Shared Decision Making for Stroke Prevention in Atrial Fibrillation (SDM4Afib): A Randomized Trial
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Mayo Clinic

 
 
Shared Decision Making for 
Stroke Prevention in Atrial 
Fibrillation (SDM4Afib): A 
Randomized Trial 
 
 
 NCT02905032 
 
 
10/12/2021 

1 
SDM4Afib Protocol 
Shared decision making for stroke prevention in atrial fibrillation (SDM4Afib) 
Investigators:   
Peter Noseworthy, MD, Principal Investigator, Mayo Clinic 
200 First Street SW, Rochester, MN 55905 
Noseworthy.peter@mayo.edu 
, Co-Investigator, Mayo Clinic (Rochester, MN) 
, Co-Investigator, Park Nicollet (St. Louis Park, MN) 
, Co-Investigator, Hennepin Medical Center (Minneapolis, MN) 
, Co-Investigator, UAB Medicine - The University of Alabama at 
Birmingham (Birmingham, AL) 
, Co-Investigator, UAB Medicine - The University of Alabama at Birmingham 
(Birmingham, AL) 
, Co-Investigator, University of Mississippi Medical Center (Jackson, MS) 
Date of version:  October 12, 2021 
Version number: 2 
Funding Source: National Heart, Lung, And Blood Institute of the 
National Institutes of Health under Award Number R01HL131535

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SDM4Afib Protocol 
 
Table of Contents 
1.0 
Aims ..................................................................................................................................... 3 
2.0 
Background and Significance .............................................................................................. 3 
3.0 
Preliminary Work................................................................................................................. 5 
4.0 
Research Design & Methods ............................................................................................... 6 
4.1      Schema ................................................................................................................................. 6 
4.2      Study Setting and Participation ............................................................................................ 6 
4.2.1  
 Eligibility Criteria for Clinicians ................................................................................. 7 
4.2.1.1  
Enrollment of Clinicians ........................................................................................... 7 
4.2.2       Eligibility Criteria for Patients ..................................................................................... 8 
4.2.3       Identification of Subjects ............................................................................................. 9 
4.3     Registration and Randomization of Patients ....................................................................... 10 
4.4     Intervention ......................................................................................................................... 11 
4.4.1      Training of Clinicians ..................................................
. 
4.5     Standard Care ...................................................................................................................... 12 
4.6     Data Collection ................................................................................................................... 12 
4.7     Outcome Measures.............................................................................................................. 15 
4.7.1      SDM quality ................................................................................................................ 15 
4.7.2      SDM processes............................................................................................................ 17 
4.7.3      Anticoagulation Use.................................................................................................... 18 
4.7.4      Safety outcomes .......................................................................................................... 19 
4.8      Follow-up Guidelines......................................................................................................... 19 
4.9   Statistical Analysis ............................................................................................................. 20 
4.9.1      Analysis Plan .............................................................................................................. 20 
4.9.1.1      Missing Data ............................................................................................................ 22 
4.9.2       Sample Size Estimation .............................................................................................. 22 
4.9.3      Site Allocation ............................................................................................................ 23 
5.0   Conflict of Interest ............................................................................................................. 24 
6.0   Human Subjects ................................................................................................................. 24 
6.1      Data safety monitoring board............................................................................................. 24 
6.2   Population .......................................................................................................................... 25 
6.3 
Potential Risks ................................................................................................................... 25 
6.4 
Protection and Confidentiality ........................................................................................... 25 
6.4.1      Subject privacy............................................................................................................ 25 
6.4.2      Data management........................................................................................................ 26 
6.4.3      Video and audio-recordings ........................................................................................ 26 
6.4.4       Registry ...................................................................................................................... 26 
6.4.5       IRB Umbrella ............................................................................................................. 27 
7.0      References .......................................................................................................................... 27 
 
 
 

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1.0 
Aims 
 
The goal of this study is to determine the extent to which standard care plus the 
Anticoagulation Choice tool promotes shared decision making (SDM) and impacts 
anticoagulation uptake and adherence versus standard care without this tool in patients with 
nonvalvular atrial fibrillation (AF).     
 
Aim 1. To what extent does use of the ANTICOAGULATION CHOICE tool promote 
high-quality SDM versus standard care? 
 
Using encounter video recordings and post-visit patient and clinician questionnaires, we 
will assess SDM quality (primary endpoint) and processes.  
 
We hypothesize that use of the tool will improve SDM irrespective of patient 
literacy/numeracy, stroke risk, anticoagulation use at baseline, or type of clinic. 
 
Aim 2. To describe the impact Anticoagulation Choice tool has on the rate of 
anticoagulation, the choice of anticoagulant, and adherence to anticoagulation in at-risk 
patients with AF versus the impact of standard care. 
 
Using medical records and pharmacy profiles, we will determine the choice of 
anticoagulation, changes in anticoagulant use over time, and 12-month drug persistence, 
in all patients and in subgroups defined by patient literacy/numeracy, stroke risk, 
anticoagulation use at baseline, and type of clinic. As safety outcomes, we will monitor 
serious bleeding or strokes requiring medical attention.  
 
