De-implementation of Low Value Castration for Men With Prostate Cancer
Phase: NA
Conditions: Cancer of Prostate
Sponsor: University of Michigan

Study Title:  De-implementation of Low Value Castration of Men With Prostate Cancer (DeADT)
PI:  Ted Skolarus, MD, MPH, FACS
NCT:  NCT03579680
Protocol Version IRB Approval Date:  11/11/2022

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PREFACE 
This document describes the elements required for a simple minimal risk research 
protocol.  Minimal risk studies may require more elements and oversight structure if the 
complexity or size of the study adds additional importance. 
“Minimal risk means that the probability and magnitude of harm or discomfort 
anticipated in the research are not greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of routine physical or psychological 
examinations or tests.”  See the Common Rule at 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.102.  
Further Guidance on what categories of research would meet minimal risk definition can 
be found at http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm .   
Minimal Risk studies, while simpler than studies of greater than minimal risk, still have 
regulatory obligations.  A well written protocol is the prologue to well conducted 
research and as such, a minimal risk protocol should include, at a minimum, sections on 
brief background/rationale, study objectives, expected risks/benefits, eligibility, subject 
enrollment, study design/procedures, data collection and management, data analysis, 
quality control and quality assurance, statistical considerations,  informed consent, 
privacy issues, unanticipated problems,  and references.  The following pages describe 
a template suitable for use. It is anticipated that the average minimal risk study can be 
described in less than 10 pages using this template.  A few thoughtful sentences in 
each section are preferred to large chunks of information cut-and-pasted from other 
documents.  
  A grant application is not acceptable as a protocol. 

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1 
Title 
De-implementation of low value castration for men with prostate cancer (DeADT) 
Principal Investigators: 
Sameer Saini, MD 
Professor (tenured), University of Michigan, Division of Gastroenterology 
Director, VA HSR&D Center for Clinical Management Research, 
VA Ann Arbor Healthcare System 
Ted A. Skolarus, MD, MPH, FACS 
Adjunct Professor of Urology, University of Michigan 
Research Investigator, VA HSR&D Center for Clinical Management Research 
VA Ann Arbor Healthcare System 
Funding Mechanism: NATIONAL CANCER INSTITUTE 1R01CA222885-01 
Institution(s): University of Michigan, VA Ann Arbor Healthcare System 
Other Identifying Numbers: HUM00133932, VA IRB 2017-1047 
Protocol Amendments: 
Updating application from a Project Lacking Immediate Plans for Involvement of Human 
Subjects to an application for research involving human subjects.  
•
Adding Co-Investigators (Section 1.3)
•
Adding VA Ann Arbor Healthcare System as a performance site (Section 3)
•
Revising study activities (Section 3.1)
Version 0.3 
March 26, 2019 
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OCTOBER 25, 2022

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 TABLE OF CONTENTS 
Page 
Title Page…………………………………………………………………………………………1 
Table of Contents ............................................................................................................ 2 
Signature Page ............................................................................................................... 3 
List of Abbreviations ........................................................................................................ 4 
1 
Background/Scientific Rationale .............................................................................. 5 
2 
Objectives ............................................................................................................... 5 
3 
Expected Risks/Benefits .......................................................................................... 5 
4 
Eligibility .................................................................................................................. 5 
5 
Subject Enrollment .................................................................................................. 5 
6 
Study Design and Procedures ................................................................................. 6 
7 
Data Collection and Management Procedures ........................................................ 8 
8 
Data Analysis .......................................................................................................... 9 
9 
Quality Control and Quality Assurance.................................................................... 9 
10 
Statistical Considerations ........................................................................................ 9 
11 
Regulatory Requirements ........................................................................................ 9 
11.1 
Informed Consent ......................................................................................... 9 
11.2 
Subject Confidentiality ................................................................................ 11 
11.3 
Unanticipated Problems ............................................................................. 11 
12 
References ............................................................................................................ 18 
Appendices ................................................................................................................... 24 
 
 
 
 
 

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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this study will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations. 
Site Investigator:* 
 
Signed: 
 
Date: 
3/26/19 
 
Name: Ted Skolarus, MD 
Title: Principal Investigator 
 
 
 
* The protocol should be signed by the clinical site investigator who is responsible for 
the day to day study implementation at his/her specific clinical site.

