PlacEbo-controlled, Randomized, Patient-Selected Outcomes N-of-1 triALs (PERSONAL-pilot): Alpha-blockers for Lower Urinary Tract Symptoms
Phase: PHASE4
Conditions: Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms
Sponsor: University of California, San Francisco

 
PlacEbo-controlled, Randomized, Patient-Selected Outcomes N-of-1 
triALs (PERSONAL-pilot): Alpha-blockers for Lower Urinary Tract 
Symptoms 
 
NCT05415748 
 
December 04, 2024 

 
 
 
Placebo-controlled, Randomized, patient-Selected 
Outcomes N-of-1 triALs (PERSONAL): 
alpha-blockers for lower urinary tract symptoms 
 
Protocol Version Number: 1.0 
Protocol Version Date: 01/20/2023 
 
Principal Investigator (Sponsor-Investigator) 
Benjamin N. Breyer MD, MAS, FACS 
University of California San Francisco 
400 Parnassus Ave, Suite 610 
San Francisco, CA 94131 
Telephone: 415-221-4810  
E-mail: Benjamin.Breyer@ucsf.edu 
 
Co-Principal Investigators (Sponsor-Investigator) 
Scott Bauer MD, ScM 
University of California San Francisco 
4150 Clement Street 
Building 2, Room 135 
San Francisco, CA 94121 
Telephone: 415-221-4810 
x24322 
E-mail: Scott.Bauer@ucsf.edu 
 
Stacey Kenfield, ScD 
University of California San Francisco 
550 16th Street 
San Francisco, CA 94158 
Telephone: 415-476-5392 
E-mail: Stacey.Kenfield@ucsf.edu 
 
Statisticians 
Charles E. McCulloch, PhD 
Kaiwei Lu, MS 
 
Revision History 
Version 1.0 
01/20/2023 
 
 
 
 
 
Proprietary and Confidential 
 
The information in this document is considered privileged and confidential and may not be disclosed to others except 
to the extent necessary to obtain Institutional Review Board approval and informed consent, or as required by 
Federal and State laws. Persons to whom this information is disclosed should be informed that this information is 
privileged and confidential and that it should not be further disclosed

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Abstract 
 
Title 
PlacEbo-controlled, Randomized, patient-Selected Outcomes N-of-1 
triALs (PERSONAL-pilot): alpha-blockers for lower urinary tract 
symptoms 
Study Description 
This study will focus on determining if placebo-controlled N-of-1 
deprescribing trials can identify older men who are likely to benefit 
from stopping ineffective chronic tamsulosin therapy for LUTS. We 
will also assess recruitment, retention, and completion rates for the 
study and other secondary outcomes among this population of older 
men receiving chronic tamsulosin therapy for LUTS to facilitate 
deprescribing decisions. 
Study Intervention 
Participants will start with a 1-week run-in period where they will use 
the PERSONAL Redcap surveys to track daily symptoms and side 
effects while taking only placebo study pills. Based on the 
pharmacokinetics and expected timeframe of symptomatic relief from 
tamsulosin (half-life=14 to 15 hours; steady state by the 5th day of daily 
dosing), all N-of-1 trials will have a duration of 12 weeks during which 
participants will complete the run-in and 2 cycles consisting of a pair of 
2-week treatment periods (taking tamsulosin or placebo) separated by 
1 week of wash-out with placebo. The order of treatment periods within 
a cycle will be random (e.g. ABAB, BABA, ABBA, or BAAB) according 
to pre-filled bubble packs given to participants during their orientation 
visit, but all patients will undergo 1 treatment of tamsulosin and 1 
treatment of placebo during each of the 2 cycles. Participants will 
receive a placebo during wash-out periods between treatment periods 
and cycles, but they will be unaware of the order or duration of 
treatment periods or cycles to prevent self-correlating symptoms to 
specific treatments. 
The PERSONAL Redcap will present participants with a daily 
questionnaire, accessible via smartphone, to track their symptoms. We 
chose to track the severity of lower urinary tract symptoms (LUTS) 
using a modified version of the widely used American Urological 
Association Symptom Index (AUASI). This modified questionnaire 
includes daily questions regarding storage and voiding symptoms. All 
participants will also be presented a global urinary symptom bother 
question. 
Study Population 
Older men age 55-80 years based on the following Inclusion criteria: 
Male sex at birth. 
An ICD-10 diagnosis consistent with BPH 
Has been taking Tamsulosin for at least 12 months with active 
prescription 
No history of urinary incontinence, acute urinary retention, recurrent 
urinary tract infections, obstructive kidney disease, or urethral stent 
Able to speak and complete questionnaires in English. 
Have an iOS or Android smartphone  
Primary Objective 
To determine if placebo-controlled N-of-1 deprescribing trials can 
identify older men who are likely to benefit from stopping ineffective 
chronic tamsulosin therapy for LUTS by assessing differences in daily 

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urinary symptom severity between treatment with tamsulosin and 
placebo. 
Secondary 
Objectives 
• 
To describe the recruitment timeframe, study retention, and 
questionnaire completion rates  
• 
To describe patient characteristics at baseline related to the 
condition and their medication  
• 
To assess medication side effects during the study 
• 
To describe magnitude of changes in quality of life (PROMIS-29) 
between treatment with tamsulosin and placebo 
Recruitment 
Methods 
We will use a mix of secure electronic health record messaging and 
phone calls to invite patients to enroll. 
Sample Size 
This pilot study will enroll at least 20 older men with LUTS/BPH. 
Duration of Study 
Participation 
All study participants will be followed for about 4 months from 
enrollment (screening/recruitment period, 3-month intervention).  
 
 

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List of Abbreviations 
 
5-ARI 
5 Alpha-Reductase Inhibitor 
AE 
 
Adverse Event 
AUASI 
American Urological Association Symptom Index 
BPH  
Benign Prostatic Hyperplasia 
CI 
 
Confidence Interval 
CRC  
Clinical Research Coordinator 
CRF  
Case Report From 
CTCAE 
Common Terminology Criteria for Adverse Event 
 
EHR  
Electronic Health Record 
HIPAA 
Health Information Portability and Accountability Act 
ICD-10 
International Classification of Disease, Tenth Revision 
 
ICF  
Informed Consent Form 
IPSS  
International Prostate Symptom Score 
IRB  
Institutional Review Board 
LURN 
Lower Urinary Tract Dysfunction Research Network 
LUTS 
Lower Urinary Tract Symptoms 
MPI  
Multiple Principal Investigator 
NIDDK 
National Institute of Diabetes and Digestive and Kidney Diseases 
PCORI 
Patient Centered Outcomes Research Institute 
PHI  
Protected Health Information 
PI 
 
