Preparing Spanish-speaking Older Adults for Advance Care Planning and Medical Decision Making
Phase: NA
Conditions: Chronic Disease
Sponsor: University of California, San Francisco

Preparing Spanish-speaking Older Adults for Advance Care Planning and Medical 
Decision Making 
This trial is registered at ClinicalTrials.gov: NCT01990235 for English-speakers, registered on 
November 4th, 2013. 
This document includes the following items: 
1. Original protocol and statistical analysis plan (March 2013)
2. Final protocol and statistical analysis plan and summary of changes (September 2017)

3 
Protocol 
12 
Original Version 
13 
March 2013 
14 
15 

 
 
4 
Original Protocol Table of Contents 
16 
Funding 
5 
ClinicalTrials.gov Information 
5 
Introduction and Rationale 
5 
Preliminary Studies 
6 
Overview of the Trial Design 
8 
Study Setting 
10 
Participants and Eligibility and Exclusion Criteria 
10 
Recruitment Methods 
13 
Consent Procedures 
15 
Intervention and Comparison Conditions 
16 
Randomization Procedures 
18 
Blinding 
18 
Intervention Fidelity 
18 
Data Collection Methods 
19 
Follow-up and Retention 
19 
Measures 
20 
Statistical Analysis Plan 
24 
Sample Size and Power Calculations 
25 
Ethics and Advisory Committees 
26 
Human Subjects Protections 
27 
Data Safety Monitoring Plan 
30 
Charter of the Data and Safety Monitoring Board 
31 
Patient-Clinician Stakeholder Advisory Committee Role 
35 
References 
37 

 
 
5 
FUNDING  
17 
For this trial, recruitment of English-speaking older adults is funded through a National Institute 
18 
on Aging R01 grant (R01 AG045043). 
19 
 
20 
CLINICALTRIALS.GOV INFORMATION 
21 
This trial is registered at ClinicalTrials.gov: NCT01990235 for English-speakers, registered on 
22 
November 4th, 2013. 
23 
 
24 
INTRODUCTION AND RATIONALE 
25 
Millions of older adults will face complex medical decisions over the course of advanced illness,2  
26 
yet most are unprepared.3,4 Lack of preparation can lead to uninformed choices, receipt of care 
27 
inconsistent with personal goals, and lack of patient empowerment during clinical encounters,5-9 
28 
especially for individuals with limited health literacy.10 Conventional preparation, called advance 
29 
care planning (ACP), has typically focused on having patients pre-specify preferences for life 
30 
prolonging procedures, such as mechanical ventilation, and to document these choices in an 
31 
advance directive (AD).11 Yet, ADs are hard to understand and are often not completed, 
32 
especially by minorities.12,13 And, even when ADs are completed, they often fail to affect the 
33 
care received at the end-of-life, decrease the stress of decision making, or result in what most 
34 
experts agree is the most important component of ACP – ongoing conversations between 
35 
patients, their loved ones (surrogates), and clinicians.5,14-17 To overcome these limitations, we 
36 
developed a new paradigm of ACP that focuses instead on preparing diverse, older adults to 
37 
communicate their evolving wishes over time and to make real-time, complex medical decisions 
38 
over the course of chronic and advanced illness.11 We propose to test this new paradigm of 
39 
ACP using a patient-centered, interactive website in a double-blind, randomized, efficacy trial. 
40 
 
41 
 
42 

 
 
6 
 
43 
PRELIMINARY STUDIES 
44 
We have experience conducting RCTs among diverse, older adults at the San Francisco 
45 
Health Network (SFHN).18 Dr. Sudore designed and tested an AD written at a 5th grade 
46 
reading level among 205 chronically ill, diverse, older adults from San Francisco General 
47 
Hospital (SFGH) with a 6-month follow-up of 85%. The AD was preferred over a standard AD, 
48 
with significant interactions for limited literacy (e.g., higher preference rates in patients with 
49 
limited literacy). It also resulted in greater 6-month AD completion rates (15% vs. 7%, p =.03), 
50 
doubling the rates from baseline. This AD has been adopted as the official AD for SFGH and is 
51 
being disseminated in California. It will serve as the active control. 
52 
We designed and tested an informed consent process for diverse, older adults with 
53 
limited literacy.19 We found that many patients do not understand simplified consent 
54 
information and were unsure how to ask questions. But, informed decisions can be improved by 
55 
providing both easy-to-read materials and a teach-back method. We will use this interactive 
56 
consent method for this study. 
57 
Multiple steps of the ACP process:20 We found that most patients go through a series of ACP 
58 
behavioral steps. Six months after exposure to the easy-to-read AD, 61% of older adults 
59 
contemplated ACP, 56% discussed ACP with family or friends and 22% with clinicians, and 13% 
60 
completed an AD. This work shows that measuring a full range of ACP outcomes, in addition to 
61 
ADs, and associated behavior change steps (contemplation to action) is important and informs 
62 
our study outcomes. Previously described barriers to ACP, such as not wanting to burden 
63 
family,21 are addressed in PREPARE. 
64 
Evidence supporting the new ACP paradigm and content of PREPARE:22 We completed 13 
65 
focus groups with 69 diverse, English- and Spanish-speaking older patients (mean age 78 +/- 8, 
66 

 
 
7 
61% non- White) and surrogates (mean age 57 +/- 10, 91% non-White) from safety-net settings 
67 
who reported making serious medical decisions. We used semi-structured interviews to ask 
68 
about what best prepared them for decision making. Qualitative analysis identified 5 overarching 
69 
themes, beyond ADs, that prepared patients and surrogates for decision making: (1) choose 
70 
surrogates wisely and verify they know their role, (2) identify goals based on past experiences 
71 
and personal values, (3) decide whether to grant leeway in surrogate decision making, (4) 
72 
inform other family and friends of one’s wishes to prevent conflict, and (5) ask clinicians 
73 
questions. These themes have been incorporated as educational domains of PREPARE. 
74 
Validity and reliability of the survey to measure ACP engagement: Surveys were designed 
75 
with input from Co-Is and extensive cognitive interviews to measure discrete ACP actions (i.e., 
76 
main outcomes: ACP discussions, AD completion,) and ACP behavior change (e.g., 
77 
contemplation, self-efficacy, readiness). We recruited 50 older adults, aged ≥ 60 years with ≥ 2 
78 
illnesses (32% female, 42% non-White). Internal consistency 7-day test-retest reliability, and 
79 
discriminant validity (scores compared to healthy young adults – 50% female, 75% non-White) 
80 
was high. Scores did not differ by race/ethnicity or literacy, p>.05. We will also use validated 
81 
surveys on ACP attitudes and methods to classify patients into behavior change categories.23,24 
82 
Preliminary evidence that PREPARE is beneficial. In a recent pilot,25 we recruited 43 diverse, 
83 
older adults from low-income senior centers. All subjects rated PREPARE easy to use (mean 
84 
9/10-point scale). Pre to post ACP behavior change scores from our validated surveys (0-124 
85 
points) increased from 72 ± 33 SD to 87 ± 22, a 15-point increase and an effect size of 0.5.  
86 
Vulnerable populations have unique needs. The aforementioned pilot demonstrated that, 
87 
unlike our work with Veterans, patients in safety-net settings are less trustful of research and 
88 
require in-person recruitment. In addition, these patients are often socially isolated and require 
89 
tailored ACP for persons without surrogates or families. They also lack ready access to health 
90 

 
 
8 
information and ancillary support such as social workers or nurses necessitating access to ACP 
91 
outside of the clinical environment. These findings add further evidence for the need to tailor 
92 
PREPARE for vulnerable populations and to test PREPARE within safety-net settings. 
 
93 
 
94 
OVERVIEW OF THE TRIAL DESIGN 
95 
Study overview: 
96 
This study is a randomized, controlled trial that uses blinded outcome ascertainment to 
97 
determine the efficacy of the ACP PREPARE website to engage ethnically diverse English- and 
98 
Spanish-speaking older primary care patients in the ACP process.1 First, we obtained a Health 
99 
Insurance Portability and Accountability Act waiver to identify individuals who meet our 
100 
inclusion/exclusion criteria and have upcoming primary care appointments. Administrative data 
101 
and chart review are used to determine potentially eligible patients. 
102 
 
103 
Then primary care clinicians’ permission is obtained to allow the study team to inform their 
104 
patients about the study. Patients are then recruited, screened for eligibility, and scheduled for a 
105 
baseline interview before an upcoming primary care appointment. To standardize the timing of 
106 
exposure to the intervention and primary care follow-up, study participants are scheduled for 
107 
baseline procedures 1-3 weeks prior to an upcoming primary care appointment.26 
108 
 
109 
Next, informed consent is obtained, and those patients who provide consent are randomized to 
110 
the PREPARE intervention arm (i.e., the PREPARE website with action plan exercises plus an 
111 
easy-to-read advance directive plus PREPARE materials to take home, which include a website 
112 
login, and a PREPARE pamphlet, booklet, and DVD) or the control arm (i.e., an easy-to-read 
113 
advance directive alone). See a full description of the intervention below.  
114 
 
115 

 
 
9 
We then conduct blinded outcome ascertainment by performing chart reviews to determine ACP 
116 
documentation at baseline and at the end of the study. We also conduct blinded outcome 
117 
ascertainment using patient surveys at 1 week, and 3, 6, and 12 months after the primary care 
118 
appointment. We are choosing an active control arm (i.e., an easy-to-read advance directive) 
119 
because we believe provision of an advance directive for chronically and seriously ill older 
120 
patients should be the standard of care, even if it is not often “usual” care in clinical practice.8 In 
121 
addition, the easy-to-read advance directive used in this study has been adopted by the San 
122 
Francisco Health Network (SFHN) and San Francisco General Hospital (SFGH) and is available 
123 
in the primary care clinics. 
124 
 
125 
Research Aims and Study Hypotheses: 
126 
The aims of this study are to (1) To determine the efficacy of PREPARE to engage diverse, 
127 
English- and Spanish-speaking older adults with chronic illness in advance care planning (ACP) 
128 
compared to controls (AD only) and (2) To determine whether PREPARE efficacy varies by 
129 
race/ethnicity, literacy, clinician-patient language concordance, and patient’s desired role in 
130 
decision making.1  
131 
 
132 
Our primary hypothesis is that the PREPARE program plus an easy-to-read advance directive 
133 
will result in greater documentation of ACP wishes, including advance directives and 
134 
documentation of ACP discussions in the medical record, than an easy-to-read advance 
135 
directive alone in elderly populations with chronic illness.  
136 
 
137 
Our secondary hypotheses are that, compared to an advance directive alone, PREPARE will 
138 
result in more engagement in behavior change processes concerning ACP, including increased 
139 
self-efficacy and readiness, as well as greater engagement in a full range of ACP actions, 
140 
including discussions with surrogate decision makers and other trusted family and friends. 
141 

 
 
10 
Secondary outcomes will be ascertained using validated surveys.23,27,28 We also hypothesize 
142 
that PREPARE will result in improved satisfaction with patient-doctor communication and 
143 
informed medical decision making and that PREPARE efficacy may vary across moderator 
144 
variables such as patient health literacy, clinician-patient language concordance, and patients’ 
145 
desired role in decision making. 
146 
 
147 
 
148 
STUDY SETTING 
149 
Recruitment for this randomized trial is occurring in 4 separate primary care clinics associated 
150 
with the San Francisco Health Network (SFHN) and the San Francisco General Hospital 
151 
(SFGH) in San Francisco, California. These 4 clinics are housed in 3 separate physical 
152 
locations in San Francisco. SFGH is an urban, public hospital that, with the SFHN, serves 
153 
racially and ethnically diverse, low-income and indigent patients; 30% of patients are Spanish-
154 
speaking.18  
155 
 
156 
PARTICIPANTS AND ELIGIBILITY AND EXCLUSION CRITERIA  
157 
There are no inclusion or exclusion criteria based on gender, race or ethnicity. We assess 
158 
eligibility in person. Older adults are included in this study if they self-report speaking English or 
159 
Spanish “well” or “very well”; are 55 years of age or older; have ≥ 2 chronic illnesses determined 
160 
by chart review; have seen a primary care clinician (physician, nurse practitioner, or physician 
161 
assistant) at SFHN/SFGH-affiliated primary care clinics ≥ 2 times in the past year (an indication 
162 
of established primary care); and have had ≥ 2 additional outpatient or inpatient visits in the past 
163 
year (an indication of severity of illness). Their primary care clinician must also give us 
164 
permission to contact them to tell them about the study.  
165 
 
166 

 
 
11 
We are recruiting patients ≥ 55 years of age (rather than ≥ 65) because adults in safety net 
167 
settings experience accelerated aging, functional decline, and sequelae of chronic disease, 
168 
necessitating decision making and ACP at a younger age than patients with higher 
169 
socioeconomic status.29,30 The goal is to start ACP early to change the trajectory of decision 
170 
making and care over the course of illness. Our inclusion criteria of ≥ 2 primary care visits and ≥ 
171 
2 additional visits in the past year ensures patients have established primary care and access 
172 
care frequently. This will enhance recruitment and follow-up.  
173 
 
174 
Patients will be excluded if their clinician is a principal investigator, co-investigator or clinician-
175 
member of the Patient-Clinician Advisory Board. They will also be excluded if they have medical 
176 
record documentation of being deaf, blind, having dementia, or being psychotic or are deemed 
177 
by their clinician to be too mentally or physically ill to participate. Through in-person or phone 
178 
screening by study staff, patients are also excluded if they self-report vision too poor to read a 
179 
newspaper, lack of a phone (needed for follow-up interviews and scheduling), or plans to be out 
180 
of the country for ≥ 3 months; if they screen positive for moderate-to-severe cognitive 
181 
impairment using the validated Short Portable Mental Status Questionnaire followed by the Mini-
182 
Cog,31-33 or self-report or are determined by study staff to be blind, deaf, intoxicated or actively 
183 
psychotic. Because ACP is an iterative process and people may change their preferences over 
184 
time,11,34 subjects with prior ACP experiences (e.g., an advance directive) are not excluded. 
185 
Inclusion and Exclusion Criteria 

 
 
12 
186 
Inclusion 
Criteria 
55 years of age or older 
Obtains care in the primary care clinics at in the San Francisco Health 
Network (SFHN). 
Has been seen at least twice in the last year by a primary care provider (a 
marker of established primary care) and had at least two additional visits to 
SFHN in the past year (a marker of illness) 
Exclusion 
Criteria 
Clinician is the PI, Co-I or member of the Patient-Clinician Advisory Board 
Dementia by ICD-9/ICD-10 codes, clinician assessment, chart review or self-
report 
Blindness or poor vision by ICD-9/ICD-10 codes, clinician assessment, chart 
review, self-report of blindness or the inability to read print on a newspaper35 
Deafness by ICD-9/ICD-10 codes, clinician assessment, self-report, chart 
review or research staff assessment  
Cognitive impairment as assessed by research staff of any deficits on the 
validated Short Portable Mental Status Questionnaire (SPMSQ)36 and the 
mini-Cog31,37 
Delirium or psychosis as assessed by a clinician or research staff 
Does not report speaking English or Spanish “well” or “very well” 
No phone for additional study contacts and follow-up interviews 
Patients who report they will be out of town during their scheduled follow-up 
interview dates outside of a window of 3 months.  
Patients who cannot answer consent teach-back questions after three 
attempts 

 
 
13 
RECRUITMENT METHODS 
187 
Data Extraction: 
188 
To facilitate recruitment, we obtained a Health Insurance Portability and Accountability Act 
189 
waiver to access patients’ names, age, primary language, phone numbers, addresses, medical 
190 
record numbers, as well as dates of outpatient primary care clinic appointments in the past year 
191 
and up to 3 months in the future, other appointments and hospitalizations and emergency room 
192 
visits in the past year, and the name of patients’ outpatient primary care providers. From these 
193 
data, we obtain a list of potentially eligible patient participants and send a secure email to their 
194 
primary care providers asking for permission for our study team to tell their patients about the 
195 
study through a recruitment opt-out study letter, followed by phone or in-person recruitment. 
196 
Weekly administrative data pulls from the electronic health record identify patients with 
197 
upcoming primary care appointments and are used to target patient recruitment efforts. 
198 
 
199 
Clinician Permission to Contact Patients: 
200 
Upon completion of the administrative data pulls, providers from all recruitment sites are sent a 
201 
letter/e-mail informing them about the research study and asking them to review a list of their 
202 
patients, to refer patient(s) on their patient list who would be appropriate for the study, and to 
203 
obtain permission to contact their patients to tell them more about the study. Clinicians are also 
204 
informed that if the study team receives their approval, their eligible participants will receive a 
205 
letter describing the research study and offering them the opportunity to decline to be contacted 
206 
by research personnel and/or will be contacted in clinic. Additionally, clinicians are informed that 
207 
if they do not respond one week after the 3rd attempt to contact them by the study team 
208 
(including by email, phone, and/or in-person), we will assume assent to contact their patients 
209 
and a letter describing the study will be sent to patients on behalf of the study team. We obtain 
210 
permission from all of the Service Chiefs before their clinicians are contacted. 
211 
 
212 

 
 
14 
Recruitment Methods and Materials: 
213 
Study-related fliers written at a 5th-grade reading level in English and Spanish are posted in 
214 
approved areas in SFHN/SFGH-affiliated primary care clinics. Because many patients may be 
215 
too ill to come to frequent clinic appointments and to be interviewed or hear about the study in 
216 
busy clinic waiting rooms, we include several recruitment strategies. Therefore, in addition, opt-
217 
out letters written at a 5th grade reading level in English and Spanish are mailed and describe 
218 
the research study as well as provide a telephone number to opt-out.  If a clinician gives us 
219 
explicit permission to contact their patients, we will inform patients that their individual doctor 
220 
gave us permission to contact them. If the clinician merely assents by not responding to multiple 
221 
attempts to reach them by study staff, patients will be sent non-personalized letters from the 
222 
study team. Although patients can opt out at any time, those who do not call study staff to 
223 
decline participation within 1 week of the mailings are deemed eligible to be contacted to 
224 
describe the study, assess willingness to participate and assess study eligibility. To standardize 
225 
the timing between intervention exposure and primary care follow-up, we schedule patients for 
226 
the baseline interview and exposure to PREPARE or the control intervention 1 to 3 weeks prior 
227 
to their upcoming primary care appointment. Weekly administrative data pulls from the 
228 
electronic health record identify patients with upcoming primary care appointments and are used 
229 
to target patient recruitment efforts. Potential participants are then contacted in the clinic. 
230 
 
231 
Patients who consent and enroll are paid $25 for a screening interview and $25 for a baseline 
232 
interview as well as given a $10 taxi voucher to come back to follow-up interviews in person if 
233 
they desire.  Participants are also reimbursed $25 for each of the 1-week, 3, 6, and 12-month 
234 
interviews.  
235 
 
236 
Diverse, vulnerable populations are often difficult to recruit for research studies. We employ 
237 
several strategies to enhance our recruitment. First, we attempt to hire individuals who have 
238 

 
 