2.0 
Background and Significance  
 
Atrial fibrillation is the most common cardiac arrhythmia affecting ~3 million Americans1,2 It 
accounts for ~$26 billion/year in healthcare costs.3 AF-related thromboembolic strokes are 
often devastating and a cause of great physical, social and economic burden.4-7   Vitamin K 

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antagonists (VKAs, e.g., warfarin) reduce the risk of stroke by ~68%.8-13  Recently, non-
VKAs oral anticoagulants (NOACs) that directly inhibit factor Xa (e.g., rivaroxaban, 
apixaban, edoxaban) or thrombin (dabigatran) have demonstrated similar to or better efficacy 
and safety than warfarin.14-16  Underuse of anticoagulation is a significant quality gap. 
Despite patients’ strong aversion to strokes,17,18  <50% of high-risk patients with AF receive 
anticoagulants.19  Of these, 30-50% stop treatment within 12 months.20-23 The low rate of 
anticoagulation suggests that clinicians are challenged in initiating anticoagulation, in part 
due to clinicians’ aversion to causing anticoagulation-related bleeding,19,24  Nonadherence 
suggests that some patients cannot implement anticoagulation in their lives: warfarin requires 
a stable diet and periodic laboratory (INR) monitoring,25-27  while NOACs are costly and lack 
bleeding reversal agents.14-16  Underuse may result also from poor patient and clinician 
access to, and deliberation with, individualized estimates of risks and benefits.28,29  Patients 
and clinicians require support in initiating and implementing anticoagulation therapy. 
 
In 2014, three major cardiovascular organizations formulated guidelines for the management 
of patients with AF. They gave their strongest class I recommendation for using SDM to 
individualize anticoagulation in at-risk AF patients.30  SDM has the potential to support 
patients and clinicians in collaborative deliberation about reasonable anticoagulation 
strategies matched to medical risk and patient circumstance.30-32 Nevertheless, this 
recommendation is based on expert consensus (level C evidence) and translating it into 
practice is challenging. The guideline provides no guidance on how to achieve this, and no 
tools were available that are both up-to-date and proven to support SDM in this context. 
Furthermore, we do not know what effect SDM may have on anticoagulation rates and 
adherence in patients with AF.30 
 
We have developed and pilot tested a new online SDM tool (Anticoagulation Choice) to 
implement the 2014 class I recommendation in usual practice. The tool promotes a SDM 
conversation in the clinical encounter between the expert on important issues that bear on 
adherence, the patient, and the expert in medical issues, the clinician. Deliberating together 
on patient-important issues and medical matters, patients and clinicians can arrive at an 
evidence-based option that patients’ value and can implement.  Building on this experience, 

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we propose to implement SDM using the Anticoagulation Choice tool and evaluate its impact 
on SDM quality and on the rate by which patients take up anticoagulation and implement it 
in their lives.  
 
3.0 
Preliminary Work 
 
The anticoagulation decision requires a conversation that discusses both the patient’s risk of 
strokes and the issues that distinguish agents by fit with patient goals and situation. Using our 
user-centered design process, we created Anticoagulation Choice, a decision aid designed to 
support the recommendation for SDM for anticoagulation in AF. The development of the 
anticoagulation choice tool was built on 10 years of experience in designing decision aids 
that promote shared decision making and provide evidence-based content. The evidence-
based content for this tool comes from systematic and expert reviews of randomized trials, 
observational studies, and qualitative studies.30, 33-42  Simultaneously, we conducted 16 direct 
observations in primary and specialty clinics of clinical encounters in which anticoagulation 
decisions took place. The goal of these observations was to identify areas of opportunity to 
improve extant conversations.43 The first “low-fidelity prototype”44 was a rough-draft paper 
version and was field-tested within 8 clinical encounters. Iterations followed, first on paper, 
and then electronically, seeking to achieve patient engagement in the conversation. We 
judged this to have taken place when patients asked questions or made statements 
considering how anticoagulation would play out in their daily lives. An electronic version 
was necessary to ensure risk tailoring for each patient and to facilitate updating (we designed 
the tool to accommodate new evidence and new agents) and distribution. The online version 
supports conversations with patients who are new to anticoagulation as well as former and 
current warfarin users. Its use in field-testing required minimal support. The baseline risk, 
tailored to the patient using the CHA2DS2-VASc score (a tool that estimates risk of stroke), is 
shown using words, numbers, and a 100-person pictograph along with the expected risk 
reduction with anticoagulation. If this benefit is compelling to the patient consideration 
moves on to the salient issues differentiating the available options. The issue cards include 
the risk of bleeding (based on HASBLED, a tool that estimates risk of bleeding), availability 
of reversal agents, and practical considerations. Practical considerations include how each 

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choice affects patients’ ability to be active, to travel, to eat a variety of meals, how the 
medicine is taken and its effects monitored, and what are the out-of-pocket costs. The final 
version of the tool is focused on the discussion of these issues after considering the risk of 
stroke and the risk reduction with anticoagulation. The tool is web-based and will be 
integrated where possible with the electronic workflow. 
 
4.0 
Research Design & Methods 
 
We will conduct a multicenter randomized trial at the patient level comparing the 
Anticoagulation Choice tool and standard care versus standard care alone where enrolled 
clinicians will administer the intervention among patients with nonvalvular AF deemed at 
high risk of thromboembolic strokes. The study will assess the impact of the interventions on 
SDM quality and impact on anticoagulation use as well as monitoring safety concerns of 
strokes and bleeds.  Also, as part of this trial, clinician training sessions will be evaluated to 
describe the normalization process of anticoagulation decision aid in the clinical sites. Data 
collection will include medical record review, survey completion, and note taking or 
video/audio recording of the clinical encounter and training sessions. 
 
4.1       Schema 
 
 
 
 
 
 
 
 
 
4.2       Study Setting and Participation 
 
The trial will take place in clinics at Mayo Clinic (academic medical center), Park Nicollet 
Health Partners (urban/suburban community medical center), Hennepin County Medical 
Center (safety-net inner-city medical center), UAB Medicine - The University of Alabama at 
Appointment 
or screen for 
AFIB 
Approach 
for consent 
Randomize 
Anticoagulation  
Choice + Standard Care
Standard Care 
EMR and 
Pharmacy 
review 

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Birmingham and University of Mississippi Medical Center that treat patients with atrial 
fibrillation.  
 
At each recruiting location designated site staff will be trained to review informed consent 
documents and obtain necessary signatures from patients and clinicians and will be observed 
doing so, by study personnel or research staff, prior to actually consenting patients or clinicians.   
 
