Quantifying Patient Preferences for Leadless Pacemaker Devices
Conditions: Cardiac Rhythm Disorder, Bradycardia, Cardiac Pacemaker Artificial
Sponsor: Abbott Medical Devices

 
Clinical Investigation Plan Cover Page 
 
 
 
 
87173 CIP Posting Cover Page Ver C 
Template 
Page 1 of 1 
 
NCT Number: 05327101 
 
 
Quantifying Patient Preferences for Leadless Pacemakers 
Study Document No: 
 
 
Date: 21-FEB-2022 
 
 
Sponsor  
 
 
Abbott 
        
 
 
 
15900 Valley View Ct. 
      
  
 
 
Sylmar, CA 91342  
        
 
 
 
USA 
 
 
 

Patient Preference Study Protocol 
 
 
 
 
February 21, 2022 
 
2 
 
 
Contents 
Abbreviations ............................................................................................................................................................... 3 
List of Tables ............................................................................................................................................................... 4 
1. 
Responsible Parties ............................................................................................................................................ 5 
2. 
Amendments and Updates ................................................................................................................................ 6 
3. 
SYNPOSIS ........................................................................................................................................................... 7 
4. 
RATIONALE FOR PATIENT PREFERENCY STUDY .................................................................................. 8 
5. 
OBJECTIVES ...................................................................................................................................................... 9 
5.1. 
Primary ........................................................................................................................................................ 9 
5.2. 
Secondary................................................................................................................................................. 10 
6. 
METHODS ......................................................................................................................................................... 10 
6.1. 
Study Design ............................................................................................................................................ 10 
6.2. 
Attribute Selection ................................................................................................................................... 10 
6.3. 
Patient Advisory Group ........................................................................................................................... 12 
6.4. 
Pretesting the Survey Instrument .......................................................................................................... 13 
6.5. 
Survey Instrument ................................................................................................................................... 13 
6.6. 
DCE Experimental Design ..................................................................................................................... 13 
6.7. 
Survey Programming .............................................................................................................................. 14 
7. 
Study Population and Recruitment ....................................................................................................... 14 
8. 
Sample Size ............................................................................................................................................. 15 
9. 
Survey administration ............................................................................................................................. 16 
10. 
Participant Compensation ...................................................................................................................... 17 
11. 
Data Management ................................................................................................................................... 17 
11.1. 
Survey Variables ..................................................................................................................................... 18 
11.2. 
Additional Variables ................................................................................................................................ 18 
References ................................................................................................................................................................. 22 
 
 
 

Patient Preference Study Protocol 
 
 
 
 
February 21, 2022 
 
3 
 
 
ABBREVIATIONS 
 
Abbreviation 
Definition 
AE 
Adverse event 
BMI 
Body mass index 
CDRH 
Center for Devices and Radiological Health 
DHHS 
Department of Health and Human Services 
DCE 
Discrete choice experiment 
DCRI 
Duke Clinical Research Institute 
 
 
 
FDA 
Food and Drug Administration 
IDE 
Investigational Device Exemption 
MAR 
Maximum-acceptable risk 
OHRP 
Office for Human Research Protections 
 
 
PAG 
Patient Advisory Group 
PHI 
Protected health information 
 
 
 
 
 
 
 
 

Patient Preference Study Protocol 
 
 
 
 
February 21, 2022 
 
4 
 
 
LIST OF TABLES 
Table 1. Responsible Parties .................................................................................................................................... 5 
Table 2. Attribute Table ............................................................................................................................................ 11 
Table 3. Items in the Ranking Exercise ................................................................................................................. 12 
 

