Recommendations and Alerting for Delirium Alleviation in Real-Time (RADAR): a Pilot Randomized Controlled Trial
Phase: NA
Conditions: Delirium
Sponsor: University of Michigan

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Recommendations and Alerting for Delirium Alleviation in Real-Time (RADAR): 
Protocol for a Pilot Randomized Controlled Trial 
 
 
Trial Registration: NCT04007523 
Protocol Version: 3.0, 02/19/2020 
 
Funding: University of Michigan Claude D. Pepper Older American Independence 
Center (P30 AG024824-14), Michigan Institute for Clinical and Health Research, 
Department of Anesthesiology (UL1TR002240), University of Michigan Medical School 
 
 
 
 

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ABSTRACT 
Background: Delirium is a common and serious complication of major surgery for older 
adults. Postoperative social and behavioral support (e.g., early mobilization, mealtime 
assistance) may reduce the incidence and impact of delirium, and these efforts are 
possible with proactive patient-care programs. This pilot trial tests the hypothesis that a 
multicomponent decision support system, which sends automated alerts and 
recommendations to patient-care programs and family members for high-risk patients, 
will improve the postoperative environment for neurocognitive and clinical recovery. 
 
Methods: This will be a randomized, controlled factorial trial at a large academic 
medical center. High-risk, non-cardiac surgery patients (≥70 years old) will be recruited. 
Patients will be allocated to a usual care group (n=15), Hospital Elder Life Program 
(HELP)-based paging system (n=15), family-based paging system (n=15), or combined 
HELP- and family-based system (n=15). The primary outcome will be the presence of 
delirium, defined by positive long-form Confusion Assessment Method screening. 
Secondary outcomes will include additional HELP- and family-based performance 
metrics along with various neurocognitive and clinical recovery measures. Exploratory 
outcomes include the incidence of positive family-based delirium assessments post-
discharge, 36-item Short Form Survey, PROMIS Cognitive Function Abilities Subset 4a, 
and 30-day readmission rates. 
 
Ethics and dissemination: This trial is pending approval by the University of Michigan 
Medical Institutional Review Board (IRBMED). Dissemination plans include presentation 

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at scientific conferences, publication in medical journals, and distribution via educational 
media. 
 
Trial registration: www.clinicaltrials.gov, NCT04007523, registered on 7/3/2019. 
 
 
 

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INTRODUCTION 
Delirium is a distressing and common surgical complication, affecting approximately 20-
50% of older surgical patients1, 2. Postoperative delirium is associated with increased 
mortality3, cognitive and functional decline4-6, and healthcare resource utilization7, 8. Of 
the diverse prevention strategies that have been tested with variable success9, 10, one 
notable proactive patient-care program, the Hospital Elder Life Program (HELP), has 
been shown to reduce delirium incidence through social and behavioral interventions 
(e.g., mealtime assistance, support with visual/hearing aids)11. However, substantial 
resources are needed for program sustainment, and delirium still persists in high-risk 
patients12-14. In 2018, we found that <50% of surgical patients ≥70 years old at Michigan 
Medicine were officially enrolled in the program by the end of the second postoperative 
day. Furthermore, the average length of cumulative therapeutic activity was only 10 
minutes across the first three postoperative days. This is pertinent given that the peak 
incidence of postoperative delirium occurs within the first 48 hours2, 15. As such, 
complementary strategies that improve patient triage and support may lead to earlier 
identification and therapeutic intervention for high-risk patients. 
  
Clinical decision support systems can serve as a candidate strategy for mitigating 
delirium risk. Such systems provide targeted patient- and disease-specific information, 
presented in a timely manner, for improving healthcare quality16, 17. In the context of 
delirium, automated pages could be sent to supportive healthcare services, such as 
HELP, along with family members and caretakers, with alerts and targeted 
recommendations. An alert page could be sent to HELP program officials on the first 

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postoperative morning requesting early evaluation and enhanced treatment protocols. 
This may improve high-risk patient triage, early resource allocation, and cumulative 
therapeutic time spent with patients. A similar paging system could be implemented for 
family members and caretakers, as family-based interventions may provide additional 
support for patients at risk for delirium. Feasibility has been demonstrated with family-
based protocols for hospitalized medical patients, with therapeutic focus on re-
orientation, visual and hearing aid assistance, and conversational stimulation18. Similar 
protocols could be adapted for surgical patients, as surgery is generally a predictable 
event (and thus may be amenable to familial planning), and family support may 
correlate with overall postoperative recovery19. A recent systematic review also 
demonstrated that family-performed delirium screens demonstrated improved 
psychometrics compared to family-informed delirium screens (i.e., those not performed 
by family members)20. Thus, family members and caretakers could be recruited to 
actively participate in postoperative recovery by performing family-based delirium 
assessments21 and implementing therapeutic protocols. An electronic, paging-based 
alerting system could provide family members with reminders and alerts for conducting 
such a program. 
 