Principal Investigator 
PSSUQ 
Post-Study System Usability Questionnaire 
RCT  
Randomized Controlled Trial 
rPATD 
Revised Patients' Attitudes Towards Deprescribing 
SAE  
Serious Adverse Event 
SD  
Standard Deviation 
SOM  
School of Medicine 
UCSF 
University of California, San Francisco 
UTI  
Urinary Tract Infection 
 
 
 
 
 
 

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Table of Contents 
 
ABSTRACT… .............................................................................................................................. 2 
LIST OF ABBREVIATIONS ............................................................................................................. 4 
TABLE OF CONTENTS.................................................................................................................. 5 
1 
INTRODUCTION ........................................................................................................................... 7 
1.1 
Background: LUTS/BPH .................................................................................................. 7 
1.2 
Background: Alpha-blocker deprescription ...................................................................... 7 
1.3 
Risk/Benefit Assessment ................................................................................................. 8 
2 
STUDY OBJECTIVES.................................................................................................................... 9 
3 
STUDY DESIGN ......................................................................................................................... 10 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS ...................................................................... 11 
4.1 
Eligibility Criteria ............................................................................................................ 11 
4.2 
Recruitment and Screening ........................................................................................... 11 
4.3 
Participant Registration ................................................................................................. 12 
5 
SCREENING, CONSENT, AND RANDOMIZATION .......................................................................... 13 
5.1 
Screening 
…………………………………………………………………………………13 
5.2 
Informed Consent .......................................................................................................... 13 
5.3 
Randomization and Blinding.......................................................................................... 13 
6 
STUDY PROCEDURES AND ASSESSMENTS ................................................................................ 14 
6.1 
Schedule of Activities .................................................................................................... 14 
6.2 
Assessments ………………………………………………………………………………... 15 
6.3 
Questionnaire Data……………………………………………………15 
6.4 
Study Assessments by Visit………………………………………….16 
7 
INTERVENTION .......................................................................................................................... 18 
8 
ENDPOINTS…………………………………………………………………………….19 
9 
STATISTICAL CONSIDERATIONS ………………………………………………………….20 
9.1 
Power and Sample Size ............................................................................................ …20 
9.2 
Statistical Analysis Plans ......................................................................................... …..20 
10 
ADVERSE EVENTS AND REPORTING REQUIREMENTS ................................................................ 22 
10.1 
DEFINITIONS………………………………………………………………22 
10.2 
EXPECTEDNESS………………………………………………………….22 
10.3 
ATTRIBUTION……………………………………………………………….22 
10.4 
SEVERITY…………………………………………………………………23 
10.5 
REPORTING REQUIREMENTS……………………………..……………….23 
11 
PROTOCOL VIOLATION AND WITHDRAWAL OF PARTICIPANTS…………………….…………25 
11.1 
PROTOCOL VIOLATION……………………………..……………………….25 
11.2 
WITHDRAWAL OF PARTICIPANTS……………………………………………25 
12 
DATA MANAGEMENT AND MONITORING……………………………...…………………26 
12.1 
INDIVIDUALS OVERSEEING DATA MANAGEMENT………...………………26 
12.2 
CASE REPORT FORMS AND SOURCE DOCUMENTS………...…………....26 
12.3 
DATA MANAGEMENT PROCEDURES………...……………………………26 
12.4 
DATA QUALITY CONTROL AND REPORTING. ………...……………………..26 
12.5 
DATA AND SAFETY MONITORING PLAN………...………………………….27 

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13 
PROTECTION OF HUMAN SUBJECTS……………………………………….….…………..28 
13.1 
INFORMED CONSENT………...……………………….…………………..28 
13.2 
POTENTIAL RISKS………...……………………………..………………..28 
13.3 
POTENTIAL BENEFITS………...………………………………………..…. 28 
13.4 
ALTERNATIVES………...…………………………………………………..28 
13.5 
CONFIDENTIALITY………...………………………………………………..29 
13.6 
VOLUNTARINESS OF RESEARCH PARTICIPATION……………………………..29 
13.7 
PATIENT PRIVACY………...…………………………………...………….29 
14 
STUDY MANAGEMENT………...………………………………………………..……….30 
14.1 
Pre-study Documentation ............................................................................................. .30 
14.2 
Institutional Review Board Approval ............................................................................ 30 
14.3 
Informed Consent ......................................................................................................... 30 
14.4 
Changes in the Protocol ............................................................................................... 30 
14.5 
Record Retention .......................................................................................................... 30 
14.6 
Publications …………………………………………………………………………………31 
15 
REFERENCES .......................................................................................................................... 32 

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1.0 INTRODUCTION 
 
1.1 Background: Lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH) 
 
Lower urinary tract symptoms (LUTS) comprise a syndrome of overlapping symptoms that occur 
when urine is being generated and stored it in the bladder (i.e., storage LUTS, such as urgency, 
daytime frequency, nocturia, etc.), or during the initiation and process of urination (i.e., voiding 
LUTS, such as weak stream, straining, incomplete voiding, etc.).1 More than 30% of men will 
develop clinically significant LUTS in their lifetime, and the majority of male LUTS, including both 
storage and voiding subtypes, are attributed to benign prostatic hyperplasia (LUTS/BPH).2 In 
addition to worse health-related quality of life,3-7 older men with LUTS/BPH have an increased risk 
of new mobility impairment, falls, fractures, disability, and death.8-11 In 2000, the estimated direct 
costs of treating LUTS/BPH in the United States were $1 billion and increased to $4 billion after 
including indirect costs.2,12 Since then, the cost of caring for men with LUTS/BPH has increased 
dramatically.13,14 
 
Because more than 80% of men develop histologic evidence of BPH on autopsy by age 80 years,15 
prostate-centric therapies targeting bladder outlet obstruction have dominated the pharmaceutical 
and surgical treatment landscape for LUTS/BPH. However, growing evidence suggests that older 
man are more likely to suffer from LUTS caused by systemic, non-prostatic conditions that are not 
targeted by existing interventions, such as obstructive sleep apnea, kidney disease, or heart 
failure.16,17 This is compounded by the failure of current diagnostic tests to accurately identify the 
specific cause of LUTS/BPH.18,19  
 
One consequence of our limited diagnostic accuracy for LUTS/BPH is that older men are 
empirically prescribed medications that target prostatic smooth muscle and prostate enlargement at 
significantly higher rates than younger men with the same diagnosis (the new prescription rate for 
men with LUTS/BPH ages 50-59 years increases from 15 to 32 per 100 person-years for men ages 
60-64 years), and this trend is increasing over time.20 However, these medications have modest 
efficacy on LUTS severity21 and have potentially harmful side effects in older men (e.g., orthostatic 
hypotension and dizziness, falls, fractures, depression),22-28 leading to low adherence and high 
rates of discontinuation.29,30 In addition to being particularly susceptible to the harmful side effects of 
these medications, older men with LUTS/BPH have lower levels of physical activity, increased 
obesity and metabolic syndrome, and increased frailty,4,7,31-33 which further increases their risk of 
developing poor clinical outcomes. 
 
