Preparation for Lung Transplant Discussions and Decisions Among People With Cystic Fibrosis
Phase: NA
Conditions: Cystic Fibrosis
Sponsor: University of Washington

 
 
 
Page 1 of 55 
 
 
 
Sponsor Protocol  
Title:      
Preparation for lung transplant discussions and 
decisions among people with cystic fibrosis (1 
R01 NR 020470-01A1) 
 
Alternate Title:  
Lung Transplant Resources for Education And 
Decision-making for Your CF 2 Study: A Multi-
Site Randomized Controlled Clinical Trial 
 
Alternate Short Title: 
LTx READY CF 2: A Multi-Site RCT 
Date: 
6/9/2023 
Protocol Version: 
2.0 
Principal Investigator: 
Kathleen Ramos-Alexander, MD MSc 
                
Associate Professor 
 
University of Washington Medical Center 
 
1959 NE Pacific St. Box #356522 
 
Seattle, WA 98195-6522 
 
206-543-0393 
 
 
 
 
 
 
 
 
 

 
 
 
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Table of Contents 
ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................................................ 4 
A 
BACKGROUND ......................................................................................................................... 7 
A1 
PRIOR LITERATURE AND PREVIOUS STUDIES ................................................................................. 9 
B 
APPROACH ..............................................................................................................................11 
B1 
AIM 1 & SUB-AIM 1A [CF PATIENTS] ..........................................................................................11 
1.a 
Rationale......................................................................................................................................11 
B2 
AIM 2 [CF PHYSICIANS/APPS] .....................................................................................................12 
2.a 
Rationale......................................................................................................................................12 
C 
STUDY DESIGN .......................................................................................................................12 
C1 
STUDY DESIGN .............................................................................................................................12 
C2 
SUBJECT SELECTION .....................................................................................................................14 
2.a 
Aim 1 & Sub-Aim 1A [CF Patients] ............................................................................................14 
i 
Subject Population ...................................................................................................................14 
ii 
Eligibility Criteria .......................................................................................................................14 
iii 
Third-Party Subjects .................................................................................................................15 
2.b 
Aim 2 [CF Physicians/APPs] ......................................................................................................15 
i 
Subject Population ...................................................................................................................15 
ii 
Eligibility Criteria .......................................................................................................................15 
C3 
COMPENSATION ............................................................................................................................15 
C4 
DATA SOURCES & VARIABLES .....................................................................................................16 
C5 
RISKS AND BENEFITS ....................................................................................................................17 
5.a 
Potential Risks .............................................................................................................................17 
5.b 
Potential Benefits to the Subjects ................................................................................................19 
5.c 
Protections Against Risk ..............................................................................................................19 
D 
STUDY PROCEDURES ...........................................................................................................21 
D1 
SCREENING FOR ELIGIBILITY ........................................................................................................21 
D2 
RECRUITMENT METHODS .............................................................................................................21 
D3 
INFORMED CONSENT.....................................................................................................................23 
D4 
DESCRIPTION OF STUDY PROCEDURES ..........................................................................................23 
4.a 
Schedule: Aim 1 & Sub-Aim 1A [CF Patients] ............................................................................26 
i 
Baseline Session (V1) ..............................................................................................................26 
ii 
2-Week Session (V2) ...............................................................................................................27 
iii 
2-3 Months after Baseline ........................................................................................................27 
iv 
3-Month Session (V3) ..............................................................................................................27 
v 
6-Month Session (V4) ..............................................................................................................27 
D5 
DATA COLLECTION PROCEDURES .................................................................................................27 
E 
DATA SAFETY MONITORING PLAN .................................................................................27 
E1 
MONITORING ENTITY: DATA SAFETY MONITORING BOARD.........................................................29 
E2 
MONITORING FOR COMPLIANCE ...................................................................................................31 
E3 
DATA MANAGEMENT PRACTICES AND QUALITY CONTROL ..........................................................34 
E4 
IDENTIFYING, MANAGING, AND REPORTING ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ..36 
E5 
MONITORING OF MULTI-SITE STUDY .............................................................................................40 
E6 
ASSESSMENT OF EXTERNAL FACTORS IMPACTING PARTICIPANT SAFETY ......................................41 
E7 
INTERIM ANALYSIS .......................................................................................................................41 
E8 
COMMUNICATION PLAN ................................................................................................................42 
F 
STATISTICAL PLAN ..............................................................................................................45 
F1 
SAMPLE SIZE DETERMINATION AND POWER .................................................................................45 

 
 
 
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F2 
ANALYSIS PLAN............................................................................................................................46 
G 
DATA HANDLING AND RECORD KEEPING ....................................................................48 
G1 
CONFIDENTIALITY AND SECURITY ................................................................................................48 
G2 
DATA SHARING AND POSSIBLE SECONDARY USE .........................................................................48 
H 
STUDY ADMINISTRATION ..................................................................................................48 
H1 
ORGANIZATION AND PARTICIPATING CENTERS ............................................................................48 
H2 
STUDY TIMETABLE .......................................................................................................................50 
I 
DISSEMINATION & PUBLICATION ...................................................................................51 
I1 
PLANS FOR PUBLICATIONS ............................................................................................................51 
I2 
DISSEMINATION PLAN ..................................................................................................................51 
J 
REFERENCES ..........................................................................................................................51 
 
 
 
 

 
 
 
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Abbreviations and Definitions of Terms 
AE 
Adverse event 
AESI 
Adverse event of special interest 
APPs 
Advanced Practice Providers 
BMI 
Body mass index 
CF 
Cystic Fibrosis 
CFF 
Cystic Fibrosis Foundation 
CFFPR 
Cystic Fibrosis Foundation Patient Registry 
CFTR 
Cystic fibrosis transmembrane conductance regulator 
CIRG 
Clinical Informatics Research Group 
CTCAE 
National Cancer Institute’s Common Terminology Criteria for Adverse 
Events 
DSMB 
Data safety monitoring board 
DSMP 
Data safety monitoring plan 
eCRF 
Electronic case report form 
EHR 
Electronic health record 
ETI 
Elexacaftor/Tezacaftor/Ivacaftor 
FEV1 
Forced expiratory volume in 1 second 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
IPDAS 
International Patient Decision Aid Standards  
LTx 
Lung transplant 
MM 
Medical monitor 
PI 
Principal Investigator 
PrepDM 
Preparation for Decision Making Scale 
SAE 
Serious Adverse Event 
SD 
Standard deviation 
SES 
Socioeconomic status 
ToT 
Take on Transplant 
UNOS 
United Network for Organ Sharing 
UW 
University of Washington 
 
 
 

 
 
 
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Statement of Compliance 
 
The trial will be conducted in accordance with International Council on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal 
Regulations (CFR), and the National Institute of Nursing Research (NINR) Terms and 
Conditions of Award. The Principal Investigator will assure that no deviation from, or 
changes to the protocol will take place without prior agreement from the funding agency 
and documented approval from the Institutional Review Board (IRB), except where 
necessary to eliminate an immediate hazard(s) to the trial participants. All personnel 
involved in the conduct of this study have completed Human Subjects Protection and 
ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant 
materials will be submitted to the IRB for review and approval. Approval of both the 
protocol and the consent form(s) must be obtained before any participant is consented. 
Any amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study. All changes to the consent form(s) will be IRB 
approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent 
form. 
 

 
 
 
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Investigator’s Signature 
 
The signature below constitutes the approval of this protocol and provides the necessary 
assurances that this study will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines, as 
described in the ‘Statement of Compliance’ above. 
 
Principal Investigator: 
 
Signed: ___________________________________ 
 
Date:   
 
 
 
Name: Kathleen Ramos-Alexander, MD MSc 
 
Title: Associate Professor 
 
Investigator Contact Information 
 
Affiliation: University of Washington 
 
Address: 1959 NE Pacific Street, Seattle, WA 98195-6522 
 
Telephone: 206-543-0393 
 
Email: ramoskj@uw.edu 
 
 
Clinical Site Investigator: 
 
Signed: ___________________________________ 
 
Date:   
 
 
 
Name: 
 
Title: 
Affiliation:

 
 
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A Background 
Cystic fibrosis (CF) is a genetic disease that leads to premature death, typically due to 
progressive respiratory failure (median age at death was 34 years in 2020).[1] Median predicted 
survival age is 65.6 years for people born in 2021, due in large part to the introduction of a new 
highly-effective CF therapeutic, elexacaftor/tezacaftor/ivacaftor (ETI), introduced in 2019.[1] The 
CF Foundation (CFF) lung transplant (LTx) referral guidelines recommend annual discussion of 
LTx for CF patients once their lung function falls to forced expiratory volume in one second 
(FEV1) <50% of predicted[2], but there is no guidance for approaching the topic of LTx when it 
may be a decade or more away. Further, CF physicians may lack transplant-specific 
knowledge[3] or may feel ambivalent about discussing LTx given the beneficial impact of ETI. 
CF patients with low FEV1 have high rates of anxiety and depression[4, 5]; anxiety may 
contribute to patients’ avoidance of conversations about LTx. Mental health concerns are likely 
multifactorial, related to worsening medical acuity, adjustment-related concerns, including new 
social dynamics of needing assistance/caregivers, and a loss of control over the trajectory of 
their lung disease.[6] Patients with CF may also experience shame or stigma from the perceived 
association between progression of lung disease necessitating LTx and medical non-
adherence[6]; these feelings may exacerbate avoidant behavioral tendencies, impeding LTx 
discussions and adversely impacting relationships with physicians and caregivers. CF 
physicians may avoid early LTx discussions because of the topic’s emotional nature. Based on 
decreased access to transplant for people with low socioeconomic status (SES), non-White race 
or Hispanic ethnicity, implicit bias may hinder LTx discussions in some cases. Importantly, 
approximately 10% of patients with advanced CF die without LTx each year, while only 6-8% 
undergo LTx.[7] Deliberation is an iterative process in which patients explore what matters most 
to them, often requiring collaboration over time with health professionals and patients’ social 
networks.[8] The decision to undergo LTx is complex and fraught with uncertainty about timing, 
which is worse in the setting of unclear benefits of LTx given the difficulty of predicting survival 
and quality of life without LTx in the setting of ETI. Prognostic uncertainty in advanced CF on 
ETI promotes decisional conflict and psychological discomfort[9], which may delay decision 
making about LTx, leading to missed opportunities for LTx.[7, 10] Data suggest LTx and death 
without LTx will occur despite ETI at half the rate of untreated individuals.[11, 12] Decreased 
rates of LTx may lead physicians to feel less equipped to provide LTx education and guidance. 
 
Medicaid health insurance is used as a proxy for low SES; CF patients with lower SES have 
decreased referral for LTx and are less likely to undergo LTx after listing.[13, 14] CF patients in 
the US with public health insurance (Medicaid or Medicare) have worse survival compared to 
those on private health insurance in the US or to CF patients in other countries.[15, 16] While 
health insurance is frequently used as an SES proxy, a more nuanced set of SES markers, 
including insurance, race, education, and geography, showed a similar association of lower SES 
with decreased access to LTx.[17] Hispanic CF patients have a nearly 3-fold increased risk of 
death without LTx compared to non-Hispanics, adjusted for disease severity and health 
insurance.[18] Non-White race is associated with worsened survival in CF, regardless of 
country.[15, 16] The impact of lower SES, race, and ethnicity on lung transplant-related health 
disparities may be related to limited health literacy, among other factors.[19, 20] Limited health 
literacy is associated with decreased access to kidney transplant for people with chronic kidney 
disease.[21] For individuals who speak English as a second language, effects of lower health 
literacy on health outcomes may be amplified.[22] A systematic review and meta-analysis of 
shared decision making interventions found interventions targeting the needs of disadvantaged 

 
 
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groups were most effective and may benefit groups with lower health literacy more than those 
with higher SES and health literacy.[23] 
 
Two decision aids exist for LTx in CF: the first, developed in Canada and Australia in 2006, 
reduced decisional conflict in an RCT and is publicly available but is no longer accurate[24]; the 
second, developed from interviews and focus groups with 24 CF patients hospitalized in the 
intensive care unit (2015-2016), addresses decisions around mechanical ventilation and LTx for 
end-stage CF[25]. This second decision aid targets a limited group of patients, is not publicly 
available and was not evaluated in an RCT.[25, 26] Our published findings[27] show CF patients 
favor learning about LTx in advance of when referral is medically necessary, and prefer to avoid 
LTx discussions during a crisis, consistent with the deliberation process[8]. For this reason, we 
developed Take on Transplant (ToT). ToT incorporates guidelines-based medical information 
(Resource Library), CF patient and caregiver experiences (CF Stories), and answers to 
common questions from the LTx journey (Frequently Asked Questions).[28] ToT tailors content 
recommendations based on the patient’s disease severity (My CF Stage). Importantly, ToT was 
developed in partnership with CF patients of varied backgrounds, including those with non-
White race and lower SES; diverse patients contributed personal narratives as “CF Stories” that 
serve as clinical vignettes (40% with Medicaid insurance). 
 
For people with CF, premature death 
is a reality. Having LTx discussions 
with the CF care team is an important 
health behavior that can identify 
treatment options that contribute to 
avoiding premature death. We 
approached this work using the Health 
Beliefs Model theoretical framework 
(Table 1). Given the difficulty of 
determining optimal timing of LTx 
referral in the ETI era, and that patient 
preference often contributes to 
delayed referral[3, 10], arming CF 
patients with the information needed 
to help them to understand their 
susceptibility (likely need for LTx) and 
severity of end-stage CF, while 
helping to clarify perceived benefits 
and reduce perceived barriers to LTx 
discussion, is critical to prepare them 
for high-quality LTx discussions and help them make informed decisions. Moreover, ToT 
provides cues to action in the form of prompts to log in to the ToT website and to initiate a LTx 
discussion at their next clinic visit. Finally, the ToT components are designed to support self-
efficacy by empowering patients to engage in proactive LTx discussions, as measured with the 
Preparation for Decision Making (PrepDM) Scale[29]. A patient’s perceived self-efficacy 
correlates strongly with approach-oriented coping styles and mood function. It is key to measure 
the impact of ToT on mental health outcomes because patients and physicians may avoid LTx 
discussions due to the emotional nature of the conversation. ToT has the potential to help CF 
patients live long and fulfilling lives, and avoid premature death, by increasing understanding of 
Table 1: The Health Beliefs Model (HBM) addresses 
whether, how, and why CF patients engage in LTx 
discussions and frames how ToT can impact discussions.  
HBM Theoretical Constructs and RCT Measures 
• 
Perceived susceptibility: patient perception of 
vulnerability to future end-stage CF and need for 
LTx  
• 
Perceived severity: patient perception of 
symptom burden and potential consequences of 
end-stage CF 
• 
Perceived benefits: patient perception of potential 
for LTx discussions to increase access to LTx  
• 
Perceived barriers: costs of LTx discussion (e.g. 
negative emotions, social impact, facing implicit 
bias) 
• 
Cues to action: exposure to factors prompting 
LTx discussion and decision-making processes  
• 
Self-efficacy: confidence in the ability, or feeling 
empowered, to have LTx discussion 

 
 
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LTx as a treatment option.[28]  
A1 Prior Literature and Previous Studies 
Initial Survey Assessment of Transplant Education Needs: 
An online survey of individuals who were followed in the University of Washington (UW) Adult 
CF Center, distributed March-May 2020, had 159 responses (71% response rate): 87 (55%) 
male respondents; 44 (28%) Medicaid/Medicare health insurance; average FEV1 68% predicted 
(SD 23%, range 24-112%). One hundred twenty-seven (80%) of the respondents reported using 
ETI. Most respondents (n=108, 68%) reported that highly effective CF medications are 
moderately likely or very likely to impact their need to ever have LTx. Only 56 (35%) 
respondents endorsed feeling moderately or very prepared to make decisions about LTx, while 
113 (71%) reported that it is moderately or very important to feel prepared. The survey revealed 
knowledge gaps related to 1) low or high body mass index (BMI) as a potential barrier to LTx, 2) 
FEV1 as an important component of the decision to refer for LTx, 3) survival benefit of LTx, and 
4) improvements in health-related quality of life. More than 75% of respondents reported that a 
LTx decision support tool would be moderately or very useful and >75% would be moderately or 
very willing to use it once their FEV1 is <50% of predicted. Despite high rates of ETI use, 
individuals with CF are interested in a LTx decision support tool. 
 