The premise of this pilot proposal is thus formed by the above considerations: 
preliminary evidence that suggests (1) suboptimal delirium prevention resource 
utilization and (2) the potential role for a clinical decision support system involving HELP 
and family members. The primary objectives of this study are to determine whether 
pager-based clinical decision support systems bolster HELP- and family-based 

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therapeutic activities. A secondary objective will be to identify facilitators and barriers to 
delivering therapeutic interventions for both HELP and family members. Overall, this 
pilot trial will test the hypothesis that a multicomponent decision support system will 
improve the postoperative environment for neurocognitive and clinical recovery in older, 
high-risk surgical patients. 
 
 
 
 
 

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METHODS AND ANALYSIS 
Study Overview and Design 
This is a single-center, randomized, factorial pilot trial at Michigan Medicine (Ann Arbor 
MI, USA). Approval was obtained from the University of Michigan Medical School 
Institutional Review Board (HUM00165251), and the trial has been registered at 
www.clinicaltrials.gov (NCT04007523). This protocol is also compliant with the 
Consolidated Standards of Reporting Trials (CONSORT) extension for pilot and 
feasibility trials and the Standard Protocol Items: Recommendations for Interventional 
Trials (SPIRIT) Guidelines22, 23. Lastly, all study team members are certified in Good 
Clinical Practice.  
 
After enrollment, patients (n=60) will be allocated (1:1:1:1), via block-randomization, 
stratified by gender, to one of four groups: usual care (n=15), HELP-based paging 
system (n=15), family-based paging system (n=15), or both HELP- and family-based 
paging system (n=15) (Figure 1). The randomization code will be created by the 
biostatistician (AT) and concealed from the rest of the research team. On the morning of 
surgery, allocation assignments will be delivered via sequentially numbered, opaque, 
sealed envelopes to unblinded research team members who will initiate arm-specific 
operations. The support systems will consist of automated pager alerts to the HELP 
program and/or family members and caretakers, depending on group allocation, for 
providing additional delirium evaluation and therapeutic prevention activities (see 
Interventions – Clinical Decision Support Paging System). Family members in the 
intervention group will also be provided with preoperative education on delirium and 

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training in the Family Confusion Assessment Method (FAM-CAM) instrument21. 
Although it will not be possible to blind patients and family members to family-based 
interventions, study team members will remain blinded to group allocation during daily 
assessments. Study flow is illustrated in Figure 1. 
 

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Figure 1. CONSORT study flow diagram. HELP = Hospital Elder Life program; CAM = Confusion 
Assessment Method, LTAC = Long-Term Acute Care  

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Recruitment 
Participants will be screened and recruited at preoperative clinics, preoperative holding 
areas, and surgical wards (if patients are pre-admitted). Written informed consent will be 
obtained from all participants prior to scheduled surgery. Written informed consent will 
also be obtained from a designated family member of caretaker for each participant, 
given the family-based nature of interventions being tested. Supplemental recruitment 
materials will be distributed in conjunction with the Michigan Institute for Clinical and 
Health Research, the NIH-funded Clinical and Translational Science Award institute at 
the University of Michigan. Specifically, recruitment fliers will be posted throughout 
preoperative clinics, and informative postcards will be sent to potentially eligible patients 
preoperatively.   
 
Eligibility criteria 
Eligibility criteria will reflect the pragmatic nature of the trial balanced with the aim of 
recruiting patients at high risk for postoperative delirium. Based on a validated geriatric 
assessment tool for predicting postoperative complications, surgical patients ≥ 70 years 
of age presenting for major inpatient surgery demonstrated a seven-fold increased risk 
of major complications compared to minor surgery24. Inclusion criteria will thus reflect 
such patients, and overall eligibility criteria are outlined below: 
 
Inclusion criteria: 
• Age ≥ 70 years of age 

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• Major non-cardiac, non-intracranial neurologic, and non-major vascular surgery, 
as defined by work-related value units suggestive of high surgical complexity24. 
• Anticipated length of hospital stay at least 72 hours 
• At least one family member, or caretaker, available on each of the three first 
postoperative days for trial operations 
Exclusion criteria: 
• Emergency surgery 
• Severe cognitive impairment (precluding ability to perform delirium assessments) 
• Planned post-operative ICU admission (HELP unavailable in the ICU) 
• Non-English speaking 
 
