A Randomized Trial of Nudges To Enhance Enrollment in Critical Care Research
Phase: NA
Conditions: Critical Illness
Sponsor: University of Pennsylvania

A Randomized Trial of Behavioral Nudges to Improve 
Enrollment in Critical Care Trials 
Study Protocol 
Updated: April 2020 
 
A randomized trial to assess the effect of a novel pre-consent survey comprised of nudges on 
critical care randomized controlled trial enrollment among surrogates of mechanically 
ventilated patients.  
 
 
Co-Principal Investigator: 
Dustin C. Krutsinger, MD 
Perelman School of Medicine, Division of Pulmonary, Allergy and Critical Care 
University of Pennsylvania 
825 Gates Building, 3400 Spruce St 
Philadelphia, PA 19104 
Phone: 319-400-4964 
Fax: 215-614-0869 
Email: dustin.krutsinger@uphs.upenn.edu 
 
Co-Principal Investigator: 
Katherine R. Courtright, MD, MSHP 
Perelman School of Medicine, Division of Pulmonary, Allergy, and Critical Care 
University of Pennsylvania 
303 Blockley Hall, 432 Guardian Dr 
Philadelphia, PA 19104 
Phone: 215-746-0256 
Email: katherine.courtright@uphs.upenn.edu 
 
 
 

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Table of Contents 
1. Abstract .................................................................................................................................................. 4 
2. Background and Introduction ................................................................................................................. 4 
3. Objectives ............................................................................................................................................... 5 
3.1 
Overall Objectives ............................................................................................................................ 5 
3.2 
Primary Outcome Variable(s) .......................................................................................................... 5 
3.3 
Secondary Outcome Variable(s) ...................................................................................................... 5 
4. Design ..................................................................................................................................................... 5 
5. Recruitment ............................................................................................................................................ 5 
5.1 
Subjects ............................................................................................................................................ 5 
5.2 
Informed Consent ............................................................................................................................ 6 
5.3 
Accrual ............................................................................................................................................. 6 
5.4 
Key Inclusion Criteria ....................................................................................................................... 6 
5.5 
Key Exclusion Criteria ....................................................................................................................... 6 
5.6 
Remuneration .................................................................................................................................. 6 
6. Randomization........................................................................................................................................ 6 
6.1 
Groups .............................................................................................................................................. 6 
6.2 
Assignment ...................................................................................................................................... 6 
7. Procedures .............................................................................................................................................. 6 
8. Consent ................................................................................................................................................... 8 
9. Analysis Plan ........................................................................................................................................... 8 

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10. Confidentiality of Subjects and Data ...................................................................................................... 8 
10.1 Data Management ........................................................................................................................... 8 
10.2 Subject Confidentiality ..................................................................................................................... 9 
10.3 Subject Privacy ................................................................................................................................. 9 
11. Human Subjects Protection .................................................................................................................... 9 
11.1 Potential Risks .................................................................................................................................. 9 
11.2 Potential Benefits ............................................................................................................................. 9 
11.3 Risk/Benefit Assessment .................................................................................................................. 9 
12. Study Instruments ................................................................................................................................ 10 
12.1 Pre-consent Nudge Survey ............................................................................................................. 10 
12.2 Sham Mechanical Ventilation Trial Consent Form ......................................................................... 11 
12.3 Risk Perception Assessment ........................................................................................................... 15 
12.4 Surrogate Demographic Survey ..................................................................................................... 16 
12.5 Patient Demographic Survey .......................................................................................................... 17 
12.6 Debriefing Form ............................................................................................................................. 18 
12.7 Script .............................................................................................................................................. 19 
13. References ............................................................................................................................................ 26 
 
 
 

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1. Abstract 
Difficulty recruiting patients is a widely recognized barrier to successful completion of randomized 
controlled trials (RCTs) and a significant contributor to the cost of conducting such studies. Difficulty 
recruiting patients is particularly problematic for critical care trials which often rely on surrogate 
decision makers (SDMs) for enrollment decisions. Evidence suggests that behavioral interventions, or 
nudges, may offer novel approaches to increase enrollment in RCTs by reframing decisions without 
restricting choice. We aim to determine the effectiveness of a scalable bundle of non-monetary nudges 
on increasing enrollment rates in a sham RCT among critically ill patients.  
2. Background and Introduction 
 