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LIST OF ABBREVIATIONS  
AAVA 
VA Ann Arbor Healthcare System 
ADT 
androgen deprivation therapy 
CCMR 
VA Center for Clinical Management Research 
CDW 
VA Corporate Data Warehouse 
Co-I 
Co-Investigator 
DCE 
discrete choice experiments 
HIPAA 
Health Insurance Portability and Accountability Act 
HSR&D VA Health Services Research & Development 
PC 
Prostate Cancer 
PHI 
protected health information 
RA 
Research Assistant 
TACT 
target, action, context, time 
TDF 
Theoretical Domains Framework 
TIDieR 
Template for Intervention Description & Replication 
VA 
Veterans Affairs 
VIReC 
VA Information Resource Center 
VREC 
Veteran Research Engagement Council 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
BACKGROUND/SCIENTIFIC RATIONALE 
A. BACKGROUND & SIGNIFICANCE 
A1. Evidence for castration as prostate cancer treatment 
Because prostate cancer cells are dependent on androgens, i.e., testosterone, depriving them 
of this hormone through castration can improve clinical outcomes, for some patients.1 The 
highest levels of evidence for chemical castration with androgen deprivation therapy (ADT) 
injections to treat prostate cancer occur in two scenarios: 1) high risk localized disease in 
combination with radiation therapy, and 2) metastatic cancer with spread to bones or 
other organs causing symptoms.2-4 However, a significant amount of castration in Medicare and 
integrated delivery systems (e.g., VA), occurs outside scenarios where high levels of benefit 
exist.5,6 For example, using castration for the primary treatment of localized prostate cancer is 
likely ineffective and harmful, yet remains common in VA with five-fold variation across facilities 
(Figure 1). Neither long-term studies nor current guidelines support castration as primary 
treatment for localized prostate cancer.1,3,4 Many times, this castration is continued indefinitely. 
Even in cases of metastatic prostate cancer without symptoms, an American Society of Clinical 
Oncology Panel could not make a recommendation for treatment with ADT until symptoms of 
disease progression (e.g., bone pain) occur due to a lack of an overall survival advantage for 
those treated early.7 
 
A2. There is a disconnect between the value and use of castration in prostate cancer 
A2.1 Surgery to remove testicles is no longer needed for castration 
The discovery that castration could be used as palliation for patients with metastatic prostate 
cancer revolutionized the oncology field in 1941.8 Depriving prostate cancer cells of 
testosterone to relieve urinary tract blockage and decrease bone pain from metastatic lesions 
ushered in a new way to think about treating the disease that continues to fuel treatment 
approaches today. However, surgical castration via orchiectomy (i.e., testicular removal) fell by 
the wayside in the 1990s as long-acting injectable approaches to androgen deprivation 
(GnRH agonists) became available, and even lucrative, leading to dramatic increases in use 
across all stages of the disease (Figure 2).9-11 This phenomenon essentially lowered the 
threshold for treatment with ADT injections due to ease of use, patient acceptability as they no 
longer needed their testicles removed, biological plausibility, and low appreciation for side 
effects of chemical castration among the surgical specialists prescribing ADT (i.e., urologists) 
with little training in primary care. 
 
A2.2 Lucrative business practice thwarted by Medicare payment reform 
The story of Medicare reimbursement for ADT is a fascinating example of how financial 
incentives can drive medical overuse.9 In short, Medicare reimbursed providers at 95% of the 
average wholesale price for these injections throughout the 1990s making it profitable since 
many providers acquired the drug at 82% or less of the average wholesale price.12 Up to 40% of 
urology practice revenues were derived from this business practice in some cases.13 
Orchiectomy was driven out of practice, and thresholds for castration were lowered such that 
nearly half of prostate cancer patients received ADT by 2000.10 Despite a stable evidence-base, 
more patients were getting injections in cases where there was no evidence to support use 
(e.g., primary treatment) alongside a growing awareness of harms. When the Medicare Part B 
tab for ADT injections reached $1 billion in 2003, the practice came under intense scrutiny.14 As 
a result, the Medicare Modernization Act reduced payments by approximately 50% leading to 
significant reductions in inappropriate use as published in the New England Journal of Medicine 

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by Co-Investigator Dr. Shahinian.9,15 Despite a decrease in what was termed ‘inappropriate use’ 
of ADT for localized prostate cancer through this policy intervention, such use persists today 
indicating other interventions are needed. 
 
