronic data capture (REDCap), a secure web 
application database, which will be accessed by a secure UM web connection with 
authentication and data logging. The Project Director will review all data for completeness and 
appropriate entries before it is entered into the study database. At the beginning of the data 
entry process a minimum of 1 in every 10 participant records will be checked against the 
original medical record for data errors. Records for review will be randomly chosen by the data 
manager. As the study progresses, the frequency of monitoring will be based on the results of 
the previous data review. If the error rate is unacceptable then the monitoring will increase until 
the error rate is acceptable (less than 5% of all data). The Data Manager in consultation with the 
Principal Investigator will develop reports that will help in the coordination and management of 
the project and also allow project staff to monitor the quality of the data and the progress of the 
study. Furthermore, only a unique identifier, assigned by the Principal Investigator or Data 
Manager, in the database will identify each subject. The data files will be backed up daily during 
the data entry process and once a week during other times by the Project Director. All data files 
will be housed on the university server which is backed up every 24 hours and copies are stored 
off-site for additional security. Access to the database will be password protected and limited to 
the investigators, Project Director, and Data Manager. 
Data Analysis Plan 
The primary specific aim of the proposed project is to test the effect of the Family Automated 
Voice Reorientation (FAVoR) intervention on delirium in critically ill, mechanically ventilated 
adults during hospitalization in the ICU. We hypothesize that subjects who receive the FAVoR 
intervention will have less delirium than control subjects who do not receive the intervention. 
Secondary aims of this project are to: (1) explore if the effect of FAVoR on delirium is mediated 
by sleep, (2) explore if selected biobehavioral factors may potentially moderate the effects of 
FAVoR on delirium, and (3) examine the effects of FAVoR on short term (immediately after ICU 
discharge) and long term (1 and 6 months after hospital discharge) outcomes, including 
cognitive function and patient-reported health status. 

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There will be two parts of the data analysis: Part I: A traditional statistical data analysis for 
randomized controlled trials for the Primary Specific Aim, and Part II: Pathway analytic model 
analyses to address the secondary aims. Dr. Ji will work closely with the Data Manager to 
perform all the planned data analyses for this study. 
Part I: We will follow the research and regulatory guidelines for statistical analysis of clinical 
trials including the ICH Guideline77 and the CONSORT guidelines78. First, descriptive statistics 
will be performed to describe and compare the characteristics of the intervention and the control 
groups. Descriptive statistics will be reported as means +/- standard deviation for continuous 
variables and as frequencies and percentages for categorical variables. Shapes of the data 
distributions, missing data and outliers will be examined by both graphics and statistical tests. 
Any data issues identified will be discussed with the PI and other investigators and addressed 
before formal data analysis. For example, skewed variables may be transformed so that their 
distributions are close to the Normal Distribution. Outliers may be excluded or included in two 
separate analyses. Missing data may be imputed or handled by other missing data techniques. 
Distributions of continuous variables and categorical variables will be compared between the 
intervention and the control group by using the t-test or Wilcoxon rank sum test and the 
Chisquare test, respectively. Any baseline covariate that is differentially distributed in the two 
groups will be adjusted in the subsequent analysis for testing the intervention effect. Assuming 
the randomization produces well balanced intervention and control groups, a Chi-square test for 
a 2x2 table with the number of delirium free days and the treatment assignment will be 
performed to test the primary hypothesis. If there are unbalanced covariates, then covariance 
adjustment will be performed by using logistic regression that includes both the treatment 
assignment and the unbalanced covariates. If there are missing values in the primary outcome, 
then multiple imputation will be performed using SAS PROC MI for missing at random (MAR) 
data.79,80 Sensitivity analysis for potentially not missing at random data will be performed using 
the Yau and Little81 Intent-to-Treat Analysis for Longitudinal Studies with Dropouts. 
Part II: Given the large number of variables measured for activity/sleep, disease severity, 
environment and demographics and the potential complex pathways among these variables, we 
plan to use partial least square structural equation models (PLS-SEM) to analyze the relative 
importance and the pathways of these variables. 
Partial least squares (PLS) is a predictive modeling method that can predict high dimensional 
outcomes from high dimensional, correlated predictors. The variance importance in projection 
(VIP) measure in PLS models can be used to compare the relative importance of different 
predictors which is a useful tool for variable selection in high dimensional data.82 In recent 
years, PLS-SEM was developed to use PLS fit pathway models with both manifested and latent 
variables.83-86 PLS-SEM is implemented in the R package semPLS. We will perform the 
predictive PLS using SAS PROC PLS for variable screening so that important predictors from 
the high dimensional raw data (such as the sleep measure) will be identified. Then we will fit 
PLS-SEM using the R package semPLS to the mediation effect of sleep and other empirically or 
theoretically hypothesized pathways. Specifically, for secondary aim 1, we will perform 
meditation analysis within multilevel SEM; for secondary aim 2, we will test moderation in 
PLSSEM to test the biobehavioral factors as multiple moderators; and for secondary aim 3, we 
will fit path analytic models from the FAVoR intervention to the short-term and the long term 
cognitive function and patient-reported health status measures, respectively. 