Development of Take on Transplant: 
Human-centered design is an iterative process comprised of four distinct phases to: 1) 
understand user needs and context, 2) specify user requirements, 3) generate design solutions, 
and 4) evaluate design against requirements. We recently published our process of 
development of ToT.[28] In Phase 1, we used interviews and surveys of CF patients (pre- and 
post-transplant) and surveys of CF physicians to understand user needs. In Phase 2, we 
analyzed these data to identify qualitative themes that specified key functionality that the web 
application must support (i.e., requirements) – including topics identified as important content for 
LTx education by patients. Pretransplant interviews highlighted the need to personalize the 
concept of LTx as a treatment option, the belief that one’s CF physician should offer access to 
information about the process, and certain topics that could improve preparedness to discuss 
transplant with one’s physician. Post-transplant CF patients reported connections with previous 
LTx recipients as a major component of preparing for LTx. CF LTx recipients identified their CF 
doctors, LTx team (doctors, social worker), and the Internet (e.g. unos.org) as sources for LTx 
information. In Phase 3 of the human-centered design approach, we produced possible design 
solutions as prototypes (example web interfaces), which we co-designed with CF patient focus 
groups. Each group included 4-7 individuals who met 6 times via teleconference. We iteratively 
refined the prototype, incorporating patient input on content and features. Next, we developed 
an interactive prototype. In Phase 4, evaluations focused on usability testing of the interactive 
prototype. In collaboration with the Clinical Informatics Research Group (CIRG), we developed a 
web-based implementation of the ToT intervention. 
 
Feasibility Testing of Take on Transplant: 
As a key step in creating ToT, we assessed the feasibility of the CF Stories embedded in ToT, 
which include narratives for individuals with a range of outcomes after LTx, consistent with 
International Patient Decision Aid Standards (IPDAS)[30, 31]. We enrolled 25 CF patients, from 
Dec 2020-Mar 2021, in a single-arm study with pre-/post-intervention design (no control arm). 
We utilized the CFF Community Voice (an organization of people with CF engaged in research 

 
 
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and advocacy) for participant recruitment to avoid depleting the available population of CF 
patients with low FEV1 at the study sites for the proposed RCT. We assessed the effect of a 90-
minute Zoom-based intervention using only the CF Stories portion of the ToT prototype web 
application. We approached 31 potential participants, 3 of whom did not respond and 3 declined 
to participate. Therefore, 25/31 (81%) participated in the feasibility testing. Participants had an 
average FEV1 47% predicted (SD 15%, range 29-89%). 
 
Participants read an average of 3.2 (SD 0.9) CF Stories during the 90-minute intervention. 
Feasibility testing showed improvements in multiple domains. Participants’ Decisional Conflict 
Scale[32] decreased from a mean of 37.9 before vs 28.6 after, p=0.015 (lower is better), with an 
effect size of 0.52. Likert scale ratings of preparedness to discuss LTx improved ≥1 point for 
74% of potential responders; 6 people were “very prepared” before vs. 13 people “very 
prepared” after intervention. Knowledge about LTx also improved (for example, % correct 
increased from 68% to 96% for survival benefit of LTx) after the 90-minute Zoom intervention. 
Qualitative data from interviews revealed high levels of satisfaction with ‘CF Stories.’ 
Participants voiced interest in didactic medical information to complement experiential learning 
from ‘CF Stories’. 
 
Pilot Randomized Controlled Trial (RCT) of Take on Transplant vs. Attention Control (unos.org): 
In December 2021, we began a recently completed pilot RCT of ToT compared to the United 
Network for Organ Sharing (UNOS) website (an attention control website that provides more 
general LTx information), clinicaltrials.gov identifier NCT05135156. We included CF patients 
who were referred from 15 CF Centers that advertised a screening survey collecting limited 
protected health information in accordance with UW IRB approval (target enrollment n=50). 
Referring centers pre-screened local CF registry data to identify eligible individuals with an FEV1 
<50% predicted and prioritized individuals from communities of concern (Medicaid insurance, 
non-White race, Hispanic ethnicity, or high school education or less). No clinical data was 
available from CF Centers or medical records for pilot RCT participants. Pilot RCT participants 
underwent 1:1 randomization stratified by patient-reported FEV1 (<30% or 30-50% predicted) to 
either ToT or UNOS for 2 weeks, followed by 2 weeks of access to both websites. All 
participants in both arms of the pilot RCT received reminders to log in to the research website 
via email and/or text regardless of usage patterns. The Preparation for Decision Making 
(PrepDM) Scale[29] was administered at 2- and 4-weeks after randomization. Co-primary 
outcomes were feasibility of completion of the 2-week assessment and difference in 2-week 
PrepDM[29] in ToT vs UNOS arms. The pilot RCT was not powered to detect a difference in 
PrepDM between the two arms. Preliminary efficacy was planned for assessment via PrepDM.  
 
Of 50 eligible patients surveyed who opted-in to being contacted for additional research 
opportunities on the screening survey, 37 (74%) agreed and enrolled in the pilot RCT. Fifteen 
patients were recruited from the University of Washington. Of the 52 enrolled, 2 participants 
were lost to follow up prior to starting the intervention (before the baseline study visit), but the 
remaining 50 people completed all study visits, yielding 4% attrition. Three (6%) participants 
were provided a hotspot for reliable Internet access (Franklin 4G LTE Mobile Hotspot from 
Straight Talk with 2GB/month data plan); no one requested a tablet or device. Of the 52 enrolled 
participants, median age was 38.9 years (SD 10.8) and 25 (48%) were women. Thirty-three 
participants (63%) are members of communities of concern, with 16 (31%) using Medicaid 
insurance, 3 (6%) are non-White, 3 (6%) with Hispanic ethnicity, and 11 (21%) with high school 
education or less. Low literacy was possibly (15%) or highly likely (5%) to be present for 20% of 

 
 
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participants, based on the Newest Vital Sign[33]. Preliminary usage data notes average time 
spent on the research website was 3.0 hours (SD 1.7 h) in the first 2 weeks and 2.0 h (SD 1.8 h) 
in the second 2 weeks (data pooled across both arms). The PrepDM Scale is a validated 
measure of preparedness for decision making with known variance and high internal 
consistency (α 0.92-0.96)[29], but it has not been studied in the CF population. At 2 weeks, the 
ToT arm had higher PrepDM scores (71, 95% CI 64-77 vs 57, 95% CI 47-66), with a between-
arm difference of 14 points, p=0.02. Participants in the pilot RCT reported that 2 hours was a 
reasonable minimum recommendation for research website use and 2 weeks was sufficient to 
explore content. During qualitative interviews, no one in the pilot RCT reported finding the 
content on either website to be emotionally distressing.  
 
In summary, we performed extensive multi-methods research and utilized human-centered 
design to create and demonstrate the usability, feasibility, and preliminary efficacy of ToT. We 
incorporated stakeholders from the CF Community in the design, development, and evaluation 
of ToT. This web-based resource is accurate, up-to-date, and informed by recent CFF guideline 
recommendations.[2, 34] CF patients have preparedness and knowledge gaps when 
considering LTx as a treatment. Evaluation of ToT is imperative to determine if it improves 
patients’ preparedness for discussions about LTx, a treatment option underutilized by CF 
patients[7, 15], particularly among those from communities of concern[13, 14, 17]. Studying ToT 
use will provide insights about potential emotional or psychological benefits or harms of early 
LTx education in the setting of prognostic uncertainty due to ETI. Prior to implementation and 
widespread use of ToT, these factors must be assessed. 
B Approach 
The primary study objective is to determine whether “Take on Transplant” (ToT), a CF-specific 
LTx educational website, improves patient-reported preparedness for LTx discussions, as 
measured by the Preparation for Decision Making (PrepDM) Scale at 3 months after 
randomization, compared to an attention control transplant website (unos.org, UNOS).  
B1 Aim 1 & Sub-Aim 1A [CF Patients] 
Aim 1 – Test whether ToT improves patient preparedness for discussions about LTx compared 
to an attention control, assessed with the PrepDM Scale, using a multicenter single-blind RCT. 
Hypothesis: ToT will increase preparedness for LTx discussions relative to unos.org, an 
attention control, as indicated by higher PrepDM Scale[29] ratings; effect sizes may be 
different in communities of concern. 
Sub-Aim 1A – Explore the effect of the ToT intervention on psychosocial functioning. 
Hypothesis: Serial measures of anxiety (GAD-7[35]), depression (PHQ-9[36]) and self-
efficacy (General Self-Efficacy Scale[37]) will elucidate the beneficial or harmful 
psychological impacts of ToT or attention control. 
1.a 
Rationale  
Many patients with advanced CF will require LTx despite ETI and some will die without LTx; 
patients in communities of concern more often die without LTx than undergo the 
operation.[15, 16, 18] UNOS was selected as an attention control because it provides 
general transplant education, is publicly available, and is often recommended to patients 
seeking LTx information. ToT coaches CF patients for LTx discussions by exposing them to 

 
 
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CF-specific LTx education. Preparing patients for high-quality discussions could improve 
clinical outcomes for people with advanced CF by increasing engagement with the CF team 
and changing attitudes and choices related to LTx. ToT does not involve physician training, 
but this initial study could uncover a need to develop a physician component. The RCT 
incorporates a CF clinic visit to assess the physician’s role.(Sub-Aim 1A) Behavioral and 
educational studies often assume that there will be positive psychological benefit. While 
this study may reduce anxiety by improving knowledge about LTx, nurturing the emotional 
capacity to consider LTx, and helping the sense of being more prepared for the future (i.e., 
reduce anxiety and/or depression), it is possible that ToT or the control condition (UNOS) 
may increase psychological distress (temporarily or longer-term) by increasing focus on 
one’s own mortality or declining health. For this reason, we will assess anxiety (GAD-7[35]) 
and depressive symptoms (PHQ-9[36]) at each study visit (V1-V4). 
B2 Aim 2 [CF Physicians/APPs] 
Aim 2 – Assess perceptions of LTx education and observe LTx discussions through analysis of 
semi-structured interviews, website usage, and audio recordings of clinic visits in patient-
physician dyads. 
Anticipated findings: Content analysis of transcripts from clinic visits, patient interviews, 
and evaluation of website usage, will highlight deliberation, LTx education, and 
prognostic uncertainty. 
2.a 
Rationale 
These data are critical to determine whether CF patients armed with LTx education raise 
the topic of LTx in their CF clinic visits, which questions they ask, and whether physicians 
or advanced practice providers (APPs) respond in a way that facilitates building trust and 
preparedness for LTx. If the RCT has a null result, these data may help to explain why. The 
lack of data regarding the timing of disease progression for advanced CF in the ETI era 
may result in physician ambivalence about discussing LTx. Physicians’ implicit bias may 
prevent them from raising the topic of LTx in some cases. Patients’ mental health or coping 
mechanisms may prevent conversations about LTx. The longstanding relationship between 
the patient and physician may facilitate exploration of difficult topics. Understanding barriers 
to LTx discussions and identifying markers of high-quality LTx discussions could improve 
our approach to this important treatment option during shared decision making.  
C Study Design  
C1 Study Design 
This is a prospective, multicenter, randomized, controlled, single-blind, roll over study to 
investigate the effect of ToT, a CF-specific LTx educational website, versus an attention control 
website (unos.org, UNOS) on preparedness for LTx discussions among individuals with CF. 
(Figure 1) 
 

 
 
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CF patient participants in Aim 1 and Sub-Aim 1A will have 3 months of access to one of two 
websites (ToT or UNOS). CF patients from participating sites will be randomized 1:1 to ToT or 
UNOS. We will use REDCap to configure the randomization allocation constructed by the study 
statistician using a permuted block scheme with varying block sizes, stratified by CF Center, 
FEV1% predicted (≥ or <30%) and member of communities of concern (yes/no). The 4 small 
centers (n=5 each) plus the medium center (n=10) will be pooled into one (n=30) for the 
purposes of randomization allocation to allow for varying block sizes within CF Center strata. 
Each study arm will have 66 participants.  
 
Surveys will be collected from CF patient participants by study staff at the University of 
Washington during remote study sessions at baseline (V1), 2-weeks (V2), 3-months (V3), and 
6-months (V4) to assess ToT efficacy and psychological endpoints. Between 2 and 3 months 
after randomization, a routine CF clinic visit will occur for all participants, separately from study 
visit V3. Participants and their CF physician or APP will complete online surveys after the clinic 
visit. After study visit V3, all participants will gain access to both ToT and UNOS for an 
additional 3 months (6 months total time in the study). Participants will be paired with their CF 
physician in dyads for in-depth qualitative data collection including audio-recording of their CF 
clinic visit. The UW Clinical Informatics Research Group (CIRG) will continuously capture 
identifiable, individual-level research website usage data (ToT and UNOS) for all participants 
throughout the RCT and during long-term follow up. 

 
 
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C2 Subject Selection  
2.a 
Aim 1 & Sub-Aim 1A [CF Patients] 
i 
Subject Population 
Study participants will be volunteer CF patients aged 18 years or older with FEV1 of 
less than 50% predicted and have not yet undergone LTx. In total, approximately 150 
patients who give informed consent, meet eligibility criteria will be enrolled in the study.  
ii 
Eligibility Criteria 
The proposed study does not involve children (by NIH definition of age <18 years). 
Adult patients with CF who are greater than or equal to 18 years of age will be included 
in this study. All patient participants in the proposed research have a diagnosis of CF. 
We will not discriminate based on gender, race, or ethnicity. We will oversample CF 
patients with low socioeconomic status based on Medicaid insurance status. Research 
teams will also prioritize enrollment of CF patients with non-White race, Hispanic 
ethnicity, or high school education or less. English and Spanish-speakers will be 
included in this study. The Take on Transplant (ToT) intervention and all study 
documents will be available in Spanish. Study staff at the University of Washington will 
include a native Spanish-speaker who will be available for consent purposes and 
during all study procedures. 
 
The composition of the cohort (with regard to gender and racial/ethnic groups) is 
largely based on the demographics of the CF patient population nationally. In 2020, the 
racial/ethnic composition in the CF Foundation Patient Registry was 93.4% White, 
4.7% African American, and 3.9% other race; Hispanic ethnicity (any race) makes up 
9.6% of the population.[1] The CF population nationally in 2020 was 48.2% females.[1] 
Our cohort of eligible patients, defined by severely impaired lung function (FEV1 <50% 
predicted), will likely be composed of fewer racial minorities and fewer women, but this 
is not due to discrimination on the part of the investigators, and instead reflects the 
composition of the patient population with reduced lung function nationally[1, 7] and 
locally. We will oversample individuals with Medicaid health insurance, non-White race, 
and Hispanic ethnicity, as above, to increase their representation in the clinical trial. CF 
patients with Medicaid are more often non-White than CF patients with private health 
insurance. We will ensure a balanced recruitment of men and women and plan to 
evaluate usage of the research websites and clinical trial outcomes by gender. 
 
Pregnant women will not be excluded from this study because the study poses low risk 
to participants and the research has the prospect of direct benefit to the pregnant 
woman by giving her access to resources that may increase her preparedness to 
consider LTx as a treatment option in the future. 
 