A2.3 Growing recognition of castration harms has led to patient safety concerns 
Not surprisingly, the side effects of castration are common and impact a host of physiologic 
mechanisms that rely on the male hormone testosterone.16 Castration results not only 
phenotypic changes due to feminization, but also osteoporosis, metabolic syndrome, 
cardiovascular disease, loss of sexual function, and decrements to overall quality of life (Table 
1).17 Evidence also suggests the risks of diabetes,18 cataracts,19 deep vein thrombosis,20,21 
stroke22 and even acute cardiac death23 all increase for men receiving ADT. This led the 
American Cancer Society and American Heart Association to issue a 2010 consensus 
statement on the importance of secondary preventative measures for men treated with ADT.24 
 
A2.4 Reasons castration harms overlooked by providers and patients 
ADT decreases the serum PSA level, a biomarker of prostate cancer activity, falsely reassuring 
people there is a ‘remission’ of the prostate cancer. This is potentially harmful in at least 2 ways. 
First, depriving prostate cancer cells of testosterone too early in the disease process may foster 
castration resistance, limiting effects when it is actually needed (e.g., metastatic setting).25,26 
Second, PSA is a poor surrogate marker for survival in localized disease. That is, lowering PSA 
in localized disease is not associated with improved overall survival, creating false optimism.6,27 
In addition, surgical specialists are prescribing a drug with devastating metabolic and 
cardiovascular effects creating a disconnect between treating PSA levels and the 
consequences, often dealt with in primary care. While lowering PSA might make sense on the 
surface, understanding beliefs and preferences for using ADT is a critical step in stopping its low 
value use. In many respects, this is an ideal model for understanding de-implementation of low 
value cancer care. 
 
A3. Provider barriers for de-implementation of low value castration are critical, yet 
unknown 
The majority of ADT is prescribed by urologists across all stages of prostate cancer.28 Therefore, 
this proposal will focus on urologists and their patients. Our preliminary data (Section B1) 
indicate thousands of men are at risk of ongoing low value castration, especially when it comes 
to castration for localized disease, with tremendous variation across integrated delivery system 
facilities. Indeed, this calls for effective deimplementation strategies grounded in an 
understanding of context, provider preferences, and evidencebased behavior change 
techniques.29-31 Moreover, a significant scientific and clinical knowledge gap remains in 
prioritizing which barriers to stopping castration in low value settings need to be targeted for 
effective de-implementation. While a major focus in this study pertains to barriers, and 
prioritizing and overcoming barriers, facilitators for stopping ADT that are transferable across 
settings also need to be considered. In addition, using a discrete choice experiment (Section 
C2.1), we will be able to prioritize both positive (facilitators, preferences) and negative factors 
(barriers) to guide theory-based de-implementation strategies as a promising stakeholder-based 
approach applicable to other low value cancer care. 
 
A4. The benefits of unlearning ineffective, low-value clinical practices and ties to 
behavior change 
Unlearning routinized clinical practices is challenging even if they are no longer or never were 
considered effective.32,33 This is particularly true when it comes to treating patients with cancer 

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where provider reluctance to hold off on treatment is often a significant barrier to stopping or not 
initiating treatment when there are no symptoms. Unlearning clinical behaviors such as 
prescribing ADT in low evidence settings can have substantial benefits. First, patients are no 
longer subjected to treatment harms with little to no benefit. Second, unlearning misaligned 
castration practices can provide opportunity for more efficient, higher value use of specialists. 
Last, acquiring the skill of unlearning can increase flexibility and willingness to adapt to 
evidence more proactively.33 We believe unlearning is captured in the Behavioral Regulation 
domain of the Theoretical Domains Framework (TDF), our behavior change framework, for 
which there are evidencebased behavior change techniques to consider. This novel TDF 
connection to a limited unlearning literature may play a significant role in advancing de-
implementation science. 
 