Interventions – Clinical Decision Support Paging System 
This proposal will build upon previous decision support systems launched by our 
department for reducing intraoperative awareness and delivering protective lung 
ventilation strategies25, 26. For participants randomized to the HELP-based support 
system, a single page will be sent to the on-call HELP staff during the first postoperative 
morning as the team begins ward rounds (Table 1). The page will request an enhanced 
treatment protocol, which includes HELP visitations three times daily. Therapeutic 
treatment will be administered during each visit per program protocols, which generally 
includes cognitive engagement, mealtime assistance, mobility and range of motion 
exercises, and assistance with visual and hearing aids. During the final evening visit, a 
sleep protocol will be implemented. For this protocol, HELP officials offer sleep and 
relaxation exercises, relaxation massages, and warm milk and/or tea. 

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For participants randomized to the family-based system, family members (or caretakers) 
will receive preoperative education on delirium (including an educational video), a folder 
with an informational flyer and therapeutic activities checklists, and FAM-CAM training. 
Suggested therapeutic activities include daily assistance with visual and hearing aids, 
providing assistance with drinking and mealtime assistance, handwashing, re-
orientation to time and place, and cognitive stimulation activities (Supplementary 
Appendix). Lastly, family members will also receive a pager, and automated pages will 
be sent twice daily with reminders to perform these activities (Table 1). Completion of 
activities will then be logged daily in conjunction with unblinded members of the 
research team. Study activities for each group are listed in Table 2. 
 
Days 
Timing 
Alphanumeric Paging Message 
HELP-Based Paging System 
Postoperative 
day 1 
Morning – 
9:00 AM 
Patient LAST NAME, FIRST NAME, MRN is at high-risk for 
postoperative delirium. Please evaluate patient as soon as possible 
and enroll in the enhanced treatment protocol. 
Family-Based Paging System 
Postoperative 
days 1-3 
Morning – 
9:00 AM 
Good morning! please complete the morning tasks listed in your 
folder (Morning Tasks 9:00 AM). The stimulating activity can then be 
performed anytime during the day. Call 734-647-8129 with questions 
or concerns. 
Postoperative 
days 1-3 
Afternoon – 
3:00PM 
Good afternoon! please complete the afternoon tasks in your folder 
(Afternoon Tasks – 3:00 PM). After these are complete, perform a 
FAM-CAM. Make sure to also complete a stimulating activity today. 
Call 734-647-8129 with any questions. 
Table 1. Real-time clinical decision support – family paging system. FAM-CAM = Family Confusion 
Assessment Method 
 
 
 

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Usual Care Group 
(n=15) 
HELP-Based System 
(n=15) 
Family-Based System 
(n=15) 
Combined Systems 
(n=15) 
Preoperative Phase 
Preoperative Phase 
Preoperative Phase 
Preoperative Phase 
Standard Care 
Standard Care 
Preoperative delirium 
education, materials, 
FAM-CAM training 
Preoperative delirium 
education, materials, 
FAM-CAM training 
Intraoperative Phase 
Intraoperative Phase 
Intraoperative Phase 
Intraoperative Phase 
Standard Care 
Standard Care 
Standard Care 
Standard Care 
Postoperative Care 
Postoperative Care 
Postoperative Care 
Postoperative Care 
HELP evaluation and 
treatment per ward 
routine 
 
Standard care 
otherwise 
HELP pager alerts 
 
• 
Early evaluation 
request 
• 
Enhanced 
therapeutic protocol 
request 
 
Daily family pager 
alerts 
• 
FAM-CAM 
reminders 
• 
Reminders for 
behavioral/social 
support and 
prevention activities 
HELP pager alerts and 
associated activities 
 
Family pager alerts and 
associated activities 
Table 2. Participants will be randomized to one of four groups: usual care, HELP-based paging support, 
family-based paging support (automated pages for the first three postoperative days), or combined HELP- 
and family-based paging support. HELP = Hospital Elder Life Program; FAM-CAM = Family Confusion 
Assessment Method. 
 
Intervention Fidelity 
During this pilot phase, characterizing the success and barriers encountered with trial 
interventions will be essential for analyzing fidelity. As a separate, but complimentary 
line of investigation, facilitators and barriers to support system implementation will be 
characterized for both HELP personnel and family members. All family members will be 
provided with surveys on postoperative day three (or discharge, whichever is sooner). 