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11. Provisions to Monitor the Data to Ensure the Safety of Subjects 
In addition to the Data Safety and Monitoring plan described below, the study will be monitored 
under the quality assurance procedures of the SONHS which includes a review of the regulatory 
binder, review of consents upon enrollment of the first 5 participants and every 6 months 
thereafter until human subjects activities are completed.  
Data Safety and Monitoring Plan 
Purpose: 
The purpose of the DSM Plan is to: 
1. Assure monitoring of the progress of the trial and the safety of participants 
2. Assure compliance with reporting requirements for adverse events 
3. Assure data accuracy and protocol compliance. 
Required elements: 
a. Monitoring entity or who will monitor the study: The project involves minimal risk and will be 
conducted at a single site. The PI and an independent Safety Monitoring Committee (SMC) 
will have responsibilities for monitoring the study. The PI, Dr. Munro, will be directly 
responsible for ongoing data and safety monitoring of the study. An independent Safety 
Monitoring Committee (SMC) will be responsible for oversight of the safety of participants, 
including but not limited to review of adverse events. The SMC will be composed of 3 
members who are not directly associated with the project. A statistician will serve as chair; 
two PhD nurse researchers with expertise in research in critical care settings will serve as 
members.  
b. Procedures for  
1) 
monitoring study safety to include monitoring schedule, auditing selected cases for 
compliance with IRB requirements, conformance with informed consent requirements, 
verification of source documents, and investigator compliance:  Enrollment, study fidelity, and 
safety data will be reviewed regularly at study team monthly meetings. The SMC will convene 
after data collection has been completed for the first 20 subjects and every six months 
thereafter to review monitoring plan data, including safety and adverse events data. The 
monitoring plan, including data sources and reporting intervals, is summarized in the 
accompanying table below. Written minutes of monthly team meetings will be kept and will 
include reports detailed in the monitoring plan table. Written minutes of SMC meetings will be 
forwarded to the IRB and NIH as part of the annual reporting process. 
2) 
minimizing research-associated risk: We anticipate minimal additional physical and 
psychological risks associated with this study. Reorientation is routinely provided to critically ill 
patients by bedside nurses as part of clinical care. The intervention will be interspersed with the 
care team’s activities, and at no time will the study personnel delay or interfere with clinical care; 
if the needs and activities of providers are such that the study personnel are unable to access 
the subject to provide interventions, the subject will be withdrawn from the study. At all times, 
we will place the subject’s need for medical treatment, and avoidance with interference with 
treatment, foremost. Because these subjects are receiving clinical care in the hospital, the 
attending clinical nursing and medical providers will be promptly informed of any adverse effects 
to the subjects; if an adverse event occurs, necessary interventions will be determined and 
delivered by the clinical providers. 
3) 
protecting the confidentiality of participant data: In order to reduce risks to privacy of 
individuals or confidentiality of data, we will not include personally identifiable data in the 

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database files. All computers and data files will be password protected, and data will be stored 
on the University server, with access only to study personnel, under the direct supervision of the 
PI, Dr. Munro. Each subject will be assigned an arbitrary code number to conceal the identity of 
the research data, and no identifiable private information will be associated with any data files. 
All data will be collected on laptops in the clinical setting; these laptops will remain in the 
possession of study personnel at all times (unless locked in a cabinet in the locked research 
office), and all study-related files will be password protected. At the conclusion of each segment 
of the subject’s participation (ICU, hospital discharge, 1 month post-hospital, 6 months 
posthospital), that subject’s data will be transferred from the laptop computer to a secure, 
password protected file on the UM server, under the direct supervision of Dr. Munro, with 
access limited to study personnel. Study information obtained will be kept strictly confidential, 
and it will not be possible to identify any participant from the reports that may result from this 
research. 
c. Procedures for identifying, reviewing, and reporting adverse events and unanticipated 
problems to the IRB and NINR (FDA not applicable): Research staff will report any unusual 
occurrence or possible adverse event immediately to the PI, and will provide the PI with a 
detailed written description of the circumstances, the event, and immediate actions taken to 
reduce harm to subjects or others. The PI will review the situation, using UM IRB policy 
HRP024 
(https://eprost.med.miami.edu/eProst/Doc/0/HL7O55VBRRQ4BAAQ5NVBGFT62B/HRP- 
024%20-%20SOP%20-%20New%20Information_rev04.29.2016.pdf) and OHRP guidance  
(http://www.hhs.gov/ohrp/policy/advevntguid.htmland) to determine required reporting. All 
adverse events will be reported to the SMC, IRB and to NINR following institutional and NIH 
guidelines. All unusual occurrences and adverse events will be reviewed in monthly study team 
meetings. The PI will report any unanticipated problems (including those that are serious 
adverse events and those involving risks to subjects or others) to the IRB immediately upon 
becoming aware of the problem, in accordance with UM policy. In addition, a summary of 
adverse events will be included in biannual reports to the SMC and annual progress reports to 
the UM IRB and to NINR.  
  
Because we anticipate that the study involves minimal risk, if any serious adverse events or 
unanticipated problems occur (i.e., those that suggest that the research places subjects or 
others at greater risk of harm than previously known) we will halt accrual and engage the SMC 
to conduct a complete review of eligibility, monitoring, assessments, and intervention. 
Resumption of accrual will occur only following SMC recommendation and IRB approval of any 
required changes to the study to reduce future risks to subjects (or IRB determination that no 
changes are required and accrual may resume). 
  
d. The study will be conducted at a single site (not a multi-site study). 
  
e. An assessment of external factors or relevant information (i.e., developments in the literature, 
results of related studies) that may have an impact of the safety of participants or on the 
ethics for the research study: The PI will conduct monthly reviews of related projects in 
recently published literature and Clinicaltrials.gov, and assess the relevance for subject safety 
and ethics to this project. Identified issues will be discussed in monthly study team meetings, 
and communicated to the IRB and NINR as appropriate.  
f. No interim analysis nor futility analysis is planned.  

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Format 
The format for the DSM Plan will consist of: 
1. 
Continuous, close monitoring by the principal investigator, including regularly scheduled 
research team staff meetings; 
2. 
Review of and action on reports by study team, SMC, and others at scheduled intervals 
and as needed (see monitoring plan table below); and 
3. 
Reporting by the principal investigator to the IRB and NIH in compliance with institutional 
and NIH policy. 
Safety Monitoring Plan 
 
Report  
Purpose 
Report 
elements 
Prepared by 
Report 
interval 
Distributed 
to 
Action 
Accrual 
update report 
Monitor 
enrollment to 
ensure that 
accrual goals 
are met in a 
timely manner 
Monitor inclusion 
of women and  
racial/ ethnic 
diversity to 
ensure adequate 
representation 
For current 
month, and 
cumulative, 
reported by 
ICU unit and 
total: 
-Number 
screened -
Number  
eligible for 
inclusion  
-Number not 
enrolled 
(subcategories  
for reason) -
Number 
enrolled    -
Gender 
   -Race 
   -Ethnicity 
Project  
Director,  
Data  
Manager 
Monthly 
PI, Study 
team 
Review at 
team 
meeting 
Corrective 
action plan 
as required 