A5. Strategies to stop chemical castration as prostate cancer treatment are sorely 
needed 
De-implementation, or stopping practices that are not evidence-based, has tremendous 
potential to improve patient outcomes and mitigate rising healthcare costs.29,30 This is important 
given recent campaign attempts to curb overuse of services. In fact, one group has called for 
including castration as primary prostate cancer treatment in the next generation of Choosing 
Wisely.34 De-implementation efforts have addressed analgesic35 and antibiotic36 use, glucose 
control,37 and blood transfusions.38 For this study, stopping low value castration might help 
prevent fractures, heart disease, and metabolic syndrome, preserve sexual function, in addition 
to freeing up provider time and decreasing pharmacy spending. 
2 
OBJECTIVES 
Specific Aim 1: To assess preferences and barriers for de-implementation of chemical 
castration in prostate cancer. The goal of Aim 1 is to clarify barriers and facilitators to 
stopping castration with ADT as primary prostate cancer treatment using an individual behavior 
change framework, the Theoretical Domains Framework (TDF).70 This approach will identify key 
barriers to de-implementation of low value ADT-based castration. We will conduct semi-
structured interviews with urologists to clarify preferences for (i.e., facilitators) and barriers to 
stopping ADT use. This will prepare us for development of a theory-based discrete choice 
experiment (DCE) among a national sample of urologists in Aim 2 to quantify the relative 
importance of barriers, and to direct intervention strategy tailoring to increase acceptability and 
effectiveness. Using TDF is state-of-the-art, and embedding it within a DCE is extraordinarily 
innovative. 
 
Specific Aim 2: To use a discrete choice experiment, a novel barrier prioritization 
approach, for deimplementation strategy tailoring. The goal of Aim 2 is to then prioritize 
barriers and facilitators to deimplementation of chemical castration with ADT discovered in Aim 
1. The highest priority barriers will need to be addressed during strategy development and 
tailoring for our pilot interventions in Aim 3 to support acceptability and feasibility in practice. We 
will accomplish this using a discrete choice experiment (DCE), a method in which respondents 
(urologists) react to hypothetical choice sets based on a combination of attributes 
(characteristics of the product under study, in this case the approach to de-implementing ADT) 
and levels (descriptors of each attribute). In our DCE, the barriers and themes with the highest 
frequency 

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and most conflicting beliefs across respondents identified in Aim 1 will be refined and presented 
as the “attributes” and associated levels will be developed. In short, we will use data obtained 
from Aim 1 to develop TDF-based choice sets for inclusion in a national urologist discrete 
choice experiment. Once we have the most important, not just most common or conflicting, 
themes and barriers based on a national urologist DCE, we can select the most effective 
evidence-based behavior change techniques to direct deimplementation tailoring efforts in Aim 
3.39-41,46,47,77 Marketing expert Dr. Sriram (Co-I) will align our efforts with state-of-the-art discrete 
choice and marketing practices. 
 
Specific Aim 3: To pilot two tailored de-implementation strategies to reduce castration as 
localized prostate cancer treatment. Based on findings from Aims 1 and 2, Aim 3 pilot work 
plays a critical role to help us understand the acceptability, feasibility, and scalability of these 
complex interventions in preparation for a full-scale randomized de-implementation evaluation 
trial.45 In fact, the UK Medical Research Council guidance indicates piloting is essential to 
complex intervention development and testing prior to large-scale evaluation.93 The main goal of 
both pilot interventions will be to decrease castration rates for patients with localized prostate 
cancer, but to do this in a way that is acceptable to the clinicians who treat these patients. 
We are purposely choosing intervention strategies from opposite ends of the behavior change 
continuum because of their evidence-based potential to change provider behavior. Specifically, 
we are selecting one approach (formulary restriction policy) that operates at the organizational 
level and is widely perceived as a forcing function, giving providers little leeway to exercise 
judgment. The other, physician/patient shared decision-making, operates at an individual and 
dyadic level, and is perceived as maximizing the opportunity for discussions between patients 
and providers. The first approach requires little to no learning on the part of providers, while the 
second requires considerable upfront learning (“cost” to the provider and possibly also to the 
patient). This approach sets up a testable hypothesis for our subsequent comparative 
effectiveness trial, that a blunt de-implementation policy may be effective in the short term but 
that it will lose its effects as providers learn work-arounds. Conversely, a shared or informed 
decision-making approach to de-implementation might take longer to observe measurable 
decreases in castration rates, but its effects will create sustainable change as providers 
internalize and routinize this clinical practice.94 
 
Specific Aim 4: To conduct a secondary data analysis using national VA CDW, workforce 
(VSSC), and Central Cancer Registry data, exploring facility factors associated with use 
of low value ADT. This information could potentially inform development of Aims 2 and 3 of our 
study. 
3 
EXPECTED RISKS/BENEFITS 
Aim 1: no UM patients or providers will be interviewed for Aim 1. Only risk is to VA patients and 
providers. 
 