   4.2.1  
Eligibility Criteria for Clinicians 
 
 
 
 
All clinicians (MDs, NP/PAs, PharmDs) that are responsible for the modality of 
Anticoagulation in eligible AF patients at participating sites, without exclusion. 
 
 4.2.1.1  
Enrollment of Clinicians 
 
The research team and site champions will present an overview of the study at a department 
meeting. The informed consent document will be reviewed with interested clinicians before 
the clinician receives training on using the decision aid at the initial recruitment meeting or at 
their convenience throughout the duration of the study, prior to their first enrolled patient. 
Study staff will observe the clinician trainings, described in 4.2.1.2. The clinician will have 
the option to consent to recordings (video/audio or audio only) of clinical encounters with 
enrolled patients.  If the clinician declines to do the recording they are still eligible for 
participation within the study.  If the clinician agrees to recording of the clinical encounters 
on the consent they can still decline at time of the clinical encounter.   
 
The study coordinator will quickly setup and start recording before leaving the room. The 
participants can stop this recording (video, aimed at the desk, or audio when the video 
camera is aimed at the ceiling) at any time (the device has a large red start/stop button and an 
on/off indicator light). 
 
Consent only needs to occur one time (prior to being trained to use the decision aid and prior 
to the visit with the first enrolled patient). There will be no monetary or other sort of 

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reimbursement for clinicians participating in the trial. The participation of clinicians as 
subjects will not affect their current or future employment or be shared with their supervisor.  
4.2.1.2     Training of Clinicians 
 
Study personnel will do a demonstration in the use of the decision aid during in-person 
visits with participating clinics. Training session proceedings will be documented using 
discretionary video photographing, recording, or note-taking. Clinicians will complete a 
brief survey after trainings to describe promoting and inhibiting factors to the 
normalization of the anticoagulation decision aid in clinical practice. Similarly, transcripts 
and notes from trainings will undergo qualitative analysis to identify promoting and 
inhibiting factors to the implementation of the shared decision making tool in the clinical 
sites.  Study personnel may also do a reminder of how to use the decision aid as needed 
(including just-in-time training) or in response to deviations in the quality of delivery 
observed on video/audio recordings.  Brief video clips and storyboards that demonstrate the 
basic use of decision aids are publicly available at 
for 
clinicians to review at their convenience.   
 
 
 
4.2.2   Eligibility Criteria for Patients 
 
Each criterion must be addressed and documented in the patient’s case report form for 
eligibility assessment by the study coordinator.  No waivers or exemptions to any eligibility 
criteria will be permitted. 
 
 
Inclusion Criteria: 
1. ≥ 18 years of age 
2. Nonvalvular AF deemed at high risk of thromboembolic strokes (CHA2D2-VASc 
Score ≥ 1 in men, or 2 in women). 
3. Able to read and understand (despite cognitive, sensorial, hearing or language 
challenges) the informed consent document as determined by the study coordinator 
during consent.   

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Exclusion Criterion 
1.  Clinician indicates that patient is not a candidate for a discussion about 
anticoagulation medication. 
2. Cognitive impairments 
3. Mechanical values 
4. Left appendage occlusion devices (example: Watchman) 
5.   
 
 
4.2.3  Identification of Subjects 
 
 
 
 
Participants for all aims will be patients, their caregivers when pertinent, and clinicians. 
Participation is completely voluntary and we have procedures in place, sanctioned by the Mayo 
Clinic Institutional Review Board, Hennepin County Medical Center Institutional Review Board 
(HCMC), Park Nicollet Health Partners Institutional Review Board, UAB Medicine - The 
University of Alabama at Birmingham Institutional Review Board and University of Mississippi 
Medical Center Institutional Review Board to ensure that participants have the opportunity to opt 
out at any time and will not be further approached for participation or to provide data.  
 
At the Mayo Clinic site, upcoming appointment lists for Atrial Fibrillation (AF) patients in 
primary care, cardiology, neurology, thrombophilia and anticoagulation clinics ECG result 
lists, medical records and clinician referrals will be reviewed for patient eligibility. Eligible 
patients will be approached and recruited in person, in a private location (i.e., clinic/exam 
room) prior to their appointment. Consent will occur by a trained research member as long 
as needed and until all questions by the subject have been answered. All study activities 
will occur within scheduled appointments, avoiding the need for additional research visits.  
 
The patient and caregivers (if present), will be asked to provide consent to the recording 
(video/audio or audio only) of the clinical encounter.  If the patient chooses to decline the 
recording they are still eligible to participate in the study.  The study coordinator will 
quickly setup and start recording before leaving the room. The participants can stop this 

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recording (video, aimed at the desk, or audio when the video camera is aimed at the 
ceiling) at any time (the device has a large red start/stop button and an on/off indicator 
light). 
 
The consent process will include the patient signing authorization to release protected 
health information forms to allow study personnel to obtain pharmacy prescription records 
and medical records from outside clinics. If a patient declines to sign an authorization form, 
he/she will still be eligible for the study but will be excluded from the analysis where 
information about medication and/or other medical records use is necessary (i.e. adherence 
analysis). The research team will contact the pharmacies and outside clinics for follow-up, 
so the patient will not be burdened with additional measures. There will be no monetary or 
other sort of reimbursement for participants. 
 
4.3  Registration and Randomization of Patients 
 
Prior to registering patients to the study, all of the eligibility criteria on the eligibility 
checklist will have been met.  
 
Patients will be randomized by the study coordinator after completion of standard informed 
consent for participation in clinical research including permission to use protected health 
information.   
 
Registration/randomization is available via REDCap 
 this is a secure, web-based application that is 
HIPPA compliant.  Registration/randomization is available 24 hours a day via the REDCap 
website.  Site staff will be provided a login and password by the study statistician.  
 