1.2 Background: Alpha blocker deprescription 
 
Despite widespread use, the impact of α1-blockers compared to placebo on LUTS is small.34  
Clinical studies suggest that many patients, who are on α1-blocker monotherapy or combination 
therapy with 5-alpha-reductace inhibitors (5-ARIs), can discontinue α1-blocker therapy after initial 
improvement without the need to restart treatment. 35-37 Harms of α1-blockers, such as orthostatic 
hypotension and dizziness which lead to falls and fractures, have led to recommendations that they 
be used with caution in older men.38,39  A recent study by Renoncourt et al suggested that over 79% 
of patients taking α1-blockers may be doing so inappropriately.39 Another study by Edelman et al 
showed that most men would be willing to stop taking α1-blockers at the request of their doctor. 40 
In the setting of modest benefits and known harms, a more personalized and patient-centric 
approach is needed to ensure that only men in whom benefits outweigh the harms continue to 
receive chronic α1-blocker therapy.  
 

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1.3 Risk/Benefit Assessment 
 
Our eligibility criteria and screening procedures are established to exclude individuals for whom the 
study is not appropriate. Per the exclusion criteria, this includes patients with specific urologic or 
psychiatric conditions. After obtaining participant consent, the screening process will include 
verification of these factors by the clinician. This multi-gated comprehensive approach should 
systematically identify and screen out any individual for whom this study is not indicated. There are 
no direct benefits to the participants (financial compensation is purposely not presented as a 
benefit), except as to their feelings of being involved as participants in an important research study. 
Additionally, patients will learn about their results regarding response to tamsulosin which may lead 
to better informed decisions of whether to continue the medication.  
 
This study will provide valuable insights into the feasibility of tamsulosin deprescription across a 
diverse patient population. The potential public health benefit to society in this study could be large, 
as we are targeting a common condition in older men (one in three older men develop LUTS/BPH 
in their lifetime). Our overarching goal is to build the evidence needed for a full-scale efficacy trial 
testing deprescription, thus this research has great potential to change the paradigms for 
LUTS/BPH management. Scientific and clinical knowledge gained from this study could be 
extremely useful to practicing clinician, individuals, policy makers, insurers, and public health 
planners developing interventions to prevent or treat LUTS/BPH. Thus, given the importance of 
knowledge to be gained and the anticipated benefit to research participants and others, the risks to 
subjects are reasonable. 
 
 
 

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2.0 STUDY OBJECTIVES  
 
Primary Objective Aim 1 
To determine if placebo-controlled N-of-1 deprescribing trials can identify older men who are likely 
to benefit from stopping ineffective chronic tamsulosin therapy for LUTS  
Secondary Objective(s):  
 
Aim 2: To describe the recruitment timeframe, study retention, and questionnaire completion rates.  
Aim 3: To describe patient characteristics at baseline related to the condition and their medication. 
 
Aim 4: To assess medication side effects during the study. 
 
Aim 5: To describe magnitude of changes in quality of life (PROMIS-29) between treatment with 
tamsulosin and placebo.

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3.0 STUDY DESIGN  
 
Overview 
We propose to conduct a 12-week N-of-1 study of at least 20 older men taking chronic tamsulosin 
therapy for urinary symptoms due to benign prostatic hyperplasia (BPH). During the 12-week 
course, all men will receive multiple 2-week treatment blocks on tamsulosin or placebo. Men ages 
55-80 years of age who speak, read and write English with an ICD-10 diagnosis of BPH, at least 12 
months of chronic tamsulosin therapy for BPH-related urinary symptoms, who have a personal 
smartphone, and are willing to self-report urinary symptoms and medication side effects will be 
recruited from several sites at the University of California, San Francisco.  
4.0 SELECTION AND ENROLLMENT OF PARTICIPANTS 
 
To ensure we recruit a diverse sample, eligible participants will be identified by the electronic health 
record at UCSF Health. 
 
4.1 Eligibility Criteria  
 
Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Urology patient at UCSF with ICD-10 diagnosis of BPH 
2. Must own Android or iPhone smartphone  
3. Taking tamsulosin for urinary-related symptoms for at least 12 months 
4. Able to speak and read English  
5. Male 55-80 years old of age at telephone screening.  
6. Written informed consent (and assent when applicable) obtained from subject or subject’ s legal 
representative and ability for subject to comply with the requirements of the study 
7. Willing to receive electronic PERSONAL daily intake surveys for 3 months 
8. Willing to self-report urinary symptom or medication side effect data at specified frequency 
9. Have home WiFi access.  
10. Patients with h/o prostate cancer may be enrolled but is not required 
11. Patients with h/o kidney stones may be enrolled but is not required 
 
Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. International Prostate Symptom Score <5 or >25  
2. Current participation in any other mobile app-based clinical study. 
3. Planning to relocate from area within the study duration. 
4. Impaired vision that could limit the use of the mobile apps (participant-reported). 
 
4.2 Recruitment and Screening Methods 
 
The recruitment and screening procedures outlined below present no more than minimal risk to 
the privacy of the participants who are screened, and a screening log containing minimal patient 

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health information (PHI) will be maintained.  
 
Potentially eligible patients will be identified through the electronic health record (EHR) by UCSF 
Research Participant Services. University of California, San Francisco (UCSF) patients who meet 
inclusion criteria based on data available in the EHR and who have previously agreed to be 
contacted by UCSF Research Participant Services will receive a secure EHR message informing 
them about the study and inviting them to contact research staff if interested in participating, as we 
have done before.  
 
If needed, based on recruitment rates, we will post flyers and contact clinicians at UCSF primary 
care and urology clinics who are willing to sponsor clinic-specific recruitment efforts. If needed, we 
will also engage with community partners to disseminate study recruitment information and flyers. 
 
If an individual is interested in learning more about the study, research staff will meet with the 
potential participant by phone to discuss the study and screening procedures. If the patient is 
interested in participating in the study, he will be asked to respond to the screening questions 
by phone to further assess eligibility. 
 
4.3 Participant Registration 
 
A written or electronic informed consent form (ICF) must be signed or acknowledged before 
any study-specific assessments are initiated. A copy of the signed ICF will be given to the 
participant and a copy will be filed in the medical record. The original will be kept on file with 
the study records. 
 
All participants consented to the study will be registered in OnCore®, the UCSF Helen Diller 
Family Comprehensive Cancer Center Clinical Trial Management System. The system is 
password protected and meets HIPAA requirements. 
 