Eligibility Criteria:  
1. Adult, greater than or equal to 18 years of age 
2. Documentation of a CF diagnosis as evidenced by one or more clinical features 
consistent with the CF phenotype and/or one or more of the following criteria: 
a. Sweat chloride ≥ 60 mEq/liter 

 
 
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b. Two well-characterized mutations in the cystic fibrosis transmembrane 
conductance regulator (CFTR) gene 
3. FEV1 less than 50% of the predicted normal value 
4. Informed consent obtained from subject, able to communicate with the Investigator 
and read (in English or Spanish) and comply with the requirements of the protocol 
5. No prior LTx 
6. No prior participation in pilot RCT testing of the “Take on Transplant” website 
iii 
Third-Party Subjects 
CF patient participants may be asked to provide contact information for third-party 
subjects for the purpose of informing them about additional research opportunities. 
Additionally, any third-party subjects who attend a clinic visit with CF patient 
participants must provide verbal approval to being recorded prior to when any audio 
recording occurs. 
2.b 
Aim 2 [CF Physicians/APPs] 
i 
Subject Population 
CF physicians or advanced practice providers (APPs) at each of the research locations 
assisting with the recruitment of Aim 1 and Sub-Aim 1A participants and/or providing 
medical care during the routine CF Clinic visit at 2-3 months after participant’s 
randomization will be consented for participation as subjects in the study. In total, 
approximately 50 CF physicians and APPs will be enrolled in the study. 
ii 
Eligibility Criteria 
All CF physicians and APPs practicing at recruiting research locations will be eligible to 
participate in Aim 2 study procedures. 
 
Eligibility Criteria:  
1. CF physician or APP at a participating site who assists in the recruitment of 
patients or provides CF care for potential participants in Aim 1 & Sub-Aim 1A 
study procedures. 
C3 Compensation 
Per CFF Therapeutics Development Network guidelines regarding patient compensation, our 
payment incentive meets the minimum of $30/hr. Payments are not exorbitant as to 
unintentionally coerce potential subjects. All compensation provided will be distributed in the 
form of a Tango gift card within 1-3 business days following each session. 
 
Participants in Aim 1 & Sub-Aim 1A will receive compensation totaling approximately $170. 
Those who participate in a clinic visit audio recording will receive an additional $30. If 
participants complete all applicable study sessions and attend a CF clinic visit (see section 4.a), 
they will receive a completion bonus of $50. Compensation will be pro-rated for those who may 
become unable to complete all study procedures. Visit compensation is as follows: 
• 
Baseline Session (30 min.): $15 
• 
2-Week Session (15 min. + 2 hr. website use regardless of actual usage): $70 

 
 
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• 
Clinic Visit Audio Recording (60 min.): $30 – if applicable 
• 
Post-Clinic Visit Survey (15 min.): $10 
• 
3-Month Session (15 min. – primary endpoint survey completion): $10 
• 
6-Month Session (30 min.): $15 
• 
Completion Bonus: $50  
 
Participants in Aim 2 (Physicians and APPs) will receive $10 for the completion of each survey. 
No additional compensation will be provided if they participate in a clinic visit audio recording. 
Total compensation will vary depending on how many of their patients are enrolled in Aim 1 & 
Sub-Aim 1A study procedures. 
 
Clinical team members (e.g. social worker, CF nurse, etc.) identified as local champions will be 
invited to take part in an information session to learn about the study. Local champions will not 
be enrolled as participants in the study and will only assist in recruitment efforts. Those who 
attend this information session will be eligible to receive a $20 Tango gift card as a courtesy for 
the reimbursement of their time. 
 
A device and/or reliable internet connection (mobile Wi-Fi hotspot with pre-paid data) can be 
requested to make patient participation in this study possible. They may be used for the duration 
of the study, but must be returned to the study team at the University of Washington once active 
study involvement is completed. 
C4 Data Sources & Variables 
Local electronic health records (EHR) at research locations and/or PortCF (CF Foundation 
Patient Registry) may be used to access and obtain data for screening purposes and for the 
collection of relevant study data. Study staff at the University of Washington will obtain 
appropriate HIPAA Authorization consent, per local site requirements, from CF patient 
participants prior to research locations access and/or obtain study data. For screening and 
recruitment purposes, HIPAA Authorization will be waived for all research locations.  
 
For screening purposes, research locations will obtain the following data to identify potential CF 
patient participants: Name, date of birth (DOB), clinic appointment dates, date of screening, lung 
function testing results, sex, race/ethnicity, insurance status, zip code, contact information, lung 
transplant referral status/history, pertinent information from recent clinic notes (i.e. 
documentation of exacerbations, prior metal health screening results), reason(s) for refusal to 
participate in the research, etc. All screening data will be retained and shared with the University 
of Washington, even if participants do not consent to enrolling in the study as a means to 
describe the demographics and clinical characteristics of individuals who decline to enroll. 
Additionally, these data will be kept for the purposes of future research study recruitment and 
follow-up purposes.  
 
Research locations will require separate, active Cystic Fibrosis Foundation Patient Registry IRB 
approval to gain access to patient records via PortCF. Individuals with CF at care centers 
consent separately to having their information available to researchers for screening purposes. 
Information that may be accessed and/or obtained from PortCF includes: Name, CFF ID, date of 
birth (DOB), CFTR genotype, sweat test result, visit summaries, annual report, education level, 
insurance status, etc. 

 
 
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For enrolled CF patient participants, research locations will view their local EHR (i.e. EPIC) to 
access and/or obtain the following information: name, date of birth, medical record number, 
phone number(s), email address, complete address, pertinent clinic appointment dates and 
notes, lung function testing results, vital signs, BMI, demographic information, CFTR genotype, 
CFTR modulator status, 6-minute walk test distance, supplemental oxygen requirement, blood 
gas results, history of diabetes on insulin, documentation of pulmonary hypertension on 
echocardiogram or right heart catheterization, prescription of non-invasive mechanical 
ventilation (e.g. BiPAP), dates of hospitalizations (all causes), hospitalization diagnoses, dates 
of pulmonary exacerbations and treatments, insurance status, lung transplant referral history, 
PHQ-9 and GAD-7 scores, etc. Data may be retrospective or collected prospectively. 
 
Additional data variables to be obtained from all participants via self-report and from the 
intervention website(s) will include: responses to survey assessments described in section D4, 
qualitative data obtained during clinic visits (if applicable), and user data collected from website 
analytics (e.g. session length, number of clicks, page views, IP address, etc.). 
 
Study staff at the University of Washington will have access to and will obtain direct and indirect 
identifiers for all participants recruited from the University of Washington and from all research 
locations. Data Use Agreements will be established between the University of Washington and 
each research location prior to sharing of identifiable data. 
 
All identifiers (or links between identifiers and data/specimens) and data that are part of the 
research records will not be destroyed until after the end of the applicable records retention 
requirements by Washington State. 
C5 Risks and Benefits 
5.a 
Potential Risks 
This multicenter interventional clinical trial places human subjects at low risk. We plan to 
use a Data Safety Monitoring Board (DSMB), as described in the data safety monitoring 
plan (DSMP). 
 
Overall Level of Risk 
Participants may be exposed to low risk associated with the conduct of the study, whether 
they are in the ToT (intervention) or UNOS (attention control) group, related to the 
completion of questionnaires and accessing information about LTx online. 
 
Psychological risks: 
Questionnaires: There are no physical risks associated with the study surveys. The risks to 
participants completing surveys are minimal and consist mainly of perceived or real 
invasion of privacy or psychological impacts related to surveys about symptoms of anxiety 
or depression. To minimize concerns about invasion of privacy, we will make it clear that 
surveys are confidential; however, results from surveys regarding psychological symptoms 
(GAD-7 and PHQ-9 scores) will be shared with a patient’s CF clinician(s) regardless of 
results. If they meet diagnostic thresholds for anxiety or depression or if there is report of 
possible suicidality, the patient’s care team will be notified with urgency (described in 

 
 
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DSMP). Participants may choose not to answer select questions in the surveys if they are 
uncomfortable providing responses. 
 
Accessing information about LTx: There are no physical risks associated with accessing 
websites about LTx. The potential risks to participants are low and are primarily 
psychological, including the potential for increasing anxiety, depression, or distress. The 
level of psychological impact of the LTx educational resources (the “Take on Transplant” 
website or the UNOS website) depends on many factors, including whether the patient has 
previously considered LTx as a treatment option, has been denied from LTx in the setting 
of a contraindication, has experience with others who underwent LTx, the amount of 
information they know about LTx (and whether that information is correct), and how sick 
they are. 
 
In a study of 153 University of Washington adult CF patients in 2015, there was a 
surprisingly high rate of report of suicidality with 7 (5%) of clinically stable patients who 
reported suicidality on routine PHQ-9 screening questionnaires.[39] Of the 7 patients with 
suicidal ideation, 2 had co-morbid clinically-significant depression (PHQ-9 >10) and anxiety 
symptoms (GAD-7 >10), 1 patient had clinically-significant anxiety symptoms alone (GAD-7 
>10), and the remaining 4 did not have clinically-significant depression or anxiety 
symptoms but had elevated PHQ-9 scores between 5 and 10 corresponding to mild 
depression symptoms. Only FEV1 % predicted was independently associated with the 
presence of diagnostic PHQ-9 depression scores[39], raising the concern for risk of 
depression for people with severe CF in the proposed RCT. A separate study of CF 
patients in the United Kingdom found that 10% of patients reported suicidality on routine 
screening PHQ-9 surveys.[40] We are enrolling patients with a large range of lung function 
with many who will be “too well” for LTx. While initially learning about LTx may be 
distressing, over the longer term it may be beneficial to one’s mental health to have a better 
understanding of the context for LTx. Qualitative data will be important for understanding 
the psychological implications (potential harms and benefits) of LTx education in this 
population. Understanding background rates of depression, anxiety and suicidality in the 
CF population inform the interpretation of the psychological risks of study participation. 
 
Risks to confidentiality: 
Access to private medical records: One risk of this study involves the access to private 
medical documents and patient level data that is not anonymous. We will take precautions 
to ensure the confidentiality of patient specific data. All researchers who participate in the 
study will sign a confidentiality statement. Identifying information will be kept separate from 
survey results and clinic transcripts in a password-protected computer to which only study 
staff will have access as noted below.  
 
Individual-level web usage analytics: There are no physical risks associated with tracking 
individual-level web usage analytics, and most people have this type of data collection 
occurring in their daily lives. Patients will be informed of usage tracking on the research 
website. There is the potential for perceived or real invasion of privacy because the web 
analytics can track location precisely. We will take precautions to ensure the confidentiality 
of patient-specific data. All researchers who participate in the study will sign a 
confidentiality statement.  
 

 
 
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Recording of CF clinic visit: There are no physical risks associated with recording a CF 
clinic visit, but it is possible for patients to have a perceived or real invasion of privacy 
because the recording may contain sensitive health information unrelated to LTx 
considerations. We will take precautions to ensure the confidentiality of patient-specific 
data. Additionally, physicians or APPs may have a perceived or real invasion of privacy as 
their conversation with the patient may contain sensitive information related or unrelated to 
LTx. We will de-identify the physician, APP, and CF center in clinic visit transcripts to avoid 
ascribing conversation(s) to a specific physician, APP, or center. All researchers who 
participate in review of the audio recordings will sign a confidentiality statement. Identifying 
information will be kept separate from the audio recordings. Audio recordings will be 
transmitted from collaborating sites to the University of Washington research team using 
secure transfer method within 5 days and recording devices will be cleared of original files 
immediately after transfer. 
 
There are no research procedures that may have risks that are currently unforeseeable. 
Additionally, it is unlikely that significant new safety findings will be discovered as this study 
is minimal in risk and there were no significant new findings in the pilot RCT study. 
 
Alternatives 
Participation will be voluntary. Patients that choose not to participate in the study will 
continue to receive clinical care at their local CF center. 
5.b 
Potential Benefits to the Subjects 
Preliminary testing of ToT suggests research participants may experience improvement in 
key outcomes like preparedness for LTx discussions, LTx knowledge, decisional conflict 
about LTx, and others. Based on feedback from CF patients who have pilot tested ToT, we 
hypothesize that the proposed intervention will be well-received and will lead research 
participants to have an improved understanding of the questions they have about LTx for 
their own CF doctor. Further, the current study will yield important feedback to refine ToT 
for future users with low SES and/or low health literacy. This study may also inform the 
future implementation of ToT, with respect to the timing and context of LTx discussions in 
CF clinic. 
5.c 
Protections Against Risk 
Psychological risks: Given the sensitive nature of LTx as a treatment option for CF, it is 
possible that patients may experience psychological distress from reading about LTx, 
especially in cases where CF patients have died after LTx. We have worked to mitigate this 
risk by allowing participants to moderate the amount of information they read about 
particular patient stories or ‘Resource Library’ content. Specifically, we have applied “story 
highlights” to ‘CF Stories,’ which describe an overview of the content and are visible prior to 
entering the story. We also give an overview of ‘Resource Library’ content prior to entering 
the topic. More than 100 CF patients (pre- and post-transplant) have reviewed the content 
and provided feedback on the content and presentation of sensitive information. 
Additionally, most CF clinics have a mental health coordinator embedded in the clinic. 
Screening for depression and anxiety is the standard of care at CFF accredited care 
centers. We have the contact information for the CF providers, including social workers and 
mental health coordinators, at all participating sites in case we need to contact them 

 
 
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acutely about a participant. Further, we are collecting robust measures of mental health 
outcomes, including the PHQ-9 and GAD-7, which will be monitored closely for evidence of 
harm to study participants. We will administer the PHQ-9, and GAD-7 at baseline (V1), 2-
weeks (V2), 3-months (V3), and 6 months (V4). The UW research facilitator will review all 
PHQ-9 and GAD-7 results immediately to identify new onset of psychologic symptoms 
worsening to diagnostic level (PHQ-9 ≥10 or GAD-7 ≥10) or evidence of possible suicidality 
(an affirmative response to #9 on the PHQ-9) and will consider any of these an adverse 
event. The Data Safety Monitoring Plan outlines in detail how abnormal mental health 
outcomes will be addressed as adverse events of special interest and how a Data Safety 
Monitoring Board will monitor for risks to human subjects. 
 
Herein, we will describe our approach to an affirmative response to question #9 on the 
PHQ-9 (“Over the last 2 weeks, how often have you been bothered by: Thoughts that you 
would be better off dead or of hurting yourself in some way”). It is important to note that an 
affirmative response to this question does not necessarily indicate that a person is suicidal. 
Given the severity of the symptom burden in end-stage CF, some people may have 
thoughts that they may be better off dead without actually wanting to die or kill themselves. 
It is important to assess individuals for evidence of suicidality in this setting. First, all study 
sessions for completion of surveys in REDCap (i.e. PHQ-9) are scheduled to ensure 
availability of a physician to contact a participant in the event of the report of an affirmative 
response to #9 on the PHQ-9. Dr. Ramos and the UW research facilitator receive an 
instantaneous automatic email alert from REDCap in the setting of an affirmative response 
to #9 on the PHQ-9. The UW research facilitator will notify the participant during the Zoom-
based study session to expect a call from Dr. Ramos or another study physician. The study 
physician will call the patient within 4 hours of the result, perform the Columbia-Suicide 
Severity Rating Scale triage for primary care[41], provide information for the national 
suicide and crisis hotline (9-8-8), and establish a safety contract with the patient in the 
interim, as indicated. Additionally, the study physician will notify the participant’s CF 
clinician directly via secure communication within 4 hours of the result. All episodes of 
reported suicidality documented on PHQ-9 administered during study sessions will be 
reported to the medical monitor within 24 hours, to the DSMB within 2 working days, and to 
the central IRB in accordance with the standard operating procedures and policies of the 
IRB. If Dr. Ramos is unavailable, Dr. Goss (co-I) or Dr. Kapnadak (co-I) will perform these 
duties. 
 
Risks to Confidentiality: As with any research study, there is a potential risk of breach of 
confidentiality. Study personnel will enter personally identifiable data into a protocol-specific 
electronic Case Report Form (eCRF), managed through REDCap. We will take precautions 
to ensure the confidentiality of patient specific data. Further, audio recordings of CF clinic 
visits may contain sensitive health information that is beyond the scope of the current 
research project. Research staff who perform the role of observer to rate the quality of 
shared decision making will have HIPAA training and will access the audio recordings via a 
secure web interface. Study participants will not be identified by name in the study 
database or on any data capture screens but will be identified by a subject identification 
number unique to this study. Participants will have different identification numbers in Aims 1 
and 2 to limit the potential for accidental unblinding by comparing numbers across the 
projects within the study. Only authorized individuals will be able to link the study ID to the 
participant’s name. All investigators and staff involved in the proposed research will have 

 
 
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completed human subject protection training, have HIPAA training, and will be bound by 
the agreement of confidentiality. All study databases at the UW will be maintained on 
password protected computers and routinely backed up to an encoded password protected 
file. All procedures for the handling and analysis of data will be conducted using GCP, 
meeting FDA guidelines for the handling and analysis of data for clinical trials. Data 
presentations will include only group data and will be presented in a way that ensures 
individual participants and institutions cannot be identified. If respondents may be identified 
by a specific subgroup (e.g., male minority CF patients), these subgroup data will not be 
presented in any format.  
 