The joint problems of under-enrollment and selective enrollment in RCTs have long plagued efforts 
to evaluate new and existing medical interventions1-4. Under-enrollment occurs when too few research 
participants are enrolled to provide adequate statistical power to answer the study’s primary research 
question, degrading the study’s scientific value and hence, ethics5-7. Selective enrollment occurs when 
specific subgroups within the target population are enrolled in proportions greater or less than their 
representation in that population, limiting the generalizability of the trial’s results and curtailing 
scientific value8. 
 
Forty percent of National Cancer Institute-sponsored trials are never completed, according to an 
Institute of Medicine report9. Studies often go unfinished due to enrollment difficulties5,10-12. Trials that 
fail to achieve target enrollment due to enrollment difficulties have been called the “ultimate 
inefficiency”9. Recruitment has been referred to as “the most difficult and challenging aspect of clinical 
trials13. Even when investigators enroll an adequate number of participants, they rarely do so on 
schedule12,14, or in a manner that attracts the full range of available participants8,15. Further, participant 
recruitment represents one of the most substantial costs of conducting clinical trials, requiring an 
average of 13 hours and $500 per subject in cancer trials at academic medical centers16. Given the 
resources needed to successfully recruit patients to RCTs, and the gap between important research 
questions and available research funding, it is essential to find ways to enhance recruitment of patients 
to clinical trials17. Authorities have suggested that trialists should embed evaluations of recruitment 
strategies within their trials18,19.    
 
Behavioral economics is a relatively new discipline which merges psychology and economics to gain 
insights into how people make decisions. A key aspect of behavioral economics is the use of nudges. 
Nudges are behaviorally informed interventions which predictably influence behavior without limiting 
choices. Nudges have been proposed as a possible way to address difficulties in trial enrollment20. 
Financial incentives are one form of a nudge. However, many nudges are non-monetary. An example of 
a non-monetary nudge is providing information about norms. Injunctive norms involve the perception of 
what behavior is acceptable, while descriptive norms highlight what behaviors others are engaging in. 
Individuals are more likely to participate in an activity if they perceive it as acceptable and common. The 
duty of reciprocity is the sense that one should repeat pro-social behavior from which they have 
benefited. The mere-measurement effect is also known as the self-prophecy nudge. It reflects a 
tendency to perform actions after being asked about the action in a hypothetical setting. The foot-in-
the-door nudge involves asking a participant to complete a small request which has a high consent rate 
followed by a larger request. 

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3. Objectives 
3.1 Overall Objectives 
The goal of this study is to test whether a novel pre-consent survey with incorporated nudges 
increases the enrollment rate into a sham RCT among critically ill patients. To accomplish this goal we 
will assess quantitatively how many surrogates assigned to each study arm enroll a patient into the 
sham RCT. We will also quantitatively assess for undue and unjust inducement.  
3.2 Primary Outcome Variable(s) 
This randomized trial has the single primary outcome of proportion of SDMs who enroll the patient 
into the sham RCT. 
3.3 Secondary Outcome Variable(s) 
 
Secondary outcomes included undue inducement, unjust inducement, patient and surrogate 
characteristics associated with enrollment. Undue inducement was defined as an interaction between 
intervention and risk perception on enrollment rate.  Unjust inducement was defined as an interaction 
between intervention and highest level of education completed on enrollment rate.   
4. Design 
 
This is a single-blinded randomized controlled among surrogates of patients requiring mechanical 
ventilation admitted to one of ten ICUs across two University of Pennsylvania Health System (UPHS) 
hospitals.  
5. Recruitment 
5.1 Subjects 
 