Patient Preference Study Protocol 
 
February 21, 2022 
7 
3. SYNPOSIS
Abbott’s dual chamber leadless pacemaker (Leadless DR System) will offer an alternative to 
traditional dual chamber pacemakers among patients in need of dual-chamber rate-responsive 
bradycardia pacing therapy.  Relative to conventional transvenous pacemakers, the Leadless DR 
System offers advantages including that it is totally self-contained and does not require separate 
components (leads and generator), thereby eliminating complications associated with 
transvenous pacemakers, for example pocket infection, lead fracture, and lead dislodgment.  In 
addition, because the device is placed directly in the heart, it is not visible, and does not 
necessitate a lump and scar on the chest.  However, its drawbacks relative to transvenous 
pacemakers include a potentially higher rate of complications like cardiac perforation, shorter 
battery life requiring more frequent replacement procedures, and less historical evidence about 
its safety and efficacy. Obtaining scientific information on the relative importance of the 
advantages and disadvantages of both types of pacemakers from the patient perspective will 
provide valuable information to regulators, providers, and patients. 
A quantitative patient preference survey, using a discrete-choice experiment (DCE), will be 
developed, tested and fielded amongst individuals undergoing evaluation for a cardiac pacemaker 
at US clinical sites participating in Abbott’s single-arm Investigational Device Exemption (IDE) trial 
for the Aveir dual-chamber leadless pacemaker. Adult patients who are referred to the study site 
for evaluation for a pacemaker or with a known indication for a de-novo pacemaker will be eligible 
to complete the patient-preference survey via online administration.  All participants will complete 
the patient-preference survey before being approached about their potential interest in enrolling 
in the trial, and thus before they receive information about dual-chamber pacemakers and before 
they receive their pacemaker. 
 
 
 
The primary objective of the study is to quantify patient preferences for pacemaker device 
features. The secondary objective is to explore and characterize heterogeneity in patient 
preferences. 
 
 
 

Protocol 
 
 
 
 
February 21, 2022 
8 
 
 
4. RATIONALE FOR PATIENT PREFERENCY STUDY 
Abbott’s dual chamber leadless pacemaker will offer an alternative to traditional dual chamber 
pacemakers. The dual chamber leadless implantable pacemaker system, henceforth referred 
to as the “Leadless DR System”, is a programmable system comprising two implanted 
leadless pacemaker devices that monitors and regulates the patient’s heart rate by providing 
dual chamber rate-responsive bradycardia pacing therapy. Each leadless pacemaker device 
of a Leadless DR System is a self-contained pulse generator with built-in battery and 
electrodes that provide bradycardia therapy (sensing and pacing). As a leadless pacemaker, 
it does not require a pacing lead or its associated connector, nor does it require a pulse 
generator pocket.  Instead, it is intended for direct implantation into the right ventricle and/or 
the right atrium. 
The Leadless DR system eliminates complications associated with the leads, surgical pocket, 
and connectors required with a traditional dual chamber pacemaker (e.g. pocket infection, 
lead fracture, and lead dislodgment). Among leadless pacemaker systems, Abbott’s system 
is unique in its ability to upgrade from a single to a dual chamber leadless configuration and 
the retrievability of the dual chamber system. The system also provides other important, non-
clinical benefits. First, a leadless system may improve patient comfort because it is implanted 
directly in the heart; therefore, patients cannot feel the device. With a traditional pacemaker, 
some patients report pain or discomfort around the generator pocket.i Second, the leadless 
system eliminates the visible lump and scar at a traditional pacemaker’s pectoral implant site. 
A leadless system also minimizes the need for activity restrictions after surgery, which are 
required following traditional pacemaker surgery to prevent lead dislodgement.  
At the same time, the Leadless DR system presents certain disadvantages compared to a 
traditional pacemaker. First, although the Leadless system avoids risks associated with leads, 
pockets and connectors, it increases the risk of cardiac perforation during implantation. 
Second, the battery life of the two generators in a Leadless DR system will be shorter than 
the battery life of the generator in a traditional pacemaker, meaning the Leadless generators 
will have to be replaced more often than a traditional generator. The Leadless DR system is 
also a new technology, while traditional pacemakers have been commercially available for 
over 50 years. As such, there is less evidence available regarding physicians’ and patients’ 
experience with leadless systems, particularly in the longer term, compared to traditional 
pacemakers.  
Conventional transvenous pacemakers provide significant improvements in physical 
functioning and outcomes in individuals with bradyarrhythmia. Although generally well 
tolerated, serious adverse events, including pocket-related issues (i.e. infections, hematomas, 
skin erosion, twiddler’s syndrome) and lead-related issues (i.e. infections, fractures, connector 
issues, lead-induced tricuspid regurgitation, venous obstruction or thrombosis), pose 

Protocol 
 
 
 