Prior to accessing the REDCap website, site staff should verify the following: 
• All eligibility criteria have been met. 
• Informed consent has been obtained. 
• Site staff has access to REDCap. 

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4.4       Intervention 
 
In the intervention group, clinicians will conduct the encounter per standard care 
procedures with the addition of having access to the Anticoagulation Choice tool. The tool 
will be accessed online or through an available link in the Electronic Medical Record 
(EMR).  Patient information to complete the calculators of risk (CHA2DS2-VASc) and 
bleeding (HAS-BLED; if needed) are: history of hypertension, congestive heart failure, 
stroke, vascular disease, diabetes mellitus, renal disease, liver disease, prior or 
predisposition to bleeding, unstable and/or high INR, whether the patient takes a 
medication predisposing him or her to bleeding, and the number of alcoholic drinks per 
week will be entered by the clinician into the tool or will be uploaded from the patients 
EMR to the tool and a personalized risk will be calculated (Table 1).  CHA2DS2-VASc 
score of 0: recommend no antithrombotic therapy. CHA2DS2-VASc score of 1: recommend 
antithrombotic therapy with oral anticoagulation or antiplatelet therapy but preferably oral 
anticoagulation. CHA2DS2-VASc score ≥2: recommend oral anticoagulation.2 A HAS-
BLED score of ≥3 indicates that caution is warranted when prescribing oral anticoagulation 
and regular review is recommended.2  Patients can request to receive a printed copy of the 
tool from their clinician which they can use later to share their decision with others, and to 
review, confirm or revisit their decision.  
 
 
 
Table 1. Assessment of Stroke (CHA2DS2-VASc)14 and Bleeding Risk (HAS-BLED)15 
in Atrial Fibrillation Patients 
CHA2DS2-VASc 
Score 
HAS-BLED 
Score 
Congestive heart failure 
1 
Hypertension (SBP >160 mm Hg) 
1 
Hypertension 
1 
Abnormal renal and liver functionb  
1 or 2 
Age ≥75 y 
2 
Stroke 
1 
Diabetes mellitus 
1 
Bleeding tendency/predispositionc 
1 
Stroke/TIA/TE 
2 
Labile INRs (if on warfarin)d 
1 
Vascular diseasea  
1 
Elderly (e.g., age >65 y) 
1 
Aged 65 to 74 y 
1 
Drugs or alcohol (1 point each)e 
1 or 2 
Sex category (i.e., female sex) 
1 
 
 

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Maximum score 
9 
Maximum score 
9 
Acronym def.: TIA indicates transient ischemic attack; TE, thromboembolic; and INR, international 
normalized ratio.  
 
a- 
Prior myocardial infarction (MI), peripheral artery disease (PAD), or aortic plaque. 
b- 
Abnormal renal function is classified as the presence of chronic dialysis, renal transplantation, or 
serum creatinine ≥200 mmol/L. Abnormal liver function is defined as chronic hepatic disease (eg, 
cirrhosis) or biochemical evidence of significant hepatic derangement (bilirubin 2 to 3 times the upper 
limit of normal, in association with aspartate aminotransferase/alanine aminotransferase/alkaline. 
phosphatase 3 times the upper limit normal, etc).  1 point for each. 
c- 
History of bleeding or predisposition (anemia). 
d- 
Labile INR (ie, time in therapeutic range <60%). 
e- 
Concomitant antiplatelets or nonsteroidal anti-inflammatory drugs, or excess alcohol. 
 
 
4.5        Standard Care 
 
The clinician will conduct the encounter per their standard of care.  As access to the tool 
will be available to ensure contamination does not occur the study coordinator will inform 
the clinician prior to entering the room that the patient is to receive standard care and that 
the tool is not to be accessed. 
 
4.6         Data Collection 
 
Patients approached by study staff that agrees to participation will be captured in the 
remote data capture system (REDCap45).  Potential eligible patients found to be ineligible 
or eligible but decline participation will be captured in a recruitment tracking log.  The 
reason for ineligibility or reason for decline will be captured along with patients’ age, sex, 
and race/ethnicity.   
 
Self-reported responses from patients and clinicians will be collected at the end of the 
clinical encounter.  At the time of their enrollment clinicians will complete a survey that 
collects data on their demographics.  The post baseline survey will be given to the patient 
and clinician to complete at the clinic at the end of the encounter by the study coordinator 
or site appointed staff.  Patients may be given the option to fill out part of the survey, prior 
to their visit if time allows.  If a patient requests a return envelope, one will be provided to 
return the survey by mail.  If the survey is not received in the 10 days post encounter a 

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reminder will be mailed to them with a copy of the survey along with a return envelope. A 
courtesy call will be made within 5 days post the mailing. Every effort will be made to 
complete the survey at the clinic immediately post encounter as this is the best chance for 
complete data collection. Another option for patients will be to have a follow up phone call 
approximately 1-2 days after their clinical encounter, to remind the patient to send their 
survey back or they will be given the option to complete their survey over the phone at that 
time.  
 
Data from the medical record will be abstracted for all enrolled patients to capture 
demographic, clinical and medication prescription data.  The time frame for collection will 
be from prior to enrollment to 12 months post enrollment.  For patients that do not have 
any encounters at the institution for the past 12 months, a scan will be conducted up to 6 
months after the 12-month timeline to verify continuity of care at the institution, change in 
contact information and/or survival status. If no records are available at that time, we will 
call the patient (number of attempts as authorized by each IRB), followed by a postal 
survey if nonresponse persist. 
 