We will be recruiting 182 surrogate decision-makers of patients requiring mechanical ventilation 
admitted to one of ten ICUs across two UPHS hospitals. The research coordinator will review the 
electronic medical record of patients admitted to the ICUs to identify eligible participants. The 
coordinator will contact the attending physician for any identified patient to confirm eligibility and seek 
approval for the study team to approach the patient’s family. The coordinator will approach approved 
families if they are present in the patient’s room at the time of recruitment. The coordinator may defer 
approach if there is a procedure underway or if the family is in visible distress.  
The eligibility criteria for participation are as follows:  
 
 
 
Eligibility Criteria 
ICU length of stay >24hrs 
Mechanically ventilated via an endotracheal tube 

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Over 18 years of age 
Anticipated to remain using an endotracheal tube at least 24 more hours 
No limitations on life extending care 
Surrogate fluent in English 
Not enrolled in an active ICU trial 
Patient unable to consent for self 
ICU attending is not a study investigator 
ICU attending identifies the patient’s family as distrustful of the medical system 
ICU attending declines approach for any reason (reason to be documented) 
Surrogate present in patient’s room 
 
5.2 Informed Consent  
A waiver of informed consent has been approved by the University of Pennsylvania Institutional 
Review Board. Once patients have been chart screened for eligibility, study personnel will approach 
potentially eligible surrogate. Study personnel will introduce themselves to the patient, inform the 
patient that they are part of a group conducting a research study, and ask permission to sit down and 
tell the patient more.    
5.3 Accrual 
We have received approval from the University of Pennsylvania IRB-approved protocol and obtained 
approval to conduct this study in all 6 ICUs located at the Hospital of the University of Pennsylvania and 
all 4 ICUs located at Presbyterian Hospital. Using an estimated baseline enrollment rate of 30% in the 
control group, a total of 182 participants achieves at least 80% power to detect a 20% absolute 
difference at alpha of 0.05. We will consecutively recruit all eligible surrogates from the ICU until we 
reach our target sample size. We will attempt visit each ICU session at least once a day. The research 
coordinator will approach eligible surrogates while they are present in the patient’s room. For 
surrogates who initially defer a decision we will attempt to reengage the following day and each 
subsequent recruiting day until we either have a definitive decision or until the patient is ineligible. We 
anticipate that we can recruit at least 4 patients per week. 
5.4 Key Inclusion Criteria 
The eligibility criteria, all of which must be met, are: 
1. Patient and surrogate must be 18 or older 
2. ICU length of stay > 24 hours 
3. Mechanically ventilated via an oral endotracheal tube 
4. Patient is unable to consent for themselves 
5.5 Key Exclusion Criteria 
Patients will be excluded if one of the following criteria is met: 
1. Limitations on life extending care 
2. Anticipated extubation or tracheostomy placement in next 24 hours 
3. Enrolled in another ICU trial 
4. ICU attending is a study investigator 
Surrogates will be excluded if one of the following criteria are met: 
1. Not fluent in English 
2. Identified by the ICU attending as having mistrust in the healthcare system 

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3. Not present in the patient’s room at the time of recruitment 
 
5.6 Remuneration 
Subjects will not receive any compensation for participation. 
6. Randomization 
6.1 Groups 
Surrogates who indicate they are willing to hear about a research study will be randomized to 
receive either a pre-consent nudge survey or standard informed consent procedures. The two groups 
only differ in the initial approach, whether they are asked to complete a survey before being informed 
of the sham trial or whether they are invited to consider the sham trial without a pre-consent survey. 
Both groups then fill out identical risk assessments and demographic surveys. After indicating their sham 
trial enrollment decision and completing risk assessments and demographic surveys, surrogates will be 
debriefed (see debriefing script).  
 
6.2 Assignment 
 
Group allocation will be determined by the REDCap randomization module with assignment 
probabilities of 50% to each group stratified by research coordinator.  
 