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These surveys contain a combination of Likert-scale and open-ended questions to 
identify barriers to completing delirium screening and prevention activities. The 
substudy analysis for HELP is described in a separate, secondary application 
(HUM00166883). Lastly, a sensitivity analysis will be performed, which will report daily 
proportions – and reasons – for missing HELP- and family-based assessments (see 
Sensitivity Analysis and Missing Data). 
 
Outcomes 
The primary outcome of this pilot trial will be the presence of delirium, defined by a 
positive long-form Confusion Assessment Method (CAM) screening. To complement 
CAM screening, delirium will also be assessed each day via validated chart review 
method.27 The following secondary outcomes will also be collected and analyzed: 
delirium severity (long-form CAM severity scale), new symptoms of depression or 
anxiety (using the Hospitalized Anxiety and Depression Scale, HADS),28 falls 
(proportion, %), length of hospital stay (days), discharge disposition (e.g., home, long-
term care facility), delayed discharge due to cognitive impairment (proportion, %), 
incidence of any new non-surgical site infection (%), incidence of new multidrug 
resistant organism colonization (%), and mortality (%). Exploratory outcomes will 
include the incidence of positive FAM-CAM assessments (%) 30 days post-discharge, 
PROMIS Cognitive Function Abilities (Short Form 4a), 36-Item Short Form Survey, and 
30-day readmission rates. 
 

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Protocol Fidelity Measures:  Lastly, protocol fidelity measures will be reported for both 
HELP- and family-based interventions. HELP-based measures include the following: 
total therapeutic time spent with HELP staff during the first three postoperative days, 
proportion of participants visited and enrolled by HELP (%), and time to initial HELP 
evaluation. For family-based interventions, the following measures will be reported: 
cumulative time family members spent with patients, proportion of daily tasks (e.g., 
assistance with glasses/hearing aids, handwashing), successfully completed, length of 
time spent on stimulating activity, and overall agreement of the FAM-CAM with 
interview-rated CAM assessments. 
 
Data Collection 
At Michigan Medicine, HELP data collection is standard throughout surgical and medical 
wards. The time at which patients are first evaluated, total therapeutic time (minutes) 
spent with patients, and nature of therapeutic activities (e.g., cognitive stimulation, 
mealtime assistance) are all collected daily and logged on computer files. Unblinded 
research team will have access to these logs via secured, shared drive within the 
Michigan Medicine network. These research personnel will review HELP logs daily and 
meet with HELP leadership as needed to discuss problems that may arise regarding 
HELP data collection and logging. 
 
For delirium assessment, research team members will screen for delirium using the 
long-form CAM29 twice daily – once in the morning, and again in the afternoon, for the 
first three postoperative days. These team members will be blinded to group allocation. 

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Our research group has extensive experience with CAM in prior trials2, 30, 31, and our 
international group has created a program for training investigators in CAM 
methodology with a previously high inter-rater reliability (Fleiss kappa=0.88 [95% CI 
0.85 to 0.92])31. Our study team members who have previously received this training will 
lead CAM assessment efforts for this trial. Additionally, the study PI (Vlisides), has 
received complementary CAM training from the NIH-funded (K07AG041835) Center of 
Excellence for Delirium in Aging: Research, Training and Educational Enhancement 
(CEDARTREE). For new team members not previously trained, the PI will lead an on-
site training session using online long-form CAM training videos available from the 
Hospital Elder Life Program. Then, after each team member has successfully scored 
two non-delirious and two delirious patients identically – in terms of symptom 
recognition – with a previously trained study team member, the trainees will be 
considered independently trained for CAM assessment2. For those enrolled in the 
intervention bundle, family members (or caretakers) will perform the FAM-CAM21 
independently of the research team. FAM-CAM assessments will also be requested 
only daily in the afternoon. 
 
Depression and anxiety measures will take place both at preoperative baseline and 
during postoperative day three (or day of discharge, whichever is sooner). For 
assessment of falls, study team members will ask about fall occurrences during each 
study visit, and the medical record will also be reviewed for any falls during the study 
period. Additional clinical secondary outcomes described will be collected from the 
electronic medical record. On postoperative day three, for patients not randomized to 

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the family-support groups, the research team will ask family members about cumulative 
time spent with patients, and any interactive activities performed, during the first three 
postoperative days for comparison to family-based intervention groups. 
 