Aims 2 and 3: these aims have not yet been developed and sites are not yet selected. 
 
Aim 4: Only VA data will be used. Only risk is to VA data. 

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4 
ELIGIBILITY 
VA urologists (and possibly other providers prescribing a significant amount of ADT) 
from VA facilities with the highest and lowest use of castration as primary treatment who 
express interest in prostate cancer (PC) care will be eligible to participate in an 
interview. VA patients from high outlier sites identified as receiving ADT as primary 
prostate cancer treatment will be eligible to participate in an interview. These criteria are 
necessary in order to maximize the likelihood that data collected from participants will 
address our study aims. 
 
VA patients with dementia or other significant mental impairment noted in their medical 
record will be excluded from participation. There will be no benefit to patients from 
participation in this study. 
We will not exclude patients enrolled in another protocol. 
5 
SUBJECT ENROLLMENT 
No subject enrollment will take place at UM. 
 
VA PROVIDERS: 
We will purposefully sample up to 20 urologists from high outlier facilities with highest and lowest use of 
chemical castration with androgen deprivation therapy (ADT) as primary treatment. Facilities will be updated 
using our algorithm combined with Medicare claims data for years 2016 and 2017 obtained from the VA 
Information Resource Center (VIReC) to validate we are not missing unidentified prostate cancer treatment 
outside VA. 
 
Provider data from facilities with the highest and lowest rates of chemical castration for localized disease 
will be collected using lists of providers from the most recent Federal Practitioner directory and national 
urologist email listserv. We will identify Urology Chiefs at each site using lists of providers from the most 
recent Federal Practitioner directory and national urologist email listserv. Dr. Skolarus will email Urology 
Chiefs, describe participation in the study, and request approval to contact facility urologists for 
interviews. 
 
Urologists will be emailed a study information sheet (to be submitted with a future amendment prior to 
start of recruitment activities) briefly describing the nature and purpose of the study as well as the types 
of questions they will be asked. The option to refuse participation will be clearly stated. Urologists who 
respond to emails agreeing to participate will be contacted either by phone or email and screened for 
purposeful sampling (e.g., do they routinely prescribe ADT). Any urologist who has experience caring for 
prostate cancer patients on ADT and expresses interest in prostate cancer care will be eligible to participate. 
Providers who are eligible and agree to be interviewed will be contacted by phone or email and scheduled for 
an interview. If email responses are below our target recruitment number, we may follow up recruitment 
emails to providers with 1 or 2 phone calls. We will also consider interviewing non-physician providers (e.g., 
nurse practitioners) if they prescribe a significant amount of ADT. 
 
VA PATIENTS: 
We will use VA cancer registry data for years 2016 and 2017 to identify patients at high outlier sites on 
primary ADT for prostate cancer. Patients will be ineligible if they have dementia or other significant 
mental impairment noted in their medical record. Patients will be mailed a recruitment letter and study 
information sheet (to be submitted with a future amendment prior to start of recruitment activities) 

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describing the nature and purpose of the study as well as the types of questions they will be asked. The 
option to refuse participation will be clearly stated. Patients that do not opt out will be contacted by 
phone a week later and invited to participate. We will attempt up to 5 or 6 attempts per patient, 
including leaving voice mails and providing call-back information. Patients will be scheduled for a phone 
interview at a date and time of their choosing. We plan to conduct up to 15 patient interviews from high 
outlier sites. 
6 
STUDY DESIGN AND PROCEDURES 
AIM 1: 
 
All interviews conducted for Aim 1 will involve VA providers and patients only. UM investigators will help 
develop and refine the provider and patient interview guides. Drs. Wittman and Skolarus may assist VA staff 
with provider and patient interviews. VA staff conducting interviews have many years’ experience conducting 
qualitative data collection. We have been granted waivers of written informed consent and HIPAA 
authorization by the AAVA IRB. 
 