7. Procedures 
Study procedures are as following:  
1.  The research coordinator will review the electronic medical record of patients admitted to each 
of 10 ICUs to determine eligibility and documenting the results in the study screening database. 
2.  The research coordinator will contact the ICU attending of patients screened as eligible to 
confirm eligibility.  
3.  The research coordinator will visit each eligible patient’s room to assess for the presence of 
visitors.   
4.  If visitors are present the research coordinator will enter patient information into the REDCap 
study module on the screening tablet. 
5.  The research coordinator will enter the room, identify themselves and confirm that the visitor is 
the patient’s surrogate decision maker.  
6.  The research coordinator will ask the patient’s identified surrogate decision maker if they are 
willing to hear about a research study. 
7.  Surrogate decision makers who indicate their wiliness to hear about a research study will then 
be randomized in the REDCap randomization module (as above). 
8.  If the participant is randomized to the intervention arm the research coordinator will follow the 
script (see below) introducing the survey. Following completion of the survey the research 
coordinator will then ask if they are willing to hear about a research trial.  
9.  If the participant is randomized to the control arm the research coordinator will follow the script 
(see below) introducing the sham mechanical ventilation weaning trial.  

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10.  After the surrogate makes an enrollment decision (regardless of the decision) for the sham 
mechanical ventilation trial they will be asked to complete the risk perception assessment and 
demographic surveys.  
11.  If the surrogate askes for more time to make an enrollment decision the research coordinator 
will ask for a good time to return for a decision. Risk perception assessment and demographic 
survey data will be deferred until after a decision is made. The research coordinator will follow 
up the following day (or time set by surrogate) to seek an enrollment decision. Repeated 
attempts to obtain an enrollment decision will continue each recruitment day until a decision is 
made or until eligibility criteria is no longer met.  
12. Immediately following the sham trial enrollment decision, risk assessment and demographic 
surveys the research coordinator will debrief the surrogate (see script below).  
13.  The research coordinator will update the screening database with the results of the recruitment 
attempt.  
14.  The research coordinator will document additional clinical data from the electronic medical 
record for participating patients into the REDCap study database.  
15.  We will continue subject recruitment until target enrollment is reached. 
8. Consent 
A waiver of informed consent has been approved by the University of Pennsylvania Institutional 
Review Board. Once patients have been chart screened for eligibility, study personnel will approach 
potentially eligible surrogate. Study personnel will introduce themselves to the patient, inform the 
patient that they are part of a group conducting a research study, and ask permission to sit down and 
tell the patient more. Following the study procedures and debriefing the participant will retain the 
debriefing handout which includes instructions on how to withdrawal from the study.  
9. Analysis Plan 
As we do not have any strong a priori evidence that any of the collected demographic will be 
strongly associated with the primary outcome, we will perform an unadjusted analysis as the primary 
analysis. The primary outcome will be an intention-to-treat analysis of the proportion of participants 
who enroll in the sham clinical trial.  The intervention arm will be compared to the control arm using a 
chi-square test. In secondary analyses, we will test for undue inducement by assessing the interaction 
between the study group and risk perception on enrollment rate. We will test for unjust inducement by 
assessing the interaction between study group and level of education on enrollment rate.  Stata v14 will 
be used for all analyses. Unless otherwise specified, a p-value <0.05 will be considered significant. 
We will conduct a post-hoc exploratory analysis of patient and surrogate variables associated with 
sham trial enrollment. We will have a third party with critical care trial recruitment expertise, blinded to 
the data, review and rank the variables based on their mechanistic plausibility to impact enrollment 
decisions. The number of included variables in the final model will be determined by the number of 
events (enrollments into the sham trial) to not exceed a 1:10 covariate to event ratio.  
10. Confidentiality of Subjects and Data 
10.1 Data Management 
 

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Prudent steps will be taken to ensure that all information will be kept confidential and secure, 
including medical and survey data. All survey data will be collected on-site by trial research nurse/staff 
and entered into REDCap (Research Electronic Data Capture), hosted at the University of Pennsylvania. 
We will implement multiple, redundant protective measures to guarantee the security of participant 
data. All data for this project will be stored on UPHS secure/firewalled servers. These data servers are 
maintained in a guarded facility behind several locked doors, with very limited physical access rights. 
They are also cyber-protected by extensive firewalls and multiple layers of security comparable to what 
is used in commercial financial transactions. This multi-layer system of data security, identical to the 
system protecting the University of Pennsylvania Health Systems medical records, greatly minimizes 
privacy risks. Direct identifiers for patients and their surrogates will be omitted from all analytic files. 
 