In addition to the issues discussed above, participants will be informed that involvement in 
the study is voluntary and that refusing to participate will not be associated with any loss of 
rights or benefits to which they are otherwise entitled. To minimize perception of coercion, 
we will make it clear that subjects may withdraw from the study at any time without penalty 
by notifying study staff. If participants choose to withdraw, they will be given the choice of 
having their data kept as part of the dataset, as identifiable or de-identified, or removed. 
D Study Procedures  
D1 Screening for Eligibility 
Potential subjects involved in Aim 1 and Sub-Aim 1A procedures will be largely, if not 
exclusively, known to the investigators at research locations as patients are followed at the CF 
Care Center. Study Staff (i.e. research coordinators/assistants, research nurse, etc.) and/or the 
lead researcher at each site will use local access to the CFF Patient Registry data (PortCF) 
and/or local EHR (i.e. EPIC) to screen and identify patients who meet eligibility criteria. 
Additionally, potential participants may be screened by viewing the CF clinic schedule in the 
EHR. To determine if a patient is eligible, study staff and/or the site-PI at each research location 
will review the screening variables described in section C4. We aim to over-enroll participants 
with disadvantaged backgrounds (from communities of concern – Medicaid insurance, non-
White race, Hispanic ethnicity, or high school education or less). We will close enrollment to 
individuals outside communities of concern after 85 participants not meeting these criteria, 
balancing across sites, to achieve a sufficient sample to target at least 1/3 (n=40) from 
communities of concern. Participants meeting eligibility criteria will be recruited for participation.  
 
For Aim 2 participants, there will be no formal screening procedure. Study staff at each site will 
provide the University of Washington with a physician/APP roster which includes contact 
information for recruitment purposes. 
D2 Recruitment Methods 
Once an eligible CF patient is identified, designated study staff at each recruiting research 
location will contact the patient to provide information about the study. Study staff can contact 
potential participants in person, by phone and/or email using IRB-approved phone call script or 
email templates. Research locations will use their best-practices depending on local guidelines.  
 
Some CF clinics maintain a list of email addresses for patients interested in notifications about 
relevant clinical research, and these email addresses may be used to send IRB-approved 

 
 
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email templates to describe the study and provide study contact information. Alternatively, 
patients may be approached in-person during a CF clinic visit and provided with an IRB-
approved informational handout. In clinic, the patient’s CF physician or local champion 
(described below) may introduce the study prior to an approach by study staff to increase the 
likelihood of participation.  
 
Our recruitment efforts will oversample difficult to engage patients, including people from 
communities of concern (Medicaid insurance, non-White race, Hispanic ethnicity, or high school 
education or less); study staff and local champions for the project will make a coordinated effort 
to recruit individuals from communities of concern to fill at least 1/3 of the study population. The 
University of Washington will track demographics of the enrolled participants as the study 
progresses to assess whether we are achieving the desired demographics. Sites will be asked 
to keep an updated screening log (via REDCap), including a record of individuals who are 
approached and decline enrollment. If we are not reaching enrollment targets, we will engage 
with individual sites to identify reasons for not enrolling from the patient groups of interest, to 
see what changes, if any, could be made to improve recruitment. Additionally, patients who 
state refusal to participate or are unable to be contacted after multiple attempts may be re-
screened and re-approached for participation after approximately three months elapse, as a 
change in health status may prompt their interest in participating. Participants who state refusal 
to participate, will be asked to share their reason(s) for refusal which will be obtained as part of 
the study data. 
 
Once an interested individual has been identified, study staff may provide the potential 
participant with a copy of consent documents to review and a link to schedule a study session or 
information session with study staff at the University of Washington. To schedule their visit, 
participants will be asked to provide their name, contact information, and mailing address if a 
device and/or Wi-Fi hotspot is requested. Alternatively, study staff at research locations may 
share the potential participant’s contact information with study staff at the University of 
Washington (via email and/or REDCap), if the patient provides verbal permission for sharing this 
information. Study staff at the University of Washington will then contact the participant for 
scheduling of the baseline session where electronic documentation of informed consent will be 
obtained. 
 
For CF physicians and APPs recruited for enrollment into Aim 2 study procedures, study staff at 
participating sites will be asked to provide the University of Washington with a physician/APP 
roster which will include names, phone numbers, and emails. Study staff from the University of 
Washington will contact all physicians and APPs via email with information about the research 
study using an IRB-approved email template. Study staff from the University of Washington will 
be available in person or via Zoom or phone to describe the study in detail to the CF clinical 
teams at participating research locations. This will allow for the identification of local champions 
(e.g. social worker, CF nurse) who can identify individuals from disadvantaged backgrounds 
who are eligible for participation in the RCT. Clinical team members (i.e. social worker, CF 
nurse, etc.) identified as local champions will not be enrolled as participants in this study. They 
will only assist in the recruitment efforts of participants.  
 
CF patient participants enrolled into Aim 1 and Sub-Aim 1A will be asked to provide contact 
information for third-party subjects. Study staff at the University of Washington may contact 

 
 
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these individuals by phone and/or email using IRB-approved phone call script and/or email 
template, covered under separate study protocols and IRB(s). 
D3 Informed Consent 
Informed consent will be obtained electronically for all participants by study staff at the 
University of Washington using a University of Washington installation of REDCap. It is unlikely 
that documentation of consent will not be able to be obtained electronically as internet access is 
a requirement to participating in this study and can be provided to participants if necessary.  
 
Aim 1 and Sub-Aim 1A [CF Patients]: 
Eligible participants will join the baseline session remotely via Zoom where they will first review 
electronic consent documents with University of Washington study staff. Participants will be 
given ample time to review the consent form between when they were notified of the study and 
the scheduled baseline session. They will also be given the opportunity to have all questions 
answered to their satisfaction before providing an electronic signature and continuing with 
baseline session study procedures. All participants will be informed that involvement in the 
study is voluntary and that deciding not to participate will not be associated with any loss of 
rights or benefits to which they are otherwise entitled. To minimize perceptions of coercion, we 
will make it clear that participants may withdraw from the study at any time without penalty by 
notifying study staff. All participants will receive a PDF copy of their signed consent documents 
to keep for their records and will be encouraged to contact study staff if any questions arise. 
 
Additionally, at the start of all sessions study staff will review an agenda of study procedures to 
be completed with participants. Participants will be allowed to ask the study staff any questions 
prior to proceeding and University of Washington study staff will provide clarifications if 
necessary. 
 
Aim 2 [CF Physicians/APPs]: 
Study staff from the University of Washington will be available via Zoom, email, or phone to 
describe the study in detail to the CF clinical teams, including the physicians and APPs, at 
participating research locations. Study staff at the University of Washington will provide all CF 
physicians and APPs with a link via email where they will be able to review consent documents. 
Consent documents will provide sufficient information, and providers will be encouraged to 
contact the University of Washington study staff if there are any questions prior to providing an 
electronic signature. 
D4 Description of Study Procedures 
Aim 1 & Sub-Aim 1A [CF Patients]: 
Survey Assessments: Participants will be asked to complete surveys during each session. 
Surveys will take approximately 15-30 minutes to complete. For individuals with CF, surveys 
may include questions from the following measures: demographics, shortened test of functional 
health literacy in adults (S-TOFHLA), assessment of health numeracy (Newest Vital Sign), 
Assessment of digital health care literacy, Preparation for Decision Making (PrepDM) Scale, 
investigator-designed lung transplant knowledge assessment, Decisional Conflict Scale, Likert 
rating of preparedness to discuss lung transplant, Patient Health Questionnaire (PHQ-9), 
Generalized Anxiety Disorder scale (GAD-7), General Self-Efficacy Scale, Perceived Social 
Support Scale, Shared Decision Making Questionnaire (SDM-Q-9), patient report of 

 
 
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discrimination during medical care, Big Five Inventory (BFI), etc. (Table 2, next page) Additional 
questions may be asked to confirm medical record information (i.e. occurrence of lung 
transplant conversations, adverse events, etc.) and/or information pertaining to website usage 
(i.e. barriers to use, future website implementation, access outside of the research website, 
etc.). Additionally, all participants will be asked at the baseline visit to share their reason(s) for 
choosing to participate in the research study. 
 
Research Website Access: Participants will be introduced to the research website during the 
Baseline Session via a pre-recorded video housed on the research website. The research 
website will contain two interventions including a CF-specific LTx education website (“Take on 
Transplant”) and an attention control (UNOS.org). Before accessing the research website during 
the baseline session, participants will be randomized 1:1 to either the CF-specific website 
(“Take on Transplant”) or the attention control (UNOS.org). Participants will be given unlimited 
access to the website from their study arm assignment for 2 weeks. After the 2-week session, 
participants will have ongoing access to the website to which they were randomized for 3 
months. At the 3-month session, access to the opposite arm assignment will be unlocked and 
participants will have unlimited access to both the CF-specific website (“Take on Transplant”) 
and the attention control (UNOS.org). All participants will receive up to weekly text message 
and/or email reminders to log into the research website for the first 3 months of the study, 
regardless of study arm assignment. 
 
Clinic Visit Audio Recording (if applicable): Participants will be asked to have their next 
routinely-scheduled CF clinic visit audio recorded. No recordings will occur without expressed 
verbal permission from CF patients, the CF provider, and third-party subjects (if applicable). By 
recording these visits, we will assess the dyadic relationships between patients and their CF 
providers and their role in decision making about LTx as a potential treatment option. Study staff 
at the University of Washington will evaluate the recordings for duration of visit, duration spent 
discussing LTx, rating the quality of shared decision making using the Observing Patient 
Involvement in Decision Making (OPTION) score, and content analysis. If participants do not 
have a routine CF clinic visit scheduled during the specified window (at least 6 weeks after 
enrollment and before the 3-month study visit), they may be approached to have a clinic visit 
recorded after their 3-month study visit but before their 6-month study visit (if a routine clinic visit 
occurs). 
 
Medical Record Review: Study staff at each research location will access and obtain all data 
variables described in section C4 for all participants. At approximately 6-12 months after study 
completion, local study staff will assess the clinical impact of the study via assessment for 
documentation of LTx discussion and/or LTx referral in local EHR records. Study staff will list 
dates of all CF clinic visits (including telemedicine), changes in disease severity (e.g. 
exacerbations, FEV1, BMI), and dates of clinic notes that document LTx discussion or LTx 
referral. Additionally, long-term follow-up data will be captured from local EHR records annually 
for up to 4 years following study termination. Information collected may include variables listed 
in section C4.  
Table 2: Assessment schedule for Aim 1 and Sub-Aim 1A CF patient participants at baseline (V1), 2-weeks 
(V2), 3-months (V3), 6-months (V4) and during a routine CF Clinic visit (2-3 months after randomization). 
Key survey assessments (collected via REDCap) 
Assessment Schedule 

 
 
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Aim 2 [CF Physicians/APPs]: 
Survey Assessments: CF physicians and APPs will be asked to complete a survey after one CF 
clinic visit per patient for all patients who are enrolled in this study. The CF clinic visit should 
occur 2 to 3 months after the patient is randomized, but surveys will be collected even if the visit 
occurs after this window as long as it occurs before study visit 4 (6 months). The survey will take 
approximately 15 minutes to complete. The survey may include the following measures: 
demographics, Shared Decision Making Questionnaire – physician version (SMD-Q-Doc), Likert 
rating of provider’s satisfaction with LTx discussion during the visit, Likert rating of patient 
preparation for LTx discussion, Likert rating of patient’s knowledge about LTx during the visit, 
etc. (Table 3) 
 
Clinic Visit Recording (if applicable): CF physicians and APPs will be asked to have their CF 
clinic visits audio recorded. No recordings will occur without expressed verbal permission from 
CF patients, CF providers, and third-party subjects (if applicable). By recording these visits, we 
will assess the dyadic relationships between patients and their CF providers and their role in 
decision making about LTx as a potential treatment option. Study staff at the University of 
Washington will evaluate the recordings for duration of visit, duration spent discussing LTx, 
rating the quality of shared decision making using the Observing Patient Involvement in 
Decision Making (OPTION) score, and content analysis.  
 
 
 
V1 
V2 
CF 
Clinic 
V3 
V4 
Demographics survey (e.g. highest education level attained, annual 
household income, race/ethnicity, languages spoken in the home) 
x 
 
 
 
 
Shortened Test of Functional Health Literacy in Adults (S-TOFHLA)[42] 
x 
 
 
 
 
Assessment of health numeracy (Newest Vital Sign)[33] 
x 
 
 
 
 
Assessment of digital health care literacy[43] 
x 
 
 
 
 
Efficacy measures: 
Preparation for Decision Making (PrepDM) Scale[29]  
 
x 
 
Primary 
patient 
outcome 
x 
Investigator-designed lung transplant (LTx) knowledge assessment and 
patient’s Likert rating of preparedness to discuss LTx  
x 
x 
 
x 
x 
Decisional Conflict Scale[32]  
x 
x 
 
x 
x 
Psychological and social support measures: 
Patient Health Questionnaire (PHQ-9)[36]  
x 
x 
 
x 
x 
Generalized Anxiety Disorder 7-item scale (GAD-7)[35]  
x 
x 
 
x 
x 
General Self-Efficacy Scale[37]  
x 
x 
 
x 
x 
Perceived Social Support Scale[46]  
x 
x 
 
x 
x 
CF clinic measures 
Patient’s Likert rating of satisfaction with LTx discussion  
 
 
x 
 
 
Shared Decision Making Questionnaire (SDM-Q-9)[48]  
 
 
x 
 
 
Patient report of discrimination during medical care[49]  
 
 
x 
 
 
Table 3: Assessment schedule Aim 2 CF provider/APP participants, occurs only after a routine CF Clinic visit. 
Physicians and advanced practice providers (APPs) survey measures 
Assessment Schedule 

 
 
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4.a 
Schedule: Aim 1 & Sub-Aim 1A [CF Patients]  
All study visits, apart from any in-person routine CF clinic visits, will occur remotely via Zoom 
videoconferencing with study staff at the University of Washington. To ensure patient privacy, 
individual meeting links will be sent to participant’s confirmed email addresses. The waiting 
room setting will be enabled so that only the research participant will be able to join the call. 
Additionally, participants will not be required to enable their video if they prefer not to. 
 
Study staff may communicate with participants throughout their involvement in the study via 
email, text, and/or phone for reminders pertaining to study visits, website usage, or to address 
any questions. 
 
Unless approved by study staff at the University of Washington, study windows should be 
scheduled as follows: 
2-Week Session (V2): -3 / +3 days 
2 to 3-Month CF clinic visit: at least 6 weeks after randomization/until 3-Month Session 
(V3)* 
3-Month Session (V3): -7 / +7 days 
6-Month Session (V4): -7 / +7 days 
 
*If participants do not have a routine CF clinic visit scheduled during the specified window 
(at least 6 weeks after enrollment and before the 3-month study visit), they may be 
approached to have a clinic visit recorded after their 3-month study visit but before their 6-
month study visit (if a routine clinic visit occurs). 
 
 
i 
Baseline Session (V1) 
• 
Survey – 30 minutes 
• 
Gain access to Website #1 
V1 
V2 
CF 
Clinic 
V3 
V4 
Demographics (e.g. age, gender, race, ethnicity, years in practice, clinical 
practice specialties) – Once per MD/APP 
 
 
x 
 
 
Shared Decision Making Questionnaire–physician version (SDM-Q-Doc)[50] 
 
 
x 
 
 
Provider’s Likert rating of satisfaction with LTx discussion 
 
 
x 
 
 
Provider’s Likert rating of patient preparation for LTx discussion and patient’s 
LTx knowledge  
 
 
x 
 
 

 
 
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ii 
2-Week Session (V2) 
• 
Survey – 15 minutes 
• 
Continued access to Website #1 
iii 
 2-3 Months after Baseline 
• 
Routine CF clinic visit 
• 
Post-Clinic visit survey – 15 minutes 
• 
Clinic visit audio recording 
• 
Continued access to Website #1 
iv 
3-Month Session (V3) 
• 
Survey – 15 minutes 
• 
Gain access to Website #2 (in addition to Website #1) 
v 
6-Month Session (V4) 
• 
Survey – 30 minutes 
• 
End of active study participation and start of long-term follow up 
D5 Data Collection Procedures 
All study data will be collected and maintained using a University of Washington installation of 
REDCap. Research locations will have limited access with permissions set to only view data 
from their site. Only authorized study staff at the University of Washington will be able to view all 
data from each research location. To protect patient data, each research location will require a 
Data Use Agreement with the University of Washington prior to sharing any identifiable data. 
 