15 
experience with diverse populations and individuals who are bilingual (native Spanish-speaking) 
239 
and bicultural. Furthermore, we conduct extensive sensitivity training with all research staff and 
240 
require staff to use approved study scripts when speaking to patients. These study scripts and 
241 
all study materials used for recruitment are vetted, updated and approved by both our patient 
242 
advisory and clinical advisory boards. All materials and study scripts are written at a 5th grade 
243 
reading level and are provided to patients in their preferred language (i.e., English or Spanish). 
244 
 
245 
CONSENT PROCEDURES 
246 
We use a modified consent process that several co-authors designed for vulnerable 
247 
populations.19,26 Consent forms written at the 5th grade reading level are provided and read to 
248 
participants in English or Spanish. This review is then followed by standardized “teach-to-goal” 
249 
questions to ensure understanding. If potential participants cannot correctly complete the teach-
250 
back process after 3 attempts, the patient is deemed ineligible.  
251 
 
252 
The consent form has been approved by the UCSF and SFGH Institutional Review Boards, the 
253 
patient/clinical advisory board, and the Data and Safety Monitoring Board (DSMB). The consent 
254 
form states the following for the purpose of the study: “Why is this study being done? 
255 
Sometimes patients and their families have to make hard medical decisions. We want to design 
256 
and test an easy-to-understand handout to help.  This handout will help people think about their 
257 
values, or what is most important to them in their life. It will also help prepare patients to make 
258 
medical decisions.” We use the word “handout” because, in pilot testing, both groups are given 
259 
handout materials and written advance directives. For randomization we explain, “We will ask 
260 
you to look over a handout and answer some questions about your experience with making 
261 
medical decisions. There will be two groups that will be given different handouts. You will have a 
262 
50/50 chance of being in either group.” 
263 
 
264 

 
 
16 
INTERVENTION AND COMPARISON CONDITIONS 
265 
PREPARE arm 
266 
As previously described, PREPARE is an easy-to-use, patient-centered, interactive website that 
267 
is available in English or Spanish, is written at a 5th grade reading level, includes voice-overs of 
268 
all text for the reading-impaired and closed-captioning of all videos for the hearing impaired 
269 
(www.prepareforyourcare.org).25,26 The conceptual framework for PREPARE has been 
270 
previously published and is based based primarily on Social Cognitive Theory, 38,39 with 
271 
elements from the Health Belief Model,40 the Theory of Planned Behavior,41 and Behavior 
272 
Change Theory.39,42 In these theories and in behavioral studies, modeling of behaviors helps 
273 
people change their behavior. Successful behavioral change interventions model skills, enhance 
274 
self-efficacy, and address perceived barriers,43,44 especially literacy-appropriate interventions.18 
275 
Modeling behaviors (as in PREPARE) can also improve patients’ ability to communicate with 
276 
clinicians and improve outcomes,45,46 such as increased question asking behavior and a sense 
277 
of control during a clinical visit,46,47 an increased desire to participate in decision making, and 
278 
even improved affect and functional status.43,48-50  PREPARE incorporates these successful 
279 
teaching methods through the modeling of behaviors in videos. Video and interactive websites 
280 
are more powerful mediums to teach information and change behavior than written materials, 
281 
especially for those with language/literacy barriers.51-57 PREPARE includes a training and goal 
282 
setting component which has been shown to be effective in changing outpatient behaviors, such 
283 
as exercise.58  
284 
 
285 
In the design of the PREPARE website, we included essential, theory-based health education 
286 
strategies, such as the use of video modeling of ACP behaviors and tailored and interactive 
287 
content based on patients’ values and decision preferences. To ensure PREPARE is easy to 
288 
read and understand, we use clear health communication principles (e.g., targeting text to the 
289 
5th grade reading level) informed by extensive formative research and cognitive interviewing 
290 

 
 
17 
with the target population (i.e., racially and ethnically diverse older adults with limited health 
291 
literacy and English proficiency) to ensure PREPARE content is acceptable to individuals from 
292 
diverse cultural backgrounds.25 The PREPARE website leads people through a 5-step ACP 
293 
process that ranges from choosing a surrogate decision maker to asking their clinicians the right 
294 
questions. While going through the website, PREPARE also helps individuals answer personal 
295 
values questions about their medical care, and helps them create an action plan to engage in 
296 
some form of ACP. Patient-generated action plans have been shown to help patients engage in 
297 
other preventative and disease management activities in the outpatient setting.59  
298 
 
299 
After the baseline interview, participants in the PREPARE arm review all 5 steps of the 
300 
PREPARE website in English or Spanish in our research offices. Participants are asked to 
301 
review PREPARE on their own and in its entirety. Research assistants are available to answer 
302 
questions only if needed, but do not go through the website with the participants. At the end of 
303 
the program, a summary of the patient’s medical wishes and action plan are automatically 
304 
generated from the PREPARE website in written format. This information along with the 
305 
participant’s PREPARE website login information is included in a take-home folder that also 
306 
contains PREPARE information in pamphlet, booklet, and DVD format. We include PREPARE 
307 
content in non-website formats because some patients may not have access to the internet at 
308 
home. PREPARE arm participants are also given an easy-to-read advance directive in English 
309 
or Spanish to review and consider completing.18,60 Participants are asked to review the advance 
310 
directive form for at least 5 minutes and up to 15 minutes in research offices, and then to take 
311 
the form home to discuss with their potential surrogates and/or their clinicians. The time frame 
312 
of 5-15 minutes was chosen because our goal is only to introduce the advance directive and 
313 
allow participants to ask questions. The goal is not to have patients complete the form on the 
314 
day of the study, before potential discussions with clinicians or surrogates, unless the participant 
315 
would like to do so.  
316 

 
 
18 
 
317 
AD-only arm 
318 
Participants in the control arm are only given the easy-to-read advance directive, are asked to 
319 
review it for at least 5 minutes and up to 15 minutes, and to take the form home to discuss with 
320 
their potential surrogates and clinicians.  
321 
 
322 
Both arms: Reminder of primary care appointments 
323 
One to 3 days before the patient’s next scheduled primary care appointment, research staff call 
324 
the PREPARE arm participants to remind them to bring in their study materials (i.e., action plan 
325 
and advance directive) and to talk to their clinician about ACP. For the control arm, research 
326 
staff members only remind patients about their upcoming appointment and do not provide 
327 
additional encouragement about ACP. 
328 
RANDOMIZATION PROCEDURES 
329 
A statistician not involved in recruitment or data collection uses a computer-based random 
330 
number generator to create a randomization scheme using block randomization by health 
331 
literacy (adequate health literacy versus limited health literacy, as determined by a validated 
332 
question concerning confidence with medical forms) and race/ethnicity (non-white versus 
333 
white).61 Random block sizes of 4, 6, and 8 are used to ensure an equal number of patients with 
334 
limited health literacy in each group. Randomization information is associated with a unique 
335 
patient identification number and is kept separate from other patient data. Due to the need to 
336 
secure interview rooms for the duration of the baseline questionnaire and intervention (i.e., 
337 
approximately 2 hours for the AD-only arm and 3 hours for the PREPARE arm), randomization 
338 
occurred prior to scheduling a baseline interview.  
339 
 
340 
BLINDING 
341 

 
 
19 
Clinicians are blinded to patient group assignment. Although we obtain clinicians’ permission to 
342 
recruit their patients, the interventions are not described, and no clinician education is provided. 
343 
Participants could not be blinded to the intervention; however, they are told during consent there 
344 
is a “50/50 chance” of getting one of two different ACP guides, and the non-assigned 
345 
intervention is not described. Because each group obtains ACP materials, such as the easy-to-
346 
read advance directive, blinding is enhanced. The research assistant who administers the 
347 
intervention cannot be blinded to the study arm, but all follow-up outcome assessments are 
348 
conducted by different and blinded staff.  At the start of all follow-up interviews, participants are 
349 
reminded not to discuss the study materials they reviewed with assistants recording if they 
350 
became unblinded. If unblinding occurs, a different blinded assistant conducts all subsequent 
351 
interviews.  
352 
 
353 
INTERVENTION FIDELITY  
354 
All staff members are rigorously trained and are required to read and adhere to a standardized 
355 
study protocol manual, standardized study scripts, and standardized checklists for each contact 
356 
and interview with participants. Several training videos have also been developed for staff. 
357 
Research staff are not allowed to conduct study tasks independently until they have reviewed all 
358 
written and video training materials and can demonstrate complete mastery of all scripts and 
359 
checklist items. In addition, a 10% random sample of all interviews is observed by senior 
360 
research staff to ensure study fidelity.  
361 
 
362 
DATA COLLECTION METHODS 
363 
Paper surveys are collected and entered into REDCap. REDCap is managed by the UCSF 
364 
Academic Research Systems Team and is stored behind strong-string password protected 
365 
firewalls on UCSF servers, not on individual laptops or desktops. All patients are given a unique, 
366 
non-identifying patient identification number that is removed from any personally identifying 
367 

 
 
20 
information (PII) or personal health information (PHI). All PII and PHI are stored in a Microsoft 
368 
ACCESS database behind strong-string password protected firewalls on UCSF and SFGH 
369 
servers. All paper files are stored in secure, locked research offices in secure, locked file 
370 
cabinets. 
371 
 
372 
FOLLOW-UP AND RETENTION: 
373 
We conduct follow-up interviews one week and 3, 6, and 12-months after the primary care visit 
374 
in the clinic, by phone. We utilize several measures to help ensure follow-up. Each follow-up 
375 
interview takes between 30 to 45 minutes and participants are reimbursed $25.  
376 
 
377 
Method of contact for follow-up surveys: 
378 
Upon enrollment, we ask participants to provide alternative phone numbers (e.g., cell or work 
379 
numbers) and one to three additional phone numbers of close contacts who may know how to 
380 
contact the patient in the event our study staff is unable to reach them. Many patients in safety 
381 
net settings are marginally housed, have intermittent phone access, and may change locations 
382 
and phone numbers during the study period. We also ask participants if they prefer a text 
383 
message or an email to schedule follow-up visits and will use their preferred mode of 
384 
communication. If these other modes of communication fail, we send out reminder letters. If 
385 
needed, we also attempt to contact patients during scheduled clinic visits.  
386 
 
387 
Reminders for the primary care visit: 
388 
Participants receive a brief reminder call one to 3 days before their next primary care visit. 
389 
Participants in the AD-only arm are reminded to come to their scheduled appointment while 
390 
participants in the PREPARE arm are reminded of their appointment and to bring the PREPARE 
391 
materials to the visit. 
392 
 
393 

 
 
21 
Reminders for study interviews: 
394 
For all follow-up interviews, participants in both arms receive reminders of their upcoming study 
395 
interview by phone or in person.  
396 
 
397 
Ascertaining reasons for loss of follow-up or withdrawal: For participants who want to 
398 
withdraw, we ask them why in open-ended questions. If they cannot provide an answer, we 
399 
prompt them from a list of reasons we obtained from prior advance care planning trials, such as 
400 
the study is too long, they are too busy, the study topic is too upsetting, they are too ill, etc.62  
401 
 
402 
 
403 
MEASURES  
404 
Overview 
405 
Because ACP ideally is a process that occurs over time, we felt it important to measure a full 
406 
range of ACP measures including ACP documentation (primary outcome) over time, and 
407 
several behavior change constructs and several additional ACP actions over a 12-month period 
408 
(secondary outcomes). The main outcome measures are described in detail below. 
409 
 
410 
Primary Outcome 
411 
The primary outcome is documentation of ACP wishes in the SFHN/SFGH medical record. ACP 
412 
documentation for the purposes of this study includes the easy-to-read advance directive or 
413 
other valid advance directives or living wills, a durable power of attorney for health care 
414 
document (DPOAHC), a Physicians Orders of Life Sustaining Treatment form, or other 
415 
documentation of discussions concerning patients’ wishes for medical care (i.e., documentation 
416 
of oral directives by a physician or notes describing patients’ goals for medical care by 
417 
clinicians).  
418 
 
419 

 
 
22 
We assess baseline and 12-month ACP documentation rates and the date of documentation to 
420 
determine the length of time from study enrollment to subsequent documentation.  Patients in 
421 
our study are enrolled, randomized, and exposed to the intervention 1 to 3 weeks prior to a 
422 
primary care appointment. ACP documentation is timed to the date of intervention exposure as 
423 
patients may have engaged in ACP prior to seeing their primary care provider. The patient-
424 
reported outcomes in the follow-up surveys (1 week, 3, 6, and 12-months), however, are timed 
425 
to the primary care visit because those questions concern engagement in discussions with 
426 
clinicians (see secondary outcomes below).  
427 
 
428 
Because legal forms and documented discussions can be used to direct medical care, we 
429 
created a composite variable of any ACP documentation (forms and/or discussions); we also 
430 
plan to report the percentage of forms and discussions separately. All medical review data is 
431 
double coded by 2 independent, blinded research assistants. Discrepancies are adjudicated by 
432 
the principal investigator (R.L.S.). 
433 
 
434 
Secondary Outcomes 
435 
Main Patient-Reported Outcome 
436 
The main patient-reported secondary outcome, the validated Advance Care Planning 
437 
Engagement Survey,25-27 was chosen to measure the full process of ACP. The Advance Care 
438 
Planning Engagement Survey measures both ACP Behavior Change Processes, such as 
439 
knowledge, contemplation, self-efficacy, and readiness on a validated 57-item scale. The ACP 
440 
Behavior Change Process scale is measured on a 5-point Likert scale and average 5-point 
441 
scores will be calculated. We will also measure ACP actions on the validated 25-item Action 
442 
scale, which assesses ACP activities (yes or no) such as identifying a surrogate decision maker, 
443 
identifying values and goals for medical care, choosing the level of leeway in surrogate decision 
444 
making, discussing one’s wishes with clinicians and surrogates, and documenting one’s wishes 
445 

 
 
23 
in an advance directive.  Validity and reliability of the ACP Engagement Survey, as well as the 
446 
questionnaire’s ability to detect change in response to an ACP intervention, have been 
447 
previously described.25-27  
448 
 
449 
Feasibility and Satisfaction 
450 
To evaluate whether and how PREPARE will be used in clinical practice and in the community, 
451 
we also assess acceptability of the PREPARE website compared to an advance directive alone 
452 
using validated scales of ease-of-use (10-point scale, “On a scale of 1 to 10, with 1 being very 
453 
hard and 10 being very easy, how easy was it to use this guide?”) and satisfaction (comfort: 
454 
“How comfortable were you viewing this guide?”, helpfulness: “How helpful was this guide?”, 
455 
and recommendations: “How likely are you to recommend this guide to others?” assessed on a 
456 
5-point Likert scale (not-at-all to extremely) from our prior work.18 For the PREPARE arm only, 
457 
and at the end of the 12-month interview and after unblinding, we also ask how likely patients 
458 
are to recommend the PREPARE intervention to others.63 
459 
 
460 
Adverse Event Outcomes 
461 
In addition, to ensure that the PREPARE program does not cause undue harm, we also assess 
462 
both depression64,65 and anxiety.66,67  We administer the Patient Health Questionnaire (PHQ)-4 
463 
at baseline and at each follow-up interview.68 The PHQ-4 includes the PHQ-2 for depression 
464 
and the Generalized Anxiety Disorder (GAD)-2 anxiety screening tool. A score of 3 or greater on 
465 
a 0 to 6 scale suggests possible depression or anxiety. 
466 
 
467 
Potential Mediating or Moderating Variables & Participant Characteristics 
468 
Based on the previously published conceptual framework of PREPARE,25 we also hypothesize 
469 
that PREPARE efficacy may vary across several moderator or mediator variables (e.g., health 
470 
literacy using the validated Short form Test of Functional Health Literacy in Adults s-TOFHLA, 
471 

 
 
24 
scores 0-3669 and dichotomized to limited = 0-22 & adequate = 23-36, and patient’s desired role 
472 
in decision making with the medical provider using the validated Decision Control Preferences 
473 
Scale (i.e., wants to make their own decision versus wants doctors/family to make decisions for 
474 
them).70 We also hypothesize that PREPARE efficacy may be affected by several confounding 
475 
variables (e.g., self-rated health, “How would you rate your health?” (5-point Likert)71,72 
476 
dichotomized as fair-to-poor and good-to-excellent and past experiences with ACP including 
477 
prior documentation of legal forms and documented discussions. We will also assess a full 
478 
range of patient-reported characteristics, as these factors may impact patient-clinician 
479 
communication,73,74 such as age (“What is your date of birth?”), self-reported gender (“What 
480 
gender do you consider yourself to be? male, female transgender, other”), finances (able to 
481 
make ends meet versus not make ends meet), having a potential surrogate decision maker or 
482 
not, education (“What is the highest educational level you have completed?” less than or equal 
483 
to high school or greater than high school), internet access in the home (yes or no), and 
484 
religiosity and spirituality (i.e., “How religious/spiritual do you consider yourself to be?” on 5-
485 
point Likert scale from not-at-all to extremely).  
486 
 
487 
STATISTICAL ANALYSIS PLAN 
488 
Our primary analyses will compare change in ACP documentation between study arms from 
489 
baseline to 12 months. Secondary outcomes will include ACP Engagement with respect to 5 
490 
ACP Actions (yes/no and a 0-25-point scale) and Behavior Change Process scores (average 5-
491 
point Likert scores) from baseline to 1 week, and 3, 6, and 12 months. Variables will be 
492 
assessed for distributional and outlier values using standard summary statistics. Baseline 
493 
comparability will be assessed between groups using unpaired t-tests, Chi-square tests or 
494 
Fisher’s exact tests. We will use intention-to-treat analysis using SAS version 9.4 (SAS Institute 
495 
Inc.) and STATA 15.0 (College Station, TX). All p-values will be 2-tailed and set at .05 for the 
496 
primary outcome. To compare outcomes between the two arms longitudinally, we will use mixed 
497 

 
 
25 
effects linear, Poisson, or negative binomial regression for continuous measures and mixed 
498 
effects logistic regression for dichotomous measures. The mixed effects models will include 
499 
fixed effects for the primary modeling terms of time (baseline and 12 months for ACP 
500 
documentation and baseline and 1 week, 3 months, 6 months, and 12 months for ACP 
501 
Engagement with time modeled using dummy variables to allow for non-linearity); arm (AD-only 
502 
versus PREPARE); an interaction term of study arm and time; and a random effect for subjects. 
503 
We will adjust for the randomization blocking factors limited vs. adequate literacy,75 and any 
504 
predictor variables that differ between arms. All models also will include random physician 
505 
intercepts to account for nesting of patients within physicians.  
506 
 
507 
For moderator analysis, we will test for interactions by adding interaction terms to the group by 
508 
time variable for health literacy (limited versus adequate) controlling for prior ACP 
509 
documentation and clustering effects by clinician. All other interaction terms are adjusted for 
510 
health literacy (randomization blocking variable) prior ACP documentation and clustering effects 
511 
by clinician. Additional interaction terms to be added to the group by time variable include 
512 
decision control preferences for making decisions (i.e., makes own decisions versus doctor 
513 
makes decisions), age (i.e., < 65 years versus 65 years of age), sex/gender (i.e., self-reported 
514 
man versus woman), race/ethnicity (i.e., white versus non-white), health status (i.e., good-to-
515 
excellent versus fair-to-poor), presence of a potential surrogate (i.e., yes versus no), and 
516 
internet access at home (i.e., yes versus no). For Spanish-speakers, we will also asses patient-
517 
clinician language (concordance vs. discordance). A p-value for interaction <0.05 is considered 
518 
significant.    
519 
 