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Monthly 
progress 
report 
Summarize  
status of 
subjects  
Assess progress 
on the study  
For current 
month, and 
cumulative, 
reported by 
ICU unit and 
total: 
-Number of 
subjects 
completed 
intervention -
Number of 
subjects with 
intervention 
completed, 
data 
collection 
continuing -
Number of 
subjects off 
study (by 
reasons) -
Number of 
subjects lost 
to follow-up 
(by reason) -
Inclusion/ 
exclusion 
violations  
Project  
Director,  
Data  
Manager 
Monthly 
PI, Study 
team 
Review at 
team 
meeting 
Corrective 
action plan 
as required 
Data 
completeness 
report  
Identify missing 
data elements 
Minimize missing 
data Remedy  
data collection 
issues 
Data collection 
forms 
Data  
Manager 
Monthly for first 
year, then 
quarterly 
PI, Study 
team 
Review at 
team 
meeting 
Corrective 
action as 
required 
 
Protocol 
deviation log 
Document 
deviations  
Facilitate 
regulatory 
reporting 
Protect safety of 
human subjects 
- Detailed 
description of 
protocol 
deviation 
Project  
Director, PI 
Monthly 
Study team 
Review at 
team 
meeting 
Corrective 
action and 
report to IRB 
as required 

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AE report 
Protect safety of 
human subjects 
Detailed 
description of 
the adverse 
event, incident, 
experience, or 
outcome  
-Explanation of 
the basis for 
determining 
whether the 
adverse event, 
incident, 
experience, or 
outcome 
represents an 
unanticipated 
problem  
-Description of 
any changes to 
the protocol or 
other 
corrective 
actions that 
have been 
taken or are 
proposed in 
response to 
the 
unanticipated 
problem. 
PI 
As stated in  
UM HRP-024  
UM IRB 
As 
determined 
by UM IRB 
Urgent 
communication 
as needed to 
address issue  
Study team 
-Corrective 
action as 
required to 
protect 
subjects -
As 
determined 
by UM IRB 
Annual 
summary (or 
more frequent 
as directed by  
UM IRB) 
NIH 
Include in 
annual 
progress 
report 
Intervention 
fidelity and 
Protocol 
compliance 
report 
To maintain 
intervention 
fidelity and 
compliance with 
protocol 
-Performance 
testing of  
GRAs to  
ensure that all 
critical  
elements of 
each 
procedure are 
included -
Audit of 
randomly 
selected 
research 
records for 
protocol 
compliance 
Project 
Director,  
Data  
Manager 
Quarterly 
PI, Study 
team 
Review at 
team 
meeting 
Corrective 
action as 
required 
during 
performance 
testing 

-       St u d y #: 2 0 1 7 0 7 7 1        Eff e cti v e D at e: 3/ 1 8/ 2 0 2 1  
I R B St u d y N u m b er: 2 0 1 7 0 7 7 1, V er si o n #1. 8 , D at e: 0 3/ 1 0 / 2 1, PI: Ci n d y L. M u nr o 
 
P a g e 2 3  of 3 9  
R e vi s e d: M ar c h 1 0 , 2 0 2 1 
S M C  
m o nit ori n g 
d at a 
r e p ort 
M o nit ori n g a n d 
o v er si g ht of 
h u m a n s u bj e ct 
s af et y  
P a st 6 m o nt h s 
a n d 
c u m ul ati v e 
s u m m ar y 
r e p ort s of: -
A c cr u al 
u p d at e r e p ort 
-M o nt hl y 
pr o gr e s s 
r e p ort -D at a 
c o m pl et e n e s s  
r e p ort -
Pr ot o c ol 
d e vi ati o n l o g -
A E r e p ort -
I nt er v e nti o n 
fi d elit y a n d 
Pr ot o c ol 
c o m pli a n c e 
r e p ort 
-Ot h er d at a a s  
r e q u e st e d b y  
S M C  
PI,  
Bi o st ati sti ci a n  
Fir st 2 0 
s u bj e ct s, t h e n 
e v er y 6 
m o nt h s, a n d a s 
n e e d e d t o 
r e s p o n d t o 
ur g e nt i s s u e s  
S M C  
R e c o m m e n d  
c orr e cti v e 
a cti o n a s 
r e q uir e d t o 
pr ot e ct 
s u bj e ct s  
R e c o m m e n d  
e arl y  
st o p pi n g of 
t h e tri al f or 
r e a s o n s of 
p arti ci p a nt 
s af et y  
1 2. Wit h dr a w al of S u bj e ct s  
Fr o m o ur e x p eri e n c e i n cli ni c al r e s e ar c h wit h criti c all y ill p ati e nt s, w e a nti ci p at e c h a n g e s i n t h e 
cir c u m st a n c e s of s u bj e ct s t h at n o l o n g er m a k e t h e m eli gi bl e t o c o nti n u e t h e st u d y (i. e. e x cl u si o n 
crit eri a - a nti ci p ati o n b y t h e cli ni c al pr o vi d er of i m mi n e nt p ati e nt d e at h). W e will cl o s el y m o nit or 
f or c h a n g e s i n cir c u m st a n c e t h at i m p a ct eli gi bilit y (i. e., or d er s f or C ar e M e a s ur e s O nl y or 
t er mi n al e xt u b ati o n) a n d c o n si d er t h e st u d y c o m pl et e f or t h e s u bj e ct. W e will u s e all i nf or m ati o n 
c oll e ct e d u p t o t h e c o m pl eti o n p oi nt f or i n cl u si o n i n a n al y si s. W e will pr o c e e d wit h t h e f oll o wi n g 
st u d y c o m pl eti o n pr o c e d ur e s:  
• 
St o p c oll e cti n g r e s e ar c h d at a.  
• 
R e m o v e all r e s e ar c h e q ui p m e nt.  
• 
M ail T h a n k Y o u c ar d wit h $ 2 5 gift c ar d t o s u bj e ct’ s h o m e a d dr e s s.  R e d a ct P HI fr o m 
E nr o ll m e nt Tr a c ki n g L o g. 
I n t h e e v e nt t h e s u bj e ct ( or t h eir L A R) wit h dr a w s fr o m t h e st u d y, w e will c o n si d er t h e st u d y 
c o m pl et e f or t h e s u bj e ct a n d u s e all i nf or m ati o n c oll e ct e d u p t o t h e p oi nt of st u d y wit h dr a w al. 
T h e s a m e st u d y c o m pl eti o n pr o c e d ur e s a b o v e wil l b e f oll o w e d.  
1 3. Ri s k s t o S u bj e ct s  
T h e ri s k s of p arti ci p ati o n i n t h e st u d y ar e mi ni m al. Ri s k s of t h e i nt er v e nti o n m a y i n cl u d e 
tr a n si e nt c h a n g e s i n vit al si g n s fr o m sti m ul ati o n c a u s e d b y t h e r e c or d e d m e s s a g e. Ot h er ri s k s 
i n cl u d e s ki n irrit ati o n fr o m t h e a cti gr a p h y w at c h a n d sl e e p pr ofil er -p ol y s o m n o gr a p h y, a s w ell a s 
fr u str ati o n or a n xi et y wit h t h e NI H T o ol b o x C o g niti o n B att er y t e sti n g or a n y of t h e q u e sti o n n air e s 
( s e e T a bl e 1). N o n e of t h e s e ri s k s w er e o b s er v e d t o o c c ur i n pr eli mi n ar y st u d y # 2.  
F oll o wi n g  c o n s e nt a n d st u d y e nr oll m e nt, ri s k of br e a c h of c o nfi d e nti alit y i s al s o p o s si bl e si n c e 
i d e ntif yi n g i nf or m ati o n will b e c oll e ct e d i n a n el e ctr o ni c e nr oll m e nt tr a c ki n g li st, o n a p a s s w or d 