 
 

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5.0 SCREENING, CONSENT, RANDOMIZATION 
 
5.1 Screening 
 
Eligible patients at the UCSF Mission Bay and Parnassus sites will be identified through a medical 
records query using MyChart Recruitment. Our inclusion criteria include patients who are already 
on the study drug, tamsulosin.  
 
My Chart Recruitment: 
MyChart (Apex) conducts a search for patients based on the study’s inclusion and exclusion 
criteria. This is a completely computer-aided search, meaning the computer—and not a person-- 
searches patient charts. When a patient is identified as potentially eligible, they receive an email 
from MyChart that says to log in to MyChart to read about a study they might be interested in. The 
email is short and is the same for every recipient—there is no patient-specific, study-specific or 
disease information in it. 
 
When the patient logs into MyChart, there is a new “Research” tab with template information about 
participating in research and how to opt out of receiving recruitment messages. Then, the patient 
can click through to learn about a specific study they may be eligible for. The patient has the option 
of clicking a link/button to let the study team know that they are interested in learning more about 
the study. Only if the patient takes this action will the study team receive information about the 
patient. If the patient clicks “No thanks” or simply does not respond, they will not be contacted by 
the study team, they won’t receive any follow-up emails from MyChart about this study, and their 
information will not be shared with the study team.  
 
If the patient indicates interest, our research staff will reach out to eligible patients for a telephone 
screening to determine eligibility. Phone screening will determine if the participant owns a personal 
smartphone, participant age, abbreviated medical history specifically checking for diagnosis of 
benign prostatic hyperplasia (BPH) and use of tamsulosin for the past 12 months for urinary 
symptoms. Study visits and procedures will be described, and eligible persons will be invited to 
attend a baseline visit held remotely. Likely eligible individuals will be asked to provide informed 
consent using an IRB-approved electronic informed consent process before any study activities 
take place. At the conclusion of the telephone screening, participants will be sent a secure email 
through the REDCap database with links to the study mobile application, with instructions to 
download the applications prior to the baseline visit. 
 
 
5.2 Informed Consent 
 
All study participants must willingly consent after being informed of the study activities and 
procedures to be followed, the experimental nature of the intervention, alternatives, 
potential benefits, side effects, risks, and discomforts. Human protection committee approval 
of this protocol and its consent form are required, as well as any material that is seen by 
study participants. Informed consent is required before any study-specific procedures are 
performed. We will used UCSF DocuSign to obtain an electronic signature of consent, and 
paper version as alternative method. 
 
5.3 Randomization and blinding 
This will be a double-blinded, N-of-1 RCT. The randomization scheme will be computer-generated 
by the study statistician without participant contact. Participants will be randomized into 1 of 4 
treatment schedules with 2 cycles each containing treatment blocks of tamsulosin and placebo (e.g. 

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ABAB, BABA, ABBA, or BAAB). Data analysts, and investigators will remain blinded to participants’ 
randomization arm. Primary outcomes will be collected using self-administered questionnaires 
without risk of unblinding. Intervention status and any variables related to intervention status will be 
recorded and stored in a separate database by unblinded Clinical Research Coordinator (CRC).

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6.0 STUDY PROCEDURES and ASSESSMENTS  
6.1 Schedule of Activities (Table 1) 
 
Assessments/Proc
edures 
Screening 
Study Period 
Post-
treatment 
Timeline 
Screening Run-
in 
Period 1a 
Wash
out 
Period 1b 
Wash
out 
Period 2a 
Wash
out 
Period 2b 
 
Week (W) 
 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
W9 
W10 W11 
W12 
W14 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical History 
(medical, 
medication use, 
symptoms) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Socio-
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Questionnaires: 
medication 
adherence, 
urinary 
satisfaction, 
health-related 
quality of life 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Placebo only 
(daily) 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Randomized to 
Placebo or 
Tamsulosin 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Daily 
Questionnaires 
(AUASI, side 
effects) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Continuous 
monitoring for 
adherence 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Review Results 
with patient 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Adverse event 
reporting 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: Urological Association Symptom Index (AUASI) 
 
 
 

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6.2 Assessments 
 
6.2.1 Medical screening 
 
The medical screening process is described in Section 5.1.  
 
6.2.2 Demographic/Clinical Information 
 
Demographic information (e.g., date of birth, race, ethnicity, marital status, education) will be 
recorded at Screening. Clinically relevant medical history, including history of current disease, other 
pertinent clinical conditions, and information regarding underlying diseases will be recorded at 
Screening. 
 
The following items should be reported: 
- 
Medical History: includes medical conditions that are commonly associated with LUTS, other 
urologic history, psychiatric history, health-related behaviors, and cardiovascular comorbidities. 
- 
Comprehensive BPH/LUTS treatment history: current/past/never use of BPH/LUTS 
medications, procedures, behavioral interventions (e.g., pelvic floor physiotherapy, bladder 
training, timed voiding, double voiding, diet) 
- 
Concomitant Medications/Therapies: Every medication or treatment taken by the participant 
during the trial and the reason for its administration must be recorded on the CRF. All concomitant 
medication and concurrent therapies will be documented from informed consent until end of study. 
Name, indication for administration, and dates of medication or therapy will be captured. 
 
6.3 Questionnaire Data  
 
Once eligibility is determined, participants will complete a set of questionnaires, that is 
estimated to take approximately 60 minutes. During week 14 (post-study), a subset of 
questionnaires will be repeated.  During the study period, a smaller questionnaire assessing 
lower urinary tract symptoms will be administered daily via the phone app. 
 
Questionnaires to be completed for primary and exploratory outcome assessment include:  
- 
International Prostate Symptom Score (IPSS)41: We will assess LUTS severity via the 7-
item IPSS, which is the most widely used male LUTS instrument in both clinical and research 
settings. IPSS total score is continuous (range: 0 to 35) and has clinically relevant categories (0-7, 
8-19, 20-35) indicating no/mild, moderate, and severe LUTS, respectively, as well as validated 
storage and voiding subscores.42 The minimally important difference is 2-3 points for the IPSS, 
based on therapeutic response to BPH surgery.43 
 
- 
Revised Patients' Attitudes Towards Deprescribing (rPATD)44: We will assess patient 
attitudes toward deprescribing using this standard set of 22 questions each graded on a 5-point 
Likert scale. The subdomains include burden (perceived burden of routine medication taking), 
appropriateness (perceived benefits/harms of the medication), concerns about stopping (concerns 
related to stopping the medication), and involvement (perceived involvement in care and 
understanding of the medication). 
 
- 
Perceived benefit from tamsulosin: We will assess patient perceived benefit from 
tamsulosin by asking a single question of perceived benefit in which patients can choose between 3 
options: “none”, “little”, and “much”. 
 
- 
Satisfaction with chronic tamsulosin therapy: This will be assessed with a question with 4 
individual option choices: “much satisfied”, “little satisfied”, “little dissatisfied”, and “much 
dissatisfied”. 