520 
Missing data for the primary outcome will be assessed. If there is 10% or more of missing data, 
521 
we will use a mean imputation approach and all available data will be included in mixed-effects 
522 

 
 
26 
models. We will assess whether any research staff member became unblinded during follow-up 
523 
assessment and conduct sensitivity analysis as needed. 
524 
 
525 
SAMPLE SIZE AND POWER CALCULATIONS 
526 
We will measure a full range of ACP behaviors including discussions. However, written advance 
527 
directive completion of legal forms is a primary outcome and is the most well-studied.76  Power 
528 
from longitudinal analyses with repeated measures will be stronger, but to be conservative, we 
529 
consider power for a single post-intervention time point (e.g., 12 months). A recent meta-
530 
analysis of written advance directive documentation studies demonstrated a pooled effect size 
531 
of 0.50 (95% CI; 0.17 -0.83),76 as did an RCT of an ACP workbook that included both behavior 
532 
change constructs and a social work visit,77 and our prior RCT of an easy-to-read AD at SFGH 
533 
which showed an increased AD completion rate from 7% to 15%.18  Because both the 
534 
intervention and control arm will receive the easy-to-read advance directive, we assume that 
535 
both arms will have an advance directive completion rate of ≤ 15%. Based on prior studies, we 
536 
assume PREPARE will result in additional benefit of advance directive completion with a 
537 
minimum effect size of 0.5 (two-fold increase) above 15%. A sample of 350, (175 per arm), will 
538 
afford us 92% power (2-tailed alpha of 0.05) to detect a difference of advance directive 
539 
completion rates of 15% in controls vs. 30% in the PREPARE arm and 80% power to detect a 
540 
difference of 15% vs. 27%. Power is also expected to be strong for the ACP behavioral change 
541 
scale outcomes (preliminary data demonstrated a pre-to-post improvement of 0.5 SD).25 With a 
542 
conservative assumption that controls will improve by 0.1 to 0.2 SD, we will have 85% to 98% 
543 
power, respectively, to conclude that the improvement is better in the PREPARE arm.  We 
544 
expect a 15% drop out rate at 12 months based on our prior randomized, controlled trial at 
545 
SFGH,18 and will therefore attempt to recruit 402 patients, or 201 in each arm for each language 
546 
(English and Spanish) for a total recruitment of 804 patients.  
547 
 
548 

 
 
27 
Our sample size will also allow adequate power to detect clinically important interactions based 
549 
on potential moderators (literacy, control preferences, language concordance) for our outcomes. 
550 
In a prior trial of an easy-to-read advance directive in the same patient population with only 200 
551 
patients, we found significant interactions for literacy.8 Thus, if we consider the power scenario 
552 
of the control group ACP documentation rate of 15% and the PREPARE group of 28%, and 
553 
suppose the control group rate is the same (15%) for both levels of the moderating factor, then 
554 
for a moderating factor split of 1:1, we would have 80% power to detect an interaction. If the 
555 
PREPARE arm ACP documentation rate is 18% for one level of the factor and 40% for the 
556 
other, this corresponds to a relative rate of ACP documentation of 2.2 times as high for one 
557 
level of the factor compared to the other. A 2:1 split of the moderating factor still allows 
558 
detection of a 2.4-fold increase in the relative rate of documentation. Power to detect 
559 
interactions will likely be stronger for continuous outcomes (e.g. engagement/behavioral scales).  
560 
 
561 
ETHICS AND ADVISORY COMMITTEES 
562 
This study is approved by the University of California, San Francisco (UCSF) (IRB reference 
563 
#13-10847). This study is guided by a Patient-Clinical Stakeholder Advisory Board that is 
564 
comprised of patients and patient advocates (including native Spanish-speakers), surrogates, 
565 
and SFHN/SFGH primary care clinic staff and medical directors. It is also guided by a DSMB 
566 
consisting of 4 experts in randomized trials, human subjects research and consent, vulnerable 
567 
populations, palliative care, advance care planning, and biostatistics. Both advisory groups will 
568 
review and approve all study protocols and related materials. In addition, we continue to meet 
569 
with both groups every 4-6 months to review the progress of the trial, make suggestions for 
570 
recruitment, review any potentially adverse events, and ensure that we are following our study 
571 
protocols in a way that protects vulnerable patient populations. 
572 
 
573 
HUMAN SUBJECTS PROTECTIONS 
574 

 
 
28 
Protection of the rights and welfare of participants: 
 
575 
All study staff are required to take annual training regarding the rights and protections of 
576 
research participants. Additionally, weekly study team meetings will ensure that all study staff 
577 
are following the research protocol and that all study participants are consented according to 
578 
our study protocol. 
579 
 
580 
Furthermore, our consent process ensures that study participants have a clear understanding of 
581 
the study and understand that they can choose to not participate in the study at any point in 
582 
time, and that the care they receive will not be affected by declining to participate in our study. 
583 
Our consent process involves using a consent form written below a 6th-grade reading level, 
584 
reading the form to potential subjects verbatim, allowing time for questions and discussion, and 
585 
then assessing comprehension using teach-to-goal. If questions are not answered correctly, 
586 
repeated education and reassessment of comprehension are continued until complete 
587 
comprehension is achieved. If subjects take more than three passes through the 
588 
comprehension assessment, formal assessment for cognitive impairment will be completed. If 
589 
patients are found to be cognitively impaired, they are excluded from the study. If they are not 
590 
cognitively impaired, we will re-do teach back once more, after which the participant will be 
591 
deemed ineligible for the study if they are unable to demonstrate comprehension of the study. 
592 
 
593 
Additionally, we include UCSF Clinical Research Office contact information on all consent forms 
594 
as required for all non-biomedical studies. 
 
595 
 
596 
Steps taken to minimize risks to subjects: 
597 
We have developed a modified research consent process that has been shown to be successful 
598 
in vulnerable patient populations as described above.19 All study fliers, consent forms, and 
599 
questionnaires are read to the subjects in their entirety by native English- and Spanish-speaking 
600 

 
 
29 
research staff. Participants are reminded that they can opt out of the study at any time. All study 
601 
materials are in an easy-to-read (5th grade reading level, large 14-point font) format. The 
602 
consent materials and the study interviews are conducted in the language the participant is 
603 
most comfortable speaking (English or Spanish). 
604 
 
 
605 
This study will employ research assistants who are fluent in English or Spanish. Only fluent 
606 
research assistants will be in contact and will communicate with Spanish-speaking participants. 
607 
We will also ensure that all study materials are accurately translated into Spanish by having 
608 
them initially translated from English to Spanish by native Spanish- speakers. We will then have 
609 
them back translated into English to ensure accuracy. Finally, we will have the final translated 
610 
documents reviewed for accuracy by third party native Spanish- speakers. To help participants 
611 
follow along during the interview, they may review a large font Participant Version of the survey 
612 
at baseline and all follow-ups that can be reviewed while the research assistant is asking 
613 
research questions verbatim. We use 14-point font and color-coded, standardized, large font 
614 
response options to help with understanding. 
615 
 
616 
Data security: 
617 
- Data are stored securely in the encrypted, secure UCSF MyResearch environment 
618 
- Data are coded; data key is kept separately and securely  
619 
- Data are kept in a locked file cabinet 
620 
- Data are kept in a locked office or suite  
621 
- Electronic data are protected with a password  
622 
- Data are stored on a secure network 
 
623 
- Data are collected/stored using REDCap or REDCap Survey  
624 
 
625 
Measures to ensure confidentiality and protect identifiers from improper disclosure 
626 

 
 
30 
Risks to subjects are minimal and may include loss of confidentiality and psychological 
627 
discomfort about discussing end-of-life issues. Subjects are assured that their answers to study 
628 
questions will not be directly linked to their names. Instead, any identifying information is coded 
629 
and separated from the data. The identifying information will only be known to the primary 
630 
investigators but will not be used in data analysis. In addition, signed consent forms are kept in 
631 
locked file cabinets and kept separate from the data collection instruments. Study subjects are 
632 
also reminded that the information obtained will not be shared with their providers except in non-
633 
identifying aggregate form at the end of the study. We also make clear that the responses to the 
634 
PREPARE guide are only for research purposes and will not be shared with their clinicians or 
635 
put in their medical record. 
636 
 
637 
We will store all study materials in locked offices and locked storage cabinets. We will utilize 
638 
UCSF MyResearch and REDCap to enter and maintain data in a secure environment. The 
639 
paper files are stored in secure, locked research offices in secure, locked file cabinets.  
640 
 
641 
As some of the questions concerning end-of-life may cause psychological discomfort for some 
642 
study subjects, subjects are reminded at the beginning of the interview of their right to refuse to 
643 
answer any and all questions and their right to terminate the interview at any time. We will also 
644 
reassure subjects that if they choose not to be in the study or choose to terminate the interview, 
645 
it will not change the medical care that they normally receive from their clinic or their clinician. In 
646 
addition, we will reiterate that the information shared within the research interview will not be 
647 
shared with their clinicians or used in medical care. However, subjects can take home a copy of 
648 
the PREPARE guide with them and bring it back to their clinicians if they wish. Subjects are 
649 
given the name and number of the primary investigator and may call if they have questions or 
650 
are concerned about their participation in the study. 
651 
 
652 

 
 
31 
Required reportable information: 
653 
As these interviews may be completed in people’s home and, in the interviews, we are asking 
654 
patients to describe their experiences and opinions, it is possible that reportable events such as 
655 
elder abuse, suicidal or homicidal ideation may be detected. If they are detected, they will be 
656 
handled according to the American Psychological Association code of ethics. If elder abuse is 
657 
suspected, the participant will be encouraged to take steps to ensure their safety. They will be 
658 
offered contact information for local supportive services and informed that the concerns will be 
659 
discussed with the elder abuse hotline for assistance. When there are concerns about self-harm 
660 
or harm to others, severity of harm will be assessed. Participants will be offered local support 
661 
services and officials will be notified as necessary. 
662 
 
663 
DATA SAFETY MONITORITY PLAN 
664 
Monitoring will focus on recruitment, baseline comparability of treatment groups, protocol 
665 
adherence, completeness of data, accrual of primary endpoint data, safety, and follow-up rates. 
666 
This monitoring will provide the basis for monthly review by the study investigators, review by 
667 
the SFGH Patient-Clinician Advisory Committee, and Data Safety and Monitoring Board 
668 
(DSMB), and yearly reporting to our IRBs. We will implement methods of verifying entered data 
669 
and of quality control. All study materials data are kept on secure, password-protected, 
670 
encrypted servers. All consent materials and any identifying information are kept in locked 
671 
cabinets within locked offices, on password-protected, encrypted servers, on card-key protected 
672 
research floors. Dr. Sudore, will be directly responsible for identifying and immediately reporting 
673 
all adverse events to the IRBs Privacy Officers, and funding agency as appropriate. The SFGH 
674 
Patient-Clinician Advisory Committee will ensure participant safety in the clinic and will meet up 
675 
to 4 times per year. The formal DSMB includes 4 experts in randomized trials, human subjects 
676 
research and consent, vulnerable populations, palliative care, advance care planning, and 
677 
biostatistics. The DSMB will review and approve the research protocol and plans for data and 
678 

 
 
32 
safety monitoring; and assess data quality; participant recruitment, accrual and retention; 
679 
baseline comparability of treatment groups, accrual of primary endpoints; and participant safety 
680 
(e.g., adverse events, protocol violations). They will also develop stopping rules for the trial. The 
681 
DSMB will meet up to 4 times per year. 
682 
 
683 
CHARTER OF DATA SAFETY MONITORING BOARD 
684 
The Data and Safety Monitoring Board (DSMB) will act in an advisory capacity to the National 
685 
Institute of Aging (NIA) and PCORI to monitor participant safety, data quality and evaluate the 
686 
progress of the study. Dr. Sudore, University of California, San Francisco is conducting a 
687 
comparative trial of two advance care planning interventions among English- and Spanish-
688 
speakers. The DSMB for this study includes 2 outside clinicians with expertise in randomized 
689 
control trials(RCTs) and an outside biostatistician. The DSMB will review and approve the 
690 
research protocol and plans for data and safety monitoring; and assess data quality; participant 
691 
recruitment, accrual and retention; baseline comparability of treatment groups, accrual of 
692 
primary endpoints; and participant safety (e.g., adverse events, protocol violations). They will 
693 
also develop stopping rules for the trial. The DSMB will meet 2 and up to 4 times per year. 
694 
 
695 
DSMB Responsibilities 
696 
The DSMB responsibilities are to:  
697 
 
review the research protocol, informed consent documents and plans for data safety and 
698 
monitoring;  
699 
 
advise the NIA on the readiness of the study staff to initiate recruitment; 
700 
 
evaluate the progress of the trial, including periodic assessments of data quality and 
701 
timeliness, recruitment, accrual and retention, participant risk versus benefit, performance of 
702 
the trial sites, and other factors that can affect study outcome; 
703 

 
 
33 
 
consider factors external to the study when relevant information becomes available, such as 
704 
scientific or therapeutic developments that may have an impact on the safety of the 
705 
participants or the ethics of the trial; 
706 
 
review study performance, make recommendations and assist in the resolution of problems 
707 
reported by the Principal Investigator; 
708 
 
protect the safety of the study participants; 
709 
 
report to NIA on the safety and progress of the trial;  
710 
 
make recommendations to the NIA and the Principal Investigator concerning continuation, 
711 
termination or other modifications of the trial based on the observed beneficial or adverse 
712 
effects of the treatment under study; 
713 
 
if appropriate, review interim analyses in accordance with stopping rules, which are clearly 
714 
defined in advance of data analysis and have the approval of the DSMB; 
715 
 
ensure the confidentiality of the study data and the results of monitoring; and,  
716 
 
assist the NIA by commenting on any problems with study conduct, enrollment, sample size 
717 
and/or data collection. 
718 
 
719 
The DSMB will discharge itself from its duties when the last participant completes the study. 
720 
 
721 
Membership 
722 
The DSMB includes experts in or representatives of the fields of: 
723 
relevant clinical expertise,  
724 
clinical trial methodology, and  
725 
biostatistics.  
726 
 
727 
The DSMB members:  
728 

 
 
34 
 
In addition to the NIA program officer members include: 
729 
 
Dr. David Bekelman, MD, MPH, an internist, psychiatrist, and palliative medicine 
730 
physician at the University of Colorado School of Medicine and is an expert in health 
731 
communication and medical decision making 
732 
 
Dr. Nathan Goldstein, MD, a geriatrician and a national expert in palliative care, 
733 
communication, and medical decision making at Mt. Sinai School of Medicine,  
734 
 
Dr. James Wiley, PhD a statistician and Professor in the Institute for Health Policy 
735 
Studies at the University of California, San Francisco. Dr. Wiley has extensive 
736 
experience with RCTs and working with safety net populations. Although Dr. Wiley is at 
737 
UCSF, he does not otherwise work with Dr. Sudore. Membership have no financial, 
738 
scientific, or other conflict of interest with the trial.  
739 
 
740 
Written documentation attesting to absence of conflict of interest has been obtained. 
741 
 
742 
Dr. Nathan Goldstein, Mount Sinai School of Medicine, has been appointed by NIA to serve as 
743 
the Chairperson and is responsible for overseeing the meetings, developing the agenda in 
744 
consultation with the NIA Program Official and the Principal Investigator. The Chair is the 
745 
contact person for the DSMB. The University of California, San Francisco shall provide the 
746 
logistical management and support of the DSMB. Dr. Nathan Goldstein is also the safety officer 
747 
and contact person for serious adverse event reporting. A log of all potential adverse events and 
748 
protocol violations will be kept and reviewed quarterly by the DSMB. Procedures for notifying 
749 
the Chair of the DSMB and the NIA Program Official will be discussed and agreed upon at the 
750 
first meeting.  
751 

 
 
35 
 
752 
Board Process  
753 
At the first meeting the DSMB will discuss the protocol, suggest modifications, and establish 
754 
guidelines to study monitoring by the Board. The DSMB Chairperson in consultation with the 
755 
Principal Investigator and the NIA Program Official will prepare the agenda to address the 
756 
review of study materials, modifications to the study protocol and informed consent document, 
757 
initiation of the trial, appointment of a safety officer, as needed, reporting of adverse events, 
758 
statistical analysis plan including interim analysis and stopping rules, etc.  
759 
 
760 
Meetings of the DSMB will be held 2-4 times per year at the call of the Chairperson and / or NIA 
761 
Program Official to ensure patient safety and to review stopping rules for the trial. The NIA 
762 
Program Official or designee will attend most of the meetings. An emergency meeting of the 
763 
DSMB may be called at any time by the Chair or by the NIA should participant safety questions 
764 
or other unanticipated problems arise. 
765 
 
766 
Meetings are closed to the public because discussions may address confidential participant 
767 
data. Meetings are attended by the Principal Investigator and members of his/her staff. 
768 
Meetings may be convened as conference calls as well as in-person.   
769 
 
770 
Meeting Format 
771 
Each meeting must include a recommendation to continue or to terminate the study and 
772 
whether the DSMB has any concerns about participant safety made by a formal DSMB majority 
773 
or unanimous vote. Should the DSMB decide to issue a termination recommendation, the full 
774 
vote of the DSMB is required. In the event of a split vote, majority vote will rule and a minority 
775 
report should be appended. The DSMB Chair provides the tiebreaking vote in the event of a 50-
776 
50 split vote. 
777 

 
 
36 
 
778 
A recommendation to terminate the study may be made by the DSMB at any time by majority 
779 
vote. The Chair should provide such a recommendation to the NIA immediately by telephone 
780 
and email. After the NIA Director makes a decision about whether to accept or decline the 
781 
DSMB recommendation to terminate the study, the PI is immediately informed about his 
782 
decision. 
783 
 
784 
Meeting Materials  
785 
DSMB interim report templates will be prepared by the study staff, to be reviewed by the DSMB 
786 
members at each meeting.  The reports will list the study aims, the status of the study, and 
787 
summarize safety data. 
788 
 
789 
Reports from the DSMB 
790 
A formal report containing the recommendations for continuation or modifications of the study 
791 
will be prepared by the DSMB Chairperson, NIA Program Official or its designee. The draft 
792 
report will be sent to the DSMB members for review and approval.  
793 
 
794 
Confidentiality  
795 
All materials, discussions and proceedings of the DSMB are completely confidential. Members 
796 
and other participants in DSMB meetings are expected to maintain confidentiality.  
797 
 
798 
PATIENT-CLINICAN STAKEHOLDER ADVISORY COMMITTEE ROLE 
799 
This study is guided by a Patient-Clinical Stakeholder Advisory Board that is comprised of 
800 
patients and patient advocates (including native Spanish-speakers), surrogates, and 
801 
SFHN/SFGH primary care clinic staff and medical directors. These individuals are paid key 
802 
personnel on the study and have agreed to meet up to 4 times per year to oversee all aspects of 
803 