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protected server limited to project director and research assistants, to track the location of 
subjects as inpatients and contact information for follow up home visits.   
There is no alternative therapy. However, subjects may elect not to participate and may 
withdraw from the study at any time without affecting the care they receive. 
Protections Against Risk 
The FAVoR intervention will be interspersed with the care team’s activities, and at no time will 
the study personnel delay or interfere with critical care procedures; if the needs and activities of 
providers are such that the study personnel are unable to access the subject to provide audio 
reorientation, the subject will be withdrawn from the study. At all times, we will place the 
subject’s need for medical treatment, and avoidance with interference with treatment, foremost. 
Following study enrollment, we will keep an active list of enrolled subjects (FAVoR Study 
Enrollment Tracking List) that require study procedures as inpatients at UMH and JMH and 
follow up home visits to be performed. All identifying information is redacted from this list as 
each subject’s participation is complete. The enrollment tracking list will be maintained on a 
password protected server, with limited access to only the project director and research 
assistants. The enrollment tracking list will be completely destroyed upon the last subject’s 
completed participation.  
No personal protected information (none of the HIPAA elements) are ever recorded in study 
forms or in the study database. The information obtained will be kept strictly confidential, 
protecting the identity of participants in all reports or publications that may result from this 
research. Each participant will be assigned an arbitrary code number to conceal their identity on 
all research data, and all research data will be maintained in locked file cabinets under the 
direct supervision of the PI. 
To ensure confidentiality, each participant will be assigned an arbitrary study identification 
number to conceal their identity on all research data. All hard copy research material (i.e., 
consent forms) will be maintained in locked file cabinets, electronic data will be kept on 
password protected computers under the direct supervision of the PI. Study information 
obtained will be kept strictly confidential, protecting the identity of participants in all reports or 
publications that may result from this research. To ensure privacy, all interactions with subjects 
and LARs will be conducted in the subject’s hospital room or a private area of the ICU. 
To reduce skin irritation from applied devices, the Sleep Profiler and ActiWatch will not be 
placed on skin that is not intact or damaged in any way. The Sleep Profiler and ActiWatch will 
be removed as soon as data collection is complete (up to 120 hours) and skin assessments will 
be conducted daily. 
If a 20% or larger fluctuation in vital signs (heart rate and blood pressure) during the recorded 
message occur, research staff will turn off the recorded message. The clinical nurse assigned to 
the subject will be immediately notified, and the clinical medical provided will be notified as well. 
The message will be restarted when the critical care nurse or physician indicates the patient is 
stable. If the 20% or larger fluctuation in vital signs re-occurs, the intervention will be 
discontinued and the in-hospital data only up to that point will be included in the study. 

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Prior to beginning the NIH Toolbox Cognition Battery testing and questionnaires, the subject will 
be told if they feel excessively frustrated or anxious during the test, they may stop. There is no 
alternative therapy. However, subjects may elect not to participate and may withdraw from the 
study at any time without affecting the care they receive. 
As of March 2020, per the updated guidance regarding research continuity from the University 
of Miami IRB and research administrations, we are complying with the COVID-19 safety 
recommendations to protect our subjects, research personnel, students, and faculty members.  
14. Potential Benefits to Subjects 
Subjects in the intervention group may benefit from this study if delirium is reduced by the 
FAVoR intervention. The data obtained will provide empirical evidence that will enable us to 
evaluate the effect of the FAVoR intervention on delirium and holds promise to translate new 
knowledge into clinical decision-making about the management of delirium in the critically ill to 
ultimately improve patient outcomes. 
15. Vulnerable Populations 
Cognitively Impaired Adults 
In our experience in conducting clinical research in the critical care areas, we have found that 
potential subjects who are mechanically ventilated are generally sedated to some degree. In 
addition, since use of mechanical ventilation primarily occurs during periods of patient instability, 
the use of sedation at these times is extensive and compromises patient’s ability to 
communicate effectively which is compounded by the presence of the endotracheal tube. As a 
result, we have always found it appropriate to contact the legally authorized representative for 
consent. However, there may be rare occurrences when potential subjects are adequately 
oriented and lucid to be able to provide informed consent. Therefore, we will use the 2-step 
procedure described by Fan et al.76 to determine the patient’s ability to provide informed 
consent. Step 1 is objective evaluation with the Richmond Agitation-Sedation Scale (RASS) and 
the Confusion Assessment Method for Intensive Care Unit (CAM-ICU). Patients who score -1, 
0,  
+1 on the RASS indicating drowsy, alert, or restless respectively and are not delirious (CAM- 
ICU = No) will move to Step 2. Step 2 is assessment for competency using the MacArthur 
Competence Assessment Tool for Clinical Research: MacCAT-CR that evaluates all four 
capacity domains for consent (understanding, appreciation, reasoning, expression of a choice). 
Evaluation of Step 1 requires approximately 2-3 minutes, Step 2 requires approximately 15 
minutes. Fan et al.76 found in consent evaluations of 150 ICU patients that 89% were 
sedated/delirious, and unable to provide consent; our experience in previous research is similar. 
Therefore, we expect that few potential subjects will move to Step 2 while critically ill and 
mechanically ventilated. The LAR will be contacted for those who fail Step 1 or Step 2. 
We will evaluate the potential subject’s level of orientation and response to our discussions of 
the study on a daily basis during the hospital phase, and if the potential subject is able to 
respond in a manner that is clearly understandable, we will use the potential subject’s own 
consent to continue participation. However, in any instance where the potential subject’s ability 
to comprehend and communicate his/her desires is in question, we will seek consent for 
continued participation from the LAR and will invite the research subject to provide his/her 
assent.  