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- 
Voils DOSE-Nonadherence measure45: We will assess patient’s baseline adherence using 
this questionnaire which consists of two sections. The first summarizes the frequency of missed 
doses and the second section assesses the cause of the missed dose. 
 
- 
Urological Association Symptom Index (AUASI)41: LUTS will be assessed daily using a 
modified version of the widely used Urological Association Symptom Index (AUASI), including 
seven individual items on urinary frequency, urgency, intermittency, straining, weak urinary stream, 
incomplete bladder emptying, and nocturia. Specifically, we will adapt the recall period to 24 hours 
from 1 month to allow for more frequent assessments.  This measure along with an additional 
quality of life question constitutes the IPSS score. 
 
- 
PROMIS-29 Profile 2.0: The Patient-Reported Outcomes Measurement Information System 
(PROMIS®) is a National Institutes of Health initiative to develop state-of-the-science self-report 
measures to assess functioning and well-being in physical, mental and social domains of health. 
PROMIS measures are potentially useful to screen for disability, identify health care disparities, 
enhance communication between patients and clinicians, and improve population health.  
 
6.4 Study Assessments by Visit 
 
Screening Prior to Baseline: 
1) Eligible patients at the UCSF Mission Bay, Parnassus, and Zuckerberg San Francisco General 
Hospital sites will be identified through a medical records query and sent an email through 
MyChart to participate in the study. Patients who are interested will e-confirm their interest.  
2) Research staff will reach out to interested patients and conduct a telephone screening call to 
determine eligibility.  
3) Study visits and procedures will be described and eligible persons will be invited to attend the 
baseline visit.  
Baseline (Orientation) Visit 
 
Consented participants who completed the appropriate assessments prior to baseline will complete 
the following procedures at the baseline visit: 
1) If an in-person baseline visit is not feasible, it will be held remotely over a Zoom Conference. 
2) Study coordinators will obtain written informed consent from eligible participants.  
3) Participants will be asked to complete a self-administered questionnaire. A complete medical 
history will be ascertained, including smoking and alcohol use.  
4) We will also be measuring patient attitudes toward deprescribing using questionnaires including 
the Revised Patients' Attitudes Towards Deprescribing (rPATD), Voils Dose-nonadherence 
measure, and satisfaction with tamsulosin.  
5) At the end of the orientation visit, research staff will provide verbal and written instructions for 
the study. Research staff contact information will be provided for reporting severe or concerning 
symptoms for the duration of the study. 
End of study remote visit 
1) After finishing the 12 weeks of the study, participants will be contacted by telephone to assess 
adherence to the program via phone and complete a follow-up questionnaire.  
2) Participants will be asked to complete self-administered questionnaires via REDCap. These will 
include the same questionnaires measuring patient attitudes toward deprescribing using tools 

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including the Revised Patients' Attitudes Towards Deprescribing (rPATD), Voils Dose-
nonadherence measure, and satisfaction with tamsulosin. 
3) A study clinician will review the patients’ individual results with them in detail. 
 
 
 

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7.0 Intervention Period 
 
7.1 Intervention 
 
All N-of-1 trials will have a duration of 12 weeks during which participants will complete the run-
in and 2 cycles consisting of a pair of 2-week treatment periods (taking tamsulosin or placebo) 
separated by 1 week of wash-out on placebo. The order of treatment periods within a cycle will 
be random (e.g. ABAB, BABA, ABBA, or BAAB). 
 
Participants will receive a bubble pack with 11 weeks of tamsulosin (at their previously prescribed 
dose) or matching placebo and will be instructed to start taking the study medications after 
successfully completing the 1-week run-in period.  
Participants will start with a 1-week open label run-in period where they will use the daily symptom 
questionnaires, accessible via smartphone or computer to track daily symptoms and side effects 
while not taking their tamsulosin or any study pills. Participants will receive a placebo during wash-
out periods between treatment periods and cycles, but they will be unaware of the order or duration 
of treatment periods or cycles to prevent self-correlating symptoms to specific treatments.  
The PERSONAL REDCap project will present participants with a daily questionnaire, accessible via 
smartphone, to track their symptoms. We chose to track the severity of lower urinary tract symptoms 
(LUTS) using a modified version of the widely used Urological Association Symptom Index (AUASI). 
This modified questionnaire includes daily questions regarding storage and voiding symptoms. All 
participants will also be presented a global urinary symptom bother question. Medication adherence, 
global urinary satisfaction questions, and health-related quality of life will be assessed as baseline 
and at the end of the study. 
Participants will view a graphical representation of their responses during tamsulosin and placebo 
treatment at the end of the study. To maximize adherence to daily questionnaires, participants will 
be contacted via email or phone if they do not complete the daily symptom questionnaire for more 
than 3 consecutive days during their N-of-1 trial. Then, a PERSONAL clinician will review N-of-1 
trial results with the participant. 
 
 8.0 ENDPOINTS 
Aim 1: To determine if placebo-controlled N-of-1 deprescribing trials can identify older men 
who are likely to benefit from stopping ineffective chronic tamsulosin therapy for LUTS  
• 
change in urinary symptoms measured with the IPSS score between treatment with 
tamsulosin and placebo 
Aim 2: To describe the recruitment timeframe, study retention, and questionnaire 
completion rates.  
 
• 
recruitment timeframe (months)  
• 
study completion rate (goal >70% of participants)  
• 
questionnaire completion rate (% completing >50% of daily questionnaires)  
 
 
Aim 3: To describe patient characteristics at baseline related to the condition and their medication  

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• 
urinary bother  
• 
Tamsulosin satisfaction  
• 
Tamsulosin adherence  
• 
patient attitudes towards deprescribing  
 
 
Aim 4: To assess medication side effects during the study 
 
• 
% reporting any side effects in text 
 
 
Aim 5: To describe magnitude of changes in quality of life (PROMIS-29) between treatment with 
tamsulosin and placebo 
• 
change in quality of life measured with PROMIS-29 between treatment with tamsulosin and 
placebo 
9.0 STATISTICAL CONSIDERATIONS 
 
9.1 Power and Sample Size 
Sample size justification. We determined sample size based on expected attrition rates. Based 
on our previously published protocol paper and prior mobile health studies 46,47we expect to fail to 
meet our study goals (i.e., recruit and retain sufficient participants, achieve sufficient daily 
questionnaire and N-of-1 trial completion rates, and achieve sufficient “usefulness” scores among 
participants) at least 10% of the time. Therefore, with a sample size of 20 participants, we will have 
90% power to observe at least one failure during this feasibility study.48,49  
9.2 Statistical Analysis Plans 
 