 
 
37 
the study. Native Spanish-speaking staff will be present to translate for our Spanish-speaking 
804 
patient stakeholders during advisory meetings. All study materials will be translated into 
805 
Spanish. The advisory committee will be involved in providing ongoing advice about the 
806 
following important study related activities: 
807 
 
Recruitment, including study scripts, fliers, methods 
808 
 
Eligibility and exclusion 
809 
 
Patient safety and research staff safety 
810 
 
Clinic workflow and clinical champions 
811 
 
Informed consent 
812 
 
Research outcomes 
813 
 
Presentation of findings 
814 
 
Dissemination of results 
815 
 
816 
 
 
817 

 
 
38 
ORIGINAL PROTOCOL REFERENCES:  
818 
1. 
Sudore RL, Barnes DE, Le GM, et al. Improving advance care planning for English-
819 
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820 
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822 
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829 
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831 
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22. 
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adults for decision making and advance care planning: a pilot study. J Pain Symptom 
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planning PREPARE study among older Veterans with serious and chronic illness: study 
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to detect behavior change in multiple advance care planning behaviors. PloS one. 
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predictor of functional decline. MacArthur studies of successful aging. Journal of clinical 
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31. 
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Pfeiffer E. A short portable mental status questionnaire for the assessment of organic 
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Bergman B, Sjostrand J. A longitudinal study of visual acuity and visual rehabilitation 
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Street RL, Jr. Interpersonal Communication Skills in Health Care Contexts. In: Greene 
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Champion VL, Skinner CS. The health belief model. In: Glanz K, Rimer BK,Viswanath K, 
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Street RL, Jr., Slee C, Kalauokalani DK, Dean DE, Tancredi DJ, Kravitz RL. Improving 
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physician-patient communication about cancer pain with a tailored education-coaching 
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intervention. Patient Educ Couns. 2010;80(1):42-47. 
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Kravitz RL, Tancredi DJ, Street RL, Jr., et al. Cancer Health Empowerment for Living 
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without Pain (Ca-HELP): study design and rationale for a tailored education and 
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coaching intervention to enhance care of cancer-related pain. BMC Cancer. 2009;9:319. 
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evidence. Med Care. 2007;45(4):340-349. 
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communicate with physicians. Fam Med. 2002;34(5):344-352. 
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systematic review of intervention studies. Patient Educ Couns. 2004;52(1):7-16. 
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satisfaction for patients and physicians. J Clin Oncol. 2002;20(11):2695-2700. 
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advance care planning in dementia: randomised controlled trial. BMJ. 2009;338:b2159. 
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Bickmore TW, Pfeifer LM, Byron D, et al. Usability of conversational agents by patients 
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with inadequate health literacy: evidence from two clinical trials. Journal of health 
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Handley M, MacGregor K, Schillinger D, Sharifi C, Wong S, Bodenheimer T. Using 
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literacy in a large VA outpatient population. J Gen Intern Med. 2008;23(5):561-566. 
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Sudore RL, Boscardin J, Feuz MA, McMahan RD, Katen MT, Barnes DE. Effect of the 
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PREPARE Website vs an Easy-to-Read Advance Directive on Advance Care Planning 
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Documentation and Engagement Among Veterans: A Randomized Clinical Trial. JAMA 
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Intern Med. 2017;177(8):1102-1109. 
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population. J Affect Disord. 2010;122(1-2):86-95. 
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development and validation studies. Qual Life Res. 2012;21(1):161-165. 
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1019 
Schillinger D. Unraveling the relationship between literacy, language proficiency, and 
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Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment 
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Med. 2002;21(19):2917-2930. 
1024 
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Ramsaroop SD, Reid MC, Adelman RD. Completing an advance directive in the primary 
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1026 
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1027 
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1028 
the Veterans Affairs System: results of a multifaceted intervention. Arch Intern Med. 
1029 
2005;165(6):667-674. 
1030 
 
1031 
 
 
1032 

 
 
45 
 
1033 
Protocol 
1034 
Final Version 
1035 
September 2017 
1036 
 
 
1037 

 
 
46 
Final Protocol Table of Contents 
1038 
Funding 
45 
ClinicalTrials.gov Information 
45 
Introduction and Rationale 
45 
Preliminary Studies 
47 
Overview of the Trial Design 
49 
Study Setting 
53 
Participants and Eligibility and Exclusion Criteria 
53 
Recruitment Methods 
56 
Consent Procedures 
58 
Intervention and Comparison Conditions 
59 
Randomization Procedures 
61 
Blinding 
62 
Intervention Fidelity 
62 
Data Collection Methods 
63 
Follow-up and Retention 
63 
Measures 
65 
Statistical Analysis Plan 
74 
Sample Size and Power Calculations 
75 
Ethics and Advisory Committees 
77 
Human Subjects Protections 
77 
Data Safety Monitoring Plan 
81 
Charter of the Data and Safety Monitoring Board 
82 
Patient-Clinician Stakeholder Advisory Committee Role 
86 
Summary of Protocol Changes Table  
88 

 
 
47 
Summary of Statistical Analysis Plan Changes 
92 
References 
93 
 
1039 
 
 
1040 

 
 
48 
FUNDING  
1041 
For this trial, recruitment of English-speaking older adults is funded through a National Institute 
1042 
on Aging R01 grant (R01 AG045043) and recruitment of Spanish-speaking older adults is 
1043 
funded through the Patient-Centered Outcomes Research Institute (CDR-1306-01500). Dr. 
1044 
Sudore is also funded in part by a National Institute on Aging K24 (K24AG054415). 
1045 
 
1046 
CLINICALTRIALS.GOV INFORMATION 
1047 
This trial is registered at ClinicalTrials.gov: NCT01990235 for English-speakers, registered on 
1048 
November 4th, 2013 and NCT02072941 for Spanish-speakers, registered on February 4th, 2014. 
1049 
 
1050 
INTRODUCTION AND RATIONALE 
1051 
Background 
1052 
The population is aging,1,2 and the prevalence of chronic disease is increasing, especially 
1053 
among underserved and vulnerable populations (i.e., economically disadvantaged, racial and 
1054 
ethnic minorities, the uninsured, etc.).3 A critical aspect of chronic and serious disease 
1055 
management is advance care planning (ACP), a process whereby patients plan for their future 
1056 
medical care. Traditionally, advance directives have been the main focus of ACP, but 
1057 
unfortunately, most are written with complex, legal language.4 This lack of attention to limited 
1058 
health literacy and limited English proficiency may explain why advance directives are often not 
1059 
completed and may explain, in part, why less than 20% of racially and ethnically diverse, older 
1060 
adults engage in advance care planning (ACP) by the end-of-life.5-8  
1061 
 
1062 
Furthermore, for ethnic minorities, a population rapidly increasing in the U.S., medical decisions 
1063 
are often complicated by a lack of trust and perceived racism.9-11 Ethnic minorities are also more 
1064 
likely to prefer aggressive treatment, mistrust advance directives, and have non-autonomous 
1065 
views on decision making (i.e., prefer that family and doctors make medical decisions for 
1066 

 
 
49 
them).9,12-16 Hispanics/Latinos account for 15% of the U.S. population, a proportion projected to 
1067 
grow to 30% by 2050.1,2 Spanish-speaking patients face significant communication barriers, and 
1068 
literacy- and language-appropriate ACP tools that address unique aspects of Latino culture 
1069 
(e.g., familismo or a strong commitment and orientation to the family) are lacking.10 In addition, 
1070 
the mean reading level in the U.S. is only at the 8th grade level, and for adults over 65 years of 
1071 
age it is only at the 5th grade level.17,18  Patients with limited literacy often lack self-efficacy to 
1072 
communicate their wishes or ask questions,19 and the combination of limited literacy and limited 
1073 
English-proficiency results in low satisfaction with doctor-patient communication and decision 
1074 
making.20-22 However, studies show that patients can be motivated to take action in response to 
1075 
culturally- and linguistically-appropriate information they trust and can understand.8,23 
1076 
 
1077 
To address these gaps in advance care planning and shortcomings of advance directives, we 
1078 
developed a novel, comprehensive paradigm of ACP focused on preparing patients to identify 
1079 
their wishes, communicate with surrogate decision makers and clinicians, and make complex, 
1080 
decisions over the course of chronic and serious illness.24 This approach recognizes patients’ 
1081 
wishes change based on changing clinical contexts and that advance directives are but one tool 
1082 
to be used to inform in-the-moment decision making.25,26 To address the gaps in advance care 
1083 
planning for racially and ethnically diverse older adults, and based on the new comprehensive 
1084 
ACP paradigm, we created the interactive, patient-centered PREPARE website 
1085 
(prepareforyourcare.org) in English and Spanish that is culturally, linguistically, and literacy-
1086 
appropriate. PREPARE has been shown in pilot studies among English-speakers to help older 
1087 
adults engage in the ACP process, but it has yet to be tested in a randomized trial with both 
1088 
English- and Spanish-speaking older adults.27 Both the new ACP paradigm and the PREPARE 
1089 
intervention have been described in detail elsewhere.27,28 In addition, a description of a related 
1090 
trial of the efficacy of PREPARE among U.S. Veterans describes the theoretical framework 
1091 
underlying the PREPARE website.28   
1092 

 
 
50 
PRELIMINARY STUDIES 
1093 
We have experience conducting RCTs among diverse, older adults at the San Francisco 
1094 
Health Network (SFHN) primary care clinics.8 Dr. Sudore designed and tested an AD written 
1095 
at a 5th grade reading level among 205 chronically ill, diverse, older adults from Zuckerberg San 
1096 
Francisco General Hospital (ZSFG) with a 6-month follow-up of 85%. The AD was preferred 
1097 
over a standard AD, with significant interactions for limited literacy (e.g., higher preference rates 
1098 
in patients with limited literacy). It also resulted in greater 6-month AD completion rates (15% vs. 
1099 
7%, p =.03), doubling the rates from baseline. This AD has been adopted as the official AD for 
1100 
ZSFG and is being disseminated in California. It will serve as the active control. 
1101 
We designed and tested an informed consent process for diverse, older adults with 
1102 
limited literacy.29 We found that many patients do not understand simplified consent 
1103 
information and were unsure how to ask questions. But, informed decisions can be improved by 
1104 
providing both easy-to-read materials and a teach-back method. We will use this interactive 
1105 
consent method for this study. 
1106 
Multiple steps of the ACP process:30 We found that most patients go through a series of ACP 
1107 
behavioral steps. Six months after exposure to the easy-to-read AD, 61% of older adults 
1108 
contemplated ACP, 56% discussed ACP with family or friends and 22% with clinicians, and 13% 
1109 
completed an AD. This work shows that measuring a full range of ACP outcomes, in addition to 
1110 
ADs, and associated behavior change steps (contemplation to action) is important and informs 
1111 
our study outcomes. Previously described barriers to ACP, such as not wanting to burden 
1112 
family,31 are addressed in PREPARE. 
1113 
Evidence supporting the new ACP paradigm and content of PREPARE:32 We completed 13 
1114 
focus groups with 69 diverse, English- and Spanish-speaking older patients (mean age 78 +/- 8, 
1115 
61% non- White) and surrogates (mean age 57 +/- 10, 91% non-White) from safety-net settings 
1116 

 
 
51 
who reported making serious medical decisions. We used semi-structured interviews to ask 
1117 
about what best prepared them for decision making. Qualitative analysis identified 5 overarching 
1118 
themes, beyond ADs, that prepared patients and surrogates for decision making: (1) choose 
1119 
surrogates wisely and verify they know their role, (2) identify goals based on past experiences 
1120 
and personal values, (3) decide whether to grant leeway in surrogate decision making, (4) 
1121 
inform other family and friends of one’s wishes to prevent conflict, and (5) ask clinicians 
1122 
questions. These themes have been incorporated as educational domains of PREPARE. 
1123 
Validity and reliability of the survey to measure ACP engagement: Surveys were designed 
1124 
with input from Co-Is and extensive cognitive interviews to measure discrete ACP actions (i.e., 
1125 
main outcomes: ACP discussions, AD completion,) and ACP behavior change (e.g., 
1126 
contemplation, self-efficacy, readiness). We recruited 50 older adults, aged ≥ 60 years with ≥ 2 
1127 
illnesses (32% female, 42% non-White). Internal consistency 7-day test-retest reliability, and 
1128 
discriminant validity (scores compared to healthy young adults – 50% female, 75% non-White) 
1129 
was high. Scores did not differ by race/ethnicity or literacy, p>.05. We will also use validated 
1130 
surveys on ACP attitudes and methods to classify patients into behavior change categories.33,34 
1131 
Preliminary evidence that PREPARE is beneficial. In a recent pilot,27 we recruited 43 diverse, 
1132 
older adults from low-income senior centers. All subjects rated PREPARE easy to use (mean 
1133 
9/10-point scale). Pre to post ACP behavior change scores from our validated surveys (0-124 
1134 
points) increased from 72 ± 33 SD to 87 ± 22, a 15-point increase and an effect size of 0.5.  
1135 
Vulnerable populations have unique needs. The aforementioned pilot demonstrated that, 
1136 
unlike our work with Veterans, patients in safety-net settings are less trustful of research and 
1137 
require in-person recruitment. In addition, these patients are often socially isolated and require 
1138 
tailored ACP for persons without surrogates or families. They also lack ready access to health 
1139 
information and ancillary support such as social workers or nurses necessitating access to ACP 
1140 

 
 
52 
outside of the clinical environment. These findings add further evidence for the need to tailor 
1141 
PREPARE for vulnerable populations and to test PREPARE within safety-net settings. 
 
1142 
PREPARE has been shown to increase ACP Documentation and Engagement among 
1143 
Veterans. A prior trial of PREPARE was conducted among 414 Veterans.35 The mean age of 
1144 
the cohort was 71.1 (7.8) years, 91% were men, 57% were white, 20% had limited literacy, 29% 
1145 
reported fair-to-poor health status, and 51% had evidence of prior ACP documentation. The 
1146 
follow-up time point was 6 months and there was a 90% retention rate. There were no 
1147 
differences in demographic characteristics between study arms. In this VA population, advance 
1148 
care planning documentation 6 months after enrollment was higher in the PREPARE arm vs the 
1149 
AD-alone arm (adjusted 35%vs 25%; odds ratio, 1.61 [95%CI, 1.03-2.51]; P = .04). PREPARE 
1150 
also resulted in higher self-reported ACP engagement at each follow-up, including higher 
1151 
process and action scores; P <.001 at each follow-up). These findings add further evidence of 
1152 
the validity of PREPARE. However, PREPARE has never been tested among diverse, English- 
1153 
and Spanish-speaking older adults in a safety-net setting.  
1154 
 
1155 
OVERVIEW OF THE TRIAL DESIGN 
1156 
Study overview: 
1157 
This study is a randomized, controlled trial that uses blinded outcome ascertainment to 
1158 
determine the efficacy of the ACP PREPARE website to engage ethnically diverse English- and 
1159 
Spanish-speaking older primary care patients in the ACP process.36 First, we obtained a Health 
1160 
Insurance Portability and Accountability Act waiver to identify individuals who meet our 
1161 
inclusion/exclusion criteria and have upcoming primary care appointments. Administrative data 
1162 
and chart review are used to determine potentially eligible patients (Figure, Study Flow Chart).  
1163 
 
1164 

 
 
53 
Then primary care clinicians’ permission is obtained to allow the study team to inform their 
1165 
patients about the study. Patients are then recruited, screened for eligibility and scheduled for a 
1166 
baseline interview before an upcoming primary care appointment. To standardize the timing of 
1167 
exposure to the intervention and primary care follow-up, study participants are scheduled for 
1168 
baseline procedures 1-3 weeks prior to an upcoming primary care appointment.28 
1169 
 
1170 
Next, informed consent is obtained, and those patients who provide consent are randomized to 
1171 
the PREPARE intervention arm (i.e., the PREPARE website with action plan exercises plus an 
1172 
easy-to-read advance directive plus PREPARE materials to take home, which include a website 
1173 
login, and a PREPARE pamphlet, booklet, and DVD) or the control arm (i.e., an easy-to-read 
1174 
advance directive alone). See Study Flow Figure and a full description of the intervention below.  
1175 
 
1176 
We then conduct blinded outcome ascertainment by performing chart reviews to determine ACP 
1177 
documentation at baseline and at the end of the study. We also conduct blinded outcome 
1178 
ascertainment using patient surveys at 1 week, and 3, 6, and 12 months after the primary care 
1179 
appointment. We are choosing an active control arm (i.e., an easy-to-read advance directive) 
1180 
because we believe provision of an advance directive for chronically and seriously ill older 
1181 
patients should be the standard of care, even if it is not often “usual” care in clinical practice.8 In 
1182 
addition, the easy-to-read advance directive used in this study has been adopted by the San 
1183 
Francisco Health Network (SFHN) and Zuckerberg San Francisco General Hospital (ZSFG) and 
1184 
is available in the primary care clinics. 
1185 
 
1186 
Research Aims and Study Hypotheses: 
1187 
The aims of this study are to (1) To determine the efficacy of PREPARE to engage diverse, 
1188 
English- and Spanish-speaking older adults with chronic illness in advance care planning (ACP) 
1189 
compared to controls (AD only) and (2) To determine whether PREPARE efficacy varies by 
1190 

 
 
54 
race/ethnicity, literacy, clinician-patient language concordance, and patient’s desired role in 
1191 
decision making.36  
1192 
 
1193 
Our primary hypothesis is that the PREPARE program plus an easy-to-read advance directive 
1194 
will result in greater documentation of ACP wishes, including advance directives and 
1195 
documentation of ACP discussions in the medical record, than an easy-to-read advance 
1196 
directive alone in elderly populations with chronic illness.  
1197 
 
1198 
Our secondary hypotheses are that, compared to an advance directive alone, PREPARE will 
1199 
result in more engagement in behavior change processes concerning ACP, including increased 
1200 
self-efficacy and readiness, as well as greater engagement in a full range of ACP actions, 
1201 
including discussions with surrogate decision makers and other trusted family and friends. 
1202 
Secondary outcomes will be ascertained using validated surveys.33,37,38 We also hypothesize 
1203 
that PREPARE will result in improved satisfaction with patient-doctor communication and 
1204 
informed medical decision making and that PREPARE efficacy may vary across moderator 
1205 
variables such as patient health literacy, clinician-patient language concordance, and patients’ 
1206 
desired role in decision making. 
1207 
 
1208 
 
1209 
 
 
1210 

 
 
55 
Figure 1: PREPARE Study Flow Diagram 
1211 
 
1212 
 
1213 
 
1214 
 
 
1215 
Administrative data pull and chart review from ZSFG 
 Language listed as English or Spanish 
 ≥ 55 years of age and ≥ 2 chronic illnesses 
 Seen by primary care physician ≥ 2 times in the past year + ≥ 2 additional inpatient  
  or outpatient visits 
 Not deaf, blind, demented, or psychotic 
Obtain clinicians’ permission to tell their patients about the study 
Screen for eligibility 
 Excluded if they report not speaking English or Spanish “well” or “very well” 
 Excluded if they report poor vision, lack of a phone, out of the country ≥ 3 months 
 Excluded if they test positive for moderate-to-severe cognitive impairment 
Baseline Survey: 1-3 weeks prior to primary care visit 
 Chart review to assess ACP documentation 
 In-person survey to assess baseline ACP engagement, moderator and mediator variables, and 
demographic variables  
Block randomized by health literacy level (limited vs. adequate literacy) 
CONTROL 
 