Finally, research data recorded on paper will be stored in participant research records 
that will be located in locked cabinets in the Department of Anesthesiology at Michigan 
Medicine. Electronic data will be de-identified and stored online using the REDCap 
electronic research database, which resides on a secured, password-protected network 
managed by the Michigan Institute of Clinical and Health Research. 
 
Statistical Analysis 
Sample Size and Power 
Given its fluctuating and recurrent nature, delirium presence will be primarily assessed 
over time with logistic generalized estimating equation models as we have done 
previously32. In brief, time and group will serve as fixed factors, and a group by time 
interaction term will be included. Interaction terms will be removed from models if no 
significant interaction effect is observed. These models allow for longitudinal data 
analysis in the setting of incomplete and missing data. Group models will be constructed 
individually with the control group serving as a reference. Power calculations were then 
conducted with generalized estimating equations for the time-averaged difference 
between two groups (i.e., control group and intervention group, either HELP- or family-
based support) in a repeated-measures design with the binary outcome of delirium. 
Accounting for six equally spaced measurements (twice daily delirium assessments for 

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the first three postoperative days), with an autoregressive correlation structure (baseline 
correlation 0.3) and linear missing data structure, a total sample size of 60 patients 
(n=30 in each intervention group) will provide >80% power to detect a difference in 
proportions of 15% (approximate Cohen’s effect size difference of 0.9) for experiencing 
an episode of delirium between groups (assuming a baseline proportion of 20% in the 
control group) with α=0.05. Power analysis was conducted using PASS 16 (PASS 2019 
Power Analysis and Sample Size Software [2019]. NCSS, LLC. Kaysville, Utah, USA, 
ncss.com/software/pass). As an exploratory analysis, the interaction between HELP- 
and family-based support groups will be assessed using a generalized estimating 
equations model. 
 
Descriptive statistics will be reported for secondary and exploratory outcomes. 
Inferential statistics will be deferred given the small sample size and pilot nature of the 
trial. Rigorous statistical analysis will be deferred for planned, follow-up, large-scale 
investigation. However, inferential statistics will be reported for fidelity measures 
described previously (Outcomes – Protocol Fidelity Measures). For continuous data, the 
Shapiro-Wilk test will be used to assess for normal distribution, and either independent 
t-tests or the Mann-Whitney U-test will be used, as appropriate. For categorical data, 
chi-squared or Fisher’s exact test will be used, as appropriate. Cohen’s kappa will be 
used to assess agreement between research-based CAM delirium assessments and 
FAM-CAM assessments. 
Sensitivity Analysis and Missing Data 

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Missing data are anticipated for multiple outcomes described in this study. For each 
HELP visit, cumulative therapeutic time is routinely logged, as are reasons for deferred 
visits. Thus, the proportion of deferred shift visits, compared to all available shifts 
(excluding shifts missed due to early discharge) will be reported along with associated 
reasons (Table 3). Nine total visits are anticipated during the first three postoperative 
days – daily morning, afternoon, and evening sleep visits. Similarly, missing FAM-CAM 
data are expected as well. Reasons for missing assessments will be presented in 
conjunction with barriers that family members and caretakers report for conducting 
FAM-CAM assessments. 
 
HELP Program – Reasons for deferred visits 
Family and Caregivers – Reasons for deferred 
FAM-CAM completion 
HELP staff unavailable 
Family unavailable for assessment  
Patient engaged with other clinical staff 
Patient engaged with other clinical staff 
Undergoing medical testing or procedure 
Undergoing medical testing or procedure 
Visitors present 
Not comfortable with performing evaluation 
Patient sleeping 
Patient sleeping 
Patient declines visit 
Patient refusal 
Early discharge 
Early discharge 
Other 
Other 
Not specified 
Not specified 
Table 3.  Anticipated Reasons for Missing Data 
 
Pre-Specified Secondary and Exploratory Analyses 

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As described, a complementary line of analysis will focus on facilitators and barriers to 
implementing therapeutic protocols described, both from HELP- (HUM00166883) and 
family-based perspectives. Results will be used to inform therapeutic protocol design for 
a larger, follow-up trial. Descriptive reporting, based on mixed methods and Likert scale 
survey methodology33, 34, will also be used to report experiences with clinical decision 
support systems. 
 