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Subjects will be withdrawn if they appear to be unduly distressed. For example, if a 20% or 
larger fluctuation in vital signs (heart rate and blood pressure) during the delivery of the 
recorded message occur, research staff will turn off the recorded message. The clinical nurse 
assigned to the subject will be immediately notified, and the clinical medical provider will be 
notified as well. The message will be restarted when the critical care nurse or physician 
indicates the patient is stable. If the 20% or larger fluctuation in vital signs re-occurs, the 
intervention will be discontinued and the in-hospital data only up to that point will be included in 
the study. 
Verbal consent to continue participation and for post-hospital follow up will be obtained from the 
subject as soon as their medical condition permits. We will follow UM IRB, JMH, and UMH 
policies and procedures. The consenting process for Spanish patients, family members, and/or 
LAR's will be the same process only with the addition of an individual UMH or JMH Spanish 
translator or by use of the UMH translation language line phone service, which is available 24 
hours a day, 7 days a week. 
Pregnant Women 
This minimal risk study carries no added risk to pregnant women and the well-being of their 
unborn child. 
16. Sharing of Results with Subjects 
Individual subject results will not be shared with subjects or others (i.e., health care providers) 
during the study. De-identified study group results will be made available through publications 
and summarized on clinicaltrials.gov. 
17. Setting 
Subject recruitment, enrollment, and interventions will be conducted in the adult intensive care 
units (Cardiac Care, Medical, Neuro, Surgical, and Specialty critical care) at University of Miami 
Hospital (UMH) and Jackson Memorial Hospital (JMH), both in Miami, Florida. UMH is licensed 
for 560 beds that includes 52 critical care beds. JMH is a 1,500 bed facility that includes 194 
critical care beds and is the primary teaching hospital for the University of Miami Miller School of 
Medicine. Miami-Dade County is comprised of approximately 67.7% minority population. In our 
current and completed projects, we have established excellent research relationships and have 
been successful in meeting target enrollments in critical care. We will use mechanisms 
established in previous and current studies for providing staff in-services, unit meetings, and 
frequent communication about the study for nurses, physicians, and other ICU team members 
at UMH and JMH.  
 18. Resources Available 
This 4-year R01 study is funded by National Institutes of Health, National Institute of Nursing 
Research. We have substantial experience, which enhances the likelihood that we can 
successfully accomplish the specific aims. We have conducted preliminary work to develop and 
refine important components of the project, including the intervention, study measures, and data 
analysis. We have completed a small RCT, which provided suggestive support for the proposed 
study’s primary aim and informed decisions about the research plan. We have been active in 
funded research related to care of critically ill adults for over 2 decades, and have successfully 
conducted multiple RCTs in the critically ill population. We have direct and extensive experience 

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in time-sensitive recruitment and enrollment of critically ill subjects; delivering and maintaining 
intervention fidelity of interventions in intensive care settings, including oral care interventions; 
obtaining, measuring, and analyzing systemic and oral biomarker data; quantifying 
complications, including HAIs; and controlling for confounding variables in critically ill subjects. 
Our results have had direct impact on clinical practice, including contributing to national 
guidelines for care of mechanically ventilated adults.37 Dr. Zhan will support regulatory 
compliance, data interpretation and analysis, preparation of presentations and publications and 
will be a co-author in dissemination of study results and methodologies.  Dr. Ji will serve as  the 
senior statistician and provide expertise to achieve maximum rigor in research design and 
methodology, develop the data analysis plan, final data analyses, as well as preparing reports 
and manuscripts. Staffing resources are presented in Table 4.  
Table 4. Staffing Resources 
Name and Title 
Responsibility 
Address 
Phone  
Cindy Munro, PhD, RN, ANP-BC,  
FAAN, FAANP, FAAAS 
UM School of Nursing and Health  
Studies,  
Dean and Professor 
Principal 
Investigator 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2107 
Zhan Liang, RN, PhD 
University of Miami School of  
Nursing and Health Studies, 
Assistant Professor 
Co-Investigator 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
5468 
Ming Ji, PhD 
USF College of Nursing, 
Professor of Biostatistics 
Co-Investigator 
USF 
12901 Bruce B. Downs Blvd.,  
MDC22 
Tampa, FL 33612-4766 
813-396- 
9073 
Maya Elias, PhD, RN 
University of Miami School of  
Nursing and Health Studies 
Post-Doctoral Associate 
Post-Doctoral 
Associate  
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
407-925- 
4916 
Karel Calero, MD 
USF College of Medicine, 
Assistant Professor 
Pulmonary Critical Care, Sleep  
Medicine 
Consultant 
USF 
2 Tampa General Circle 
Suite C, 6th Floor 
Tampa, FL 33606 
813-259- 
0619 
Wes Ely, MD 
Vanderbilt University School of  
Medicine, 
Professor 
Consultant 
6109 Medical Center East 
Vanderbilt University School of  
Medicine 
Nashville, TN 37232-8300 
615-936- 
3395 
Xusheng Chen 
University of Miami School of  
Nursing and Health Studies 
Data Manager 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 
Cristobal Padilla Fortunati, MSN,  
BSN 
University of Miami School of  
Nursing and Health Studies 
Research 
Assistant 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 