 
February 21, 2022 
9 
 
 
significant risks to patients, especially as these devices are frequently implanted in older and 
frail patients. Patients also report chest discomfort, physical restriction, and cosmetic 
concerns with traditional pacemakers.ii, iii The advent of leadless pacemakers offers patients 
the same benefits of conventional pacemakers, but without the visible scar and lump of a 
traditional pacemaker. Leadless pacemakers also offer the possibility of lower infection risks 
and less chest discomfort than traditional pacemakers, but possibly higher risks of 
complications during placement and extraction. Patients may place different levels of 
importance on the features of transvenous pacemakers and leadless pacemakers and their 
associated risks.  
The Investigational Device Exemption (IDE) clinical trial that will be used to support market 
approval for the Leadless DR System is currently under development. It will be conducted in 
a global patient population with cardiovascular issues in which a pacemaker is indicated.  The 
purpose of the global IDE study is to evaluate the clinical safety and efficacy of a dual chamber 
leadless pacemaker in patients indicated for dual chamber pacing.  
Abbott is conducting a patient preference study among sites participating in the trial, in 
collaboration with the Duke Clinical Research Institute’s (DCRI) 
 
, to quantify patient preferences pertaining to risks and features of 
conventional transvenous pacemakers and leadless pacemakers. The preference study is 
designed to elicit patient preferences for risks and features that vary between a dual chamber 
leadless pacemaker system and a dual chamber transvenous pacemaker system, to quantify 
their relative importance. The results of the patient preference study will inform technology 
development, support regulatory review, and potentially support Abbott dual-chamber 
leadless system product labeling to provide patients’ perspectives on perceived advantages 
versus the risks of a leadless dual chamber system compared to a dual chamber transvenous 
pacemaker.  
 
5. OBJECTIVES 
5.1. Primary 
The primary objective of the study is to quantify patient preferences for pacemaker device 
features. This includes estimates of the following: 
o The conditional relative importance of device features included in the DCE 
o Maximum percentage-point increases in the acceptable risk of complications or infection 
for an improvement in another attribute (for example: to get a preferred device type, to 
avoid discomfort, or to have a device with longer battery life)  

Protocol 
 
 
 
 
February 21, 2022 
10 
 
 
o Other value equivalents (for example: What patients will give up in terms of years of 
battery life to move from a less-preferred device type to a more-preferred device type). 
o Predicted choice probabilities for product profiles relative to specified comparators (i.e. 
the likelihood that an average respondent in the sample would choose a device profile 
with specific features, compared with a profile with different features) 
o Mean ranking of select device features not included in the DCE (i.e. insertion procedure, 
visible lump of the generator, and scar on chest or groin) 
5.2. Secondary 
The secondary objectives of the study include the following: 
o Use latent-class analysis to investigate whether there are classes of respondents with 
systematically different preferences and to investigate whether these differences in 
preferences are correlated with self-reported characteristics  
o Test for differences in preferences in the following subgroups:  
• 
Participants who agreed (verbal or written) to be screened for participation in the IDE 
study compared with those who did not (see Section 7) 
• 
Gender 
• 
Age 65 years and older compared with those younger than 65 years 
• 
Body mass index (BMI) stratified by CDC definition of obesity (i.e. BMI≥ 30 versus 
>30) 
• 
History of major surgery (self-report) requiring a hospital stay of 2 or more nights in 
the past 5 years  
• 
Those with a sedentary lifestyle compared with those with a non-sedentary lifestyle 
where sedentary is defined as not exercising and non-sedentary is any amount of daily 
exercise.  
 
6. METHODS 
6.1. Study Design 
In the DCE, respondents will be asked to select their preferred device alternative in a series 
of experimentally controlled pairs of hypothetical device alternatives. The alternatives will be 
defined in terms of specific levels of device features (attributes).  
6.2. Attribute Selection 
The DCRI team, which includes an expert clinical researcher and electrophysiologist, 
collaborated with Abbott and patient advisors (see Section 6.3) to select the study attributes. 
Selection of attributes and corresponding levels were informed by a scoping review of the 
published literature, scientific abstracts, and product information available from manufacturers 
of traditional and leadless pacemaker devices. Priority was given to treatment features 
thought to be of concern to patients and those that differentiate device alternatives.  