10.2 Subject Confidentiality 
Only authorized project personnel will have access to the data. All study data will be stored behind 
firewalls on UPHS servers; none will be stored on stand-alone PCs or laptops. All study personnel who 
work with these data will have undergone required human subjects training. We will implement 
multiple, redundant protective measures to guarantee the privacy and security of the participant data. 
All data for this project will be stored on the secure/ firewalled servers of the UPHS in data files that will 
be protected by multiple password layers. These data servers are maintained in a guarded facility behind 
several locked doors, with very limited physical access rights. They are also cyber-protected by extensive 
firewalls and multiple layers of communication encryption. Electronic access rights are carefully 
controlled by Penn system managers.  
10.3 Subject Privacy 
We will approach surrogates in the patient’s room. We will offer them the option to speak in the 
patient’s room or in an alternative private location.  Individual-level medical data for patients will be 
kept confidential and will only be stored on highly secure servers available for patient-level data. Only 
authorized project personnel will have access to the data and the data will be stored on servers only and 
not stand-alone PCs or laptops. All study personnel who work with this medical data will have 
undergone all of the required human subjects training. 
11. Human Subjects Protection 
11.1 Potential Risks 
Potential risks include loss of confidentiality, disappointment in not being able to participate in the 
described simulated trial and negative impact on clinician-family trust with the use of deception. We 
protect the data in several ways as outline in the data protection section. We purposefully selected a 
simulated trial of prioritizing decreases in FiO2 vs PEEP in weaning of mechanical ventilation as a trial 
that would unlikely result in excessive optimism and therefor would yield minimal disappointment once 
it is disclosed that it is a simulated trial.  
11.2 Potential Benefits 
Participants will be instructed that this is research, and like all research, it is being conducted with 
the primary goal of producing generalizable knowledge. Thus, the primary benefits to be gained are 
those related to the knowledge to be gained. However, patients, as well as their families, may benefit 
directly from the opportunities to discuss their thoughts on research participation. In addition, the 
knowledge to be gained in this study may help develop a simple way to increase research participation.  

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11.3 Risk/Benefit Assessment 
 
Participants will be offered enrollment in a sham randomized controlled trial comparing the effects 
of prioritizing decreases in FiO2 vs PEEP in weaning of mechanical ventilation. Thus, temporarily 
deceiving patients on the purpose of the study. Importantly, the risk is minimal because: (1) their 
participation in the main study and decision whether or not to participate in the sham RCT will not affect 
the treatment their loved one receives; (2) the proposed intervention in the sham RCT is within standard 
of care for mechanically ventilated patients and is minimally invasive, so discussion about this sham RCT 
and intervention is not expected to lead to additional distress for the participant; (3) the evidence to 
date suggests that the behavioral nudges employed in this study are without ethical concerns  (4) we 
offer participants the opportunity to opt-out after a thorough debriefing procedure. Difficulty recruiting 
patients is a widely recognized barrier to successful completion of clinical trials and a significant 
contributor to the cost of conducting such studies. If a simple intervention such as the behavioral 
economic nudges we are testing are found to increase trial recruitment without blunting perception of 
risk it could have a dramatic effect on future critical care trials. 

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12. Study Instruments  
12.1 Pre-consent Nudge Survey 
 
 
 
12.2 
Sham Mechanical Ventilation Trial Consent Form 
 

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12.3 
Risk Perception Assessment 
 
 

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12.4 
Surrogate Demographic Survey 
 
 

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12.5 
Patient Demographic Survey 
 
 
 
 

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12.6 
Debriefing Form 
 
 

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12.7 
Script 
 
 
 

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