We will interview urologists (and possibly other providers) and patients from facilities with the highest and 
lowest castration rates using androgen deprivation therapy (ADT) across VHA. We will start by sending 
emails to VA Urology Chiefs (UCs) and VA Medical Center Directors (MCDs) at high outlier sites. At sites that 
have no Urology Chief on staff, we will obtain approval as requested by the MCD from others in VA 
leadership such as COS, DCOS, Specialty Chiefs, Section Chiefs, as well as Research staff when requested. 
These situations will be dealt with on a case-by-case basis. We will attempt to contact providers up to 5 
times via email, phone, or VA instant messaging. We will confirm provider eligibility prior to scheduling an 
interview. (Please see attached provider recruitment email and follow-up eligibility email). We will attempt 
to interview up to 2 providers at each site. If provider response from some sites is insufficient, we will 
increase the number of providers interviewed at each site to up to 4 and/or send emails to the UCs and 
MCDs at additional high outlier facilities. We will continue in this manner until all 20 provider interviews are 
complete or until we feel we have reached saturation, whichever comes first. We will consider interviewing 
non-physician providers if they prescribe a significant amount of ADT.  
 
Similarly, we will send recruitment letters and study information sheets to patients at high outlier facilities. 
We will attempt up to 5 or 6 attempts per patient, including leaving voice mails and providing call-back 
information. We will attempt to interview 1-2 patients from each site, with no more than 15 interviews total. 
If patient response from some sites is insufficient, we will increase the number of patients interviewed at 
each site to up to 4 and/or send recruitment letters and study information sheets to patients at additional 
high outlier sites. We will continue in this manner until all 15 patient interviews are complete or until we feel 
we have reached saturation, whichever comes first. Patients will be mailed a $20 gift card following their 
completion of the interview. 
 
We will pilot provider interviews with study consultants. Pilot interviews will be conducted by phone and in 
person and will NOT be audiotaped. We will also obtain feedback on the patient interview guide from CCMR's 
Veteran Research Engagement Council (VREC). We will refine the draft semi-structured interview guides for 
providers and patients to elicit beliefs and attitudes regarding starting and stopping ADT as localized 
prostate cancer treatment, as well as informed decision-making preferences, and to ensure it can be 
completed in a timely fashion. Interview guides are developed iteratively - questions are developed, tested, 
and then refined based on what one learns from asking participants these questions. However, any 
substantial change or addition to interview guide questions will be submitted to the IRB for approval. 
 
Semi-structured interviews with both patients and providers will be recorded using the Olympus DS-7000 
DVR so that authorized study staff can turn the interview responses to written text to help identify 
common themes. Each phone interview will last approximately 30 - 45 minutes. Please note that we will 
ask permission to record interviews. After each interview, the audio file of the recording will be uploaded 
to a restricted folder located on a secure VA computer server protected behind the VA firewall. Only 
authorized study staff will have access to this folder. Once the interview information is located on the VA 
server, the original interview recording will be deleted from the recording device according to VA policy. 
 

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Interview data will be transcribed, coded and entered into NVivo software for analysis. We will use a 
preliminary coding scheme based on the Theoretical Domains Framework (TDF) and prior work by Huijg and 
Birken consisting of a three step process including: 1) coding affirmative and negative utterances regarding 
ADT use as localized treatment into TDF domains, 2) collecting responses across respondents into themes, 
3) tallying the total number of mentions per theme, as well as conflicting beliefs within a theme (e.g., ADT is 
good vs. ADT is bad), according to the TDF domains, with particular emphasis on those included in our 
conceptual model. This qualitative work will inform Aim 2 and gather rich information for 
our proposed pilot intervention strategies. 
 
We will provide a summary of results to participating providers and patients upon request once results 
are available. These summaries will contain only aggregate data and/or broad summaries and will be 
submitted to the IRB for approval prior to dissemination. 
 
All research data will be de-identified at the termination of the study, if not sooner. Study data will be 
moved to the VA CCMR data repository and destroyed by the CCMR data manager six (6) years following the 
end of the Fiscal Year after completion of the research project as described in the VA Records Control 
Schedule. 
 