We will use multivariable adjusted linear mixed models with individual-specific intercepts and 
treatment effects and an unstructured variance-covariance matrix to estimate variation in daily 
AUASI score and daily summary side effect score. Treatment, day, and period will be included as 
independent variables. Individual-specific intercepts and treatment effects will allow for the 
estimation of individual-specific response to treatment for both AUASI score (shown below): 
 
𝐴𝑈𝐴𝑆𝐼𝑖𝑗= 𝛽1 + 𝛽2𝑇𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑖𝑗+ 𝛽3𝐷𝑎𝑦𝑖𝑗+ 𝛽4𝑃𝑒𝑟𝑖𝑜𝑑𝑖𝑗+ 𝑏𝑖1 + 𝑏𝑖2𝑇𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑖𝑗+ 
 𝑏𝑖3𝐷𝑎𝑦𝑖𝑗+ 𝑏𝑖4𝑃𝑒𝑟𝑖𝑜𝑑𝑖𝑗+ 𝜀𝑖𝑗 
We will use individual-specific effect estimates of tamsulosin treatment on daily AUASI to 
define strong responders (upper bound of 95% confidence interval ≤ -6.0), moderate responders 
(upper bound of 95% confidence interval >-6.0 and ≤0.0), and minimal/non-responders (upper 
bound of 95% confidence interval ≥0). We selected the minimum upper bound of 95% confidence 
interval for strong responders based on the mean expected effect size of BPH surgery. We 
selected the minimum upper bound of 95% confidence interval for moderate responders to identify 
individuals with a statistically significant decrease in AUASI. Minimal/non-responders will be defined 
as those without 95% confidence intervals that include 0, suggesting no statistically significant 
difference between treatments, or those with a lower bound of 95% confidence interval ≥0. To 
visualize individual treatment effects, we will create a bar graph with the mean effect of tamsulosin 
on daily AUASI and 95% confidence interval for each participant, overall and by important 

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subgroups such as baseline LUTS severity or age. We will then repeat this process for medication 
side effects. 
To determine if there are carryover effects, we will include a variable indicating the sequence 
of each period (tamsulosin then placebo or placebo then tamsulosin) in the linear mixed model. To 
evaluate whether treatment effect is correlated with baseline characteristics, we will calculate the 
correlation between the random intercept and random treatment effect and used a likelihood ratio 
test to compare models with an unstructured covariance matrix versus an independent covariance 
matrix.  
We will use descriptive statistics to summarize the feasibility outcomes. In general, frequency 
distribution and percentage will be used to summarize categorical variables and median with 
interquartile range (IQR) to describe continuous variables. 95% confidence intervals (CIs) will be 
used to quantify the precision of these performance estimates.  
We will pre-designate drop-out rates of <15%, 15-25%, and >25% as indicating optimal, 
acceptable, and inadequate participant retention during the 12-week intervention period. Among 
non-dropouts, we will consider completion of >85%, 75-85%, and <75% of questionnaire 
completion to indicate optimal, acceptable, and inadequate intervention adherence, respectively.  
 
 
10.0 ADVERSE EVENTS AND REPORTING REQUIREMENTS 
 
10.1 Definitions  
 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a study participant, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or 
disease, temporally associated with the participants’ involvement in the research, whether or not 
considered related to participation in the research. Medical conditions or diseases present before 
starting study interventions should only be considered adverse events if they worsen after starting 
the interventions. 
 
A serious adverse event (SAE) is any AE that results in death, is life threatening, or places the 
participant at immediate risk of death from the event as it occurred, requires or prolongs 
hospitalization, causes persistent or significant disability or incapacity, results in congenital 
anomalies or birth defects, or any other important event judged by the investigators to jeopardize 
the safety of a participant based upon appropriate medical judgment. 
 
An unexpected problem is defined as any incident, experience, or outcome that meets all of the 
following criteria: 1) is unexpected, in terms of nature, severity, or frequency, given the research 
procedures described in the protocol and the characteristics of the study population; 2) is related or 
possibly related to participation in the research; and 3) suggests that the research places 
participants or others at a greater risk of harm (including physical, psychological, economic, or 
social harm) than was previously known or recognized. 
 
10.2 Expectedness 
 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed above 
or included in the following list:  
• 
Dizziness 
• 
Headache 
• 
Erectile dysfunction 
• 
Decreased libido 
• 
Rhinitis 
• 
Fatigue 

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• 
Insomnia 
• 
Diarrhea 
• 
Constipation 
• 
Nausea 
• 
Back pain 
• 
Worsening lower urinary tract symptoms   
 
10.3 Attribution 
 
A suspected adverse reaction means any adverse event for which there is reasonable possibility 
that the intervention caused the adverse event. For the purposes of safety reporting, “reasonable 
possibility” means there is evidence to suggest a causal relationship between the intervention and 
the adverse event. 
 
The investigative team will assign attribution of the possible association of the event with the study 
intervention using the following definitions: 
 
Unrelated (nonattributable) to the deprescription intervention: The adverse event is clearly not 
related or is doubtfully related to the deprescription intervention 
 
Related (possibly attributable or attributable) to the deprescription intervention: The adverse 
event may be related, is likely related, or is clearly related to the deprescription intervention 
 
10.4 Severity 
 
Signs or symptoms shall be graded and recorded by the Investigator according to the 
Common Terminology Criteria for Adverse Events (CTCAE) (use latest version at initiation of 
clinical trial). When specific adverse events are not listed in the CTCAE, they are to be 
graded as mild, moderate, severe, or life-threatening according to the following grades and 
definitions: 
 
AE Severity Grading 
 
Severity 
(Toxicity 
Grade) 
 
Description 
 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age- appropriate instrumental activities of daily living 
(ADL) 
 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL 
Grade 4 
Life-threatening consequences: urgent intervention indicated 
Grade 5 
Death related to AE 
 
10.5 Reporting Requirements 
 

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For this study, new AEs or SAEs will be considered reportable any time after the Baseline Visit 
until 7 days (for non-serious AEs) or 28 days (for SAEs) after the last day of study participation. 
All events should be followed to their resolution, until the Investigator assesses them as stable, 
irreversible, or until the study participant is lost to follow-up, whichever comes first. 
 
The study coordinator will record all reported events in the adverse event log (including subject’s 
name, date, and event description). All SAEs occurring during the study must be reported to the 
appropriate study investigator within 24 hours of their knowledge of the event. The study PI will 
consult with the co-investigators on the action to be taken. This action and date of implementation 
will also be recorded in the adverse event log. The entire investigative team will participate in 
classifying events as AEs, SAEs, or unexpected problems, as well as ‘non-attributable’, ‘possibly 
attributable’, or ‘attributable’ to the proposed study.  
 