As a final exploratory line of analysis, an additional objective will be to collect pilot data 
for testing differences in microbial patterns in delirious (vs. non-delirious) patients. 
Preliminary data suggest that colonization of multidrug-resistant organisms is common 
in older, hospitalized patients; furthermore, inpatient wards commonly harbor such 
organisms35. The attendant complications of such colonization, particularly with respect 
to neurocognitive and clinical recovery, remain unknown. These microbial patterns will 
thus be tracked in enrolled patients. Trained study coordinators will collect samples from 
the hands and nares of enrolled patients using a culture swab during baseline 
enrollment, on the first postoperative morning (prior to interventions), and again on the 
morning of the second postoperative day. Study coordinators will also collect samples 
from 5 high-touch surfaces in patient’s rooms (e.g., bed controls/rail, call button/TV 
remote, tray table, phone, and toilet seat/commode) using a culture swab. These 
samples will be plated onto Bile Esculin Agar containing 6 g/mL vancomycin, Mannitol 
Salt Agar, and MacConkey Agar, and assessed for the presence of methicillin-resistant 
Staphylococcus aureus, vancomycin-resistant Enterococcus, and resistant gram-
negative bacilli utilizing standard microbiology testing methods previously described35. 

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Pragmatic-explanatory trial continuum analysis 
The RADAR Trial interventions were designed with intentions for high generalizability. HELP is 
now present at more than 200 hospital systems worldwide, and decision-support systems may 
help triage and organize support operations across such sites, particularly for those limited by 
personnel and/or resources. Alternatively, for hospitals without HELP, this trial will also assess 
the feasibility and efficacy of similar interventions administered by family members and 
caretakers. 
 
To further study the pragmatic and explanatory elements of RADAR, trial members completed 
the PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) toolkit36. This is an 
assessment tool that characterizes the pragmatic and explanatory elements of clinical trial 
design, and the results inform as to where trial design resides on the pragmatic-explanatory 
continuum. For PRECIS-2 assessment, nine study domains are analyzed: eligibility criteria, 
recruitment, setting, intervention organization, flexibility of intervention delivery, flexibility of 
adherence, follow up, primary outcome, and primary analysis. Raters score each domain on a 
scale of 1 – 5, with lower scores reflecting explanatory trial characteristics, and higher scores 
suggesting a more pragmatic nature. RADAR Trial members independently scored each domain 
using the associated instructions, and median scores are illustrated in Figure 2. Each domain 
received a median score of 4 or 5, reflecting a relatively pragmatic study design. Regarding (1) 
eligibility criteria, the trial will recruit a heterogeneous, well-rounded group of surgical patients 
that will receive interventions similar to those administered postoperatively. There will be some 
exclusions based on family and caretaker availability, cognitive function, and surgical subtype. 
Recruitment (2) will be conducted at regularly scheduled preoperative clinic appointments, 
which occur as part of routine, standard care. The setting (3) The setting will be identical to 
where patients otherwise receive perioperative care. Regarding (4) the expertise and resources 

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needed to deliver the interventions, the HELP-based interventions are closely related to usual 
care, though they may occur sooner and more thoroughly with the pager alerting system. 
However, there will be some additional resources and training required, particularly for family-
based interventions. For (5) flexibility of intervention delivery, pager alerts can be reliably 
delivered and modified as needed. There are also many opportunities throughout the day to 
implement clinical protocols as outlined. However, to demonstrate effectiveness, the proposed 
interventions likely need to occur consistently and with adherence to the protocol. In terms of 
flexibility adherence (6), daily pager alerts will be reliably and automatically sent to HELP and 
family members to enhance protocol fidelity. Checklists will also be made available to family 
members. Follow-up (7) for most outcomes and operations will occur in the immediate 
postoperative period, and many outcomes described are obtainable via chart review. However, 
certain follow-up measures (e.g., CAM, 30-day surveys) require prospective collection from 
research team members, though raters did not raters generally did not anticipate this to be 
particularly burdensome or prohibitive. Delirium is the primary outcome (8), which is a common 
and serious postoperative outcome that is relevant to surgical patients. Lastly, the primary 
analysis plan (9) follows an intention-to-treat approach with longitudinal modeling that accounts 
for missing data. Although raters generally scored the trial design as pragmatic, raters were part 
of the trial team, and thus not independent assessors. This may introduce bias with regards to 
objectively rating explanatory and pragmatic elements of a trial37. 

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Figure 2. Pragmatic Explanatory Continuum Indicator Summary (PRECIS)-236 tool depicting where 
RADAR resides on the pragmatic-explanatory trial continuum. After reviewing training materials, 
members of the RADAR team independently scored each of the 9 domains included in the PRECIS-2 
Toolkit. For each domain, scores range from 1 to 5, with lower scores reflecting an explanatory nature, 
and higher scores reflecting pragmatic characteristics. Median scores are presented from all team 
members (n=10) that completed the PRECIS-2 toolkit scoring. The median score for each domain was 
either a 4 or 5, reflecting a fairly pragmatic study design overall. 
 