Easy-to-read  
advance directive only    
(English or Spanish) 
PREPARE INTERVENTION 
 PREPARE website in English or Spanish 
 Action plan created within the website 
 Easy-to-read advance directive in English or Spanish 
 To take home: website login and PREPARE  
   booklet, pamphlet and DVD 
Post-intervention acceptability and usability questionnaire for feasibility 
Reminder phone call 1-3 days prior to primary care visit 
PREPARE: Remind to discuss ACP materials                          Control: Remind about visit 
1-week, 3-month, and 6-months follow-up interview (phone or in-person) 
   Assess ACP engagement  
Final follow-up  
   Assess ACP engagement in 12-month interview (phone or in-person) 
   Chart review to assess ACP documentation at 15-months 

 
 
56 
STUDY SETTING 
1216 
Recruitment for this randomized trial is occurring in 4 separate primary care clinics associated 
1217 
with the San Francisco Health Network (SFHN) and the Zuckerberg San Francisco General 
1218 
Hospital (ZSFG) in San Francisco, California. These 4 clinics are housed in 3 separate physical 
1219 
locations in San Francisco. ZSFG is an urban, public hospital that, with the SFHN, serves 
1220 
racially and ethnically diverse, low-income and indigent patients; 30% of patients are Spanish-
1221 
speaking.8  
1222 
 
1223 
PARTICIPANTS AND ELIGIBILITY AND EXCLUSION CRITERIA  
1224 
There are no inclusion or exclusion criteria based on gender, race or ethnicity. We assess 
1225 
eligibility in person or over the phone. Older adults are included in this study if they self-report 
1226 
speaking English or Spanish “well” or “very well”; are 55 years of age or older; have ≥ 2 chronic 
1227 
illnesses determined by chart review; have seen a primary care clinician (physician, nurse 
1228 
practitioner, or physician assistant) at ZSFG/SFHN-affiliated primary care clinics ≥ 2 times in the 
1229 
past year (an indication of established primary care); and have had ≥ 2 additional outpatient or 
1230 
inpatient visits in the past year (an indication of severity of illness). Their primary care clinician 
1231 
must also give us permission to contact them to tell them about the study.  
1232 
 
1233 
We are recruiting patients ≥ 55 years of age (rather than ≥ 65) because adults in safety net 
1234 
settings experience accelerated aging, functional decline, and sequelae of chronic disease, 
1235 
necessitating decision making and ACP at a younger age than patients with higher 
1236 
socioeconomic status.39,40 The goal is to start ACP early to change the trajectory of decision 
1237 
making and care over the course of illness. Our inclusion criteria of ≥ 2 primary care visits and ≥ 
1238 
2 additional visits in the past year ensures patients have established primary care and access 
1239 
care frequently. This will enhance recruitment and follow-up.  
1240 

 
 
57 
Patients will be excluded if their clinician is a principal investigator, co-investigator or clinician-
1241 
member of the Patient-Clinician Advisory Board or they had been enrolled in a previous pilot 
1242 
study of the PREPARE website or been exposed to the PREPARE study materials. They will 
1243 
also be excluded if they have medical record documentation of being deaf, blind, having 
1244 
dementia, or being psychotic or are deemed by their clinician to be too mentally or physically ill 
1245 
to participate. Participants will also be excluded if they have evidence of active drug or alcohol 
1246 
abuse within the past 3 months determined by clinician assessment, self-report, chart review or 
1247 
research staff assessment. Through in-person or phone screening by study staff, patients are 
1248 
also excluded if they self-report vision too poor to read a newspaper, lack of a phone (needed 
1249 
for follow-up interviews and scheduling), or plans to be out of the country for ≥ 3 months; if they 
1250 
screen positive for moderate-to-severe cognitive impairment using the validated Short Portable 
1251 
Mental Status Questionnaire followed by the Mini-Cog,41-43 or self-report or are determined by 
1252 
study staff to be blind, deaf, intoxicated or actively psychotic. Because ACP is an iterative 
1253 
process and people may change their preferences over time,24,44 subjects with prior ACP 
1254 
experiences (e.g., an advance directive) are not excluded. 
1255 
 
1256 
To minimize the risk of unblinding by fellow research participants, any spouse/partner of a 
1257 
currently enrolled patient who is also a patient at SFHN/ZSFG, meets the eligibility criteria, and 
1258 
therefore, is also a potential patient participant, will be excluded from being a patient participant. 
1259 
This will avoid a situation where 2 closely related people living in the same home could be 
1260 
randomized to different study arms and result in unblinding. In addition, an individual who is 
1261 
named as an enrolled patient’s potential surrogate decision maker (regardless of cohabitation or 
1262 
spousal status), who is also a patient at SFHN/ZSFG, meets the eligibility criteria, and therefore, 
1263 
is also a potential patient participant, will only be eligible to be a surrogate participant in our 
1264 
study and will be excluded from being a patient participant. In addition, we are excluding any 
1265 

 
 
58 
patient who has been enrolled in a previous PREPARE-related study or is known to have 
1266 
previously been exposed to PREPARE (e.g. note in medical record). 
1267 
 
1268 
To save research staff considerable time and effort, potential participants who miss an interview 
1269 
(i.e. no show) more than 2 times (for the same baseline interview appointment) without prior 
1270 
notification and rescheduling with study staff will be considered ineligible, unless there are 
1271 
extenuating circumstances. 
1272 
 
1273 
 
1274 
 
1275 
  
1276 
Inclusion and Exclusion Criteria  
Inclusion 
Criteria 
55 years of age or older 
Obtains care in the primary care clinics at in the San Francisco Health Network 
(SFHN). 
Has been seen at least twice in the last year by a primary care provider (a 
marker of established primary care) and had at least two additional visits to 
SFHN in the past year (a marker of illness) 
Exclusion 
Criteria 
Clinician is the PI, Co-I or member of the Patient-Clinician Advisory Board 
In a prior PREPARE-related study, such as a focus group or pilot study 
Dementia by ICD-9/ICD-10 codes, clinician assessment, chart review or self-
report 
Blindness or poor vision by ICD-9/ICD-10 codes, clinician assessment, chart 
review, self-report of blindness or the inability to read print on a newspaper45 
Deafness by ICD-9/ICD-10 codes, clinician assessment, self-report, chart 
review or research staff assessment  
Cognitive impairment as assessed by research staff of any deficits on the 
validated Short Portable Mental Status Questionnaire (SPMSQ)46 and the mini-
Cog41,47 
Delirium or psychosis as assessed by a clinician or research staff 
Does not report speaking English or Spanish “well” or “very well” 
No phone for additional study contacts and follow-up interviews 
Active drug or alcohol abuse within the past 3 months determined by clinician 
assessment, self-report, chart review or research staff assessment.  
Patients who report they will be out of town during their scheduled follow-up 
interview dates outside of a window of 3 months.  
Report being a spouse or surrogate of another enrolled participant 
Patients who cannot answer consent teach-back questions after three attempts 
2 or more no-show baseline interview appointments without rescheduling 

 
 
59 
RECRUITMENT METHODS 
1277 
Data Extraction: 
1278 
To facilitate recruitment, we obtained a Health Insurance Portability and Accountability Act 
1279 
waiver to access patients’ names, age, primary language, phone numbers, addresses, medical 
1280 
record numbers, as well as dates of outpatient primary care clinic appointments in the past year 
1281 
and up to 3 months in the future, other appointments and hospitalizations and emergency room 
1282 
visits in the past year, and the name of patients’ outpatient primary care providers. From these 
1283 
data, we obtain a list of potentially eligible patient participants and send a secure email to their 
1284 
primary care providers asking for permission for our study team to tell their patients about the 
1285 
study through a recruitment opt-out study letter, followed by phone or in-person recruitment. 
1286 
Weekly administrative data pulls from the electronic health record identify patients with 
1287 
upcoming primary care appointments and are used to target patient recruitment efforts. 
1288 
 
1289 
Clinician Permission to Contact Patients: 
1290 
Upon completion of the administrative data pulls, providers from all recruitment sites are sent a 
1291 
letter/e-mail informing them about the research study and asking them to review a list of their 
1292 
patients, to refer patient(s) on their patient list who would be appropriate for the study, and to 
1293 
obtain permission to contact their patients to tell them more about the study. Clinicians are also 
1294 
informed that if the study team receives their approval, their eligible participants will receive a 
1295 
letter describing the research study and offering them the opportunity to decline to be contacted 
1296 
by research personnel and/or will be contacted in clinic. Additionally, clinicians are informed that 
1297 
if they do not respond one week after the 3rd attempt to contact them by the study team 
1298 
(including by email, phone, and/or in-person), we will assume assent to contact their patients 
1299 
and a letter describing the study will be sent to patients on behalf of the study team. We obtain 
1300 
permission from all of the Service Chiefs before their clinicians are contacted. 
1301 
 
1302 

 
 
60 
Recruitment Methods and Materials: 
1303 
Study-related fliers written at a 5th-grade reading level in English and Spanish are posted in 
1304 
approved areas in SFHN/ZSFG-affiliated primary care clinics. Because many patients may be 
1305 
too ill to come to frequent clinic appointments and to be interviewed or hear about the study in 
1306 
busy clinic waiting rooms, we include several recruitment strategies. Therefore, in addition, 
1307 
recruitment letters and postcards written at a 5th grade reading level in English and Spanish are 
1308 
mailed and describe the research study as well as provide a telephone number to either opt-out 
1309 
or to hear more about the study.  Although patients can opt out at any time, those who do not 
1310 
call study staff to decline participation within 1 week of the mailings are deemed eligible to be 
1311 
contacted to describe the study, assess willingness to participate and assess study eligibility. To 
1312 
standardize the timing between intervention exposure and primary care follow-up, we schedule 
1313 
patients for the baseline interview and exposure to PREPARE or the control intervention 1 to 3 
1314 
weeks prior to their upcoming primary care appointment. Weekly administrative data pulls from 
1315 
the electronic health record identify patients with upcoming primary care appointments and are 
1316 
used to target patient recruitment efforts. Potential participants are then contacted by phone or 
1317 
in the clinic. 
1318 
 
1319 
Patients who consent and enroll are paid $50 for the baseline interview and given $10 in MUNI 
1320 
(municipal transportation vouchers) to help participants come back to follow-up interviews in 
1321 
person if they desire. Participants are also reimbursed $25 for each of the 1-week, 3, 6, and 12-
1322 
month interviews. 
1323 
 
1324 
Diverse, vulnerable populations are often difficult to recruit for research studies. We employ 
1325 
several strategies to enhance our recruitment. First, we attempt to hire individuals who have 
1326 
experience with diverse populations and individuals who are bilingual (native Spanish-speaking) 
1327 
and bicultural. Furthermore, we conduct extensive sensitivity training with all research staff and 
1328 

 
 
61 
require staff to use approved study scripts when speaking to patients. These study scripts and 
1329 
all study materials used for recruitment are vetted, updated and approved by both our patient 
1330 
advisory and clinical advisory boards. All materials and study scripts are written at a 5th grade 
1331 
reading level and are provided to patients in their preferred language (i.e., English or Spanish). 
1332 
 
1333 
CONSENT PROCEDURES 
1334 
We use a modified consent process that several co-authors designed for vulnerable 
1335 
populations.28,29 Consent forms written at the 5th grade reading level are provided and read to 
1336 
participants in English or Spanish. This review is then followed by standardized “teach-to-goal” 
1337 
questions to ensure understanding. If potential participants cannot correctly complete the teach-
1338 
back process after 3 attempts, the patient is deemed ineligible.  
1339 
 
1340 
The consent form is approved by the UCSF and ZSFG Institutional Review Boards, the 
1341 
patient/clinical advisory board, and the Data and Safety Monitoring Board (DSMB). The consent 
1342 
form states the following for the purpose of the study: “Why is this study being done? 
1343 
Sometimes patients and their families have to make hard medical decisions. We want to design 
1344 
and test an easy-to-understand handout to help.  This handout will help people think about their 
1345 
values, or what is most important to them in their life. It will also help prepare patients to make 
1346 
medical decisions.” We use the word “handout” because, in pilot testing, both groups are given 
1347 
handout materials and written advance directives. For randomization we explain, “We will ask 
1348 
you to look over a handout and answer some questions about your experience with making 
1349 
medical decisions. There will be two groups that will be given different handouts. You will have a 
1350 
50/50 chance of being in either group.” 
1351 
 
1352 
Due to exclusions based on several missed baseline appointments and for staff safety and the 
1353 
need to exclude or withdraw participants who were intoxicated, psychotic, or threatening, the 
1354 

 
 
62 
consent also explains, “We also may ask you to stop taking part in this study if we feel it is in 
1355 
your best interest or if you do not follow the study rules.”  
1356 
 
1357 
It was determined with our Patient-Clinician Advisory Board that clinicians of patients should be 
1358 
contacted in the event that the patient reports severe depression or anxiety. Our DSMB agreed 
1359 
and our consent forms explain: 
1360 
“We would need to contact your regular doctor or a medical provider for the following reasons: 
1361 
 
You report or we observe that you are having a medical emergency, 
1362 
 
Such as a serious medical illness 
1363 
 
Or, a serious mental illness, such as major depression 
1364 
 
You report that you may harm yourself, you may harm someone else, or someone is 
1365 
harming you.” 
1366 
 
1367 
INTERVENTION AND COMPARISON CONDITIONS 
1368 
PREPARE arm 
1369 
As previously described, PREPARE is an easy-to-use, patient-centered, interactive website that 
1370 
is available in English or Spanish, is written at a 5th grade reading level, includes voice-overs of 
1371 
all text for the reading-impaired and closed-captioning of all videos for the hearing impaired 
1372 
(www.prepareforyourcare.org).27,28 The conceptual framework for PREPARE has been 
1373 
previously published and is based primarily on Social Cognitive Theory, 48,49 with elements from 
1374 
the Health Belief Model,50 the Theory of Planned Behavior,51 and Behavior Change Theory.49,52 
1375 
In these theories and in behavioral studies, modeling of behaviors helps people change their 
1376 
behavior. Successful behavioral change interventions model skills, enhance self-efficacy, and 
1377 
address perceived barriers,53,54 especially literacy-appropriate interventions.8 Modeling 
1378 
behaviors (as in PREPARE) can also improve patients’ ability to communicate with clinicians 
1379 
and improve outcomes,55,56 such as increased question asking behavior and a sense of control 
1380 
during a clinical visit,56,57 an increased desire to participate in decision making, and even 
1381 

 
 
63 
improved affect and functional status.53,58-60  PREPARE incorporates these successful teaching 
1382 
methods through the modeling of behaviors in videos. Video and interactive websites are more 
1383 
powerful mediums to teach information and change behavior than written materials, especially 
1384 
for those with language/literacy barriers.61-67 PREPARE includes a training and goal setting 
1385 
component which has been shown to be effective in changing outpatient behaviors, such as 
1386 
exercise.68  
1387 
 
1388 
In the design of the PREPARE website, we included essential, theory-based health education 
1389 
strategies, such as the use of video modeling of ACP behaviors and tailored and interactive 
1390 
content based on patients’ values and decision preferences. To ensure PREPARE is easy to 
1391 
read and understand, we use clear health communication principles (e.g., targeting text to the 
1392 
5th grade reading level) informed by extensive formative research and cognitive interviewing 
1393 
with the target population (i.e., racially and ethnically diverse older adults with limited health 
1394 
literacy and English proficiency) to ensure PREPARE content is acceptable to individuals from 
1395 
diverse cultural backgrounds.27 The PREPARE website leads people through a 5-step ACP 
1396 
process that ranges from choosing a surrogate decision maker to asking their clinicians the right 
1397 
questions. While going through the website, PREPARE also helps individuals answer personal 
1398 
values questions about their medical care, and helps them create an action plan to engage in 
1399 
some form of ACP. Patient-generated action plans have been shown to help patients engage in 
1400 
other preventative and disease management activities in the outpatient setting.69  
1401 
 
1402 
After the baseline interview, participants in the PREPARE arm review all 5 steps of the 
1403 
PREPARE website in English or Spanish in our research offices. Participants are asked to 
1404 
review PREPARE on their own and in its entirety. Research assistants are available to answer 
1405 
questions only if needed, but do not go through the website with the participants. At the end of 
1406 
the program, a summary of the patient’s medical wishes and action plan are automatically 
1407 

 
 
64 
generated from the PREPARE website in written format. This information along with the 
1408 
participant’s PREPARE website login information is included in a take-home folder that also 
1409 
contains PREPARE information in pamphlet, booklet, and DVD format. We include PREPARE 
1410 
content in non-website formats because some patients may not have access to the internet at 
1411 
home. PREPARE arm participants are also given an easy-to-read advance directive in English 
1412 
or Spanish to review and consider completing.8,70 Participants are asked to review the advance 
1413 
directive form for at least 5 minutes and up to 15 minutes in research offices, and then to take 
1414 
the form home to discuss with their potential surrogates and/or their clinicians. The time frame 
1415 
of 5-15 minutes was chosen because our goal is only to introduce the advance directive and 
1416 
allow participants to ask questions. The goal is not to have patients complete the form on the 
1417 
day of the study, before potential discussions with clinicians or surrogates, unless the participant 
1418 
would like to do so.  
1419 
 
1420 
AD-only arm 
1421 
Participants in the control arm are only given the easy-to-read advance directive, are asked to 
1422 
review it for at least 5 minutes and up to 15 minutes, and to take the form home to discuss with 
1423 
their potential surrogates and clinicians.  
1424 
 
1425 
Both arms: Reminder of primary care appointments 
1426 
One to 3 days before the patient’s next scheduled primary care appointment, research staff call 
1427 
the PREPARE arm participants to remind them to bring in their study materials (i.e., action plan 
1428 
and advance directive) and to talk to their clinician about ACP. For the control arm, research 
1429 
staff members only remind patients about their upcoming appointment and do not provide 
1430 
additional encouragement about ACP. 
1431 
 
1432 
RANDOMIZATION PROCEDURES 
1433 

 
 
65 
A statistician not involved in recruitment or data collection uses a computer-based random 
1434 
number generator to create a randomization scheme using block randomization by health 
1435 
literacy (adequate health literacy versus limited health literacy, as determined by a validated 
1436 
question concerning confidence with medical forms).71 Random block sizes of 4, 6, and 8 are 
1437 
used to ensure an equal number of patients with limited health literacy in each group. 
1438 
Randomization information is associated with a unique patient identification number and is kept 
1439 
separate from other patient data. Due to the need to secure interview rooms for the duration of 
1440 
the baseline questionnaire and intervention (i.e., approximately 2 hours for the AD-only arm and 
1441 
3 hours for the PREPARE arm), randomization occurred prior to scheduling a baseline 
1442 
interview.  
1443 
 