The study will follow UCSF Reporting Requirements: UCSF requires submission of Adverse Events 
that qualify as: Any unexpected, physical, psychological or social research-related event which 
is definitely, probably or possibly related to the study; where the risk is not included, or exceeds the 
nature, severity, or frequency described in the protocol, study consent form, or other study 
information previously reviewed and approved by the IRB. 
 
An unexpected AE also includes any AE that meets any of the following criteria: 
• Results in subject withdrawal from study participation 
• Due to an overdose of study medication 
• Due to a deviation from the IRB approved study protocol 
 
11.0 PROTOCOL VIOLATION AND WITHDRAWAL OF PARTICIPANTS 
 
11.1 Protocol Violation 
 
A protocol violation occurs when a study participant or Investigator fails to adhere to specific 
protocol requirements affecting the inclusion, exclusion, study participant safety and primary 
endpoint criteria. Protocol violations for this study include, but are not limited to: 
 
• Randomization of a participant who does not meet the inclusion/exclusion criteria 
• Inappropriate delivery of experimental or control interventions to participants in the wrong study 
arm 
• Use of prohibited co-interventions during the study treatment period 
• Any other deviation that presents significant risk or safety concerns to the study participant 
• The investigative team will determine if a protocol violation should result in withdrawal of a study 
participant. 
 
11.2 Withdrawal of participants 
 
Participants are free to withdraw from participation in the study at any time upon request. If a 
participant withdraws from the study, any data collected on him up to that point in the study will 
go forward for study analysis. This information will be stated in the participant information 
leaflet. Reasons for stopping the intervention will be recorded and reported. When appropriate, 
outcome and follow-up data will be obtained, unless the participant specifically declines further 
follow-up. 
 
An investigator may discontinue a participant from the study for the following reasons: 
 
• Significant study intervention non-compliance (compliance is an aspect of the study objectives) 

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• Lost-to-follow up; unable to contact participant  
• Any event, medical condition, procedure, surgery, or situation occurs such that continued 
collection of follow-up study data would not be in the best interest of the participant or might 
require an additional treatment that would confound the interpretation of the study 
 
12.0 DATA MANAGEMENT AND MONITORING 
 
12.1 Individuals Overseeing Data Management 
 
A Clinical Research Coordinator (CRC) will be assigned to the study. The responsibilities of 
the CRC include screening and enrolling subjects; data collection, abstraction, entry, and 
reporting; communicating with participants; scheduling study participant visits; regulatory 
monitoring; and problem resolution and prioritization. The data collected for this study will be 
entered into a secure database (REDCap). Source documentation will be available to support 
the computerized participant record. The principal investigator will maintain ultimate 
responsibility for the clinical trial. 
 
12.2 Case Report Forms and Source Documents 
 
Participant data will be collected using protocol-specific case report forms (CRF). Source 
documentation will include only those documents containing original forms of data, including 
clinic charts, shadow files, hospital charts, and clinician notes. Data recorded directly on the 
CRFs designated as source documents (i.e., no prior written or electronic record of data) will 
be considered source data. All other data recorded on the CRFs will not be considered source 
documentation. 
 
12.3 Data Management Procedures 
 
All data collected on this protocol will be securely stored and managed in a REDCap database 
system at the University of California – San Francisco (UCSF) under the stewardship of the 
principal investigator. 
 
This database will be developed and maintenance performed with support of the School of 
Medicine (SOM) at UCSF. REDCap was developed by Vanderbilt’s CTSA and is currently used 
and supported by more than 1000 consortium partners. REDCap provides: 1) a stream-lined 
process for rapidly building a database; 2) an intuitive interface for collecting data (with data 
validation and audit trail); 3) automated export procedures for seamless data downloads to 
common statistical packages (SAS, SPSS, etc.); 4) branching logic, file uploading, and 
calculated fields; and 5) a quick and easy protocol set-up. 
 
All connections to REDCap, both external and internal, occur over encrypted channels. 
Access to components of the system is role-based and can only be granted by administrators 
of the system. All collected information is stored on a standalone database server hosted by 
UCSF. The database server resides behind the UCSF internal firewall and access to the 
server is controlled via firewall rules. 
 
All collected data is backed up daily, both on the local server and by the UCSF enterprise backup 
system. 
 
12.4 Data Quality Control and Reporting 
 
Weekly registration reports will be generated to monitor study participant accruals and 

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completeness of registration data. Routine data quality reports will be generated to assess 
missing data and inconsistencies. Accrual rates and extent and accuracy of evaluations and 
follow-up will be monitored periodically throughout the study period and potential problems will be 
brought to the attention of the study team for discussion and action. The study team will conduct 
periodic random-sample data quality and protocol compliance audits. 
 
12.5 Data and Safety Monitoring Plan 
 
Level of Risk:  
 
This study involves feasibility testing of a deprescription intervention with daily questionnaires that 
is believed to be overall low-risk.  
 
Safety 
 
Participants will be contacted via email or phone if they do not complete the daily symptom 
questionnaire for more than 3 consecutive days during their N-of-1 trial or if a dramatic worsening in 
their daily IPSS questionnaires are suggestive of increased risk of retention.  
 
Other risk mitigation 
 
The following procedures will be used to minimize risk and to ensure participant confidentiality both 
during and after the study: 
• 
The eligibility criteria is a rigorous list of inclusionary/exclusionary criteria to minimize risk and 
was approved by physician MPI Dr. Bauer. 
• 
All study files, folders, and records will be kept in locked file cabinets that can be accessed only 
by study personnel. 
• 
All data with PHI be securely exchanged in accordance with UCSF-approved policies. 
• 
The study databases are housed in REDCap, a secure cloud data collection system behind IT-
regulated and firewalls of the University of San Francisco, California. REDCap has the 
protections needed for storage of PHI and backup systems. 
• 
Each participant will be assigned a unique numerical study identifier which will be used on study 
materials instead of names or other individually identifying information. 
• 
Documents with participant identifiers (e.g., name) are stored on secure servers located behind 
a fire wall and accessed only by authorized study personnel. 
• 
Information that could identify individual participants will not be released without written 
permission of the participant, except as necessary for monitoring by institutional review boards, 
the NIH, the Office for Human Research Protections, or other government agencies responsible 
for protecting participant safety. 
• 
All investigators and support staff are HIPAA certified and have completed and are current with 
regard to IRB training.  
 
13.0 PROTECTION OF HUMAN SUBJECTS  
 
13.1 Informed Consent 
 
Prior to the enrolment of each participant, the risks, benefits and objectives of the study will be 
reviewed with the participant. Alternative, non-protocol, treatment options will be discussed with the 
patient. Participants will be informed that participation in this clinical trial is voluntary and that the 
participant may withdraw consent at any time.  
 