Study staff at the University of Washington will conduct all study sessions remotely via Zoom 
videoconferencing. Study staff at each research location assisting with the recruitment of 
participants will be responsible for collecting and sharing EHR data for screening and enrollment 
purposes and facilitating and transmitting clinic audio recordings. 
E Data Safety Monitoring Plan 
 
Brief synopsis of the project: The overall research objective is to test the efficacy of an 
investigator-designed lung transplant education website, Take on Transplant, compared to an 
attention control website in a multicenter randomized controlled trial. The project incorporates 
mixed methods to assess preparedness for lung transplant discussions among cystic fibrosis 
patients with severe obstructive lung disease (FEV1 <50% predicted). Study procedures include 
surveys performed electronically and interviews conducted via Zoom videoconferencing. The 
University of Washington study staff will perform these study procedures, while all study sites 
will participate in recruitment of participants and conduct of the protocolled 3-month clinic visit 
(routine cystic fibrosis care). We will oversample from communities of concern – people with low 
socioeconomic status, Hispanic ethnicity, or non-White race – to inform improvements in a 
process that disadvantages these patients and leads to health disparities. We aim to empower 
patients to discuss lung transplant. This study will explore the impact of lung transplant 
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perceptions and use of lung transplant education. Lung transplant is a sensitive topic, raising 
concerns about mortality, health complications, and financial stress. There is a risk that 
exposure to lung transplant educational content could increase anxiety, depression, or 
emotional distress. Additionally, we will evaluate patient-physician dynamics, including implicit 
bias and experience of discrimination, which may also produce an emotional response for 
participants. For these reasons, it is warranted to form a Data Safety Monitoring Board (DSMB) 
to longitudinally assess mental health outcomes, including report of possible suicidality via the 
PHQ-9, for participants in the clinical trial.  
 
Table 5: Overview of Data Safety Monitoring Plan  
Section 
Description and location within this document 
Monitoring Entity: Data Safety 
Monitoring Board 
A Data Safety Monitoring Board (DSMB) will be established 
with the relevant expertise to oversee mental health risks to 
clinical trial participants. An independent medical monitor 
will review adverse events. Responsibilities of the DSMB 
are outlined, including addressing conflicts of interest. 
(Section E1)  
Monitoring for Compliance 
Dr. Kathleen Ramos (PI) will oversee the monitoring 
schedule and procedures for ensuring compliance with IRB 
requirements, minimizing research-associated risk, and 
verification of informed consent source documents.  
(Section E2) 
Data Management Practices and 
Quality Control 
Data management and quality control will be provided by 
the University of Washington research team (Section E3) 
Identifying, managing, and 
reporting adverse events and 
unanticipated problems 
Potential risks and benefits to participants are discussed. 
Frequency and mechanism of monitoring for adverse 
events, along with management and reporting of adverse 
events are outlined. (Section E4) 
Monitoring plan for multiple sites 
The University of Washington research team will ensure 
compliance with the monitoring plan and reporting 
requirements across all study sites (Section E5) 
Assessment of external factors 
that may impact participant safety 
The PI and co-Investigators will remain up-to-date with 
relevant developments in the literature that could have 
implications for the ethics of the study. (Section E6)  
Plans for interim safety analysis 
The DSMB will review an interim analysis to ensure the 
safety of participants in the trial. (Section E7) 
Communication plan and 
mechanisms for reporting to the 
DSMB, IRB and NINR 
This section describes communication plan details and an 
overview of responsible persons who report to the DSMB, 
IRB, and NINR in the setting of AE/SAEs, unanticipated 
problems, AEs of special interest (e.g. suicidality), IRB 
actions, or protocol changes. (Section E8) 

 
 
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E1 Monitoring Entity: Data Safety Monitoring Board 
An independent Medical Monitor will review individual serious adverse events (SAEs) 
throughout the study as they occur (see Section 1d for details related to identification, 
management, and reporting of adverse events). An external Data Monitoring Board (DSMB) will 
be created to function as an independent group of experts who will advise the study’s 
investigators with respect to participant safety and monitoring study progress and conduct.  
 
The Medical Monitor is Engi Attia, a pulmonologist (MD) from the University of Washington who 
has been trained to perform medical monitoring for Cystic Fibrosis Foundation Therapeutics 
Development Network (TDN) studies and on the current protocol and study procedures. This 
Medical Monitor will review and assess SAE reports and make the preliminary assessment of 
seriousness, expectedness, and causality with assessment for need of expedited reporting. The 
Medical Monitor will also determine if follow-up information is required and write an SAE 
narrative for each SAE. The Medical Monitor will review all adverse events, SAEs, and medical 
coding for DSMB reporting purposes and communicate safety concerns to the DSMB at least 
every 6 months. 
 
DSMB Membership 
The members of the DSMB will serve in an individual capacity and provide their expertise and 
recommendations. The DSMB will be composed of at least 4 members, including an 
experienced statistician. One of these members will have experience in clinical trial conduct and 
experience in adult CF clinical care, and another will have expertise in clinical psychology. 
There will be an Executive Secretary who will ensure that the members will not be co-
investigators of the study and will have no undisclosed conflicts of interest. The Executive 
Secretary will take notes during meetings to facilitate draft minutes for chair approval. The 
DSMB will develop and approve a Charter that will outline the roles and responsibilities of 
DSMB members, including the specifics related to participant protection oversight, monitoring of 
study operations, and ensuring data integrity. 
 
DSMB Meetings 
Prior to enrolling human subjects, the DSMB will meet to approve the Charter, review the IRB-
approved study protocol, and review the IRB-approved informed consent form. The DSMB will 
approve reporting templates that will be used at DSMB meetings. The DSMB will review 
immediately reportable events (i.e., report of possible suicidality based on an affirmative 
response to question #9 of the PHQ-9) and establish an approved mechanism for 
communication within 48 hours of the event. The statistician will review the planned interim 
safety analysis (see section E7 below) and approve or recommend modification to the proposed 
plan.  During this first meeting, the DSMB will review a summary of existing literature and make 
recommendations about whether the trial should proceed as planned or be changed based on 
new findings.  
 
Every 6 months while participants are enrolling, or more often if requested by the DSMB chair, 
DSMB meetings will occur via teleconference. The DSMB will contribute to the protection of 
participants by review of adverse event data and other safety data, and will assure the integrity 
of the study by reviewing quality and completeness of study data, and enrollment data at each 
meeting.  
 

 
 
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Data safety monitoring for the intervention will focus on evaluating mental health concerns 
raised during participation in the trial and will monitor all complaints about the study. We will 
administer the PHQ-9, and GAD-7 at baseline (V1), 2-week (V2), 3-month (V3), and 6-month 
(V4) study visits. Concern for diagnosis of depression and anxiety is defined when PHQ-9 is ≥10 
and GAD-7 is ≥10, respectively. Evidence of possible suicidality (an affirmative response to #9 
on the PHQ-9) is an immediately reportable adverse event (described in detail in section E4 
below). The DSMB will also be charged with reviewing any complaints from patients, family 
members, and clinicians about any aspect of the study including recruitment procedures and 
study implementation. All potential participants will be provided contact information to register 
complaints, if they experience coercion or other problems. The DSMB will make 
recommendations to modify or stop the study if any such complaints represent a legitimate 
concern about the study procedures or methods. 
 
The DSMB will review quarterly data safety monitoring reports and enrollment reports, prepared 
and submitted by the PI, as long as participants are being enrolled or evaluated. There will be 
one planned interim safety analysis (described in section E7 below). The DSMB will review the 
following activities associated with the intervention’s evaluation: 1) participants’ PHQ-9 and 
GAD-7 scores; 2) episodes of reported possible suicidality (an affirmative response to #9 on the 
PHQ-9); and 3) SAEs. The DSMB will monitor for rates of suicidality and the new onset of PHQ-
9 or GAD-7 scores consistent with depression or anxiety, respectively, in both arms of the RCT. 
In order to do this effectively in a trial, the DSMB is expected to review the data in an unmasked 
fashion in closed session, separate from the open session attended by the PI and other study 
team members. Blinding will be maintained during the open session. Unmasking will occur 
during the closed session. Voting members of the DSMB will attend an executive session to 
determine whether the safety data warrant changes to the protocol or terminate the study. The 
DSMB will also evaluate data on participant enrollment, site visits, study procedures, forms 
completion, data quality, losses to follow-up, and other measures of adherence to the protocol.  
At the conclusion of the sessions, the DSMB chair may provide a summary of the preliminary 
recommendations to the lead investigators to provide an opportunity for study investigators to 
ask questions to clarify the recommendations. The meeting is then adjourned. 
 
DSMB communication (see also Section E8) 
The Executive Secretary will take minutes at each DSMB meeting. The DSMB chair will be 
responsible for generating a summary report after each meeting of the DSMB. Reports of DSMB 
deliberations will be delivered as formal minutes within 14 days of each meeting or call. 
 Minutes will document whether there is conflict of interest on the part of Board members and 
will summarize the key points of the discussion and debate, requests for additional information, 
response of the investigators to previous recommendations, and the recommendations from the 
current meeting. The summary report will not contain any unmasked safety or efficacy data by 
treatment arm. The summary report will be provided to the central IRB (Advarra) and to NINR. 
 
• 
If the DSMB does not identify any safety or other protocol-related concerns, the 
Summary Report will state that: 
• A review of adverse event data, and information relating to study performance 
(e.g., data timeliness, completeness, and quality) across all centers took place 
on a given date; 
• the observed frequency of adverse events did not exceed what was 
expected and indicated in the informed consent; 

 
 
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• a review of recent literature relevant to the research took place, and; 
• the DSMB recommended that the study continue without modification of the 
protocol or informed consent 
• 
If the DSMB does identify concerns, the UW staff will distribute, as soon as feasible, 
and within 7 calendar days of the DSMB meeting, the Summary Report as outlined 
above, outlining the concerns and the basis for any recommendations that the DSMB 
has made in response to the concerns. 
• 
Dr. Ramos will ensure timely delivery of the report to study investigators and co-
investigators. 
 
Dr. Kathleen Ramos (PI) will be responsible for ensuring that the DSMB summary report is 
shared with the central IRB (Advarra) and the NIH/NINR, along with any action plan or response 
to the summary report, within 7 days of receiving the final report from the DSMB chair. Dr. 
Ramos will also be responsible for timely reporting to NINR: unanticipated problems or 
unexpected SAEs that may be related to study participation; IRB-approved changes to the study 
protocol that could impact the risk to participants; notice of any actions taken by the IRB related 
to the research. Dr. Ramos will communicate the results of the DSMB meeting to all 
participating clinical sites and they may share the summary report with their local IRB if 
indicated. 
E2 Monitoring for Compliance 
Dr. Ramos (PI) will lead the research team and provide oversight of the entire research 
program, development and implementation of all policies, procedures, and processes. (Figure 2) 
She will be responsible for the implementation of the scientific agenda and will ensure that 
systems are in place to guarantee institutional compliance with US laws, DHHS and NIH 
policies. Dr. Ramos will oversee Mrs. Lauren Bartlett (research facilitator and data manager). 
Mrs. Bartlett will be responsible for training of collaborating site personnel and will oversee 
patient recruitment and enrollment. All participants will undergo the informed consent process 
 
with trained University of Washington (UW) staff. Dr. Ramos will oversee the informed consent 
procedures, the training of study staff, and manage the resultant follow-up. She will also provide 
medical oversight for the randomized controlled trial (RCT). Monitoring visits to clinical sites 
participating in the RCT is covered in Section E5, below. Table 6 provides an overview of tasks 
and responsibilities of the UW research team and collaborating sites, including reference to 
collection of regulatory documents (e.g., 1572 forms, curricula vitae, Good Clinical Practice 
[GCP] certifications, etc.), management of participant data, and delegation of informed consent 
to the UW research team.  

 
 
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Table 6: Overview of tasks and 
responsibilities during the Award 
*Recurring tasks as noted in gray 
TASK/RESPONSIBILITY* 
PI and UW 
research team 
Collaborating 
sites/research 
locations 
Prepare and maintain study timeline 
X 
 
Ensure final IRB approvals are in place at all sites 
X 
X 
Review, negotiate, track site budgets and contracts 
X 
X 
Oversee study visit supplies (e.g. audio recorder, printed 
materials), shipping to sites 
X 
 
Collect all regulatory documents from sites (1572 forms, 
curricula vitae, Good Clinical Practice [GCP] certifications, etc.) 
X 
X 
Obtain informed consent for participation in the trial from all CF 
physicians at all sites 
X 
 
Investigator meeting for site training (site initiation) 
X 
X 
Develop publication plan 
X 
X 
Medical Monitor
Data Safety 
Monitoring Board
Primary investigators
Kathleen Ramos, MD MSc (PI)
Donna Berry, PhD MSN (co-I)
Andrea Hartzler, PhD (co-I)
Siddhartha Kapnadak, MD (co-I)
Melissa Basile, PhD (co-I)
Christopher Goss, MD MSc (co-I)
Patrick Smith, PhD MPH (co-I)
Kristin Riekert, PhD (co-I)
Data Management
William Lober, MD MS (co-I)
Clinical Informatics Research Group (CIRG) 
Lauren Bartlett, BS (University of Washington
research facilitator and data manager)
Collaborating Sites
University of 
Minnesota
PI: Jordan Dunitz, MD
University of 
Pittsburgh
PI: Joseph Pilewski, MD
National Jewish 
Health
PI: Milene Saavedra, MD
University of Kansas
Co-PI: Charles Bengtson, MD
Co-PI: Joel Mermis, MD
Yale University
PI: Jonathan Koff, MD
Maine Health
PI: Edmund Sears, MD
University of 
Cincinnati
PI: Veronica Indihar, MD
University of California 
at Los Angeles
PI: Grant Turner, MD
Seattle Children’s 
Research Institute
PI: Nicole Mayer-
Hamblett, PhD
Biostatistician: Miranda
Bradford, MS
Steering Committee
David Au, MD, MS
Margaret Heitkemper, RN, PhD, FAAN
Nadia Hansel, MD, MPH
Figure 2: Overall Structure of the Study Team  

 
 
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Develop data transfer plans and test data transfers 
X 
X 
Submit screening and recruitment logs 
review 
X 
Enter electronic health record data for participants 
review 
X 
Obtain informed consent for participation in the trial for all CF 
patients from all sites 
X 
 
Manage receipt of REDCap eCRF data transfers; perform data 
cleaning 
X 
 
Generate data management reports  
X 
 
Day-to-day site management activities 
X 
X 
Administer and track site payments 
X 
 
Perform medical monitoring including review and reporting of all 
serious adverse events 
X 
 
Perform medical coding (coding of adverse events) 
X 
 
Review informed consent records for all participants monthly 
X 
 
Track patient enrollment and retention and develop additional 
recruitment plans as needed 
review 
X 
Regular investigator and research coordinator teleconferences 
X 
X 
Prepare NIH status reports 
X 
 
Generate quarterly SAE summaries for DSMB and arrange 
meetings every 6 months 
X 
 