Protocol 
 
 
 
 
February 21, 2022 
12 
 
 
regarding leads, respondents could choose “having a pacemaker without leads” or “having a 
pacemaker with leads”, as shown in Table 3. The chosen feature of greater concern is then 
transferred to the ranking exercise so that all features shown in the ranking exercise represent 
negative aspects of pacemakers from the patient perspective.  
Table 3. Items in the Ranking Exercise  
Insertion procedure  
• 
Pacemaker inserted through cut in skin on the chest 
• 
Pacemaker inserted using tube through the groin 
Leads 
• 
Having a pacemaker with leads 
• 
Having a pacemaker without leads 
Pacemaker location 
• 
Having a pacemaker placed under the skin on the chest 
• 
Having a pacemaker attached to the walls inside the heart 
No heavy lifting is allowed for 6 weeks (versus limited activity for 
2 weeks) 
Scar on chest (versus no scar) 
Lump on chest (versus no lump) 
 
6.3. Patient Advisory Group 
 
 
  
 
  
 
 
 
 
 
 
 

Protocol 
 
 
 
 
February 21, 2022 
13 
 
 
6.4. Pretesting the Survey Instrument 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
6.5. Survey Instrument 
The final survey instrument includes the following sections: 
o Screening questions to confirm eligibility (Section 7) 
o Informed consent (Section 14.2) 
o Patient-reported information on personal health and sociodemographic characteristics 
o Attribute descriptions 
o Tutorial on risks presented graphically 
o Practice questions to familiarize respondents with the DCE question format 
o Comprehension questions 
o DCE questions 
o Ranking exercise 
 
The DCE survey is expected to take 25-30 minutes to complete. The survey will be 
administered online. 
 
6.6. DCE Experimental Design 
A D-efficient experimental design representing 48 choice questions was generated using 
design algorithms in SAS (Kuhfeld 2010).iv The design was divided into 6 blocks of 8 choice 
questions.  Each participant will be randomized to complete one block of 8 questions. 
Participants also will be asked if they are willing to complete an additional 4 choice 
questions. To generate those choice questions, an additional D-efficient design was 

Protocol 
 
 
 
 
February 21, 2022 
14 
 
 
generated representing 24 choice questions, divided into 6 blocks of 4 choice questions 
each. Survey participants will be randomized to complete one block of 4 choice questions.  
Additional information about the experimental designs are included in the Statistical Analysis 
Plan from the DCRI PrefER Group. 
6.7. Survey Programming 
 
 Access to the survey will 
require entry of unique passcodes by participants.  
7. Study Population and Recruitment 
Adult patients who are referred to Leadless DR System IDE clinical trial sites for evaluation 
for a pacemaker or with a known indication for a de-novo pacemaker will be eligible to 
complete the patient-preference survey via online administration (Figure 1). Only IDE study 
sites in the United States will participate.   
To be eligible to complete a PPI survey, patients must meet the following eligibility criteria: 
• 
Adult patients age 18 years or older  
• 
Reside in the United States 
• 
Able to read and speak English, consent to participate in the PPI survey 
• 
Willing and able to use a tablet or computer to complete the survey  
Figure 1. Flowchart for Recruitment in PPI and IDE Studies 

Protocol 
 
 
 
 
February 21, 2022 
17 
 
 
form for patients who verbally consent to participate in the IDE trial. This information will be 
used to differentiate among: 1) patients who verbally consented to be screened but did not 
meet inclusion/exclusion criteria; 2) patients who met eligibility criteria but declined to 
participate in the IDE trial; and 3) patients who ultimately enrolled in the trial and received a 
leadless pacemaker. 
DCRI will send Abbott passcodes along with information indicating whether the survey was 
completed or partially completed, and Abbott will transfer the passcodes to study sites. Using 
this method, DCRI will not receive any patient protected health information (PHI).   
Participants should complete the survey using a tablet or PC. Participants should be strongly 
discouraged from using a mobile phone to complete the survey. 
10. Participant Compensation 
As described in Section 9, study sites will maintain crosswalks linking passcodes for the 
patient preference survey with patient identifiers in order to track who has completed the 
survey and to pay any incentives that may be due to the participant. It is assumed that Abbott 
or study sites will process incentive payments.  
11. Data Management 
 
 
 
  
 
  
 
 
 
   
 
 
 
 
 
 
 
. 
 