1444 
 
1445 
BLINDING 
1446 
Clinicians are blinded to patient group assignment. Although we obtain clinicians’ permission to 
1447 
recruit their patients, the interventions are not described, and no clinician education is provided. 
1448 
Participants could not be blinded to the intervention; however, they are told during consent there 
1449 
is a “50/50 chance” of getting one of two different ACP guides, and the non-assigned 
1450 
intervention is not described. Because each group obtains ACP materials, such as the easy-to-
1451 
read advance directive, blinding is enhanced. The research assistant who administers the 
1452 
intervention cannot be blinded to the study arm, but all follow-up outcome assessments are 
1453 
conducted by different and blinded staff.  At the start of all follow-up interviews, participants are 
1454 
reminded not to discuss the study materials they reviewed with assistants recording if they 
1455 
became unblinded. If unblinding occurs, a different blinded assistant conducts all subsequent 
1456 
interviews.  
1457 
 
1458 
INTERVENTION FIDELITY  
1459 

 
 
66 
All staff members are rigorously trained and are required to read and adhere to a standardized 
1460 
study protocol manual, standardized study scripts, and standardized checklists for each contact 
1461 
and interview with participants. Several training videos have also been developed for staff. 
1462 
Research staff are not allowed to conduct study tasks independently until they have reviewed all 
1463 
written and video training materials and can demonstrate complete mastery of all scripts and 
1464 
checklist items. In addition, a 10% random sample of all interviews is observed by senior 
1465 
research staff to ensure study fidelity.  
1466 
 
1467 
DATA COLLECTION METHODS 
1468 
Live capture of research data are collected through Research Electronic Data Capture 
1469 
(REDCap) software. REDCap is managed by the UCSF Academic Research Systems Team 
1470 
and is stored behind strong-string password protected firewalls on UCSF servers, not on 
1471 
individual laptops or desktops. All patients are given a unique, non-identifying patient 
1472 
identification number that is removed from any personally identifying information (PII) or 
1473 
personal health information (PHI). All PII and PHI are stored in a Microsoft ACCESS database 
1474 
behind strong-string password protected firewalls on UCSF and ZSFG servers. To reduce 
1475 
missing data, REDCap has been programmed to not allow study staff to progress if data fields 
1476 
are left blank. We retain the use of paper surveys in the event the RedCap system is down. All 
1477 
paper files continue to be stored in secure, locked research offices in secure, locked file 
1478 
cabinets. 
1479 
 
1480 
FOLLOW-UP AND RETENTION: 
1481 
We conduct follow-up interviews one week and 3, 6, and 12-months after the primary care visit 
1482 
in the clinic, by phone, or in the home if needed due to patient functional limitations. We utilize 
1483 
several measures to help ensure follow-up. Each follow-up interview takes between 30 to 45 
1484 
minutes and participants are reimbursed $25.  
1485 

 
 
67 
 
1486 
Method of contact for follow-up surveys: 
1487 
Upon enrollment, we ask participants to provide alternative phone numbers (e.g., cell or work 
1488 
numbers) and one to three additional phone numbers of close contacts who may know how to 
1489 
contact the patient in the event our study staff is unable to reach them. Many patients in safety 
1490 
net settings are marginally housed, have intermittent phone access, and may change locations 
1491 
and phone numbers during the study period. We also ask participants if they prefer a text 
1492 
message or an email to schedule follow-up visits and will use their preferred mode of 
1493 
communication. If these other modes of communication fail, we send out reminder letters. If 
1494 
needed, we also attempt to contact patients during scheduled clinic visits or make home visits. 
1495 
 
1496 
Participant Appointment Reminder Sheet 
1497 
We created an appointment reminder sheet as a reference for patient participants. This sheet 
1498 
shows the dates and times for upcoming appointments that the patient participant will have with 
1499 
us. 
1500 
 
1501 
Reminders for the primary care visit: 
1502 
Participants receive a brief reminder call one to 3 days before their next primary care visit. 
1503 
Participants in the AD-only arm are reminded to come to their scheduled appointment while 
1504 
participants in the PREPARE arm are reminded of their appointment and to bring the PREPARE 
1505 
materials to the visit. 
1506 
 
1507 
Reminders for study interviews: 
1508 
For all follow-up interviews, participants in both arms receive reminders of their upcoming study 
1509 
interview by phone or in person. To help participants follow along during the interview, the 
1510 
participant can receive a Participant Version of the survey via mail or email, as 
1511 

 
 
68 
preferred. No survey responses or information are collected by mail or email. We use 14-point 
1512 
font and color-coded, standardized, large font response options to help with understanding. 
1513 
 
1514 
Participants who miss their primary care appointment: 
1515 
Participants who cancel or miss their primary care appointments and do not reschedule within 
1516 
30 days of the cancelled appointment receive a courtesy phone call to remind participants to 
1517 
reschedule the primary care appointments in order to move on with the study schedule. For 
1518 
participants who cancel or miss their primary care appointments after they have been enrolled 
1519 
and randomized:  
1520 
 
If they have rescheduled and attend their primary care appointment within 6 months from 
1521 
when they were randomized, they receive a brief reminder call one to 3 days before their 
1522 
primary care appointment date. We conduct follow up assessments at 1 week, and at 3, 6, 
1523 
and 12 months from this primary care appointment date, 
1524 
 
If they do not reschedule or attend their primary care appointment within 6 months from 
1525 
when they were randomized, they receive a brief reminder call one to 3 days before their 
1526 
new primary care appointment date. We conduct follow up assessments at 6 and 12 months 
1527 
from the originally scheduled primary care appointment date. 
1528 
 
1529 
Ascertaining reasons for loss of follow-up or withdrawal: For participants who want to 
1530 
withdraw, we ask them why in open-ended questions. If they cannot provide an answer, we 
1531 
prompt them from a list of reasons we obtained from prior advance care planning trials, such as 
1532 
the study is too long, they are too busy, the study topic is too upsetting, they are too ill, etc.35  
1533 
 
1534 
MEASURES  
1535 
Overview 
1536 

 
 
69 
Because ACP ideally is a process that occurs over time, we felt it important to measure a full 
1537 
range of ACP measures including ACP documentation (primary outcome) over time, and 
1538 
several behavior change constructs and several additional ACP actions over a 12-month period 
1539 
(secondary outcomes). All study measures used in this analysis, including validity and reliability 
1540 
information in English and Spanish and the schedule of administration (i.e., baseline, 1-week or 
1541 
3, 6, or 12-months), are included in the Outcome Measures table below. All outcomes, including 
1542 
secondary outcomes not used in our main analysis, are included in our published protocol.36 
1543 
The main outcome measures are described in detail below. 
1544 
 
1545 
Primary Outcome 
1546 
The primary outcome is new documentation of ACP wishes in the ZSFG/SFHN medical record 
1547 
(Table of Outcome Measures below). ACP documentation for the purposes of this study 
1548 
includes the easy-to-read advance directive or other valid advance directives or living wills, a 
1549 
durable power of attorney for health care document (DPOAHC), a Physicians Orders of Life 
1550 
Sustaining Treatment form, or other documentation of discussions concerning patients’ wishes 
1551 
for medical care (i.e., documentation of oral directives by a physician or notes describing 
1552 
patients’ goals for medical care by clinicians).  
1553 
 
1554 
We assess baseline and 15-month new ACP documentation rates and the date of 
1555 
documentation to determine the length of time from study enrollment to subsequent 
1556 
documentation.  Patients in our study are enrolled, randomized, and exposed to the intervention 
1557 
1 to 3 weeks prior to a primary care appointment. ACP documentation is timed to the date of 
1558 
intervention exposure as patients may have engaged in ACP prior to seeing their primary care 
1559 
provider. The patient-reported outcomes in the follow-up surveys (1 week, 3, 6, and 12-months), 
1560 
however, are timed to the primary care visit because those questions concern engagement in 
1561 
discussions with clinicians (see secondary outcomes below). This same timeframe for ACP 
1562 

 
 
70 
documentation was determined from a prior PREPARE trial conducted within the VA to take into 
1563 
account and to standardize the expected time from intervention exposure to the primary care 
1564 
visit and the anticipated time to schedule and complete the final patient interview.35  
1565 
 
1566 
Because legal forms and documented discussions can be used to direct medical care, we 
1567 
created a composite variable of any ACP documentation (forms and/or discussions); we also 
1568 
plan to report the percentage of forms and discussions separately. All medical review data is 
1569 
double coded by 2 independent, blinded research assistants. Discrepancies are adjudicated by 
1570 
the principal investigator (R.L.S.). 
1571 
 
1572 
Secondary Outcomes 
1573 
Main Patient-Reported Outcome 
1574 
The main patient-reported secondary outcome, the validated Advance Care Planning 
1575 
Engagement Survey,27,28,37 was chosen to measure the full process of ACP. The Advance Care 
1576 
Planning Engagement Survey measures both ACP Behavior Change Processes, such as 
1577 
knowledge, contemplation, self-efficacy, and readiness on a validated 57-item scale. The ACP 
1578 
Behavior Change Process scale is measured on a 5-point Likert scale and average 5-point 
1579 
scores will be calculated. We will also measure ACP actions on the validated 25-item Action 
1580 
scale, which assesses ACP activities (yes or no) such as identifying a surrogate decision maker, 
1581 
identifying values and goals for medical care, choosing the level of leeway in surrogate decision 
1582 
making, discussing one’s wishes with clinicians and surrogates, and documenting one’s wishes 
1583 
in an advance directive.  Validity and reliability of the ACP Engagement Survey, as well as the 
1584 
questionnaire’s ability to detect change in response to an ACP intervention, have been 
1585 
previously described.27,28,37  
1586 
 
1587 
Feasibility and Satisfaction 
1588 

 
 
71 
To evaluate whether and how PREPARE will be used in clinical practice and in the community, 
1589 
we also assess acceptability of the PREPARE website compared to an advance directive alone 
1590 
using validated scales of ease-of-use (10-point scale, “On a scale of 1 to 10, with 1 being very 
1591 
hard and 10 being very easy, how easy was it to use this guide?”) and satisfaction (comfort: 
1592 
“How comfortable were you viewing this guide?”, helpfulness: “How helpful was this guide?”, 
1593 
and recommendations: “How likely are you to recommend this guide to others?” assessed on a 
1594 
5-point Likert scale (not-at-all to extremely) from our prior work.8 For the PREPARE arm only, 
1595 
and at the end of the 12-month interview and after unblinding, we also ask how likely patients 
1596 
are to recommend the PREPARE intervention to others.72 
1597 
 
1598 
Clinical and Patient-Advisory Board Requested Outcome 
1599 
Our Patient-Advisory Stakeholders requested we quantify the number and percentage of 
1600 
patients who increased their ACP activities overtime. Our stakeholders perceive any increase in 
1601 
an ACP activity over time as clinically meaningful. Thus, in addition to mean change in ACP 
1602 
Engagement scores, they wanted to know the percent of patients who improved (i.e., had an 
1603 
estimated slope > 0) over time for both Behavior Change scores, Actions scores, and both 
1604 
combined. We therefore created this exploratory variable post-hoc. 
1605 
 
1606 
Adverse Event Outcomes 
1607 
In addition, to ensure that the PREPARE program does not cause undue harm, we also assess 
1608 
both depression73,74 and anxiety.75,76 We measure depression using the validated Patient Health 
1609 
Questionnaire (PHQ)-8 (scores 0-24) and anxiety Generalized Anxiety Disorder (GAD)-7 
1610 
(scores 0-21) at baseline and each follow-up.74,75 Scores of 5, 10, 15, and 20 represent mild, 
1611 
moderate, moderately severe and severe depression or anxiety.  
1612 
 
1613 
Potential Mediating or Moderating Variables & Participant Characteristics 
1614 

 
 
72 
Based on the previously published conceptual framework of PREPARE,27 we also hypothesize 
1615 
that PREPARE efficacy may vary across several moderator or mediator variables (e.g., health 
1616 
literacy using the validated Short form Test of Functional Health Literacy in Adults s-TOFHLA, 
1617 
scores 0-3677 and dichotomized to limited = 0-22 & adequate = 23-36; clinician-patient language 
1618 
concordance (concordant versus discordant); and patient’s desired role in decision making with 
1619 
the medical provider using the validated Decision Control Preferences Scale(wants to make 
1620 
their own decision versus wants doctors/family to make decisions for them).78 We also 
1621 
hypothesize that PREPARE efficacy may be affected by several confounding variables (e.g., 
1622 
self-rated health, “How would you rate your health?” [5-point Likert]79,80 dichotomized as fair-to-
1623 
poor and good-to-excellent and past experiences with ACP including prior documentation of 
1624 
legal forms and documented discussions. We will also assess a full range of patient-reported 
1625 
characteristics, as these factors may impact patient-clinician communication,20,81 such as age 
1626 
(“What is your date of birth?”), self-reported gender (“What gender do you consider yourself to 
1627 
be? male, female transgender, other”), finances (able to make ends meet versus not make ends 
1628 
meet), having a potential surrogate decision maker or not, education (“What is the highest 
1629 
educational level you have completed?” less than or equal to high school or greater than high 
1630 
school), internet access in the home (yes or no), and religiosity and spirituality (i.e., “How 
1631 
religious/spiritual do you consider yourself to be?” on 5-point Likert scale from not-at-all to 
1632 
extremely).  
1633 
 
1634 
 
1635 
 
1636 
 
1637 

 
 
73 
Outcome Measures Table 
1638 
Construct 
Measure 
# items 
English 
Reliability/Validity 
Spanish 
Reliability/Validity 
Baseline 
1 week 
3 months 
6 months 
12 months 
15 months 
 
Primary Outcome 
 
 
 
 
 
 
 
 
 
New ACP 
Documentation 
Chart review: ACP 
documentation (i.e., legal 
forms and documented goals 
of care discussions)35,36 
 
 
 
 
 
X 
 
 
 
 
X 
 
Secondary Outcomes 
 
 
 
 
 
 
 
 
 
The Full ACP 
Process  
 
ACP Engagement Survey: 27 
Behavior Change Process 
Measures (knowledge, 
contemplation, self-efficacy, 
readiness) 
 
Action Measures: values 
identification and discussions 
 
57 
 
 
 
 
 
25 
Behavior Change 
Measures: 
Cronbach’s α = 0.94 
(0.91-0.96), ICC= 0.70 
(0.54-0.82)27 
 
Action Measures: 
ICC*= 0.87 (0.79-0.92)27 
- 
X 
X 
X 
X 
X 
 
Implementation: 
Acceptability  
Acceptability and Usability 
(a) Ease of Use and 
Understanding 
(b) Usefulness in decisions & 
discussions   
(c) Attitudes about norms or 
expectations 
 
8 
6 
 
6 
1 factor explained 81-85% 
of variance/scale. Kuder-
Richardson >0.758 
1 factor explained 81-
85% of variance/scale. 
Kuder-Richardson 
>0.758 
X 
 
 
 
 
 
 
Adverse Event Outcomes 
 
 
 
 
 
 
 
 
 
Depression 
Patient Health Questionnaire-
8  
8 
 
Scores ≥10 100% 
sensitive and 95% specific 
for major depressive 
disorder.73,74 
 
 
Scores ≥10 77% 
sensitive and 100% 
specific for major 
X 
X 
X 
X 
X 
 

 
 
74 
Construct 
Measure 
# items 
English 
Reliability/Validity 
Spanish 
Reliability/Validity 
Baseline 
1 week 
3 months 
6 months 
12 months 
15 months 
depressive disorder82 
 
 
Anxiety 
GAD-775 
7 
Cronbach’s α = 0.9275 
ICC*= 0.83 
Cronbach’s α = 0.8876 
ICC*= 0.64 
X 
X 
X 
X 
X 
 
 
Exploratory Outcome  
 
 
 
 
 
 
 
 
 
Percent increase in 
ACP activities 
N (%) participants who 
increased their Behavior 
Change or Action scores from 
baseline (i.e., estimated slope 
> 0) 
 
- 
- 
X 
X 
X 
X 
X 
 
 
Demographic Information 
 
 
 
 
 
 
 
 
 
Demographic 
Information 
 
Age, gender, race/ethnicity83, 
marital status, and education 
 
 
 
X 
 
 
 
 
 
Finances 
“In general, how do your 
finances usually work out at 
the end of the month?” 
1 
Associated with 
functional impairment 
and co-morbidity 84 
- 
X 
 
 
 
 
 
Socioeconomic Social 
Standing 
Social standing ladder (i.e. 
place an “x” where you think 
you stand relative to other 
people in society) 
1 
Associated with 
functional decline85 
 
- 
X 
 
 
 
 
 
 
Other Measures 
 
 
 
 
 
 
 
 
 
Health Literacy  
Short form Test of Functional 
Health Literacy in Adults s-
TOFHLA, scores 0-36)77 
Continuous & dichotomized 
to limited = 0-22 & adequate 
36 
Cronbach’s α = .97 
Correlation coefficient w/ 
other literacy tests > 
0.8077 
Cronbach’s α >.9586 
X 
 
 
 
 
 

 
 
75 
Construct 
Measure 
# items 
English 
Reliability/Validity 
Spanish 
Reliability/Validity 
Baseline 
1 week 
3 months 
6 months 
12 months 
15 months 
= 23-36 
Patient-clinician 
language 
concordance 
To clinicians: “How well do 
you speak Spanish?87 Fluent, 
very well (concordant) vs. 
well, fair, or poor” 
1 
 
AUROC† 94% (CI: 90-
98%)87 
AUROC† 94% (CI: 90-
98%)87 
X 
 
 
 
 
 
Desired role in 
decision making 
Control Preference Scale 
(CPS) with clinician78 
2 
Correlation between 
preferred and actual role 
in decision making.12,88,89 
Correlation between 
preferred and actual role 
in decision making90 
X 
 
 
 
X 
 
Internet Access 
Do you have access to the 
internet in your home? 
1 
- 
- 
X 
 
 
 
 
 
U.S. Acculturation 
Based on Acculturation scale 
(USAS) “How many years 
have you lived in the U.S.?” 
1 
Cronbach’s α = .98 
Associated w/ desire to 
know prognosis91 
- 
X 
 
 
 
 
 
Functional Status 
Activities of Daily Living 
(ADL) (0-16 point scale)& 
Instrumental (IADL) measure 
(0-12 item scale)92,93 
13 
Morbidity/mortality 
correlation.126,127 
Cronbach’s alpha 
=0.9494 
X 
 
 
 
 
 
Self-rated health 
status 
How would you rate your 
health? (5pt Likert) 79,80 
1 
Cronbach α = .8080 
- 
X 
 
 
 
 
 
Prior ACP experience 
Prior ACP experiences (e.g.,  
(“Ever had to make life 
threatening medical 
decisions?”) 8 
 
5 
 
- 
X 
 
 
 
 
 
Social support 
 
Modified Medical Outcomes 
Study Social Support (scores 
11-55) 95 
 
Presence of a possible 
11 
 
 
11 
Cronbach’s α = 0.88-.9395 
 
 
 