Data and safety monitoring plan 
All participants will be monitored throughout the entire perioperative course by both the research 
team (including direct oversight by the PI) and clinical teams per standard care. The research 
team will monitor for adverse events, which will be reported per IRB guidelines. Participants will 
also have phone and pager numbers to the study coordinator and study PIs, and they are 
encouraged to contact our study team with any concerns that arise. While admitted to the 

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hospital, participants will otherwise undergo routine monitoring and management per standard 
clinical practice. There will otherwise be no additional data management committee, and no 
interim analyses or audits are planned for this trial. For data storage, primary source paper 
documents will be stored in locked files within the Department of Anesthesiology at Michigan 
Medicine. Electronic data will be de-identified and entered into the online REDCap, database, 
which is managed by the Michigan Institute of Clinical and Health Research Management Core. 
Lastly, all protocols and consent forms approved by the University of Michigan Medical School 
IRB are reviewed yearly. 
 
 
Strengths and Limitations 
Multiple strengths of this trial are worth noting. First trial design is relatively pragmatic, 
as perioperative care will be minimally altered. The HELP-based activities described 
already take place at Michigan Medicine; a single page will be sent to HELP to assist 
with triage and focus therapeutic activity on relatively high-risk patients. The system can 
conceivably benefit any patient regardless of surgical subspecialty, as supportive 
protocols outlined could be implemented – or adapted – as part of enhanced recovery 
protocols irrespective of surgical service. The study also offers an innovative approach 
to integrating family members and caretakers in the postoperative recovery process. 
Preliminary data suggest that family involvement is both feasible18 and may improve 
clinical recovery after major surgery19. Thus, both HELP- and family-based support 
systems offered might provide an effective, practical approach to mitigating delirium risk 
while minimizing strain to the healthcare system. 
 

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Considerable limitations are also worth discussion. The statistical powering strategy 
crucially assumes there is no interaction between the interventions (e.g., HELP- and 
family-based support), which may not be the case. However, this pilot phase will help 
generate effect size and feasibility data for refining future protocols and power 
calculations. Next, both HELP officials and family members may be subject to the 
Hawthorne effect38. That is, individuals may modify their behavior under study 
conditions. Both HELP officials and family members may rigorously perform study 
protocols knowing that performance is being monitored. As such, protocol effectiveness 
will likely decrease in non-research settings. For the HELP program, performance 
measures will be compared to historical controls (2018 HELP records) to mitigate this 
effect. Family members of patients not randomized to family-based support 
interventions may still elect to spend more time with patients after learning about the 
trial and proceeding with enrollment. To assess for latent family support in the control 
groups, the research team will ask family members about time and activities with 
patients for comparisons to structured family-based support allocation groups. This will 
be assessed on the afternoon of postoperative day three, at the end of the inpatient 
study window, to avoid inadvertent introduction of study-related family support 
interventions. Additionally, while family members will receive basic training and 
education on FAM-CAM administration, they will not receive rigorous training for 
assessing reliability or accuracy. Such training could be pursued in a follow-up trial. 
Lastly, only patients with family members and/or caretakers – who will be available for 
the first three days of hospitalization – will be eligible for the trial. Thus, patients without 
such social support will be ineligible. These eligibility criteria thus exclude a group of 

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patients who may be particularly vulnerable to delirium (i.e., less social support)39 and 
reduce trial pragmatism. 
 
 
Ethical Considerations 
Emanuel et al.40 have proposed seven universal requirements, drawn from landmark 
codes and declarations, for comprehensively incorporating all relevant ethical 
considerations for clinical research, particularly in the context of aiming to improve 
health and/or increase understanding of human biology. These considerations are 
presented in question format, along with responses for this trial, in Table 4.  
 