Oversee IRB renewals and updates of other regulatory 
documents 
 X 
 
Data base lock 
X 
 
Seattle Children’s Research Institute: 
- Generate analysis datasets  
- Statistical programming, analyses, and validation for final stat 
report  
- Generate final statistical report  
- Provide statistical support for primary endpoint manuscript  
- Generate data sharing datasets for NIH 
X 
 
Perform study close out activities; archive study data and 
documents 
X 
 
Perform site close out activities 
  
X 
Coordinate the communication of the trial results to the 
investigators, patients and public, including posting of results to 
ClinicalTrials.gov 
X 
X 
Publication of the primary manuscript 
X 
X 
 
Monitoring study safety 
As described above, the DSMB will receive quarterly safety reports and meet via 
teleconferencing every 6 months to review all safety data from the ongoing RCT (Section E1). 
Remote site monitoring visits will occur quarterly (Section E5) and will include audits of 
investigator compliance with IRB regulations and the study protocol, and verification of source 
documents. To minimize research-associated risk, additional monitoring will occur every month 
at the UW clinical and data coordinating center to include review of documentation of informed 

 
 
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consent for all participants, audit of one in every 10 participants to ensure compliance with IRB 
requirements, and review of data security over the prior month.  
E3 Data Management Practices and Quality Control 
All data management and quality control will be provided by the UW research team. This group 
will function as the Data Coordinating Center for the trial. This project requires the creation, 
maintenance, and analysis of data from multiple sources, including multiple questionnaires, 
audio recordings, and individual-level web usage data. Recognizing that the success of the 
proposed study critically depends on the quality of the data collected, systematic data collection, 
quality control, and data management procedures will be implemented. These methods include: 
1) specification and use of concise protocols and standardized data entry forms; 2) rigorous 
training of study staff; 3) use of electronic data capture system (REDCap); 4) validation and 
verification of all data collected with range checks, assessment of missing data, secondary 
verification of extreme data points; and 5) regular meetings between the research teams to 
discuss issues related to study implementation and conduct. Up-to-date screening logs for 
recruitment will be provided to the UW study team and will be reviewed quarterly. Study staff at 
UW will generate a report on the first of each month, which will include site enrollment and 
milestone payments to date and targets. Case report forms and any applicable monitoring 
queries are required to be complete prior to any milestone payments. Quarterly remote 
monitoring visits with each site will provide opportunities for communication about difficulties 
with recruitment, retention, study protocols, or other aspects of the clinical trial (see Section E5, 
below).  
 
Collaborating site PIs will have the primary responsibility of overseeing screening and 
recruitment of participants at their local site. The UW research team will provide benchmarks 
and feedback for enrollment targets. The UW research team will facilitate all study visits via 
Zoom and conduct all informed consent procedures via Zoom. The collaborating sites will 
schedule the CF clinic visit. If indicated, the collaborating site will be responsible for audio-
recording the CF clinic visit and securely transferring the audio file to UW. The collaborating 
sites will be responsible for data entry from participants’ local electronic health records (EHR). 
Once electronic case report forms (eCRFs) are completed, the process of milestone payments 
for participant enrollment will be managed by UW research staff. 
 
Dr. Ramos will work with Mrs. Bartlett (research facilitator and data manager) to refine their well-
established data management infrastructure. Dr. Ramos will work with Mrs. Bartlett and have 
oversight in regard to the development and implementation of a study database, study forms 
(case report forms for the electronic data base) and mechanisms for data collection. She will 
meet regularly with Mrs. Bartlett to review data quality and completion. They will review protocol 
adherence every month, with attention to completion of study visits, completion of survey data 
during study visits, and recording of CF clinic visits as planned. Our study statistician, Miranda 
Bradford, will have primary responsibility for preparing data for interim and final analyses. 
Analyses will be performed by Ms. Bradford under the guidance of the PI and Dr. Nicole Mayer-
Hamblett (co-investigator). Ms. Bradford will remain blinded to study arm assignment during the 
RCT; only the DSMB statistician and other members of the DSMB will have access to study arm 
assignment during the RCT. Once the final participant finishes the final visit, sites will have 60 
days until the database will be locked for entry of clinical data from the EHR. 

 
 
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Dr. William Lober (co-investigator) will be primarily responsible for overseeing the Clinical 
Informatics Research Group (CIRG). This team will maintain the web interface for the research 
intervention and attention control, ensure its operation on secure, actively monitored and 
maintained clinical-quality servers for the duration of the project period. CIRG will provide 
weekly summaries of usage data to the research team.  
 
Survey Data 
All survey instruments will be completed directly by participants via UW REDCap. Patient 
participants will complete surveys during study visits hosted remotely (via Zoom) by UW study 
staff. UW study staff will review the surveys in real-time to ensure no surveys were missed and 
to determine whether the PHQ-9 indicates potential suicidality (see Section E4 for identification, 
management, and reporting of suicidality). Patients will not have access to surveys outside of 
scheduled study visits. Physician participants will complete surveys independently via UW 
REDCap after CF clinic visits and responses will be reviewed for completeness within 48 hours 
of survey completion. Physicians will be prompted to complete surveys up to 3 times within the 
14 days following a CF clinic visit.  
 
Electronic Health Records Data 
The participating sites will enter clinical information from the EHR and local Cystic Fibrosis 
Foundation Registry data into a UW REDCap eCRF. Research coordinators performing EHR 
data abstraction will be blinded to a participant's study arm. These EHR data will include 
baseline demographics and markers of CF severity; documentation of LTx discussion and/or 
LTx referral in the EHR; dates of all CF clinic visits (including telemedicine); changes in disease 
severity (e.g. exacerbations, FEV1, BMI); and dates of clinic notes that document LTx discussion 
or LTx referral. Data will be reviewed with range checks, assessment of missing data, and 
secondary verification of extreme data points within 7 days of data entry. Queries will be 
returned to sites within 7 days of data entry. Co-investigators and research coordinators will 
participate in monthly investigator calls to discuss issues with data entry. Completeness and 
accuracy of data entry will be reviewed during quarterly monitoring visits with each site.  
 
CF Clinic Visit Recording 
There will be one CF clinic visit (in person or via telemedicine) at 2-3 months after 
randomization. Each site will have audio recorders to record clinic visits for participants in Aim 2. 
Recorded files will be transferred securely to the UW study team within 5 days of the clinic visit. 
Recording devices will be erased immediately after files are transferred. Recordings may be 
professionally transcribed, and transcripts will be deidentified.  Recordings will be preserved on 
a UW HIPAA compliant cloud until all analyses are complete and manuscripts are published.   
 
Interview and Focus Group Recording 
Interviews and focus groups will be conducted via Zoom and recorded. Recordings will be 
professionally transcribed, and transcripts will be deidentified.  Recordings will be preserved on 
a UW HIPAA compliant cloud until all analyses are complete and manuscripts are published.   
 
 

 
 
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Confidentiality and Security 
All study documents will be kept in a secured locked office or on a password-protected 
computer. Study participants will not be identified by name in the study database, but will be 
identified by a subject identification number unique to this study. Only authorized individuals will 
be able to link the study ID to the subject’s name. All investigators and staff involved in the 
proposed research will have completed human subjects’ protection training, have HIPAA 
training, and be bound by the agreement of confidentiality. Study data from all sites will be 
captured using a UW REDCap installation maintained on a secure server. All study databases 
will be maintained at the UW on password protected computers and backed up to an encoded 
password protected file in the UW cloud. All procedures for the handling and analysis of data 
will be conducted using good clinical practices meeting FDA guidelines for the handling and 
analysis of data for clinical trials. There will be no deletion of entered data and any corrections 
to erroneous data will be tracked with date, time, and the person responsible for the change. 
Further, all participants will be protected by the NIH Certificate of Confidentiality, which provides 
additional privacy protections. 
E4 Identifying, managing, and reporting adverse events and 
unanticipated problems 
Potential risks and benefits to participants 
Participants may be exposed to low risk associated with the conduct of the study, whether they 
are in the intervention (Take on Transplant) or attention control (UNOS) group, related to the 
completion of questionnaires and accessing information about lung transplant. Anxiety and 
depression are more common in people with CF than the general public and increase in 
prevalence with increasing CF-related lung disease severity. This study will explore the impact 
of lung transplant education on patients’ psychosocial functioning and assess patients’ and 
physicians’ perceptions and use of lung transplant education. Lung transplant is a sensitive 
topic, raising concerns about mortality, health complications, and financial stress. There is a 
risk that exposure to lung transplant educational content could increase anxiety, depression, or 
emotional distress. Additionally, we will evaluate patient-physician dynamics, including implicit 
bias and experience of discrimination, which may also produce an emotional response for 
some participants. However, preliminary testing suggests research participants may 
experience improvement in key outcomes like preparedness for lung transplant discussions, 
transplant knowledge, and decisional conflict about lung transplant. Our recently completed 
pilot RCT (NCT05135156) included 50 people with CF who were enrolled for a 4-week study, 
and only 3 (6%) of participants experienced an AE of special interest (AESI) –suicidality. Of the 
3 participants with an affirmative response to #9 on the PHQ-9, one person reported this twice 
(at V1 prior to randomization and at the 2-week session after using UNOS) and the other two 
people only reported this at baseline (V1). The abnormal PHQ-9 was deemed unrelated to 
study participation in all cases, as depression was an active medical issue under treatment and 
symptoms preceded enrollment in the study. Therefore, while we remain vigilant for potential 
negative effects of participation on mental health, we are encouraged that participants will 
experience low risk during the study and may personally experience benefit from lung 
transplant education.  
 
Identification of Adverse Events and Grading Scale 
Assessment of Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a 

 
 
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patient administered a pharmaceutical product or undergoing an investigational procedure that 
does not necessarily have a causal relationship with the treatment or procedure. An AE is 
therefore any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom or disease temporally associated with the administration of an investigational product 
or procedure, whether or not related to that investigational product. An unexpected AE is one 
of a type not identified in nature, severity, or frequency in the currently accepted risk profile for 
the treatment or procedure. 
 
The UW research staff will probe, via discussion with the participant, for the occurrence of AEs 
during each study visit (baseline, 2-weeks, 3-months, and 6-months) and record the information 
in the study’s records. AEs will be described by duration (start and stop dates and times), 
severity, outcome, treatment, and relation to study procedure, or if unrelated, the cause. 
 
Unanticipated Problems 
According to the Office of Human Research Protections (OHRP), unanticipated problems are: 1. 
Unexpected in the nature, severity or frequency of the event given the research protocol, IRB-
approved informed consent form, and the population under study; 2. Related to participation or 
there is at least a reasonable possibility that the incident, experience, or outcome may have 
been caused by the research procedure; and 3. Suggestive that the research places 
participants at greater risk of harm than was previously recognized or anticipated. Assessment 
for unanticipated problems will occur in the same manner as evaluation for AEs, via research 
staff probing at all study visits, and review of AEs by the study’s Medical Monitor. The Medical 
Monitor review will occur at least quarterly in preparation of safety reports for the DSMB 
(described further in Section E1). If unanticipated problems are identified, corrective actions to 
protect the safety of participants may include changing the study protocol, changing 
inclusion/exclusion criteria, additional monitoring of participants for early detection of problems, 
suspension of research activities, modification of the informed consent form, and/or providing 
information about newly recognized risks to people who previously enrolled in the study.  
 
Assessment of AE Severity and Relationship to Treatment 
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03, as modified for CF, will be used to assess and grade AE severity. If the 
experience is not covered in the modified criteria, the guidelines shown in Table 7 below will be 
used to grade severity. It should be pointed out that the term “severe” is a measure of intensity 
and that a severe AE is not necessarily serious. 
 
Table 7: Adverse Event Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no 
medical intervention or therapy required. The subject may 
be aware of the sign or symptom but tolerates it reasonably 
well. (e.g. fatigue after completing a study visit or reading 
the website for a long time) 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. (e.g. lightheadedness brought 
on by mild anxiety after reading the website about lung 
transplant) 

 
 
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Severe (3) 
Marked limitation in activity, medical intervention/therapy 
required, hospitalization possible. (e.g. significant 
desaturation brought on by severe anxiety/panic after 
reading the website about lung transplant) 
Life-threatening (4) 
The subject is at risk of death due to the adverse experience 
as it occurred. This does not refer to an experience that 
hypothetically might have caused death if it were more 
severe. (e.g. suicide attempt brought on by severe 
depression after reading the website about lung transplant) 
 
The relationship of an AE to the study procedure should be assessed using the following 
guidelines (Table 8): 
 
Table 8: Adverse Event Relationship to Study Procedure 
Relationship to Study Procedure 
Comment 
Definitely 
Previously known risk of procedure (e.g. reading the 
website or participating in a study visit); or an event 
that follows a reasonable temporal sequence from 
performance of the procedure/testing; that follows a 
known or expected physiologic response to the 
procedure; that is confirmed by stopping or reducing 
the intensity of the procedure; and that is not 
explained by any other reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal 
sequence from performance of the procedure; that 
follows a known or expected physiologic response to 
the procedure; that is confirmed by stopping or 
reducing the intensity of the procedure; and that is 
unlikely to be explained by the known characteristics 
of the participant’s clinical state or by other 
interventions. 
Possibly 
An event that follows a reasonable temporal 
sequence from performance of the procedure; that 
follows a known or expected physiologic response to 
the procedure; but that could readily have been 
produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have 
no relationship to the study procedure. 
 
Immediately Reportable Adverse Events 
Definition of Serious Adverse Events (SAE): An SAE is defined as any untoward medical 
occurrence that at any level of procedural intensity: 
• 
Results in death 
• 
Is considered life threatening (i.e., in the view of the Investigator the adverse 
experience places the patient or subject at immediate risk of death from the response, 
as it occurred; it does not include a reaction that, had it occurred in a more severe form, 
might have caused death) 

 
 
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• 
Requires hospital admission or prolongation of an existing hospitalization 
• 
Results in persistent or significant disability/incapacity (i.e., a substantial disruption of a 
person’s ability to conduct normal life functions) 
• 
Is an important medical event (i.e., when based upon appropriate medical judgment, 
the adverse experience may jeopardize the patient or subject and may require medical 
or surgical intervention to prevent one of the above listed outcomes) 
 
For the purposes of this study, participant report of an affirmative response to #9 on the 
PHQ-9 is an immediately reportable AE of special interest, even if it is not an SAE. An 
alternative approach would be to utilize the PHQ-8 (which excludes the question about 
suicide), but it is important to understand whether there is a risk of increasing suicidality 
through the introduction of lung transplant education in this patient population. Avoiding the 
question in our study will not prevent the thoughts/feelings from occurring and we 
determined that it is in the interest of patient safety to include the question about suicidality 
and have a plan in place for responding in the case of this AE. 
 
Management of Adverse Events of Special Interest (Suicidality) 
All study visits that include completion of surveys in REDCap (i.e. PHQ-9) are scheduled to 
ensure the availability of a physician to contact a participant in the event of the report of an 
affirmative response to #9 on the PHQ-9. Dr. Ramos and the UW research facilitator 
receive an instantaneous automatic email alert from REDCap in the setting of an 
affirmative response to #9 on the PHQ-9. The UW research facilitator will notify the 
participant during the Zoom-based study session to expect a call from Dr. Ramos or 
another qualified study physician (Dr. Goss or Dr. Kapnadak, if Dr. Ramos is unavailable). 
The study physician will call the patient within 4 hours of the result, perform the Columbia-
Suicide Severity Rating Scale triage for primary care, provide information for the national 
suicide and crisis hotline (9-8-8), probe for information about the cause of mental health 
symptoms, and establish a safety contract with the patient in the interim, as indicated. Drs. 
Ramos, Goss and Kapnadak have undergone training by a mental health expert with 
expertise in CF and were given specific questions to ask and responses to provide to 
participants with an affirmative response to #9 on the PHQ-9. Additionally, Dr. Ramos or 
the study physician will notify the participant’s CF clinician directly via secure 
communication within 4 hours of the result.  
 