Cronbach’s α = 0.9496 
 
 
 
X 
 
 
 
 
 

 
 
76 
Construct 
Measure 
# items 
English 
Reliability/Validity 
Spanish 
Reliability/Validity 
Baseline 
1 week 
3 months 
6 months 
12 months 
15 months 
Surrogate Decision maker 
 
 
Religion/Spirituality 
Self-reported extent of how 
spiritual/religious (5-pt Likert) 
and role play in decision 
making.97 
4 
Spirituality associated with 
quality of life. Religiosity 
associated with wanting all 
measures to extend life.97 
- 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Only the variables included in the current analysis are listed in the table. All measures including other secondary and exploratory outcomes not 
1639 
included in this analysis are listed in the published protocol.36 
1640 
If a validated Spanish-version of a survey was not available, we translated the English version into Spanish. 
1641 
*ICC = Intraclass correlation 
1642 
† Area under the receiver operating curve (AUROC) 
1643 
‡ While mediator variables, measured at baseline, may explain how or why a particular effect or relationship occurs, these variables may also be 
1644 
affected by the intervention and are therefore also considered secondary outcome variables measured over time (i.e., knowledge, self-efficacy, 
1645 
and readiness, as well as barriers and attitudes). 
1646 
 
1647 

 
 
77 
STATISTICAL ANALYSIS PLAN 
1648 
Our primary analyses will compare change in ACP documentation between study arms from 
1649 
baseline to 15 months. Secondary outcomes will include ACP Engagement with respect to 5 
1650 
ACP Actions (yes/no and a 0-25-point scale) and behavior change scores (average 5-point 
1651 
Likert scores) from baseline to 1 week, and 3, 6, and 12 months. Variables will be assessed for 
1652 
distributional and outlier values using standard summary statistics. Baseline comparability will 
1653 
be assessed between groups using unpaired t-tests, Chi-square tests or Fisher’s exact tests. 
1654 
Using t-tests or Chi-squared tests, we will also compare patient’s age and self-reported gender 
1655 
between those who refused versus those who enrolled and differences between arms of those 
1656 
who withdrew versus those who did not.  We will use intention-to-treat analysis using SAS 
1657 
version 9.4 (SAS Institute Inc.) and STATA 15.0 (College Station, TX). All p-values will be 2-
1658 
tailed and set at .05 for the primary outcome and Bonferroni adjusted for secondary patient-
1659 
reported outcomes. In addition, because of differences in ACP engagement among English and 
1660 
Spanish speakers,8 and based on preferences of our stakeholders and granting agencies, we 
1661 
decided, a priori, to analyze our results overall and stratified by English and Spanish language. 
1662 
To compare outcomes between the two arms longitudinally, we will use mixed effects linear, 
1663 
Poisson, or negative binomial regression for continuous measures and mixed effects logistic 
1664 
regression for dichotomous measures. The mixed effects models will include fixed effects for the 
1665 
primary modeling terms of time (baseline and 15 months for ACP documentation and baseline 
1666 
and 1 week, 3 months, 6 months, and 12 months for ACP Engagement with time modeled using 
1667 
dummy variables to allow for non-linearity); arm (AD-only versus PREPARE); an interaction 
1668 
term of study arm and time; and a random effect for subjects. We will adjust for the 
1669 
randomization blocking factors limited vs. adequate literacy,98 and any predictor variables that 
1670 
differ between arms. All models also will also be adjusted for baseline ACP documentation and 
1671 
will include random physician intercepts to account for nesting of patients within physicians. We 
1672 
will use standardized, clinically meaningful effect sizes (i.e., 0.20-0.49 small, 0.50-0.79 medium, 
1673 

 
 
78 
and ≥0.80 large).99 Per stakeholder request, we will conduct post-hoc mixed-effects regression 
1674 
to calculate the percentage of participants who increased their Behavior Change score, Action 
1675 
scores, or both Behavior Change and Action scores from baseline (i.e., estimated slope > 0) by 
1676 
study arm; p-values adjusted to a significance of 0.017.  
1677 
 
1678 
For moderator analysis, we will test for interactions by adding interaction terms to the group by 
1679 
time variable for health literacy (limited versus adequate) controlling for prior ACP 
1680 
documentation and clustering effects by clinician. All other interaction terms are adjusted for 
1681 
health literacy (randomization blocking variable) prior ACP documentation and clustering effects 
1682 
by clinician. Additional interaction terms to be added to the group by time variable include 
1683 
language (i.e., English versus Spanish), control preferences for decision making (i.e., makes 
1684 
own decisions versus doctor makes decisions), age (i.e., < 65 years versus 65 years of age), 
1685 
sex/gender (i.e., self-reported man versus woman), race/ethnicity (i.e., white versus non-white), 
1686 
health status (i.e., good-to-excellent versus fair-to-poor), presence of a potential surrogate (i.e., 
1687 
yes versus no), internet access at home (i.e., yes versus no), and, for Spanish-speakers, 
1688 
patient-clinician language (concordance vs. discordance). A p-value for interaction <0.05 is 
1689 
considered significant.    
1690 
 
1691 
Missing data for the primary outcome will be assessed. If there is 10% or more of missing data, 
1692 
we will use a mean imputation approach. All available data will be included in mixed-effects 
1693 
models. We will assess whether any research staff member became unblinded during follow-up 
1694 
assessment and conduct sensitivity analysis as needed. 
1695 
 
1696 
SAMPLE SIZE AND POWER CALCULATIONS 
1697 
We will measure a full range of ACP behaviors including discussions. However, written advance 
1698 
directive completion of legal forms is a primary outcome and is the most well-studied.100  Power 
1699 

 
 
79 
from longitudinal analyses with repeated measures will be stronger, but to be conservative, we 
1700 
consider power for a single post-intervention time point (e.g., 15 months). A recent meta-
1701 
analysis of written advance directive documentation studies demonstrated a pooled effect size 
1702 
of 0.50 (95% CI; 0.17 -0.83),100 as did an RCT of an ACP workbook that included both behavior 
1703 
change constructs and a social work visit,101 and our prior RCT of an easy-to-read AD at ZSFG 
1704 
which showed an increased AD completion rate from 7% to 15%.8  Because both the 
1705 
intervention and control arm will receive the easy-to-read advance directive, we assume that 
1706 
both arms will have an advance directive completion rate of ≤ 15%. Based on prior studies, we 
1707 
assume PREPARE will result in additional benefit of advance directive completion with a 
1708 
minimum effect size of 0.5 (two-fold increase) above 15%. A sample of 350, (175 per arm), will 
1709 
afford us 92% power (2-tailed alpha of 0.05) to detect a difference of advance directive 
1710 
completion rates of 15% in controls vs. 30% in the PREPARE arm and 80% power to detect a 
1711 
difference of 15% vs. 27%. Power is also expected to be strong for the ACP behavioral change 
1712 
scale outcomes (preliminary data demonstrated a pre-to-post improvement of 0.5 SD).27 With a 
1713 
conservative assumption that controls will improve by 0.1 to 0.2 SD, we will have 85% to 98% 
1714 
power, respectively, to conclude that the improvement is better in the PREPARE arm.  We 
1715 
expect a 15% drop out rate at 12 months based on our prior randomized, controlled trial at 
1716 
ZSFG,8 and will therefore attempt to recruit 402 patients, or 201 in each arm for each language 
1717 
(English and Spanish) for a total recruitment of 804 patients.  
1718 
 
1719 
Our sample size will also allow adequate power to detect clinically important interactions based 
1720 
on potential moderators (literacy, control preferences, language concordance) for our outcomes. 
1721 
In a prior trial of an easy-to-read advance directive in the same patient population with only 200 
1722 
patients, we found significant interactions for literacy.8 Thus, if we consider the power scenario 
1723 
of the control group ACP documentation rate of 15% and the PREPARE group of 28%, and 
1724 
suppose the control group rate is the same (15%) for both levels of the moderating factor, then 
1725 

 
 
80 
for a moderating factor split of 1:1, we would have 80% power to detect an interaction. If the 
1726 
PREPARE arm ACP documentation rate is 18% for one level of the factor and 40% for the 
1727 
other, this corresponds to a relative rate of ACP documentation of 2.2 times as high for one 
1728 
level of the factor compared to the other. A 2:1 split of the moderating factor still allows 
1729 
detection of a 2.4-fold increase in the relative rate of documentation. Power to detect 
1730 
interactions will likely be stronger for continuous outcomes (e.g. engagement/behavioral scales).  
1731 
 
1732 
ETHICS AND ADVISORY COMMITTEES 
1733 
This study is approved by the University of California, San Francisco (UCSF) (IRB reference 
1734 
#13-10847). This study is guided by a Patient-Clinical Stakeholder Advisory Board that is 
1735 
comprised of patients and patient advocates (including native Spanish-speakers), surrogates, 
1736 
and ZSFG/SFHN primary care clinic staff and medical directors. It is also guided by a DSMB 
1737 
consisting of 4 experts in randomized trials, human subjects research and consent, vulnerable 
1738 
populations, palliative care, advance care planning, and biostatistics. Both advisory groups 
1739 
reviewed and approved all study protocols and related materials. In addition, we continue to 
1740 
meet with both groups every 4-6 months to review the progress of the trial, make suggestions 
1741 
for recruitment, review any potentially adverse events, and ensure that we are following our 
1742 
study protocols in a way that protects vulnerable patient populations. 
1743 
 
1744 
HUMAN SUBJECTS PROTECTIONS 
1745 
Protection of the rights and welfare of participants: 
 
1746 
All study staff are required to take annual training regarding the rights and protections of 
1747 
research participants. Additionally, weekly study team meetings will ensure that all study staff 
1748 
are following the research protocol and that all study participants are consented according to 
1749 
our study protocol. 
1750 
 
1751 

 
 
81 
Furthermore, our consent process ensures that study participants have a clear understanding of 
1752 
the study and understand that they can choose to not participate in the study at any point in 
1753 
time, and that the care they receive will not be affected by declining to participate in our study. 
1754 
Our consent process involves using a consent form written below a 6th-grade reading level, 
1755 
reading the form to potential subjects verbatim, allowing time for questions and discussion, and 
1756 
then assessing comprehension using teach-to-goal. If questions are not answered correctly, 
1757 
repeated education and reassessment of comprehension are continued until complete 
1758 
comprehension is achieved. If subjects take more than three passes through the 
1759 
comprehension assessment, formal assessment for cognitive impairment will be completed. If 
1760 
patients are found to be cognitively impaired, they are excluded from the study. If they are not 
1761 
cognitively impaired, we will re-do teach back once more, after which the participant will be 
1762 
deemed ineligible for the study if they are unable to demonstrate comprehension of the study. 
1763 
 
1764 
Additionally, we include UCSF Clinical Research Office contact information on all consent forms 
1765 
as required for all non-biomedical studies. 
 
1766 
 
1767 
Steps taken to minimize risks to subjects: 
1768 
We have developed a modified research consent process that has been shown to be successful 
1769 
in vulnerable patient populations as described above.29 All study fliers, consent forms, and 
1770 
questionnaires are read to the subjects in their entirety by native English- and Spanish-speaking 
1771 
research staff. Participants are reminded that they can opt out of the study at any time. All study 
1772 
materials are in an easy-to-read (5th grade reading level, large 14-point font) format. The 
1773 
consent materials and the study interviews are conducted in the language the participant is 
1774 
most comfortable speaking (English or Spanish). 
1775 
 
 
1776 

 
 
82 
This study will employ research assistants who are fluent in English or Spanish. Only fluent 
1777 
research assistants will be in contact and will communicate with Spanish-speaking participants. 
1778 
We will also ensure that all study materials are accurately translated into Spanish by having 
1779 
them initially translated from English to Spanish by native Spanish- speakers. We will then have 
1780 
them back translated into English to ensure accuracy. Finally, we will have the final translated 
1781 
documents reviewed for accuracy by third party native Spanish- speakers. To help participants 
1782 
follow along during the interview, they may review a large font Participant Version of the survey 
1783 
at baseline and all follow-ups that can be reviewed while the research assistant is asking 
1784 
research questions verbatim. We use 14-point font and color-coded, standardized, large font 
1785 
response options to help with understanding. 
1786 
 
1787 
Data security: 
1788 
- Data are stored securely in the encrypted, secure UCSF MyResearch environment 
1789 
- Data are coded; data key is kept separately and securely  
1790 
- Data are kept in a locked file cabinet 
1791 
- Data are kept in a locked office or suite  
1792 
- Electronic data are protected with a password  
1793 
- Data are stored on a secure network 
 
1794 
- Data are collected/stored using REDCap or REDCap Survey  
1795 
 
1796 
Measures to ensure confidentiality and protect identifiers from improper disclosure 
1797 
Risks to subjects are minimal and may include loss of confidentiality and psychological 
1798 
discomfort about discussing end-of-life issues. Subjects are assured that their answers to study 
1799 
questions will not be directly linked to their names. Instead, any identifying information is coded 
1800 
and separated from the data. The identifying information will only be known to the primary 
1801 
investigators but will not be used in data analysis. In addition, signed consent forms are kept in 
1802 

 
 
83 
locked file cabinets and kept separate from the data collection instruments. Study subjects are 
1803 
also reminded that the information obtained will not be shared with their providers except in non-
1804 
identifying aggregate form at the end of the study. We also make clear that the responses to the 
1805 
PREPARE guide are only for research purposes and will not be shared with their clinicians or 
1806 
put in their medical record. 
1807 
 
1808 
We will store all study materials in locked offices and locked storage cabinets. We will utilize 
1809 
UCSF MyResearch and REDCap to enter and maintain data in a secure environment. In order 
1810 
to be more environmentally-conscious, we will attempt to use the LiveCapture function of 
1811 
RedCap and thus reduce the use of paper resources. We will retain the use of paper surveys in 
1812 
case the RedCap system is down. These paper files are stored in secure, locked research 
1813 
offices in secure, locked file cabinets.  
1814 
 
1815 
As some of the questions concerning end-of-life may cause psychological discomfort for some 
1816 
study subjects, subjects are reminded at the beginning of the interview of their right to refuse to 
1817 
answer any and all questions and their right to terminate the interview at any time. We will also 
1818 
reassure subjects that if they choose not to be in the study or choose to terminate the interview, 
1819 
it will not change the medical care that they normally receive from their clinic or their clinician. In 
1820 
addition, we will reiterate that the information shared within the research interview will not be 
1821 
shared with their clinicians or used in medical care. However, subjects can take home a copy of 
1822 
the PREPARE guide with them and bring it back to their clinicians if they wish. Subjects are 
1823 
given the name and number of the primary investigator and may call if they have questions or 
1824 
are concerned about their participation in the study. 
1825 
 
1826 
Required reportable information: 
1827 

 
 
84 
As these interviews may be completed in people’s home and, in the interviews, we are asking 
1828 
patients to describe their experiences and opinions, it is possible that reportable events such as 
1829 
elder abuse, suicidal or homicidal ideation may be detected. If they are detected, they will be 
1830 
handled according to the American Psychological Association code of ethics. If elder abuse is 
1831 
suspected, the participant will be encouraged to take steps to ensure their safety. They will be 
1832 
offered contact information for local supportive services and informed that the concerns will be 
1833 
discussed with the elder abuse hotline for assistance. When there are concerns about self-harm 
1834 
or harm to others, severity of harm will be assessed. Participants will be offered local support 
1835 
services and officials will be notified as necessary. 
1836 
 
1837 
Patient Depression/Anxiety Protocols 
1838 
With input from the Patient-Clinician Stakeholder Advisory Board, and to err on the side of 
1839 
caution, we created a flow diagram with detailed instructions, including study scripts and contact 
1840 
names and telephone numbers for research staff to use in the event scored in the moderately 
1841 
severe depression or anxiety range on the PHQ-8 and GAD-7 or a participant expressed suicide 
1842 
ideation. 
1843 
  
1844 
DATA SAFETY MONITORITY PLAN 
1845 
Monitoring will focus on recruitment, baseline comparability of treatment groups, protocol 
1846 
adherence, completeness of data, accrual of primary endpoint data, safety, and follow-up rates. 
1847 
This monitoring will provide the basis for monthly review by the study investigators, review by 
1848 
the ZSFG Patient-Clinician Advisory Committee, and Data Safety and Monitoring Board 
1849 
(DSMB), and yearly reporting to our IRBs. We will implement methods of verifying entered data 
1850 
and of quality control. All study materials data are kept on secure, password-protected, 
1851 
encrypted servers. All consent materials and any identifying information are kept in locked 
1852 
cabinets within locked offices, on password-protected, encrypted servers, on card-key protected 
1853 

 
 
85 
research floors. Dr. Sudore, will be directly responsible for identifying and immediately reporting 
1854 
all adverse events to the IRBs Privacy Officers, and funding agency as appropriate. The ZSFG 
1855 
Patient-Clinician Advisory Committee will ensure participant safety in the clinic and will meet up 
1856 
to 4 times per year. The formal DSMB includes 4 experts in randomized trials, human subjects 
1857 
research and consent, vulnerable populations, palliative care, advance care planning, and 
1858 
biostatistics. The DSMB will review and approve the research protocol and plans for data and 
1859 
safety monitoring; and assess data quality; participant recruitment, accrual and retention; 
1860 
baseline comparability of treatment groups, accrual of primary endpoints; and participant safety 
1861 
(e.g., adverse events, protocol violations). They will also develop stopping rules for the trial. The 
1862 
DSMB will meet up to 4 times per year. 
1863 
 
1864 
CHARTER OF DATA SAFETY MONITORING BOARD 
1865 
The Data and Safety Monitoring Board (DSMB) will act in an advisory capacity to the National 
1866 
Institute of Aging (NIA) Director to monitor participant safety, data quality and evaluate the 
1867 
progress of the study. Dr. Sudore, University of California, San Francisco is conducting the 
1868 
"Improving Advance Care Planning by Preparing Diverse Seniors for Decision Making" study 
1869 
under a R01 funded by the National Institute of Aging. The DSMB for this study includes 2 
1870 
outside clinicians with expertise in RCTs and an outside biostatistician. The NIA program officer 
1871 
is also included. The DSMB will review and approve the research protocol and plans for data 
1872 
and safety monitoring; and assess data quality; participant recruitment, accrual and retention; 
1873 
baseline comparability of treatment groups, accrual of primary endpoints; and participant safety 
1874 
(e.g., adverse events, protocol violations). They will also develop stopping rules for the trial. The 
1875 
DSMB will meet 2 and up to 4 times per year. 
1876 
 
1877 
DSMB Responsibilities 
1878 
The DSMB responsibilities are to:  
1879 

 
 