 
AIM 2: 
The goal of Aim 2 is to then prioritize barriers and facilitators to de- implementation of chemical castration 
with ADT discovered in Aim 1. The highest priority barriers will need to be addressed during strategy 
development and tailoring for our pilot interventions in Aim 3 to support acceptability and feasibility in 
practice. We will accomplish this using a discrete choice experiment (DCE), a method in which respondents 
(urologists) react to hypothetical choice sets based on a combination of attributes (characteristics of the 
product under study, in this case the approach to de-implementing ADT) and levels (descriptors of each 
attribute). In our DCE, the barriers and themes with the highest frequency and most conflicting beliefs 
across respondents identified in Aim 1 will be refined and presented as the “attributes” and associated levels 
will be developed. In short, we will use data obtained from Aim 1 to develop TDF-based choice sets for 
inclusion in a national urologist discrete choice experiment. Once we have the most important, not just most 
common or conflicting, themes and barriers based on a national urologist DCE, we can select the most 
effective evidence-based behavior change techniques to direct de-implementation tailoring efforts in Aim 3. 
Marketing expert Dr. Sriram (Co-I) will align our efforts with state-of-the-art discrete choice and marketing 
practices. 
 
AIM 3: 
 
Please note, the Aim 3 pilot and subsequent comparative effectiveness trial will be conducted at the VA Ann 
Arbor Healthcare System. Based on findings from Aims 1 and 2, Aim 3 pilot work plays a critical role to help 
us understand the acceptability, feasibility, and scalability of these complex interventions in preparation for 
a full-scale randomized de-implementation evaluation trial. In fact, the UK Medical Research Council 
guidance indicates piloting is essential to complex intervention development and testing prior to large-scale 
evaluation. The main goal of both pilot interventions will be to decrease castration rates for patients with 
localized prostate cancer, but to do this in a way that is acceptable to the clinicians who treat these patients. 
We are purposely choosing intervention strategies from opposite ends of the behavior change continuum 
because of their evidence-based potential to change provider behavior. Specifically, we are selecting one 
approach (formulary restriction policy) that operates at the organizational level and is widely perceived as a 
forcing function, giving providers little leeway to exercise judgment. The other, physician/patient shared 
decision-making, operates at an individual and dyadic level, and is perceived as maximizing the opportunity 
for discussions between patients and providers. The first approach requires little to no learning on the part 
of providers, while the second requires considerable upfront learning (“cost” to the provider and possibly 
also to the patient). This approach sets up a testable hypothesis for our subsequent comparative 
effectiveness trial, that a blunt de-implementation policy may be effective in the short term but that it will 
lose its effects as providers learn work-arounds. Conversely, a shared or informed decision-making approach 
to de-implementation might take longer to observe measurable decreases in castration rates, but its effects 
will create sustainable change as providers internalize and routinize this clinical practice. 
 
AIM 4: 
In Aim 4 (as an extension of our goals for Aim 1), we will explore facility level factors associated with low 

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value ADT use in clinically localized prostate cancer. We plan to retrospectively analyze data from VA 
facilities across the United States to determine what facility level factors are associated with low value 
ADT use in clinically localized prostate cancer. We hypothesize that academic affiliation will be associated 
with higher value prostate cancer care. More broadly, this work can begin to fill knowledge gaps 
regarding academic affiliations and the value of specialty care delivery in VA. 
 
Using national VA CDW, workforce (VSSC), and Central Cancer Registry data, we will analyze rates of 
ADT use in localized prostate cancer for VA facilities from 2016-2017. We will separate facilities into 
quartiles of low value ADT use and use regression models to identify those factors associated with higher 
value prostate cancer care (e.g., urologist workforce, resident number, hospital size, medical school 
affiliation, region). We will also examine the extent to which changes in low value ADT use over time are 
associated with changes in facility level characteristics. To better understand the influence of facility level 
factors on low value specialty care, we will identify facilities that changed quartiles of low value ADT use 
over the study period. We will then identify changes in facility factors associated with corresponding 
changes in low value ADT use using regression models. For example, if loss of urologist workforce was 
associated with increasing low value care this may inform strategies to proactively engage facilities facing 
specialty care recruitment challenges. This information could potentially inform development of Aims 2 and 3 
of our study. 
 