Reporting of SAEs, Unanticipated Problems, and Adverse Events of Special Interest 
(Suicidality)  
All SAEs that occur after a participant signs informed consent until the end of the study 
(whether procedure related or not) that occur within 48 hours of a study visit will be 
documented. SAEs that occur in the interval between study visits will be captured through 
questioning at subsequent study visits (i.e. 2-week, 3-month, and 6-month visits). All SAEs 
will be sent to the Medical Monitor within 24 hours of the identification of the event. All SAE 
and AEs of special interest (suicidality) will be reported to the central IRB in accordance with 
the standard operating procedures and policies of the IRB. Adequate documentation will be 
reviewed by the Medical Monitor to ensure that the IRB was properly notified of SAEs. SAEs 
that are expected (e.g. hospitalization for a CF pulmonary exacerbation) will be reported in 
quarterly safety reports to the DSMB. SAEs that are unexpected and at least possibly related 
to study procedures will be reported to the DSMB and IRB within 7 days (SAEs that are 
unexpected but unrelated to study participation will be included in quarterly safety reports to 

 
 
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the DSMB). All unanticipated problems will be reported within 7 days of identification. All 
episodes of reported possible suicidality documented on PHQ-9 (an affirmative response to 
#9 on the PHQ-9) administered during study visits, regardless of relatedness to study 
participation, will be reported to the Medical Monitor within 24 hours, to the DSMB within 2 
working days, and to the central IRB within 2 working days. Additionally, the patient’s CF 
clinician will be contacted directly immediately via secure communication, by the PI (Dr. 
Ramos), and a safety contract established with the patient by phone in the interim. If Dr. 
Ramos is unavailable, Dr. Goss (co-I) or Dr. Kapnadak (co-I) will perform these duties. The 
DSMB Chair will review the SAE, unanticipated problem, or AE of special interest 
(suicidality) and determine if a review by the full committee is warranted. Additional 
information or data summaries may also be requested by the DSMB at this time. In the event 
of an unanticipated problem, the PI will notify all participating clinical sites within 14 days, 
allowing time for review by the DSMB and IRB. All other SAEs and all other non-serious 
adverse events will be summarized as specified in the comprehensive quarterly safety 
reports to the DSMB. The results of DSMB and IRB reviews will be communicated to NINR 
within 7 days of the summary report or IRB action (Section E8).  
E5 Monitoring of multi-site study 
Monitoring schedule  
The UW research team will conduct a site initiation visit prior to recruitment of participants and 
will conduct quarterly remote monitoring visits during the active recruitment and enrollment 
phases of the trial. All investigators and research staff (e.g. research coordinators) will attend a 
monthly investigator call via videoconferencing (e.g. Zoom).  
 
Site initiation 
The site initiation visit will occur in person or virtually prior to recruitment of participants from 
each clinical site. This meeting will include the rationale for the proposed RCT, an overview of 
the protocol, and a description of the plan to oversample patients from communities of concern. 
All members of the CF clinical team will be invited to attend. The clinical team will contribute 
ideas to engaging difficult to reach patients who may benefit the most from the proposed 
intervention. Local champions for the study will be identified during the site initiation meeting. 
Review of regulatory documents and milestones will occur with the site PI and research staff. 
We will ensure all study supplies have been delivered (e.g. audio recorder, printed materials). 
All CF physicians will be consented for participation in advance of the site initiation visit. We will 
review screening log templates and eCRFs. We will review communication plans in the event of 
an AE of special interest (suicidality) including email addresses and cell phone numbers for 
relevant clinical staff.  
 
Monthly investigator calls 
Monthly investigator calls will occur via Zoom and will be recorded. The recording will be 
distributed to all sites within 2 business days of the meeting. The monthly investigator calls will 
focus on study operations, including updates on recruitment, retention, and targets for 
enrollment. We will highlight the number of participants from communities of concern and 
provide strategies for engaging this population. Local champions will also be invited to join the 
calls. We will also highlight issues with data entry and provide feedback to all sites to aid in 
complete and accurate data entry from the EHR. We will provide updates after DSMB meetings 
or whenever changes to the protocol are under consideration.  

 
 
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Quarterly monitoring visits 
Quarterly monitoring visits provide opportunities for communication about difficulties with 
recruitment, retention, study protocols, or other aspects of the clinical trial. Sites will provide up-
to-date screening logs for recruitment. Local champions will be invited to join when we review 
recruitment and enrollment numbers. The monitoring visit will include an audit of investigator 
compliance with IRB regulations and the study protocol. Completeness and accuracy of data 
entry will be reviewed during quarterly monitoring visits with each site. We will verify source 
documents for completed eCRFs. We will review CF clinic visit recording transmissions and 
ensure that recording devices have been promptly erased. Milestones will be reviewed and 
payments will be confirmed. At the end of the visit, Dr. Ramos (PI) will meet one-on-one with the 
site PI to discuss any additional issues related to trial conduct and review action items from the 
monitoring visit. 
E6 Assessment of external factors impacting participant safety 
Dr. Ramos (PI) will review the literature every 6 months to ensure there are no new reports or 
studies that would impact the safety of participants or the ethics of continuing the study. 
Additionally, Dr. Ramos serves as an ad hoc reviewer for multiple prominent journals in the field 
(e.g. Journal of Cystic Fibrosis, Journal of Heart and Lung Transplantation, American Journal of 
Respiratory and Critical Care Medicine, CHEST) and is often asked to review manuscripts that 
address advanced CF lung disease and lung transplantation, which keeps her informed of the 
newest findings. Co-investigators will also notify Dr. Ramos if they become aware of new data 
relevant to this project. Dr. Ramos will summarize the literature for the progress report to the 
DSMB every 6 months.  
E7 Interim analysis 
There will be one planned interim safety analysis. The DSMB will review the following activities 
associated with the intervention’s evaluation: 1) participants’ PHQ-9 and GAD-7 scores; and 2) 
episodes of reported possible suicidality (an affirmative response to #9 on the PHQ-9). The 
DSMB will monitor for rates of suicidality and the new onset of PHQ-9 or GAD-7 scores 
consistent with depression or anxiety, respectively, in both arms of the RCT.  
 
The DSMB will be provided the following formal stopping rules involving the safety endpoint of 
the rate of suicidality (an affirmative response to #9 on the PHQ-9), an AE of special interest. 
This stopping rule was constructed to permit early detection of a higher than anticipated AE rate 
in study participants and has known operating characteristics. While the DSMB is an 
independent body whose recommendations are not bound by these rules, it is anticipated that 
deviations from this stopping rule will be well-founded and explained in DSMB documentation. 
The stopping rule is subject to discussion and change during the first meeting of the DSMB 
when the Charter is formed, prior to the enrollment of any patients in the RCT. 
 
We plan to stop our study early if the observed AE of special interest (suicidality) rate among all 
who are enrolled, or among the Take on Transplant arm, exceeds 30% (>3X that observed in 
observational studies of outpatient CF patients), which may signal excessive harm from study 
participation. Specifically, we will use Fleming stopping rules to detect a high rate of AE of 
special interest during an interim analysis. With 35 persons enrolled, we have 93% power to 
identify an event rate of at least 30% versus the expected rate of only 10%. We will recommend 

 
 
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stopping for harm after 35 persons are enrolled if there are >10 participants with AE of special 
interest events (regardless of study arm). Additionally, the DSMB will compare AE of special 
interest rates in the two trial arms. These rules provide a low (<6%) probability of erroneously 
stopping the trial early if study participation is not associated with increased risk of suicidality. 
Ongoing monitoring of rates of suicidality, in addition to PHQ-9 and GAD-7 scores, will continue 
via quarterly safety reports and formal DSMB meetings every 6 months while patients are 
participating in the RCT. Of note, as described above, the pilot RCT of this intervention included 
50 people with CF who were enrolled for a 4-week study, and only 3 (6%) participants 
experienced this AE of special interest.  
 
There will be no interim statistical analyses to assess for futility of efficacy as this population will 
be eligible for other CF trials concurrently with this non-pharmacological intervention. 
E8 Communication plan 
The study team includes Clinical Coordination/Study Management by the PI, Dr. Ramos, and 
the UW research team. UW will serve as the clinical and data coordinating center for the clinical 
trial. This study organization will ensure subject and data safety, timely and accurate data 
collection, appropriate interpretation and dissemination of positive or negative study findings, 
and timely communication with relevant stakeholders. The organizational chart is shown in 
Figure 2 (above).  
 
In the development of this proposal Drs. Ramos, Berry, Hartzler, Kapnadak, Basile, and Mrs. 
Bartlett had weekly Zoom meetings with email communications interspersed between the calls 
for 6 months as part of their planning efforts to prepare for this proposed clinical trial. Drs. 
Smith, Goss, Lober, and Riekert had individual calls with Dr. Ramos over the same timeframe 
and contributed to the study design via calls and email correspondence. All collaborating site 
PIs met with Dr. Ramos via Zoom on at least 4 occasions over the past 10 months to discuss 
the Approach and feasibility of this RCT. All collaborating site PIs reviewed the entire research 
strategy multiple times and contributed to the final product. Dr. Ramos and the UW research 
team value the input of collaborators and will continue to meet as a group of primary 
investigators 1-2 times per week throughout the study. Additionally, Dr. Ramos will participate in 
monthly clinical study conference calls with all trial operations staff (described below). Dr. 
Ramos will also lead study orientation meetings as part of the study initiation and annual update 
meetings for the CF clinical teams. Additionally, meetings may be arranged by the study 
manager or site PIs if any concerns arise with data quality or protocol adherence for the 
duration of the study. Our plan for managing conflicts includes clear communication and 
expectation setting, along with utilizing the experienced mentorship in multicenter RCT 
management of the co-Is. Additionally, we will leverage input from our Steering Committee 
every 6 months and as needed if conflict arises. 
 
Communication Plan Details 
I. 
Dr. Ramos will meet weekly with UW research staff focused on trial operations 
throughout the study. The meetings will focus on: 
• 
Recruitment, with a focus on participants with lower socioeconomic status, 
non-White race, or Hispanic ethnicity (“communities of concern”) 
• 
Retention 

 
 
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• 
Assessment of all site protocol implementation performance 
• 
Status of case report form [and monitoring query] completion 
• 
Payments to sites 
• 
Monthly review of data security, informed consent documentation, and audits 
for IRB compliance 
These meetings with the UW research staff are in addition to project-specific 
meetings with co-investigators. 
II. 
Once per month a meeting with trial operations staff from all collaborating sites will 
include all aspects of study operations. 
At a minimum this will include: 
• 
Kathleen Ramos (PI) 
• 
Joseph Pilewski (site PI) 
• 
Jordan Dunitz (site PI) 
• 
Milene Saavedra (site PI) 
• 
Charles Bengtson (site PI) 
• 
Joel Mermis (site PI) 
• 
Jonathan Koff (site PI) 
• 
Veronica Indihar (site PI) 
• 
Edmund (Ted) Sears (site PI) 
• 
Grant Turner (site PI) 
• 
Donna Berry (co-I) 
• 
Christopher Goss (co-I) 
• 
Siddhartha Kapnadak (co-I) 
• 
Andrea Hartzler (co-I) 
• 
Melissa Basile (co-I) 
• 
Nicole Mayer-Hamblett (co-I) 
• 
Kristin Riekert (co-I) 
• 
Patrick Smith (co-I) 
• 
Lauren Bartlett (UW Research facilitator, data manager) 
• 
Research staff from each collaborating site 
Dr. Ramos will closely oversee the study operations with additional electronic, 
phone, or in-person meetings on an as-needed basis. Dr. Ramos and the site PIs 
will plan on a bi-monthly phone meeting during the early phases of the study to 
discuss progress and milestone management. This meeting may be replaced by 
an email every 2 weeks as the trial progresses and the needs shift, but at a 
minimum a monthly call will remain in place throughout the study. 
III. 
Dr. Ramos will conduct a site initiation visit (in person or remotely) with each 
collaborating site (Section E5). 
IV. 
The UW research team will conduct quarterly remote monitoring visits during the 
active recruitment and enrollment phases of the trial (Section E5). 
V. 
Annual CF clinical team updates will provide updates about enrollment, changes to 

 
 
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the protocol, and initial findings (as applicable). These annual updates will be via 
Zoom and recorded.  
 
Communication with the DSMB, IRB, and NINR 
Dr. Ramos (PI) is responsible for overseeing and ensuring timely communication with the 
DSMB, IRB, and NINR (Table 9). The Medical Monitor will communicate directly to the DSMB 
during DSMB meetings every 6 months or more often if there is a concern for participant safety. 
The PI will report to the DSMBin quarterly safety reports and every 6 months with a summary of 
the status of the RCT, AEs, problems encountered, site performance, and any proposed 
changes to the protocol. The PI will communicate at least annually with NINR via a progress 
report describing the research activities and results of DSMB meetings. The PI will 
communication to all collaborating sites, the IRB and NINR if the DSMB recommends changes 
to the protocol. 
 
Table 9: Communication with the DSMB, IRB, and NINR 
Event 
Communication From 
Communication To Timeline 
All AEs, SAEs, 
Unanticipated Problems 
UW research team 
Medical Monitor 
Within 24 hours of 
identification of 
event 
All non-serious AEs, 
Expected SAEs or 
Unexpected SAEs 
unrelated to study 
participation 
Medical Monitor and 
Dr. Ramos (PI) 
DSMB 
With quarterly 
safety report prior 
to DSMB meeting 
Unexpected SAE at 
least possibly related to 
study participation 
Medical Monitor and 
Dr. Ramos (PI) 
DSMB, IRB, NINR 
Within 7 days of 
identification of 
event 
Unanticipated problem 
Dr. Ramos (PI) 
DSMB, IRB, NINR 
Within 7 days of 
identification of 
event 
Unanticipated problem 
Dr. Ramos (PI) 
All collaborating 
sites 
Within 14 days of 
identification of 
event 
AE of special interest – 
suicidality at least 
possibly related to study 
participation 
Dr. Ramos (PI) 
DSMB, IRB, NINR 
Within 2 business 
days of event 
AE of special interest – 
suicidality unrelated to 
study participation 
Dr. Ramos (PI) 
DSMB, IRB 
Within 2 business 
days of event 
Final DSMB summary 
report 
DSMB Chair 
Dr. Ramos (PI) 
Within 14 days of 
DSMB meeting  

 
 
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Final DSMB summary 
report and any action 
plan or response to the 
summary report 
Dr. Ramos (PI) 
IRB, NINR 
Within 7 days of 
receiving the final 
report from the 
DMC chair  
IRB actions 
Dr. Ramos (PI) 
NINR, DSMB 
Within 7 days of 
notification  
Changes or 
amendments to protocol 
or consent form 
Dr. Ramos (PI) 
NINR, DSMB 
Prior to making 
changes and 
within 7 days of 
completion of 
changes 
Changes or 
amendments to protocol 
or consent form 
Dr. Ramos (PI) 
All collaborating 
sites 
Within 7 days of 
completion of 
changes 
AE: adverse event; SAE: serious adverse event; DSMB: Data Safety Monitoring Board; 
IRB: central IRB (Advarra); NINR: National Institute of Nursing Research 
F Statistical Plan  
F1  Sample Size Determination and Power 
Aim 1:  
Assuming 6% attrition from 132, a total sample size of 125 yields 80% power to detect a 
PrepDM score difference between UNOS and ToT means of 8.9 with a SD of 18.8, equivalent to 
an effect size of 0.48, using a test with 2-sided alpha = 0.05 obtained from a mixed model fit 
without treatment-by-center interaction and assuming the intraclass correlation for site is 0.1 
(Table 10).[54] This is a reasonable expectation based on preliminary results of the pilot RCT. 
 
Table 10: Standardized effect sizes and (in parentheses) detectable between-arm mean 
score differences for PrepDM score at 3 months (primary endpoint) 
 
 
Total N including both arms 
Power 
SD* 
100 
125 
150 
80% 
18.8 
0.53 (10.0) 
0.48 (8.9) 
0.43 (8.2 
90% 
18.8 
0.62 (11.6) 
0.55 (10.3) 
0.50 (9.4) 
*Standard deviation of PrepDM score in pilot RCT 
 
Aim 1 secondary endpoints 
There is no minimally clinically important change in Decisional Conflict Scale, though scores 
lower than 25 are associated with implementing decisions and scores exceeding 37.5 are 
associated with decision delay or feeling unsure about implementation.[55] For PHQ-9, 
minimally clinically important difference is 5. 
 