1. What scientific or social value will be gained from the proposed research? 
The proposed clinical support system may improve neurocognitive and clinical recovery for older, 
vulnerable surgical patients. Given the common occurrence of delirium in this population, along with 
related complications (e.g., falls, delayed discharge), postoperative clinical complications may threaten 
the health and functional independence of older surgical patients. By aiming to provide therapeutic, 
supportive activity early (and frequently) during postoperative recovery, these clinical support systems 
may reduce the risk of delirium and associated outcomes. As such, the proposed intervention has the 
potential for improving health and well-being for such vulnerable patients. 
2. Will accepted scientific principles and methods be used to produce reliable and valid data? 
This trial incorporates multiple strategies for rigorous data acquisition and analysis. Prospective, block-
stratified randomization will occur after trial enrollment. The randomized approach will mitigate 
selection bias during the allocation process and increase the likelihood that findings observed are 
attributable to the intervention. The sensitivity analysis will also provide transparency regarding missing 
data and challenges related to intervention fidelity. Lastly, there is a possibility of observer bias (i.e., 

27 
 
Hawthorne effect) with HELP staff and family members, as behavior may be modified given the known 
presence of an ongoing trial. As such, a historical control group will be included from 2018 for 
determining HELP measures prior to trial initiation. Ongoing family support data will also be collected 
from groups not randomized to family-based support interventions. 
3. Are participants selected such that stigmatized and vulnerable individuals are not targeted 
for risky research, and socially affluent and powerful are not targeted for beneficial research? 
As outlined in the eligibility criteria, all surgical patients (≥70 years old) at high risk for postoperative 
complications will be eligible for enrollment, regardless of demographic or social background. In a 
preliminary study that predicted postoperative risk of complications in older patients, those who were 
≥70 years of age presenting for major surgery had a seven-fold increased risk of major complications 
compared to minor surgery24. Thus, this study specifically aims to include this vulnerable demographic 
of patients for beneficial research. 
4. Is there a favorable benefit-to-risk ratio for participants? Will the benefits to the participant, 
and/or society, outweigh any potential risk to the enrolled participants? 
The risks associated with this study are minimal. Those randomized to the control group will receive 
standard perioperative care. If randomized to the interventional group, the patients will likely receive 
earlier and more frequent visits from HELP staff along with family- and caretaker-based delirium 
screening assessments and supportive care. Risks associated with these interventions are minimal, 
but may include anxiety and fatigue from cognitive and functional interventions to improve health after 
surgery. We feel that trial benefits outweigh these risks, particularly if the intervention reduces the risk 
of delirium and possible downstream consequences (e.g., falls, delayed discharge). 
5. Will independent reviews take place such that a committee, with an appropriate range of 
expertise, will have the ability to approve, amend, or terminate the study? 
The proposed trial will be reviewed by the University of Michigan Medical School Institutional Review 
Board, and operations will not commence until approval is obtained. The trial will also be subject to 
annual reviews by the Institutional Review Board, and the study team will monitor for Adverse Events 

28 
 
and Other Reportable Information or Occurrences in compliance with Institutional Review Board 
protocols. 
6. Will informed consent be obtained from all participants prior to enrollment? 
Written informed consent will be obtained from all participants prior to trial enrollment. Consent forms 
are written in conjunction with Institutional Review Board requirements, which require discussion of the 
following: purpose of the study, participant eligibility, study procedures, information about risks and 
benefits, ending participation, financial considerations, confidentiality, and study team contact 
information. 
7. Does the proposed study engender respect for potential and enrolled subjects? 
Patients will be free and able to withdraw from the trial at any time, and several measures will be taken 
to maintain participant privacy and confidentiality. If new, unanticipated risks or benefits become 
apparent during the course of the trial, the protocol will be amended and participants will be made 
aware of any new risks or benefits of study inclusion. Participant welfare will be respected and 
maintained throughout trial operations. Adverse events will be reported per Institutional Review Board 
guidelines, and clinical care will otherwise proceed per perioperative standards at Michigan Medicine. 
Table 4. Ethical considerations presented 
 
Dissemination 
The trial will be presented at academic conferences, presentations, and medical 
journals. As mentioned, the trial was registered on www.clinicaltrials.gov 
(NCT04007523). Any protocol changes will be made publicly available on this registry. 
 
If the results demonstrate improved HELP evaluation and therapeutic practices, the 
paging-based support intervention will be tested in a large-scale trial to assess 
effectiveness for reducing delirium incidence and related consequences. Family-based 
interventions may be included as well depending on success and feasibility with family-

29 
 
led delirium screening and prevention procedures described. The nature of such future 
interventions may be modified depending on survey results from HELP personnel and 
family members. 
 
Conclusions 
Delirium remains a pressing public health issue, and associated consequences bear 
significant morbidity. The proposed clinical decision support system has the potential to 
improve the environment for neurocognitive and clinical recovery for high-risk patients. 
The paging support system is also relatively pragmatic, and if successful, could be used 
across various healthcare systems and tailored accordingly. If encouraging preliminary 
results are demonstrated, the proposed interventions will be tested in a large-scale trial 
for clinical effectiveness.   
 
 
 

30 
 
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