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Revised: March 10, 2021 
TBN 
Research 
Assistant 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 
TBN 
Research 
Assistant 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 
TBN 
Research 
Assistant 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 
TBN 
Research 
Assistant 
UM SONHS 
5030 Brunson Drive  
P.O. Box 248153 
Coral Gables, FL 33124-3850 
305-284- 
2243 
Conflict of Interest. None of the investigators will benefit from subjects’ participation in this 
project or completion of the project in general.  
Personnel Training. Before subjects are enrolled in the study, a comprehensive study manual 
will be developed describing all study procedures. Under the supervision of the PI, the Project 
Director will train all research assistants (RAs) on all aspects of the study, including intervention 
delivery, use of all study equipment (SP-PSG, actigraphy), use of the electronic medical record, 
and data collection and entry, documentation, and regulatory compliance. Training will include 
completion of the Collaborative Investigator Training Initiative (CITI) education in human subject 
protections. Training will continue until RAs have achieved 100% accuracy of all procedures 
and data collection processes, assessed by return demonstrations on all study procedures. 
Training reviews will occur regularly, and each RA will also be directly observed by the Project 
Director every 3 months throughout the study period to ensure that all critical elements of the 
study continue to be correctly performed. The Project Director will retrain RAs immediately if 
any critical element is found to be omitted or inaccurate. 
19. Prior Approvals 
Approval from the UMH Ancillary Committee and Jackson Health System (JHS) Clinical 
Research Review Committee are required. 
20. Recruitment Methods 
As of March 2020, to protect human subjects, we are closely following the COVID-19 safety 
recommendations. We have resumed enrollments at UMH as of June 2020, but continue 
temporarily suspending new enrollments at JMH.  
Pre-Screening, Recruitment, and Enrollment. Subjects will be recruited from all patients 
admitted to the adult UMH and JMH ICUs including Cardiac Care, Medical, Neuro, Surgical, and  
Specialty critical care, who speak English or Spanish, are expected to remain in the ICU at least  
48 hours, have no history of dementia, and have a family member able to speak English or 
Spanish who is available and willing to audio record scripted messages. Subjects will be 

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enrolled in the study within 48 hours of intubation and ICU admission. Male and female adults 
from all ethnic and racial backgrounds will be recruited.  
A waiver of HIPAA Authorization is being requested for pre- screening and recruitment purposes 
only. It would be difficult to determine eligibility of potential participants without the waiver. Each 
patient and/or the nurse would have to be approached without the waiver, which could cause 
confusion for the patient and waste the time of the nurse in the event of ineligibility in the highly 
stressful, life-threatening, critical care environment. No identifying information will be collected 
or retained from the pre-screening and recruitment processes. Signed authorization will be 
obtained along with informed consent upon enrollment of subjects in the study.  
Pre-screening process:  
1. Project Director or RAs will make daily rounds in the adult ICUs to evaluate patients as 
potential subjects for the study.  
2. Selection of medical records to review for eligibility and exclusion criteria will be based 
on the ICU census boards that reflect patient admissions. 
3. Eligibility and exclusion criteria found on the consent checklist may be used as a 
prescreening aid while reviewing the medical record.  
4. If the patient does not meet study criteria, no identifying information will be retained. 
5. If the patient meets all study criteria, then the Project Director or RA will move on to the 
recruitment process. 
Recruitment process: 
1. If a patient meets all study criteria in the pre-screening process, the bedside nurse will 
be approached regarding availability of a family member to record scripted 
reorientation messages. 
2. If the family member is found not to be available at bedside, the Project Director or RA 
will contact healthcare proxy or family member using the phone number found in 
patient’s medical record, and will follow the Recruitment Script to speak with the family 
member regarding interest in study participation. 
a. In our experience, finding family members at the bedside during the eligibility 
window of 48 hours from admission or intubation has been a unique challenge in 
Miami hospitals.  Many family members avoid staying in the hospital setting and 
visit infrequently or for short periods of time; some of the hospital units we recruit 
from have strict limitations on visitation time (15 minutes at a time, for example).  
Placing a call directly to family members would allow for family to be invited 
directly to discuss possible study participation. 
3. If family is present at the bedside, the Project Director or RA will follow the  
Recruitment Script to address both the potential subject and family member regarding 
interest in study participation.  
4. If the patient does not have a family member available and/or willing to record the 
scripted reorientation messages, the patient is not eligible for study enrollment. No 
identifying information will be retained. 
5. If the patient has a family member available and willing to record the scripted 
reorientation messages, then the Project Director or RA will move on to the enrollment 
process.   
Enrollment process: 
2. The potential subject’s capacity to consent will be determined (see section 18. Consent 
Process).  
a. In our experience, potential subjects who are critically ill, especially during the 
first 48 hours of intubation, are always sedated to some degree, and their ability 
to communicate effectively may be compromised by endotracheal intubation; in 

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these cases, consent has been obtained from the legally authorized 
representative (LAR).  
3. If the potential subject or their LAR is not interested in consenting to participate in the  
study, no identifying information will be retained. 
4. If the LAR is contacted by phone or HIPAA compliant Zoom: 
a. Review of the consent forms will be completed over the phone or by Zoom by the 
Project Director or RAs, as is done in person. 
b. Verbal consent will be obtained over the phone or by Zoom. 
c. Waiver of wet signature will be documented by the person obtaining consent. 
5. All consent, HIPAA, and Audio Recording forms will be collected using a secured email 
server. 
6. The family member willing to record the scripted reorientation messages will be required 
to sign the Authorization for Audio Recording in Research form if recording in person. If 
the family member is recording by phone or Zoom, verbal consent to record will be 
obtained and documented by the person obtaining consent. 
7. UM IRB, JMH, and UMH policies and procedures for clinical research participant 
enrollment and tracking will be followed. 
Since this study involves continuous data collection over 120 hours, the Project Director and 
RAs will be involved in the pre-screening, recruitment, and enrollment of subjects, along with 
collection of all data. We have successfully trained RAs to pre-screen, recruit, enroll, and collect 
complex data processes in the ICU environment in several previous studies. Although data 
collection will occur continuously for 120 hours, in our experience with continuous data 
collection, we have found that providing support for automated data collection (for example, 
actigraphy) approximately 10 hours per day (i.e. 8a – 6p) in person results in collection 
processes which run exceptionally well in the hours when study personnel are not present. In 
addition, we will conduct extensive education for the unit staff about the project, although no 
study activities will be required from them. Study personnel will also be on call by telephone 
during all study hours, so that hospital staff can contact us if they have any questions about the 
equipment (SP-PSG and ActiWatch). 
21. Local Number of Subjects 
We plan to review approximately 350 medical records in order to achieve our sample size of 
182 enrollments.  
22. Confidentiality 
To ensure confidentiality, each participant will be assigned an arbitrary study identification 
number to conceal their identity on all research data. All hard copy research material (i.e., 
consent forms) will be maintained in locked file cabinets, in a locked room, electronic data will 
be kept on password protected computers under the direct supervision of the PI for 5 years after 
the final report has been submitted to the UM IRB. Study information obtained will be kept 
strictly confidential, protecting the identity of participants in all reports or publications that may 
result from this research. After the 5-year storage period, all documents will be destroyed by UM 
after the Project Director places these documents inside the locked HIPAA bins for destruction. 