86 
 
review the research protocol, informed consent documents and plans for data safety and 
1880 
monitoring;  
1881 
 
advise the NIA on the readiness of the study staff to initiate recruitment; 
1882 
 
evaluate the progress of the trial, including periodic assessments of data quality and 
1883 
timeliness, recruitment, accrual and retention, participant risk versus benefit, performance of 
1884 
the trial sites, and other factors that can affect study outcome; 
1885 
 
consider factors external to the study when relevant information becomes available, such as 
1886 
scientific or therapeutic developments that may have an impact on the safety of the 
1887 
participants or the ethics of the trial; 
1888 
 
review study performance, make recommendations and assist in the resolution of problems 
1889 
reported by the Principal Investigator; 
1890 
 
protect the safety of the study participants; 
1891 
 
report to NIA on the safety and progress of the trial;  
1892 
 
make recommendations to the NIA and the Principal Investigator concerning continuation, 
1893 
termination or other modifications of the trial based on the observed beneficial or adverse 
1894 
effects of the treatment under study; 
1895 
 
if appropriate, review interim analyses in accordance with stopping rules, which are clearly 
1896 
defined in advance of data analysis and have the approval of the DSMB; 
1897 
 
ensure the confidentiality of the study data and the results of monitoring; and,  
1898 
 
assist the NIA by commenting on any problems with study conduct, enrollment, sample size 
1899 
and/or data collection. 
1900 
 
1901 
The DSMB will discharge itself from its duties when the last participant completes the study. 
1902 

 
 
87 
 
1903 
Membership 
1904 
The DSMB includes experts in or representatives of the fields of: 
1905 
relevant clinical expertise,  
1906 
clinical trial methodology, and  
1907 
biostatistics.  
1908 
 
1909 
The DSMB members:  
1910 
 
In addition to the NIA program officer members include: 
1911 
 
Dr. David Bekelman, MD, MPH, an internist, psychiatrist, and palliative medicine 
1912 
physician at the University of Colorado School of Medicine and is an expert in health 
1913 
communication and medical decision making 
1914 
 
Dr. Nathan Goldstein, MD, a geriatrician and a national expert in palliative care, 
1915 
communication, and medical decision making at Mt. Sinai School of Medicine,  
1916 
 
Dr. James Wiley, PhD a statistician and Professor in the Institute for Health Policy 
1917 
Studies at the University of California, San Francisco. Dr. Wiley has extensive 
1918 
experience with RCTs and working with safety net populations. Although Dr. Wiley is at 
1919 
UCSF, he does not otherwise work with Dr. Sudore. Membership have no financial, 
1920 
scientific, or other conflict of interest with the trial.  
1921 
 
1922 
Written documentation attesting to absence of conflict of interest has been obtained. 
1923 
 
1924 
Dr. Nathan Goldstein, Mount Sinai School of Medicine, has been appointed by NIA to serve as 
1925 
the Chairperson and is responsible for overseeing the meetings, developing the agenda in 
1926 
consultation with the NIA Program Official and the Principal Investigator. The Chair is the 
1927 

 
 
88 
contact person for the DSMB. The University of California, San Francisco shall provide the 
1928 
logistical management and support of the DSMB. Dr. Nathan Goldstein is also the safety officer 
1929 
and contact person for serious adverse event reporting. A log of all potential adverse events and 
1930 
protocol violations will be kept and reviewed quarterly by the DSMB. Procedures for notifying 
1931 
the Chair of the DSMB and the NIA Program Official will be discussed and agreed upon at the 
1932 
first meeting.  
1933 
 
1934 
Board Process  
1935 
At the first meeting the DSMB will discuss the protocol, suggest modifications, and establish 
1936 
guidelines to study monitoring by the Board. The DSMB Chairperson in consultation with the 
1937 
Principal Investigator and the NIA Program Official will prepare the agenda to address the 
1938 
review of study materials, modifications to the study protocol and informed consent document, 
1939 
initiation of the trial, appointment of a safety officer, as needed, reporting of adverse events, 
1940 
statistical analysis plan including interim analysis and stopping rules, etc.  
1941 
 
1942 
Meetings of the DSMB will be held 2-4 times per year at the call of the Chairperson and / or NIA 
1943 
Program Official to ensure patient safety and to review stopping rules for the trial. The NIA 
1944 
Program Official or designee will attend most of the meetings. An emergency meeting of the 
1945 
DSMB may be called at any time by the Chair or by the NIA should participant safety questions 
1946 
or other unanticipated problems arise. 
1947 
 
1948 
Meetings are closed to the public because discussions may address confidential participant 
1949 
data. Meetings are attended by the Principal Investigator and members of his/her staff. 
1950 
Meetings may be convened as conference calls as well as in-person.   
1951 
 
1952 
Meeting Format 
1953 

 
 
89 
Each meeting must include a recommendation to continue or to terminate the study and 
1954 
whether the DSMB has any concerns about participant safety made by a formal DSMB majority 
1955 
or unanimous vote. Should the DSMB decide to issue a termination recommendation, the full 
1956 
vote of the DSMB is required. In the event of a split vote, majority vote will rule and a minority 
1957 
report should be appended. The DSMB Chair provides the tiebreaking vote in the event of a 50-
1958 
50 split vote. 
1959 
 
1960 
A recommendation to terminate the study may be made by the DSMB at any time by majority 
1961 
vote. The Chair should provide such a recommendation to the NIA immediately by telephone 
1962 
and email. After the NIA Director makes a decision about whether to accept or decline the 
1963 
DSMB recommendation to terminate the study, the PI is immediately informed about his 
1964 
decision. 
1965 
 
1966 
Meeting Materials  
1967 
DSMB interim report templates will be prepared by the study staff, to be reviewed by the DSMB 
1968 
members at each meeting.  The reports will list the study aims, the status of the study, and 
1969 
summarize safety data. 
1970 
 
1971 
Reports from the DSMB 
1972 
A formal report containing the recommendations for continuation or modifications of the study 
1973 
will be prepared by the DSMB Chairperson, NIA Program Official or its designee. The draft 
1974 
report will be sent to the DSMB members for review and approval.  
1975 
 
1976 
Confidentiality  
1977 
All materials, discussions and proceedings of the DSMB are completely confidential. Members 
1978 
and other participants in DSMB meetings are expected to maintain confidentiality.  
1979 

 
 
90 
 
1980 
PATIENT-CLINICAN STAKEHOLDER ADVISORY COMMITTEE ROLE 
1981 
This study is guided by a Patient-Clinical Stakeholder Advisory Board that is comprised of 
1982 
patients and patient advocates (including native Spanish-speakers), surrogates, and 
1983 
ZSFG/SFHN primary care clinic staff and medical directors. These individuals are paid key 
1984 
personnel on the study and have agreed to meet up to 4 times per year to oversee all aspects of 
1985 
the study. Native Spanish-speaking staff will be present to translate for our Spanish-speaking 
1986 
patient stakeholders during advisory meetings. All study materials will be translated into 
1987 
Spanish. The advisory committee will be involved in providing ongoing advice about the 
1988 
following important study related activities: 
1989 
Recruitment, including study scripts, fliers, methods 
1990 
 
Eligibility and exclusion 
1991 
 
Patient safety and research staff safety 
1992 
 
Clinic workflow and clinical champions 
1993 
 
Informed consent 
1994 
 
Research outcomes 
1995 
 
Presentation of findings 
1996 
 
Dissemination of results 
1997 
 
1998 

 
 
91 
Summary of Changes to the Protocol: The listed topics follow the outline and headers of the protocol  
1999 
Topic 
Date 
Summary of Changes  
Funding 
Feb 3, 2014 
We obtained funding from the National Institute on Aging (R01AG045043) to start 
recruitment of English-speakers. We then also obtained Patient-Centered Outcomes 
Research Institute (PCORI) funding (R-1306-01500) to add Spanish-speakers to our 
established trial infrastructure and protocol. 
Funding 
Mar 8, 2017 
Dr. Sudore became funded, in part, by a NIA K24 (K24AG054415). 
ClinicalTrials.gov 
registration 
Feb 27, 2014 
When PCORI funding was obtained, PCORI required a separate Clinical.Trial.gov 
number. Thus, it was added in February 2014. Although English- and Spanish-speaking 
recruitment was supported by two funders, this was one trial with the same staff, 
locations, procedures, IRB, and protocol.36  
Background 
Apr, 2016 
We updated the background to included updated references. 
Preliminary Studies 
May, 2017 
We updated the preliminary studies to include the findings from our published VA trial. 
The name of hospital was changed on May 3rd, 2015 from SFGH to Zuckerberg San 
Francisco General Hospital (ZSFG). This change was made throughout the protocol. 
Overview of Trial 
Jan 4, 2016 
We updated the protocol to include our study flow diagram for our records. 
Eligibility screening 
Jan 16, 2014 
Eligibility screening in busy, loud, outpatient clinics was often difficult. With our patient-
clinicians stakeholders, we decided to include the ability to recruit and screen by phone. 
See below under recruitment. 
Exclusion criteria 
Jul 15, 2014 
To minimize potential contamination, we excluded participants who may have been 
exposed to the PREPARE website from other sources such as being in a PREPARE-
related focus group or pilot study.  
Exclusion criteria 
Oct 3, 2014 
To ensure the safety of our research staff, we excluded potential participants with 
evidence of active drug or alcohol abuse within the past 3 months determined by 
clinician assessment, self-report, chart review or research staff assessment. 
Exclusion criteria 
Jan 16, 2014 
To minimize the risk of unblinding by fellow research participants, any spouse/partner of 
a currently enrolled patient or an individual who is named as an enrolled patient’s 
potential surrogate decision maker (regardless of cohabitation or spousal status), who is 
also a patient at SFHN/ZFG will be excluded from being a patient participant. This will 
avoid a situation where 2 closely related people living in the same home could be 
randomized to different study arms and result in unblinding. 

 
 
92 
Exclusion criteria 
Jan 27, 2014 
To save research staff considerable time and effort, potential participants who initially 
scheduled but then missed the baseline interview (i.e. no show) more than 2 times 
without prior notification and rescheduling with study staff will be considered ineligible, 
unless there were significant extenuating circumstances.  
Spanish Translation 
Nov 13, 2014 
All translated and back-translated study materials were approved by the UCSF IRB. 
Recruitment methods 
Nov 13, 2013 
We initially sent opt-out letters to potential participants. However, many SFHN/ZSFG 
patients are marginally housed, had incorrect mailing addresses, or have limited literacy. 
We also discovered that many patients were confusing the opt-out letters for bills from 
the hospital. With input from our Patient-Advisory Board and DSMB, we switched to 
more engaging recruitment letters and postcards that allowed patients to call and hear 
more about the study or to opt-out. They could also opt-out at any time. 
Recruitment methods 
Jan 16, 2014 
It was determined by our patient-clinician stakeholders that it would be acceptable to 
recruit patients by phone in addition to in clinic recruitment. In addition, because we 
were attempting to enroll patients 1-3 weeks prior to a primary care visit, it was proving 
difficult to approach patients in clinic ahead of their primary care appointments. In 
addition, our primary care stakeholders felt it would be better for their clinic workflow to 
not have research staff always in the clinic. Therefore, we expanded our recruitment 
options, after receiving permission from the clinician and sending recruitment letters, to 
both approach potential participants in clinic as well as recruit by phone.  
Recruitment-
reimbursement 
Jan 16, 2014 
We initially reimbursed $25 separately for the screening interview and $25 for the 
baseline interview that included intervention exposure. We realized that the screening 
interview was brief and often occurred over the phone because it was difficult to conduct 
in busy clinic settings. We also realized, in collaboration with our patient-clinician 
advisory board, that it made more sense to reimburse participants for $50 for the 
baseline interview since these interviews were longer and in our study offices. We also 
changed from taxi vouchers to municipal transportation tokens because of the increased 
surcharge associated with taxi vouchers and participant preference. 
Consent forms 
Jan 27, 2014 
For staff safety and the need to exclude or withdraw participants who were intoxicated, 
psychotic, or threatening, the consent also explains, “We also may ask you to stop 
taking part in this study if we feel it is in your best interest or if you do not follow the 
study rules.”  
Consent forms 
Jan 27, 2014 
Clinicians needed to be contacted if their patient reported severe depression or anxiety. 
We updated our consent forms to fully explain this to participants: 

 
 
93 
“We would need to contact your regular doctor or a medical provider for the following 
reasons: -You report or we observe that you are having:  
 
A medical emergency such as a serious medical illness 
 
Or, a serious mental illness, such as major depression 
 
You report that you may harm yourself, you may harm someone else, or 
someone is harming you 
Randomization  
Jan 16, 2014 
The initial IRB application was a Just-in-time submission for an NIH proposal. We 
initially planned to block randomize, as we did for a recent VA trial,35 by both health 
literacy and race/ethnicity. However, given the diversity of patients at SFHN/ZSFG (over 
50% non-white), in comparison to the VA, we decided to only block randomize by health 
literacy.  
Data Collection 
Methods 
Jan 16, 2014 
To be more environmentally-conscious, we switched from paper surveys to use the 
LiveCapture function of RedCap. We retained the use of paper surveys in the event the 
RedCap system was down. All paper files continued to be stored in secure, locked 
research offices in secure, locked file cabinets. 
Follow-up & Retention 
May 28, 2014 
We created an appointment reminder sheet to show the dates and times for upcoming 
primary care appointments as well as upcoming study appointments to help with 
retention. 
Follow-up & Retention 
Jan 16, 2014 
We expanded the options for follow-up interviews to be not only in the clinic or by 
phone, but also in the home if needed as many of our patients had functional limitations.  
Follow-up & Retention 
 
Jul 15, 2014 
For all participants who missed their primary care appointment and did not reschedule, 
we provided a courtesy phone call to remind participants to reschedule the primary care 
appointment. 
Follow-up & Retention 
 
Jul 15, 2014 
Patients were enrolled based on upcoming primary care appointments. All follow-up 
interviews were timed to this primary care appointment. Some primary care 
appointments were subsequently missed or cancelled. In consultation with our 
stakeholder advisory committee and the DSMB, we decided that for participants who 
reschedule and attend their primary care appointment within 6 months, we would still 
conduct interviews at 1 week, and at 3, 6, and 12 months from the primary care 
appointment date. If participants do not reschedule within 6 months, we will conduct 
follow up assessments at 6 and 12 months from the primary care appointment date. 

 
 
94 
Follow-up and Retention Jan 16, 2014 
All data capture was by verbal survey administration and many of our follow-up 
interviews occurred over the phone. To help participants follow along during the 
interview, we mailed out a Participant Version of the survey to be used during the phone 
call if desired. No data were collected by mail. 
Measures & Data 
Collection 
Jan 4, 2016 
We created a table displaying all study oucome measures, including validity and 
reliability information in both English and Spanish, number of survey items, references 
and the schedule of administration for our records and protocol. 
Measures & Data 
Collection 
Mar 12, 2013 
Correction: A priori, we planned to collect ACP documentation data at 15-months (not 
12 months as stated in our original and published protocol) to mirror the methods used 
in our previously published trial of PREPARE in the VA setting.35  We fixed this typo in 
our final protocol. From the prior VA trial,35 it was estimated that the time from the 
intervention to the primary care visit and the average time to schedule and conduct the 
final patient interview would be 3 months. Therefore, we standardized this window for all 
participants in this and our prior published trial.35    
Measures & Data 
Collection 
Jan 16, 2014 
We initially proposed to screen for depression and anxiety using the -Patient Health 
Questionnaire-2 item (PHQ-2) and the Generalized Anxiety Disorder-2 item (GAD-2). 
Our DSMB felt more precise versions of this survey should be used. Therefore, we 
updated our methods to reflect assessment of depression and anxiety using the Patient 
Health Questionnaire-8 item (PHQ-8) and Generalized Anxiety Disorder-7 item (GAD-7).  
Measures & Data 
Collection 
Sept 20, 2017 
Our Patient-Advisory Stakeholders requested we quantify the number and percentage of 
patients who increased their ACP activities overtime. Our stakeholders perceive any 
increase in an ACP activity over time as clinically meaningful. Thus, in addition to mean 
change in ACP Engagement scores, they wanted to know the percent of patients who 
improved over time for Behavior Change scores, Actions scores, and both combined. 
We defined improvement as an estimated overall slope > 0. Therefore, we created this 
exploratory variable post-hoc and used Bonferroni corrections to set the p-value of 
significance at 0.017. 
Human Subjects 
Protections 
May 28, 2014 
Because we were assessing depression and anxiety as part of the trial, to err on the 
side of caution, the Patient-Clinician Stakeholder Advisory Board helped us create a 
flow diagram with detailed instructions, scripts, and telephone numbers for how staff 
could refer participants who report severe depression/anxiety if that were to occur. As 
above, this potential disclosure of participant information was provided on the informed 
consent form.  

 
 
95 
Summary of Changes to the Statistical Analysis Plan 
2000 
 
2001 
Topic 
Date 
Summary of Changes  
Refusals & withdrawal 
comparisons 
Sep 30, 2016 
We added a description of our planned analysis to compare participants who refused 
based on age and self-reported gender. We also added a description of our planned 
analysis to compare reasons for withdrawal between study arms. 
Bonferroni corrections 
Sep 30, 2017 
We added Bonferroni adjusted p-values for all secondary and exploratory outcomes. 
Stratifying results by 
language 
Mar 1, 2014 
Our PCORI grant was funded on Mar 1st, 2014 and allowed us to add Spanish-
speaking participants to the trial. A priori and based on prior literature and the 
preferences of our stakeholders and grant funders, we added information about 
stratifying our analysis based on English and Spanish-speaking participants.  
Models 
Sep 30, 2016 
We explain more fully the modeling terms in the mixed effects models. 
Variable added to 
adjusted models 
Sep 30, 2016 
In addition to health literacy and clustering by clinician, we also adjusted all mixed 
effects models for baseline ACP documentation because, in consultation with our 
stakeholders, it was felt that these patients may be different from ACP naïve 
participants.  This also mirrors the analysis in the prior VA PREPARE trial.35  
Effect Size Definitions 
Sep 30, 2016 
We added information and references concerning clinically meaningful effect sizes. 
Exploratory Outcome 
Sep 30, 2016 
Based on stakeholder request, we included a description of an added exploratory 
outcome to calculate the percentage of participants who increased their ACP 
Engagement scores. Bonferroni adjusted p-values for this post-hoc analysis were 
adjusted to a significance level of 0.017. 
Interactions 
Sep 30, 2016 
We more clearly defined the variables used to test for interactions and how these 
variables were dichotomized for analysis. 
 
2002 

 
 
96 
FINAL PROTOCOL REFERENCES 
2003 
1. 
The United Nations Department of Economic and Social Affairs Population Division. 
2004 
World Population Aging: 1950-2050. 
2005 
http://www.un.org/esa/population/publications/worldageing19502050/. Accessed March 
2006 
29th, 2012. 
2007 
2. 
2010 United States Census. Overview of Race and Hispanic Origin: 2010. 
2008 
http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed 7-1-13. 
2009 
3. 
Wilper AP, Woolhandler S, Lasser KE, McCormick D, Bor DH, Himmelstein DU. A 
2010 
national study of chronic disease prevalence and access to care in uninsured U.S. 
2011 
adults. Ann Intern Med. 2008;149(3):170-176. 
2012 
4. 
Castillo LS, Williams BA, Hooper SM, Sabatino CP, Weithorn LA, Sudore RL. Lost in 
2013 
translation: the unintended consequences of advance directive law on clinical care. Ann 
2014 
Intern Med. 2011;154(2):121-128. 
2015 
5. 
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