Data to be collected on patients include variables necessary to estimate the risk of stroke 
and bleeding, age, gender, BMI, smoking status, alcohol consumption, marital status, 
annual income of household, highest level of education, residency (nursing home), location 
of primary healthcare and total number of medications patients is currently taking. To 
further characterize the patients, we will use Chew et al single-item health literacy 
screener,46  a 4-item modified Subjective Numeracy Scale,47, 48  and a single-item health 
status measure.49 
 
We will collect information on past use of anticoagulants through medical record review.  
We will categorize the patients into two cohorts for descriptive and analytical purposes.  
For patients who are not using an anticoagulant at the time of trial participation will form 
the ‘Start’ cohort. They may have used anticoagulation and discontinued >6 months ago, 
never used anticoagulation, or are using aspirin only. Patients that began an anticoagulant 

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within the past 10 days of the enrolled encounter that were prescribed an anticoagulant 
within the emergency department or an inpatient visit will still be considered a new ‘Start’.   
  
Patients who are on warfarin or NOACs or used them in the past 6 months will form the 
‘Review’ cohort. This cohort may include patients who have difficulty maintaining a 
therapeutic INR, or patients considering switching to a different anticoagulant or to stay on 
warfarin but switch to home INR monitoring.  
 
The post consent survey for clinicians will collect demographic data (age, gender, 
specialty, % of their practice dedicated to anticoagulation care).  
 
Calendar of Events 
 
Prior to Study 
Enrollment 
Prior to 
Encounter 
R 
A 
N 
D 
O 
M 
I 
Z 
A 
T 
I 
O 
N 
 
Post 
Encounter 
12 months 
Post 
Enrollment 
Patient Completed Forms 
 
Informed Consent 
X 
 
 
 
Pharmacy Consent 
X 
 
 
 
Survey 
 
 
X 
 
Phone 1 
 
 
 
X 
Clinician Completed Forms 
 
Informed Consent 
X 
 
 
 
Survey 
 
X 
X 
 
Clinical Data Abstracted from EMR 
 
Bleeds 
 
 
 
X 
Strokes 
 
 
 
X 
INR Tests (# and 
values outside of 2-
3 range) 
 
 
 
X 
Anticoagulation 
Prescription  
 
X 
X 
X 
Pharmacist Request 
 
Anticoagulation 
 
 
 
X2 

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Use  
1- 
Patients who do not have utilization within enrolling healthcare system will be contacted via phone for 
verification of safety data (strokes and bleeds).  If no information in the record and follow-up is necessary 
we will call patients the maximum number allowed by the IRB followed by a postal survey  
2- 
Pharmacist records will be requested for 12 months prior to enrollment through 10 months post enrollment. 
 
4.7  Outcome Measures 
 
4.7.1   SDM quality  
 
SDM quality will measure (a) knowledge transfer; (b) concordance; (c) quality of 
communication and satisfaction with shared decision making; and (d) satisfaction with the 
decision-making process. 
 
Knowledge transfer is 6 questions about AF and anticoagulation.  The 6 questions use a 
response format “true / false / do not know”, and are answered with full access to the 
decision aids since they are not meant to test recall. Correct responses will be summed and 
divided by the total number of questions asked.  If a patient answers at least 1 knowledge 
question then they will be assessed for this outcome, where all missing responses will be 
coded as incorrect.   
 
Knowledge of risk will contain one question that asks patients to estimate their own risk of 
stroke. Correct answers will be within ± 10% (strict score) and ± 30% (liberal score) 
relative to the calculated risk estimate. 
 
Collaborative agreement will assess decision concordance between the patient and the 
clinician.  Both the patient and clinician will be asked to report about what decision 
(anticoagulation no/yes-which one) was made during the index visit.  Agreement will be 
calculated between both parties and reported. 
 
Patient decision satisfaction will be assessed using the Decisional Conflict Scale (DCS). 50, 
51  The 16 items of DCS are scored on a 0-4 scale; the items are summed, divided by 16 and 

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then multiplied by 25.  The scale is from 0-100 where higher scores are reflective of 
uncertainty about the choice. There are 5 DCS subscales, where a DCS subscale consists of 
3 questions (1 subscale of 4).  If 2 of 3 (or 3 of the 4) questions within a subscale have 
responses, then the patient would be considered as a responder and a score could be 
calculated.  If more than one response per subscale is missing then that specific subscale is 
not calculated for the patient.  An overall DCS score can be calculated if no more than 5 
responses are missing as long as each missing response falls into a different subscale. 
 
Quality of Communication will be assessed with a modified version of three questions 
from the CAHPS Clinician and Group survey52.  CAHPS surveys include questions to 
assess patient perspectives of communication with their clinician.  These questions indicate 
the extent to which the communication is patient-centered. Three questions ask about 
specific aspects of technical (explain things in a way you could understand) and affective 
(show respect for what you have to say) communication.  Each item is assessed on a 3 
point scale (Yes, definitely; Yes, somewhat and No) that will be individually reported, no 
composite score will be done. Three modifications are made to improve the relevance of 
the items to the present study: (1) Instructions were changed from “These questions ask 
about your most recent visit with this doctor. Please answer only for your own health care.” 
to “Thinking of the conversation you just had with your clinician about blood thinners 
(anticoagulation medications), please select the most appropriate response to each item 
below.”  (2) “During your most recent visit” was removed from the item stems. (3) “This 
doctor” was replaced with “this clinician.”   
 
Patient satisfaction with encounter will be assessed with 1 question on a 7 point likert scale.  
Patients will be asked whether they would recommend the approach used to others for 
other discussions.   
 
Clinician satisfaction with encounter will be assessed with 2 questions.  A 5 point likert 
scale questioning satisfaction with discussion about anticoagulation medication choice.  
The clinician will also be asked whether they would recommend the approach used to other 
clinicians for other discussions on a 7 point Likert scale.   

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4.7.2    SDM processes  
 
To assess SDM processes the recordings of the clinical encounter will be evaluated 
(video/audio or audio only recordings).   
 