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23. Provisions to Protect the Privacy Interests of Subjects 
To ensure privacy, all interactions with subjects and LARs will be conducted in the subject’s 
hospital room or a private area of the ICU. The information obtained will be kept strictly 
confidential, and it will not be possible to identify any participant from the reports of publications 
that may result from this research. Participants will be assigned an arbitrary code number to 
conceal their identity on all research data, and all research data will be maintained in locked file 
cabinets in a locked room under the direct supervision of the PI for 5 years after the final report 
has been submitted to the UM IRB. After the 5-year storage period, all documents will be 
destroyed by UM after the Project Director places these documents inside the locked HIPAA 
bins for destruction. 
24. Compensation for Research-Related Injury 
Since injury is unlikely in this minimal risk study, there is no compensation for research-related 
injury. 
25. Economic Burden to Subjects 
There is no cost to subjects participating in the study. 
26. Consent Process 
Following IRB approval of the partial HIPAA waiver, the trained Project Director or RAs will 
review the potential subject's medical record, and if there are no exclusions, the subject will be 
invited to enroll. The subject and the subject’s LAR will be provided with an oral explanation of 
the nature of the study and study information, in writing. The information will include all 
elements required for informed consent, and will include all pertinent contact information as well 
as information about withdrawal from the study. Written consent will be obtained if the consent 
process is conducted in person. If the LAR is contacted by phone or HIPAA compliant Zoom, 
review of the consent forms will be completed over the phone or by Zoom by the Project 
Director or RAs, as is done in person. Verbal consent will be obtained over the phone or by 
Zoom. Waiver of wet signature will be documented by the person obtaining consent. 
If at any time the subject or LAR does not wish to continue to participate in the study, no 
additional interactions with the subject will take place, no follow-up data will be collected and 
that subject's data forms will be destroyed. Dr. Munro (study PI) has extensive experience in 
obtaining consents from family members of critically ill adults. The study staff will work closely 
with the staff of the Cardiac Care, Medical, Neuro, Surgical, and Specialty ICUs, nurse 
managers, and medical directors to ensure that all eligible patients have an equal opportunity 
for inclusion. 
In our experience in conducting clinical research in the critical care areas, we have found that 
potential subjects who are mechanically ventilated are generally sedated to some degree. In 
addition, since use of mechanical ventilation primarily occurs during periods of patient instability, 
the use of sedation at these times is extensive and compromises patient’s ability to 
communicate effectively which is compounded by the presence of the endotracheal tube. As a 
result, we have always found it appropriate to contact the legally authorized representative for 
consent. However, there may be rare occurrences when potential subjects are adequately 
oriented and lucid to be able to provide informed consent. Therefore, we will use the 2-step 
procedure described by Fan et al.76 to determine the patient’s ability to provide informed 

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consent. Step 1 is objective evaluation with the Richmond Agitation-Sedation Scale (RASS) and 
the Confusion Assessment Method for Intensive Care Unit (CAM-ICU). Patients who score -1, 
0,  
+1 on the RASS indicating drowsy, alert, or restless respectively and are not delirious (CAM- 
ICU = No) will move to Step 2. Step 2 is assessment for competency using the MacArthur 
Competence Assessment Tool for Clinical Research: MacCAT-CR that evaluates all four 
capacity domains for consent (understanding, appreciation, reasoning, expression of a choice). 
Evaluation of Step 1 requires approximately 2-3 minutes, Step 2 requires approximately 15 
minutes. Fan et al.76 found in consent evaluations of 150 ICU patients that 89% were 
sedated/delirious, and unable to provide consent; our experience in previous research is similar. 
Therefore, we expect that few potential subjects will move to Step 2 while critically ill and 
mechanically ventilated. The LAR will be contacted for those who fail Step 1 or Step 2. 
We will evaluate the potential subject’s level of orientation and response to our discussions of 
the study on a daily basis during the hospital phase, and if the potential subject is able to 
respond in a manner that is clearly understandable, we will use the potential subject’s own 
consent to continue participation. However, in any instance where the potential subject’s ability 
to comprehend and communicate his/her desires is in question, we will seek consent for 
continued participation from the LAR and will invite the research subject to provide his/her 
assent. Verbal consent to continue participation and for post-hospital follow up will be obtained 
from the subject as soon as their medical condition permits. We will follow UM IRB, JMH, and 
UMH Policies and Procedures. 
Non-English-Speaking Subjects 
The consenting process for Spanish patients, family members, and/or LAR's will be the same 
process only with the addition of an individual UMH or JMH Spanish translator or by use of the 
UMH translation language line phone service, which is available 24 hours a day, 7 days a week. 
Cognitively Impaired Adults 
In our experience in conducting clinical research in the critical care areas, we have found that 
potential subjects who are mechanically ventilated are generally sedated to some degree. In 
addition, since use of mechanical ventilation primarily occurs during periods of patient instability, 
the use of sedation at these times is extensive and compromises patient’s ability to 
communicate effectively which is compounded by the presence of the endotracheal tube. As a 
result, we have always found it appropriate to contact the legally authorized representative for 
consent. However, there may be rare occurrences when potential subjects are adequately 
oriented and lucid to be able to provide informed consent. Therefore, we will use the 2-step 
procedure described by Fan et al.76 to determine the patient’s ability to provide informed 
consent. Step 1 is objective evaluation with the Richmond Agitation-Sedation Scale (RASS) and 
the Confusion Assessment Method for Intensive Care Unit (CAM-ICU). Patients who score -1, 
0,  
+1 on the RASS indicating drowsy, alert, or restless respectively and are not delirious (CAM- 
ICU = No) will move to Step 2. Step 2 is assessment for competency using the MacArthur 
Competence Assessment Tool for Clinical Research: MacCAT-CR that evaluates all four 
capacity domains for consent (understanding, appreciation, reasoning, expression of a choice). 
Evaluation of Step 1 requires approximately 2-3 minutes, Step 2 requires approximately 15 
minutes. Fan et al.76 found in consent evaluations of 150 ICU patients that 89% were 
sedated/delirious, and unable to provide consent; our experience in previous research is similar. 
Therefore, we expect that few potential subjects will move to Step 2 while critically ill and 
mechanically ventilated. The LAR will be contacted for those who fail Step 1 or Step 2. We will 