Protocol 
 
 
 
 
February 21, 2022 
18 
 
 
11.1. Survey Variables 
The survey will collect: 
o Years since diagnosis with heart problems 
o Actions taken to manage heart problems 
o Years since first pacemaker received 
o Number of times pacemaker replaced 
o Years since last pacemaker replacement 
o Type of pacemaker 
o Experience with pacemaker discomfort, complications, and infections 
o Experience with major surgery  
o Age 
o Gender 
o Height and weight (to compute BMI) 
o Lifestyle activity level 
o Marital status 
o Race/ethnicity 
o Source of health insurance 
o Highest education completed 
o Employment status 
o Responses to comprehension questions 
o Respondents’ treatment choices in the DCE questions 
o Respondents’ ranking of items in the ranking exercise 
The survey will not collect any protected health information (PHI). 
11.2. Additional Variables 
Additional participant-level variables not collected in the survey will be tracked by participating 
IDE study sites. These data will later be merged with survey data for analysis. Variables that 
will be transferred to Duke are limited to the following: 
o Participants’ passcodes to access the survey 
o Whether the participant completed or partially completed the preference survey 
o Whether the individual agreed to participate in the IDE clinical trial 
o Study site identifier 
 
 

Protocol 
 
 
 
 
February 21, 2022 
19 
 
 
11.3. Study Endpoints 
Study endpoints will include a set of log-odds preference weights for all attribute levels 
included in the DCE.  From these preference weights, the following endpoints will also be 
calculated: 
o The conditional relative importance of device features included in the DCE 
o Percentage-point increases in the maximum-acceptable risk (MAR) of complications or 
infection for an improvement in another attribute (for example: to get a preferred device 
type, to avoid discomfort, or a have a device with longer battery life)  
o Other value equivalents (for example: What patients will give up in terms of years of battery 
life to move from a less-preferred device type to a more-preferred device type) 
o Predicted choice probabilities for product profiles relative to specified comparators (i.e. the 
likelihood that an average respondent in the sample would choose a device profile with 
specific features, compared with a profile with different features) 
Mean ranking of select device features not included in the DCE (i.e. insertion procedure, 
visible lump of the generator, and scar on chest or groin) will be estimated. 
12. Analysis 
Discrete-choice experiments generate complex cross-section/time-series choice data for each 
respondent. These data include a dichotomous dependent variable and are analyzed using 
advanced statistical methods. The basis for the analysis is the model specification assumed when 
generating the experimental design prior to survey implementation. That specification considers 
a categorical main-effects model for all study attributes. However, the specification assumed in 
the experimental design takes into account only statistical considerations. The statistical analysis 
of choices will provide a measure of the impact of changes in the attribute levels on the likelihood 
that treatments are selected by respondents, also referred to as attribute-level preference 
weights.  
Respondents’ reactions to the stimuli in DCE questions generally involve complex decision 
processes, and the final model specification must account for the pattern of choices as observed 
in the data set. The Statistical Analysis Plan from the DCRI 
 lays out the initial 
analyses that will be conducted to assess the quality of the data and describes exploratory analytic 
strategies that will inform the final model specification.  
The design and study specifications have been developed to support a robust analysis and 
reporting that will include the following: 
• 
Summary statistics of respondents’ demographic characteristics, sociodemographic 
characteristics, experience with heart problems and treatment for heart problems 