Extent of SDM that took place during the encounter will be assessing the degree of 
involvement of patients by the clinician in SDM using the OPTIONS scale.53 The scale 
consists of 12 items scored from 0, no effort to 4, exemplary effort.  The 12 items are 
summed and converted to a 100 point scale.  A sample of 20% of the recordings will be 
assessed by two or more reviewers.  Agreement will be assessed by Lin’s concordance 
index54, where any value over 0.8 will be considered concordant.  If concordance does not 
occur within the first 20%, the two reviewers will assess cases of difference and review an 
additional 10 cases to test for agreement.  Recordings scored by both reviewers will be 
averaged.   
 
Impact of SDM on Encounter will be assessed by comparing the length in minutes of the 
discussion about anticoagulation and of the office visit, when available.  Study coordinators 
when possible will time the encounters in intervention and control visits, prioritizing those 
encounters in which recording was not allowed. Potential issues preventing assessment of 
time may be recruitment of another patient. 
 
Fidelity of SDM Tool by the clinician will be assessed by a review of the recording looking 
for key items to be addressed.  A checklist of key elements will be assessed in both arms to 
assess not only the fidelity but potential contamination.  A sum of the components in the 
checklist will be calculated for each recording and compared between arms.  To score the 
recording first a sample of 20% of the video’s will be assessed by two reviewers.  
Agreement will be assessed by Lin’s concordance index54, where any value over 0.8 will be 
considered concordant.  If concordance does not occur within the first 20%, the two 
reviewers will assess cases of difference and review an additional 10 cases to test for 
agreement.  Recordings scored by both reviewers will be averaged. For encounters where 

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audio and video recording has been declined, a real-time assessment will occur at the 
consent of the clinician and the patient. The study coordinator will conduct these real-time 
reviews.   
 
Inclusion of Cost as an Element of SDM Process will be assessed by first using qualitative 
inductive content analysis of the transcripts of video-recorded clinical encounters to 
describe the scope of cost conversations. Deductive video-graphic analyses will be used to 
code the occurrence of cost conversation themes in order to determine the  impact that 
Anticoagulation Choice has on the appearance of these themes, controlling for individual 
characteristics and contexts, and the association between cost conversation themes and 
SDM quality (described above), SDM Processes (described above), and Anticoagulation 
Use (described below).  
 
 
4.7.3 Anticoagulation Use 
 
Rate of anticoagulation:  The key indicator of the choice to start an anticoagulant will be 
its prescription in the EMR prescription module (observed discussions and 
patient/clinician accounts may not reflect decisions confirmed after the visit with a 
prescription, for example, after the clinician or the patient checked other information or 
with other informants). After this primary ‘decided as prescribed’ approach, we will 
conduct secondary analyses using patient/clinician reported and video-observed 
decisions. Decisions may be for starting or not an anticoagulant in the start cohort. It is 
possible that there may be some decisions to stop anticoagulation in the review cohort, 
but we expect start and review cohorts to contribute information about choice of 
anticoagulant. 
 
Choice of anticoagulant:  We will review the EMR and 10-month pharmacy profiles 
(to stand for the 12-month profile given the automatic expiration of 
pharmacy records at 1 year) to determine the prescribed anticoagulant and 
whether and when switches to another agent or to no anticoagulant took place. 

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Together, they should capture choice and switches even when these occur as a result of 
changes in clinician (e.g., from cardiology to primary care). When available, we will 
note the documented reasons from clinical notes for choosing and switching as well as 
with which clinician the change was made (e.g primary, cardiology, etc.). 
 
Anticoagulation persistence:  Patients will identify the pharmacy(-ies) they use to fill 
their prescriptions and authorize us to obtain their prescription drug fill data. We will 
calculate anticoagulation persistence, using the percent days covered (PDC) based on 
prescription refill behaviors (total days supply of anticoagulant filled / total days of 
observation from the first prescription fill date; range 0-100%). We will also pull all 
pharmacy refills for the 12 months prior to enrollment. This will allow us to calculate 
persistence for prior use of anticoagulants for the review cohort to compare to persistence 
post encounter and see if there is an impact.  
 
Warfarin use: For patients who choose to stay on warfarin, we will also use as secondary 
measures of adherence: (a) the proportion of INR tests obtained/scheduled; and (b) 
percentage of time at therapeutic target (typically INR 2-3). 
 
4.7.4 Safety outcomes  
 
Strokes and bleeds requiring medical assistance will be monitored and reported to the data 
safety monitoring board (section 6.1). Because very few of these are expected, we will rely 
on patient/clinician self-report and medical record review 12 months post enrollment for 
each participant. Should a patient not have utilization in the 3 months prior to the 12 month 
date, then the patient will be contacted directly for confirmation.  
 
4.8 Follow-up Guidelines 
 
All patients will be followed per protocol guidelines and deviations from protocol will be 
reported to the IRB.   
 

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Withdraw: If a patient refuses to continue to participate and they withdraw consent they 
will then be considered withdrawn from the study; to uphold the intention-to-treat 
principle, we will inquire as to whether we can continue to passively collect data from the 
medical record, and if ok from 10-12 month pharmacy profiles and patient surveys. If not, 
then no further data will be collected through medical review or self-report.  Data collected 
prior to withdraw will be utilized unless expressly told otherwise by the patient. 
 
Ineligible: If a patient enrolled onto the study has been found ineligible (not meeting one of 
the eligibility criteria) they will be documented for reason of ineligible in the study chart.  
These patients will continue to receive the intervention and all data will be collected for the 
study.  This is a safe course of action as the intervention does not pose any potential harm 
to the patient beyond loss of privacy.  The patients will be identified in the results as being 
ineligible and reason but will be included in all analyses.  
 
The procedure for post-randomization exclusions will involve presenting the case to the 
trial PI blind to the participant’s allocation and to their results.  
 