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evaluate the potential subject’s level of orientation and response to our discussions of the study 
on a daily basis during the hospital phase, and if the potential subject is able to respond in a 
manner that is clearly understandable, we will use the potential subject’s own consent to 
continue participation. However, in any instance where the potential subject’s ability to 
comprehend and communicate his/her desires is in question, we will seek consent for continued 
participation from the LAR and will invite the research subject to provide his/her assent. 
Subjects will be withdrawn if they appear to be unduly distressed. For example, if a 20% or 
larger fluctuation in vital signs (heart rate and blood pressure) during the delivery of the 
recorded message occur, research staff will turn off the recorded message. The clinical nurse 
assigned to the subject will be immediately notified, and the clinical medical provider will be 
notified as well. The message will be restarted when the critical care nurse or physician 
indicates the patient is stable. If the 20% or larger fluctuation in vital signs re-occurs, the 
intervention will be discontinued and the in-hospital data only up to that point will be included in 
the study. 
Verbal consent to continue participation and for post-hospital follow up will be obtained from the 
subject as soon as their medical condition permits. We will follow UM IRB, JMH, and UMH 
policies and procedures. The consenting process for Spanish patients, family members, and/or 
LAR's will be the same process only with the addition of an individual UMH or JMH Spanish 
translator or by use of the UMH translation language line phone service, which is available 24 
hours a day, 7 days a week. 
Adults Unable to Consent 
In our experience, potential subjects who are critically ill, especially during the first 48 hours of 
intubation, are always sedated to some degree, and their ability to communicate effectively is 
compromised by endotracheal intubation; for these reasons, permission for the subject’s 
participation has generally been obtained from the LAR. Upon the initial screening of the 
medical record for eligibility, we will review the medical record for any named health care 
surrogate or a court appointed guardian. If neither of these are named, the following order of 
potential LARs will be assessed: spouse, adult child, parent, adult sibling, adult relative, a close 
friend, or a clinical social worker. 
We will evaluate the potential subject’s level of orientation and response to our discussions of 
the study on a daily basis during the hospital phase, and if the potential subject is able to 
respond in a manner that is clearly understandable, we will use the potential subject’s own 
consent to continue participation. However, in any instance where the potential subject’s ability 
to comprehend and communicate his/her desires is in question, we will seek consent for 
continued participation from the LAR and will invite the research subject to provide his/her 
assent. 
Subjects will be withdrawn if they appear to be unduly distressed. For example, if a 20% or 
larger fluctuation in vital signs (heart rate and blood pressure) during the delivery of the 
recorded message occur, research staff will turn off the recorded message. The clinical nurse 
assigned to the subject will be immediately notified, and the clinical medical provider will be 
notified as well. The message will be restarted when the critical care nurse or physician 
indicates the patient is stable. If the 20% or larger fluctuation in vital signs re-occurs, the 
intervention will be discontinued and the in-hospital data only up to that point will be included in 
the study. 

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Verbal consent to continue participation and for post-hospital follow up will be obtained from the 
subject as soon as their medical condition permits. We will follow UM IRB, JMH, and UMH 
policies and procedures. The consenting process for Spanish patients, family members, and/or 
LAR's will be the same process only with the addition of an individual UMH or JMH Spanish 
translator or by use of the UMH translation language line phone service, which is available 24 
hours a day, 7 days a week. 
27. Process to Document Consent in Writing 
The RAs and Project Director will follow the steps in the consent checklist to obtain written 
consent and HIPAA authorization. In our experience, potential subjects who are critically ill, 
especially during the first 48 hours of intubation, are always sedated to some degree, and their 
ability to communicate effectively is compromised by endotracheal intubation; for these reasons, 
permission for the subject’s participation has generally been obtained from the LAR. Upon the 
initial screening of the medical record for eligibility, we will review the medical record for any 
named health care surrogate or a court appointed guardian. If neither of these are named, the 
following order of potential LARs will be assessed: spouse, adult child, parent, adult sibling, 
adult relative, a close friend, or a clinical social worker. We will verify the subject or LAR 
understands English or Spanish and utilize the language version of their preference.  
The entire informed consent form and HIPAA authorization will be thoroughly verbally explained 
to the subject or LAR with questions of understanding throughout each section. Reinforcement 
that the level of care they receive is not impacted whether they participate in the study or not will 
be provided. The subject or LAR will be asked if they would like more time to think about their 
decision to participate or not to participate in the study. If more time is requested, the study staff 
will leave copies of the consent and HIPAA authorization forms, provide contact information of 
the study staff, and the amount of remaining time they are eligible to participate due to the 
requirement of enrollment within 48 hours of ICU admission & initial intubation. We will have the 
subject or LAR (and the person obtaining consent) personally print, sign, and date the consent 
and HIPAA authorization documents. If the LAR is contacted by phone or HIPAA compliant 
Zoom, and not available in person, verbal consent will be obtained over the phone or by Zoom. 
Waiver of wet signature will be documented by the person obtaining consent. 
Copies of the signed consent and HIPAA authorization forms will be provided to the subject or 
LAR.  Copies of the signed consent form, HIPAA authorization, and/or consent checklist will be 
provided to UMH and JMH according to their current practice. The Project Director will place 
original signed consent forms, HIPAA authorizations, and consent checklists in a study binder to 
be secured in a double-locked room at UM SONHS, supervised by the Principal Investigator, for 
at least 5 years following study completion. 
 

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