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13.2 Potential Risks 
 
Our eligibility criteria and screening procedures are established to exclude individuals for whom 
stopping tamsulosin may not be appropriate. Our eligibility criteria and screening procedures are 
established to exclude individuals for whom the study is not appropriate. Per the exclusion criteria, 
this includes patients with certain urologic conditions or psychiatric conditions. After obtaining 
participant consent, the screening process will include verification of these factors by the clinician. 
This multi-gated comprehensive approach should systematically identify and screen out any 
individual for whom this study is contraindicated.  
 
Risks of Research Participation – Participation in research involves some loss of privacy. We will 
do our best to make sure that all personal information gathered for this study is kept private. 
However, we cannot guarantee total privacy. There is also a minor risk to loss of confidentiality, 
either through the breach of data collected via the Internet, text messaging, or through the breach 
of secure study databases, physical files, etc. There is also some risk due to randomization. The 
intervention may be more burdensome and may not have a beneficial effect on their health 
outcomes compared to usual care. 
 
13.3 Potential Benefits 
 
There are no other direct benefits to the participants (financial compensation is purposely not 
presented as a benefit), except as to their feelings of being involved as participants in an important 
research study. The potential public health benefit to society in this study could be large, as we are 
targeting a common condition in older men (one in three develop LUTS/BPH in their lifetime). 
Scientific and clinical knowledge gained from this study could be extremely useful to practicing 
clinicians, individuals, policy makers, insurers, and public health planners. Additionally, study 
results may help individual patient decided if they should stay on tamsulosin. 
 
This study will provide valuable insights into the feasibility of tamsulosin deprescription across a 
diverse patient population. The potential public health benefit to society in this study could be large, 
as we are targeting a common condition in older men (one in three older men develop LUTS/BPH 
in their lifetime). Our overarching goal is to build the evidence needed for a full-scale efficacy trial 
testing deprescription, thus this research has great potential to change the paradigms for 
LUTS/BPH management. Scientific and clinical knowledge gained from this study could be 
extremely useful to practicing clinician, individuals, policy makers, insurers, and public health 
planners developing interventions to prevent or treat LUTS/BPH. Thus, given the importance of 
knowledge to be gained and the anticipated benefit to research participants and others, the risks to 
subjects are reasonable. 
 
13.4 Alternatives 
 
We will have standard UCSF Institutional Review Board (IRB)-approved language on our consent 
form about other alternatives to participation. We will let participants know that they are free to 
choose not to participate in the study, and if they decide not to take part, there is no penalty to 
them. We will let them know they can participate in other research studies at UCSF (if available and 
if they are eligible) or they can choose not to participate in any research studies. We also 
encourage them to talk to their clinician about their choices before deciding to take part in the 
study.  
 
13.5 Confidentiality 
 
Every effort will be made to maintain patient confidentiality. Research and hospital records are 
confidential. Participants’’ names and any other identifying information will not be used in reports or 

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publications resulting from this study. Other authorized agencies and appropriate internal and 
external personnel may review patient records, as required by law. Only a participant ID number 
will identify all study participants on study documents. Additional participant confidentiality issues 
are covered in the participant consent. 
 
13.6 Voluntariness of Research Participation 
 
It is stated that taking part in this study is voluntary and participants have the right to withdraw at any 
time. Participation in the study will not impact on the clinical care participants receive. 
 
13.7 Participant Privacy 
 
Medical information is confidential. The participant’s personal identity will not be used in reports that 
are written about the research. Every effort will be made to de-identify samples, reports, surveys 
whenever possible; and items will be physically labelled by an anonymous study-specific ID that is 
only linked to personal identifiers via a coded-document kept on secure computers, accessible only 
to study personnel. The results of any research using blood will not be placed in the medical record. 
The consent indicates that samples and genetic information collected may be shared with other 
qualified researchers. Such information will not include identifying information such as name. 
 
14.0 STUDY MANAGEMENT 
 
14.1 Pre-study Documentation 
 
Before initiating this trial, the PI will have written and dated approval from the Institutional 
Review Board for the protocol, informed consent form, subject recruitment materials, and any 
other written information to be provided to participants before any protocol related procedures 
are performed on any participants. 
 
14.2 Institutional Review Board Approval 
 
The protocol, the proposed informed consent form, and all forms of participant-facing materials 
related to the study (e.g., advertisements used to recruit participants) will be reviewed and 
approved by the IRB. The initial protocol and all protocol amendments must be approved by the 
IRB prior to implementation. 
 
14.3 Informed Consent 
 
All participants must be provided a consent form describing the study with sufficient information for 
each participant to make an informed decision regarding their participation. The ICFs must be 
signed by the participant or the participant’s legal representative before his participation in the 
study. The case history for each participant shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study. A copy of each signed 
ICF must be provided to the participant or the patrician’s legal representative. All signed and dated 
consent forms must remain in each participant’s study file and must be available for verification by 
study monitors at any time. 
 
The ICF should be revised whenever there are changes to procedures outlined in the informed 
consent or when new information becomes available that may affect the willingness of the 
participant to participate. Participants must be re-consented to the most current version of the 
consent forms during their participation in the study. For any updated or revised consent forms, 
the case history for each participant shall document the informed consent process and that written 

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informed consent was obtained for the updated/revised consent form for continued participation in 
the study.  
 
14.4 Changes in the Protocol 
 
Once the protocol has been approved by the IRB, any changes to the protocol must be 
documented in the form of an amendment. The amendment must be signed by the PI and 
approved by the IRB prior to implementation. 
 
If it becomes necessary to alter the protocol to eliminate an immediate hazard to participants, an 
amendment may be implemented prior to IRB approval. In this circumstance, however, the PI 
must then notify the IRB according to institutional requirements. 
 
14.5 Record Retention 
 
The PI is required to prepare and maintain adequate and accurate case histories that record all 
observations and other data pertinent to the investigation on each study participant. Study 
documentation includes all CRFs, data correction forms or queries, source documents, Sponsor-
Investigator correspondence, monitoring logs/letters, and regulatory documents (e.g., protocol 
and amendments, IRB correspondence and approval, signed participant consent 
forms). Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical research 
study. The PI shall retain records for a period of 2 years following the conclusion of the study. 
 
14.6 Publications 
The preparation and submittal for publication of manuscripts containing the study results shall be 
in accordance with a process determined by mutual written agreement among the Sponsor- 
Investigator and collaborators. 
 
 
 

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15.0 REFERENCES 
 
1. 
Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: 
report from the standardisation sub-committee of the International Continence Society. Urology. Jan 
2003;61(1):37-49.  
2. 
Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in america project: benign prostatic hyperplasia. 
J Urol. May 2008;179(5 Suppl):S75-80. doi:10.1016/j.juro.2008.03.141 
3. 
Girman CJ, Jacobsen SJ, Tsukamoto T, et al. Health-related quality of life associated with lower 
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