Protocol 
February 21, 2022 
20 
•
An evaluation of data quality including respondents’ performance on survey
comprehension questions, time to complete the survey, response non-variance, and
attribute dominance
•
A scope test to evaluate whether respondents are sensitive to actual levels of risk
presented
•
Subgroup analysis for pre-specified subgroups
•
An analysis of preference heterogeneity among respondents and associations with
different demographic, clinical, and treatment characteristics
•
Selection of the most appropriate preference model specification and reporting of the
relative importance of device features included in the DCE, equivalence values
(including MARs), and predicted choice probabilities
•
Results of a ranking exercise for additional device features not included in the DCE
Additional, detailed descriptions of planned study analyses are included in the Statistical Analysis 
Plan from the DCRI 
. 
13. Limitations of the Research Methods
Although the study will follow good survey practices to elicit truthful responses from participants, 
choices obtained with DCE questions do not have the same consequences as real-world 
treatment decisions.  
The use of a fractional-factorial D-efficient design will not allow the estimation of individual-level 
preferences or higher-order interaction likely effects between attributes. This, however, is offset 
by the fact that such a design will allow us to ask respondents to complete a more reasonable 
number of DCE questions.  
The study design can be limited by the task complexity and cognitive fatigue. However, to 
address, the study employs accepted best practice survey design strategies such as low reading 
level text, a risk tutorial, color, and graphics to engage respondents and the inclusion of 
comprehension questions to evaluate respondents who are sufficiently well prepared to provide 
valid preference data. 
14. Protection of Human Subjects
14.1. Institutional Review Board/Independent Ethics Committee 
The 
 will be the IRB of 
record for this study. The 
 has oversight of 10 convened IRBs, of which 8 meet 
monthly. The 
holds a Federal-Wide Assurance 

Protocol 
February 21, 2022 
21 
 from the Department of Health and Human Services (DHHS) Office for 
Human Research Protections (OHRP) that allows us to review and approve human subject 
procedures through our IRB committees. These committees are also registered with OHRP 
for both DHHS and Food and Drug Administration-regulated research. The FWA requires IRB 
review for all studies conducted by Duke that involve human subjects, regardless of the 
funding source.   
14.2. Informed Consent 
An electronic consent document will be provided by site research staff via website link. The 
consent document will provide information about the study and instruct participants that they 
may contact their study doctor and/or the IRB should they have any questions about the study. 
Site research staff are responsible for providing the contact information along with the link to 
the consent form. Participants will be asked to read this information, and they will be given the 
option to agree or not agree to continue with the PPI survey.  
14.3. Confidentiality 
While it is impossible to guarantee perfect data security given the electronic nature of data 
collection, every effort to ensure security will be made and this will be explained to 
respondents as part of their informed consent. The online patient preference survey will not 
collect individually identifying information. The only information that will be collected that could 
be used to identify an individual is the passcode used to access the survey. However, the 
crosswalk between the passcode and personal identifying information will be maintained at 
IDE study sites. Information from study sites transmitted back to Duke will be limited to 
variables described in Section 11.2. 
Further, to ensure data privacy, data will be collected on secure data systems by the survey 
vendor and stored and analyzed on secure Duke systems. No data will be intentionally 
disclosed to third parties.  
All data and records will be kept confidential in accordance with institutional policies and 
HIPAA on subject privacy and that the Investigator and other site personnel will not use such 
data and records for any purpose other than those specified and use upon analysis for 
potential publication purposes. Any data analyzed for publication will remain de-identified. 

Protocol 
 
 
 
 
February 21, 2022 
22 
 
 
REFERENCES 
 
 
i Magnusson, P., Liv, P. Living with a pacemaker: Patient-reported outcome of a pacemaker 
system. BMC Cardiovascular Disorders 2018;18(1). doi:10.1186/s12872-018-0849-6. 
 
ii Cabanas-Grandío P, Campo EG, Bisbal P, et al. Quality of Life of Patients Undergoing 
Conventional vs Leadless Pacemaker Implantation: A Multicenter Observational 
Study.  J Cardiovasc Electrophysiol  2020 ;31(1):330-336.  doi: 10.1111/jce.14322. 
 
iii Udo EO, van Hemel NM, Zuithoff NPA, et al. Long Term Quality-Of-Life in Patients with 
Bradycardia Pacemaker Implantation. Int J Cardiol. 2013;3;168(3):2159-63. doi: 
10.1016/j.ijcard.2013.01.253. 
 
iv Kuhfeld, W. Marketing Research Methods in SAS. 2010 
v Orme BK. Getting Started with Conjoint Analysis: Strategies for Product Design and Pricing 
Research. Vol 2nd. Madison, WI: Research Publishers, LLC; 2010. 
 
vi Yang JC, Johnson FR, Kilambi V, Mohamed AF. Sample size and utility-difference 
precision in discrete-choice experiments: A meta-simulation approach. Journal of 
Choice Modelling. 2015;16(C):50-57.