4.9  Statistical Analysis 
 
4.9.1 Analysis Plan 
 
 
 
The study will be analyzed according to the intention to treat principle (ITT), including all 
patients enrolled to the study in the arm to which they were assigned, regardless of which 
they were assigned to (e.g., standard care or Anticoagulation Choice + Standard Care).  
Reporting will include ‘Per Protocol’, complete data for each arm plus the ITT analysis 
where imputation analysis methods will be utilized to address any missing values (see 
section 4.9.1.1 for details on missing data analysis).  Baseline characteristics will be 
reported in the study results with continuous values being reported as means and standard 
deviations and categorical values reported as counts and frequencies and compared 
between study arms using t-tests and chi-squared tests.  Any baseline imbalances (p<0.05) 
will be will be explored as a possible factor to adjust for when the outcome measures are 

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analyzed.  We will adhere to the CONSORT guidelines to transparently report study results 
and ensure that sufficient information is included to allow for assessment of the study’s 
internal and external validity.  
 
We will use standard techniques appropriate for trials, with each outcome compared 
between study arms using t-tests for continuous outcomes and chi-square tests for 
dichotomous outcomes.  If there are differences in baseline characteristics found by 
statistical means or found to have clinical relevance between the two study groups, these 
will be accounted for using regression models which include an indicator for study arm.   
 
We will perform descriptive analyses to describe any potential heterogeneity of 
treatment effect (HTE) and facilitate synthesis of subgroup results in future meta-
analyses. We will conduct descriptive HTE analyses by clinic (academic, community 
and safety net), by cohort (start or review cohort), by stroke risk (CHA2DS2-VASc 
score of 1 or ≥ 2 for men and 2 or ≥ 3 for women), and by numeracy (Less than 
adequate vs. not). The outcomes assessed with HTE analyses will be the same as 
those assessed in the trial (e.g., SDM and communication quality, knowledge, and 
decisional satisfaction). 
 
For the main analyses (SDM Quality and SDM Processes), we will not assume that 
patient effectiveness outcomes are independent of the clinician, but rather test to see if 
patients seen by the same clinician have correlated outcomes. Ignoring such 
“clustering” effects would result in over-narrow confidence intervals and potentially 
false positive study results. Instead, if clustering is seen, determined by calculating 
the intra-class correlation (ICC > 0.05) for each outcome, then the value for the 
ICC will be reported in findings.  We will use cluster (cluster at clinician level) 
adjusted t-test and chi-square test for comparisons between arms and hierarchical 
generalized linear models (HGLMs) with random main effects specified at the 
clinician level when adjusting by more than arm.
55 If clustering is not present then the 
results will reduce to a model that assumes independence and reflect findings 
appropriately.   

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Some data analysis will be conducted at the Leiden University Medical Center (the Netherlands), 
by using remote access connection to the Mayo server and during the appointment time on Mayo 
Clinic campus. All data will be stored securely on a password-protected computer. Password-
protected USB drives may also be used to store electronic files in situations where connection to 
the Mayo server is limited or unavailable. These USB drives are encrypted and will be used in 
accordance with Mayo Clinic’s Portable Computing and Telecommunication Devices Policy. 
These USB drives may be shared externally to the Leiden University Medical Center (the 
Netherlands). 
 
4.9.1.1 Missing Data 
 
We will make every effort to minimize missing data.  Trial enrollment and the fidelity of 
follow-up procedures will be reviewed during bi-weekly conference calls.  A study 
biostatistician will conduct frequency reports to assess for missing data, and the study team, 
which is experienced in conducting multicenter trials, will trouble shoot any problems 
encountered.  We will report rates of missing data for each outcome by study arm and send 
missing data reports to sites.   
 
4.9.2 Sample Size Estimation 
 
 
The table shows the detectable effect for each of the outcomes of interest if we were to 
have data on that outcome from a total of 333 patients (1% of available population). 
This provides enough power (α=0.05; two-sided difference) to detect meaningful 
differences across arms for all SDM quality and process outcomes. Our intent, 
however, is to have enough power to detect important differences when we conduct 
analyses of groups or cohorts of patients. Most of these analyses will divide the 
participants into 2 cohorts (e.g., start and review cohorts), except for the subgroup 
analysis by clinic, which divides the total sample into 3 cohorts: academic, community, 
and safety net clinic. That is the only analysis with three groups. Given this, we 
would need 3 times the sample size listed in the table, or 999 participants (3% of 
available sample) to address all planned subgroup analyses. These are minimum 
targets for recruitment and we do not plan to limit recruitment in any way to enroll up 

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to this number of patients. It assumes even distribution of participants per subgroup 
(e.g., start vs. review cohort); since the only grouping with three levels is clinic, each 
clinic will be expected to recruit similar numbers. Thus, for the main analysis and for 
other subgroup analyses (n=2 levels), 
 
Outcome (n = 333) 
Rate 
(%) or 
SD 
Detectable 
effect 
Power* 
Patient level – SDM quality 
Knowledge  transfer^ 
18 
5.6 
84% 
Knowledge of risk 
55% 
15% 
81% 
Decisional conflict scale^ 
17 
5.2 
80% 
Clinician level 
 
 
Satisfaction^ 
54% 
15% 
80% 
Encounter level – SDM process 
 
 
Engagement  (OPTION12)^ 
12.6 
3.9 
80% 
                     ^ Values from iADAPT SDM tool trial; * α=0.05; two-sided 
 
We expect approximately 90% of patients to start (start cohort) or continue a medication 
(review cohort). Of those, we can reasonably expect to obtain >85% of the 
pharmaceutical records for those (records will be requested of all enrolled patients 
regardless of decision). Thus, using the trial size estimated of 999 participants, we will 
have ~765 patient records available for assessment of anticoagulant persistence at 12 
months (PDC). In our review of the Optum database, 40% of patients were adherent to 
anticoagulation (>80% PDC, the threshold used by CMS) at 12 months. Assuming an 
expected rate of 60% PDC for the usual care cohort, we would have 80% power to 
detect a 9% difference (69% PDC in the SDM tool arm), with a two-sided test and an 
alpha of 0.05. In subgroup analyses comprising 100 participants per arm and using a 
one-sided test and alpha of 0.05, we will have 80% power to detect differences of at 
least 16%. 
 