For secondary change outcomes from baseline to 3 months, we will have 80% power to detect 
between-arm differences: 
• 
Patient-reported preparedness for LTx discussions on a Likert scale of 1-4: change 
of 0.6 (SD 1.2) 

 
 
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• 
Decisional Conflict Score: change of 12.4 (SD 26) 
• 
LTx knowledge (percent correct out of 14 questions): change of 9 percentage points 
(SD 19) 
• 
For PHQ-9 scores: change of 2.0 (SD 4.2) 
 
The SDM-Q-9 has been used widely in international populations and has a Cronbach’s α 
coefficient of 0.88; a change in SDM-Q-9 of 12 to 15 has been considered clinically meaningful. 
A sample size of 125 yields 80% power to detect a difference between UNOS and ToT means: 
• 
SDM-Q-9 score difference between UNOS and ToT means of 12.4 with a SD of 26, 
equivalent to an effect size of 0.48, using a test with 2-sided alpha = 0.05 obtained 
from a mixed model fit without treatment-by-center interaction and assuming the 
intraclass correlation for site is 0.1. 
• 
For SDM-Q-doc scores, a between-arm detectable difference in means of 10.5 (SD 
22) 
• 
For OPTION scores, a between-arm detectable difference in means of 7.1 (SD 8.3) 
 
Aim 2: 
For qualitative studies, sample size is determined by achieving theoretical saturation (i.e., when 
no new themes emerge). For Aim 2, we plan to record all clinic visits. It is unknown how often 
clinic visits will contain discussions of LTx. Qualitative analyses will continue simultaneously 
with recruitment of participants. We aim to record visits until we reach a number sufficient to 
identify markers of high-quality LTx discussions, learn more about what it takes to empower a 
patient to raise the topic of LTx, and understand if/how we could intervene to get CF physicians 
ready for LTx conversations. Our analyses will also involve assessment for implicit bias in the 
recordings (e.g. speech rate, verbal dominance) and whether the topic of LTx is raised with 
different frequency among participants from communities of concern. If saturation is achieved in 
these qualitative analyses, we may stop recording clinic visits. 
F2 Analysis Plan 
Aim 1: 
The primary statistical analyses will be intention-to-treat to avoid confounding by non-random 
participant attrition. Demographics, clinical characteristics, and survey responses will be 
summarized at each time-point using descriptive statistics: frequencies and proportions for 
categorical variables, means and standard deviations for continuous variables, or median and 
interquartile range if the distribution is markedly skewed. Analyses will be adjusted for 
randomization strata CF Center, FEV1% predicted, and communities of concern status, as well 
as baseline characteristics clearly imbalanced between groups. 
 
Primary outcome: The primary outcome is PrepDM[29] at 3 months (V3) and the primary 
analysis will compare mean PrepDM score between the ToT and UNOS arms using 
linear mixed models. 
 
Secondary outcomes: Key secondary outcomes include change in Decisional Conflict 
Scale[32], change in Likert scale rating of preparedness to discuss LTx, change in LTx 
knowledge, and change in PHQ-9[36], GAD-7[35], General Self-Efficacy Scale[37], and 
Perceived Social Support Scale[46] from baseline to 3 months (V3). Secondary analyses 
will compare mean change between ToT and UNOS using linear mixed models. 

 
 
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Because amount of change depends on the initial score at baseline, we will control for 
baseline score as a covariate in the regression. Other secondary analyses will include 
between-arm comparisons of SDM-Q-9, SDM-Q-doc, documentation of LTx discussions 
or LTx referral, and ratings of satisfaction with the LTx discussion. Analyses will account 
for the presence/absence and timing of a CF clinic visit. 
 
Sensitivity analyses: We will compare results of the full RCT to those of the pilot RCT by 
assessing outcomes at 2 weeks (V2). We will describe baseline values and changes in the 
primary and key secondary outcomes between patients from smaller vs larger CF Centers, CF 
Centers located with a LTx Program versus without a LTx Program, those with higher versus 
lower FEV1% predicted (≥ or <30%), those with Medicaid versus non-Medicaid insurance, and 
those who report a prior LTx discussion with their CF physician at V1 versus those who have 
not discussed LTx. For explanatory purposes, we will consider models to test for a potential 
dose-response relationship by estimating the association between change in PrepDM from V2 
to V3 and the predictor: time spent using ToT or UNOS. The dose-response relationship will 
also be tested for the outcome of Decisional Conflict Scale change between pre-intervention 
baseline (V1) and V2 and V3. For participants in the UNOS arm (gain access to both websites 
after 3 months), changes in 3-month to 6-month outcome measures within patient, from pre- to 
post-ToT, will be measured. We will evaluate for response to the intervention by gender in the 
primary and key secondary outcomes and explore usage patterns by gender, given that women 
and men may approach LTx education differently. 
 
Communities of concern and low health literacy: The largest potential impact may be among 
communities of concern. We will compare baseline knowledge, preparedness, and decisional 
conflict among those from communities of concern to the rest of the cohort. We will use 
graphical methods and descriptive statistics to evaluate differences in usage and outcomes 
across subsets of the cohort with different SES (insurance status, education level, 
race/ethnicity, income) and health literacy (S-TOFHLA, Newest Vital Sign, digital literacy). 
 
Aim 2: 
Analysis of clinic transcripts: Audio recordings may be listened to and/or be transcribed and will 
be read in parallel with the data collection process toward achieving data saturation. Recordings 
will be listened to by at least two members of the study team for assessment or implicit bias 
(e.g. speech rate, verbal dominance) and whether the topic of LTx is raised with different 
frequency among participants from communities of concern. Initial transcripts will be read by at 
least 2 members of the study team using a deductive approach based on a provisional coding 
frame developed from: a) our earlier qualitative research, b) domains of the Health Beliefs 
Model constructs c) whether and how LTx was discussed in clinic and d) our a priori interest in 
assessing TOT and UNOS.[57] Using the Observing Patient Involvement in Decision Making 
(OPTION) Scale[58] for observer rating of shared decision making and an objective analysis of 
what occurred during the visit, researchers will evaluate the LTx discussion (audio and/or 
transcript). After coding the first transcript, the coders and the PI will discuss coding 
discrepancies and reach agreement on code application before proceeding to the next 
transcript. At each stage, categories will be analyzed independently and compared and 
contrasted across the data to confirm/identify themes by consensus.[59] This approach will 
continue until we have reconciled codes for at least six transcripts.[60] The coding frames will 
be iteratively revised based on how the initial codes and definitions have evolved, including new 
codes generated inductively. In developing the codebook, the study team will select appropriate 

 
 
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excerpts from transcripts and identify exemplar quotes that reflect themes. A final codebook (i.e. 
coding manual) with categories and subcategories, exemplar quotes, inclusion and exclusion 
criteria will be provided to coders and then all transcripts will be re-coded using the final 
codebook. All transcripts will be coded by two coders.[61] Transcripts will be coded in Atlas.ti, a 
qualitative analysis program with which our team has experience. We will calculate intercoder 
reliability for each dataset at intervals of 5, 10 and 20 “batches” of transcripts and a final coding 
comparison will be competed after all transcripts have been coded.[62]  
G Data Handling and Record Keeping  
G1 Confidentiality and Security 
All study documents will be kept in a secured locked office or on a password-protected 
computer. Study participants will not be identified by name in the study database, but will be 
identified by a subject identification number unique to this study. Only authorized individuals will 
be able to link the study ID to the subject’s name. All investigators and staff involved in the 
proposed research will have completed human subjects’ protection training, have HIPAA 
training, and be bound by the agreement of confidentiality. Study data from all sites will be 
captured using a University of Washington REDCap installation maintained on a secure server. 
All study databases will be maintained at the UW on password protected computers and backed 
up to an encoded password protected file. All procedures for the handling and analysis of data 
will be conducted using good clinical practices meeting FDA guidelines for the handling and 
analysis of data for clinical trials. 
G2 Data Sharing and Possible Secondary Use 
Results of analyses of these data will be made available publicly, but access to the data will be 
limited to individuals approved by the investigators and the Institutional Review Board at UW.  
 
All data obtained and collected for this study may be de-identified and used for future research 
not described in this protocol and/or shared with other researchers if appropriate IRB approval is 
obtained and data use agreements are established. Dr. Ramos will oversee and manage the 
sharing of this data. Data may be used for research regarding CF populations, recruitment of 
diverse clinical research participants, and/or lung transplant. 
H Study Administration 
H1 Organization and Participating Centers 
 
Lead/Coordinating Site 
Personnel/Role 
University of Washington* 
UWMC – Montlake 
1959 NE Pacific Street 
Seattle, WA 98195 
Kathleen Ramos, MD MSc 
Lead PI 
Donna Berry, PhD MSN 
Co-I 
Christopher Goss, MD MSc 
Co-I 

 
 
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Siddhartha Kapnadak, MD 
Co-I 
Andrea Hartzler, PhD 
Co-I 
William Lober, MD MS 
Co-I 
Clinical Informatics Research 
Group (CIRG) 
Data 
Management 
Non-Recruiting Research Locations 
Personnel/Role 
Northwell Health** 
Melissa Basile, PhD 
Co-I 
Seattle Children’s Hospital+ 
Seattle Children’s Research Institute 
1920 Terry Ave 
Seattle, WA 98101 
Nicole Mayer-Hamblett, PhD 
Co-I 
Miranda Bradford, MS 
Biostatistician 
University of North Carolina at Chapel Hill** 
Patrick Smith, PhD MPH 
Co-I 
Johns Hopkins University** 
Kristin Reikert, PhD 
Co-I 
Research Locations* 
Personnel/Role 
University of Minnesota 
MHealth Clinics and Surgery Center 
909 Fulton Street SE 
Minneapolis, MN 55455 
 
MN Cystic Fibrosis Center,  
420 Delaware Street SE, MMC 742 
Minneapolis, MN, 55455 
Jordan Dunitz, MD 
Site PI 
University of Pittsburgh  
UPMC Children’s Hospital of Pittsburgh 
4401 Penn Avenue 
Pittsburgh, PA 15224 
Joseph Pilewski, MD 
Site PI 
National Jewish Health 
1400 Jackson Street 
Denver, CO 80206 
Milene Saavedra, MD 
Site PI 
University of Kansas  
University of Kansas Medical Center 
3901 Rainbow Blvd 
Kansas City, KS 66160 
Charles Bengtson, MD 
Co-Site PI 
Joel Mermis, MD 
Co-Site PI 
Yale University 
6 Devine Street  
North Haven, CT 06473 
Jonathan Koff, MD 
Site PI 
University of Cincinnati 
UC Health Holmes 
200 Albert Sabin Way 
Cincinnati, OH 45220 
Veronica Indihar, MD 
Site PI 
Maine Health 
Maine Medical Center 
22 Bramhall Street 
Edmund (Ted) Sears, MD 
Site PI 

 
 
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Portland, ME 04102 
University of California, Los Angeles 
UCLA Health  
200 Medical Plaza 
Los Angeles, CA 90095 
Grant Turner, MD MHA FACP 
Site PI 
*All research locations involved in recruiting and engaged in study procedures will designate a study 
staff team of research coordinators, research nurses, research assistants, etc. All study responsibilities 
will be recorded in a study delegation log. 
**Indicated non-recruiting research locations will only participate in the analysis of de-identified data, 
study interpretation, manuscript preparation, etc. 
+Indicated non-recruiting research location will only participate in the analysis of identifiable data, study 
interpretation, manuscript preparation, etc. 
H2 Study Timetable 
Study timelines below reflect approximations. Timelines will be used as a guideline for study 
sites and may change as necessary. Enrollment numbers do not reflect participants who may be 
lost to follow-up. 
 
Study Timeline 
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Month 
1-6 
6-12 
1-6 
6-12 
1-6 
6-12 
1-12 
1-12 
Start-up Activities: 
Regulatory approvals  
x 
 
 
 
 
 
 
 
Site orientation, annual meetings 
x 
 
x 
 
x 
 
 
 
Data Safety Monitoring Board (initiate and form charter; 
meet every 6 months while patients are enrolled in Aim 1) 
x 
x 
x 
x 
x 
x 
 
 
Specific Aim 1:  
 
 
 
Trial enrollment (# of patients) 
 
35 
33 
32 
32 
 
 
 
Data preparation and interpretation 
 
 
 
 
x 
x 
x 
x 
Manuscripts: write, submit 
 
 
 
 
x 
x 
x 
x 
Follow up with cystic fibrosis clinic for clinical outcomes 
 
 
 
 
 
 
x 
x 
CIRG data collection ongoing 
 
x 
x 
x 
x 
x 
 
 
Specific Aim 2: 
 
Clinic visits recorded (# of visits) 
 
35 
33 
32 
32 
 
 
 
Data preparation, analysis, and interpretation 
 
x 
x 
x 
x 
x 
x 
x 
Manuscripts: write, submit 
 
 
 
 
 
x 
x 
x 
Refine Take on Transplant for communities of concern 
 
 
 
 
 
 
 
x 
Close-out Activities: 
Regulatory close out 
 
 
 
 
 
 
 
x 
 
Site Enrollment Timeline 
Research Location 
Year 1 
Year 2 
Year 3 
Total* 
University of Washington 
7 
12 
8 
27 
University of Pittsburgh 
7 
12 
6 
25 
University of Minnesota 
7 
12 
6 
25 
National Jewish Health 
7 
12 
6 
25 
University of Kansas  
3 
5 
2 
10 
University of California at Los Angeles (UCLA) 
1 
3 
1 
5 
Yale University 
1 
3 
1 
5 
University of Cincinnati 
1 
3 
1 
5 
Maine Medical Center 
1 
3 
1 
5 
CF Patient Participant Total* 
35 
65 
32 
132 

 
 
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* Totals may exceed the number of participants needed for analysis due to attrition.  
I 
Dissemination & Publication 
I1 
Plans for publications 
After completion of all study procedures and analyses, results will be interpreted with the help of 
all participating site PIs. All manuscripts will be submitted to a peer-reviewed journal for 
publication. This publication will be available through PubMed, the free resource developed and 
maintained by the National Center for Biotechnology information, at the U.S. National Library of 
Medicine, located at the National Institutes of Health. Results of analyses will be made available 
publicly, but access to the data will be limited to individuals approved by the investigators and 
applicable Institutional Review Boards. 
I2 
Dissemination Plan 
The proposed multicenter randomized clinical trial will be registered on ClinicalTrials.gov and 
results will be submitted according to policy. Dr. Ramos (PI) will be responsible for ensuring all 
regulatory requirements are met, including registering and updating the study on 
ClinicalTrials.gov. Key time points for registration and submission of results will be adhered to, 
including registration on ClinicalTrials.gov not later than 21 calendar days after the enrollment of 
the first participant. Results from this trial will be submitted not later than one year after the trial's 
primary completion date. The informed consent document will contain a statement relating to 
posting clinical trial information at ClinicalTrials.gov. 
 
We will also present our results at national meetings (e.g. the North American Cystic Fibrosis 
Conference, the American Thoracic Society Annual Conference, the International Society for 
Heart and Lung Transplantation Annual Meeting). 
 
All participants will be informed about the results of the study via a letter to their Cystic Fibrosis 
Center after the results of the study are publicly presented. Additionally, results will be shared 
with the CF community via the Cystic Fibrosis Foundation’s Community Voice. Community 
Voice is an empowering volunteer opportunity for people with CF to share their experiences, 
perspectives, and knowledge, bringing their insights and priorities to the forefront of CF 
research, care, and programs. The Community Voice has a monthly newsletter that highlights 
research that is relevant to individuals with CF and their caregivers. We leveraged Community 
Voice participation in the pilot testing of Take on Transplant and we share project updates with 
them regularly (including grants, manuscripts, and new projects). We will disseminate results of 
the clinical trial via the Community Voice newsletter. 
J 
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