4.9.3  Patient Allocation 
 

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Eligible patients will be allocated into either the usual care arm or to the usual care + 
ANTICOAGULATION CHOICE SDM tool (intervention) arm using a random sequence 
the trial statistician will generate a priori. The allocation will be stratified by clinic 
(academic, community or safety net), by cohort (start or review), and stroke risk 
(CHA2DS2-VASc score of 1 or ≥ 2 for men and 2 or ≥ 3 for women) using blocks of 
random size.   
 
5.0  Conflict of Interest 
 
The tool under evaluation is not part of any existing effort to commercialize or profit from 
its use; the researchers involved in this study have not received -- and will not receive with 
their application in this study -- any royalties or other monetary benefits, directly or 
indirectly, from the use of the decision aids or from the makers of the interventions being 
discussed in this tool. 
 
6.0   Human Subjects 
 
6.1   Data safety monitoring board 
 
A Data Safety and Monitoring Plan (DSMP) and charter has been formed to 
monitor participant safety, data completeness and adherence to study protocol.  In 
addition, the principal investigator, each of the site investigators and champions, 
study statisticians, and project coordinator will meet monthly to assess 
recruitment (overall and by site), baseline comparability of treatment groups, 
protocol adherence, completeness of data collection, safety, and fidelity of follow-
up procedures. They will meet monthly or as needed to review safety. Any 
potential adverse events will be entered into the study database and the 
Institutional Review Board will be notified. A Data Safety Monitoring Board 
(DSMB) has been formed and will meet bi-annually or as needed 
starting just prior to study enrollment. 
 

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6.2  Population 
 
This study will be available to all eligible patients, regardless of race, gender, or ethnic 
origin.  There is no information currently available regarding differential outcomes of the 
decision aid in subsets defined by race, gender, or ethnicity, and there is no reason to 
expect such differences to exist.  
 
6.3  Potential Risks 
 
Potential risks to patient subjects should be minimal.  Given that the intervention has been 
extensively pilot tested and no adverse outcomes occurred, we do not expect early 
termination due to harm.  The intervention is an educational tool for use during the clinic 
visit to help patients make decisions about anticoagulation medications.  The tool does not 
make recommendations or result in prescriptions without the participation of the clinician, 
and the tool is not to be used outside a clinical visit in which a clinician can place the 
information in context. 
 
6.4  Protection and Confidentiality 
 
6.4.1 Subject privacy 
 
In this study, the privacy of all study participants will be protected by avoiding the use of 
names on all research data (including field notes, transcribed conference call, meeting 
tapes, audio-and video-recordings of the interviews, transcripts). All study participants will 
be identified by a unique study code number only. The link between the code number and 
study participant’s identity will be stored within the remote data capture system.  Medical 
records will be abstracted electronically using computers that are not linked to any Mayo 
mainframe computer.  Names of those who decline participation in the study will be 
maintained in a do-not-contact list, so they will not be contacted multiple times (as patients 
are likely to have multiple appointments at participating clinics during the study).  All 
research material outside of what is stored within the remote data capture system will be 
maintained on a secure server at the KER Unit at Mayo Clinic and locked in file cabinets.   

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6.4.2 Data management 
 
All sites will be required to use the current version of all documents and forms and adhere 
to the study schedule.  Forms and documents will be returned to study coordinators via 
upload to the remote data entry system (REDCap44), Fedex or data transfer between sites.  
Data entry specialists will enter survey and medical record data into the REDCap system 
which is hosted by Mayo Clinic, which is a HIPAA compliant secure data entry system that 
allows for validated data entry, edit checks and logs of all data changes.   The data can be 
accessed by the statistical team at any time and downloaded into a statistical software 
package.  The statistical team will review the data on a bi-weekly basis to ensure data 
accuracy and completeness.  All data, documents, and analysis findings will be housed 
within the Mayo Clinic system that is password protected and backed up on a nightly basis. 
The data will be stored within the secure system following completion of the study. 
 
6.4.3 Video and audio-recordings 
 
Health visits will be recorded (video/audio or audio only) with permission of all 
participants. These recordings are conducted using a portable digital video camera that is 
placed aimed at the clinician’s desk, away from the physical examination table. The 
clinician and the patient will be instructed on how to occlude the lens, direct the camera to 
a wall, or turn off the camera at any time they feel this is appropriate.  Digital recordings 
are immediately transferred and/or uploaded to the research team’s secure server and 
deleted from portable devices after overnight back-up of Mayo’s servers.  The video and 
audio files are identified using a code number that does not include the name of the 
clinician, support staff, or patient or reference to their medical record number or date of 
birth. All recordings will be transcribed verbatim by an IRB approved transcription service 
and/or transcribe some of the video/audio recordings using Mozilla’s DeepSpeech. 
Mozilla’s DeepSpeech is offline/on-device and would stay within Mayo's firewall. 
 
6.4.4 Registry 
 

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Collected study data (including audio and video recordings) will be kept in a registry to 
conduct further analyses, future un-identified and IRB approved research, trainings, quality 
improvement and educational purposes, which includes sending data (and recordings) to 
research collaborators. The research collaborators will have research appointments with 
Mayo Clinic and will only assist in analyzing data; they will not have contact with study 
participants. 
 
6.4.5 IRB Umbrella 
 
When the study is being kept open for secondary analysis and registry purposes only, this 
IRB application may merge to an umbrella IRB application. 
 
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