7 
DATA COLLECTION AND MANAGEMENT PROCEDURES 
AIM 1: Only data from VA databases will be collected for participant identification and screening purposes. 
This data will be collected by the VA study data manager. 
 
PROVIDERS: 
For the semi-structured provider interviews, we will sample up to 20 VHA urologists from VHA facilities with 
the highest and lowest use of castration as primary treatment. We will use preliminary data from Dr. 
Skolarus' CDA but then update the data using CDW Oncology data for the years 2016 and 2017 once our 
DART application is approved. We are also applying for access to Medicare claims data from VA Information 
Resource Center (VIReC) to validate we are not missing unidentified treatment with surgery or radiation 
therapy outside VHA. We plan to pull Medicare data on 
up to 20,000 patients. We will identify Urology Chiefs at each site using lists of providers from the most 
recent Federal Practitioner directory and national urologist email listserv. If possible, we will use CDW data 
to identify providers who meet the criteria of having experience caring for patients on ADT.  
 
PATIENTS 
We will use VA cancer registry data for years 2016 and 2017 to identify patients at high outlier sites on 
primary ADT for prostate cancer. Patients will be ineligible if they have dementia or other significant 
mental impairment noted in their medical record.  
 
ACCESS TO DATA: 
All identifiers, including interview recordings, will be stored in access restricted folders on VA servers 
behind the VA firewall. Only key study team members added to the AAVA IRB approved protocol 
personnel list will have access to data files containing PHI/PII. All personal identifiers will be stripped 
from the written verbatim transcripts of the interviews. Subjects will be instructed at the start of the 
interview to refrain from mentioning names of colleagues or from identifying the medical center.  
 
DATA SAFETY MONITORING PLAN (DSMP): 
 
Dr. Skolarus will be responsible for reporting all adverse events that might arise during the course of the 
study to the University of Michigan and the Ann Arbor Veterans Affairs Health System IRB. Adverse Events 
during this study would likely consist only of breaches in confidentiality. The following precautions have been 
taken to prevent this. However, should such breaches occur, Dr. Skolarus will report these occurrences to 
the overseeing IRBs within 48 hours. 
 
All identifiers, including interview recordings, will be stored in access restricted folders on VA servers 

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behind the VA firewall. Only key study team members added to the AAVA IRB approved protocol 
personnel list will have access to data files containing PHI/PII. All personal identifiers will be stripped 
from the written verbatim transcripts of the interviews. Subjects will be instructed at the start of the 
interview to refrain from mentioning names of colleagues or from identifying the medical center. All research 
data will be de-identified at the termination of the study, if not sooner. Study data will be moved to the VA 
CCMR data repository and destroyed by the CCMR data manager six (6) years following the end of the Fiscal 
Year after completion of the research project as described in the VA Records Control Schedule. 
 
 
AIMS 2: The survey/DCE will be pilot tested at study consultants’ sites and refined based on feedback and 
any necessary troubleshooting. Once the survey/DCE is finalized, it will be disseminated to providers on the 
Society of Government Service Urologists (SGSU) listserv. Study staff will send email invites to up to 500 
providers. The email invite will include an attached study information sheet and a  link to the survey/DCE. 
Email invites will be sent from Dr. Skolarus’ VA email account. We will send up to 3 email invites to the 
listserv (allowing at least one-two weeks between each invite) and collect up to 400 completed 
surveys/DCEs.  The survey/DCE will be hosted on the Sawtooth Software platform and all data will be 
collected anonymously. Providers completing surveys/DCEs will receive a $50 Amazon eGift Card. 
 
 
 AIM 3: The pilot will be conducted at 4 VA sites under the oversight of the VA Ann Arbor RDC/IRB. 
 
AIM 4: 
We plan to retrospectively analyze data from VA facilities across the United States to determine what facility 
level factors are associated with low value ADT use in clinically localized prostate cancer. Data will be 
collected from national VA CDW, workforce (VSSC), and Central Cancer Registry data by the study data 
manager. All identifiers will be stored in access restricted folders on VA servers behind the VA firewall. Only 
key study team members added to the AAVA IRB approved protocol personnel list will have access to data 
files containing PHI/PII. Study data will be moved to the VA CCMR data repository and destroyed by the 
CCMR data manager six (6) years following the end of the Fiscal Year after completion of the research 
project as described in the VA Records Control Schedule. 
 
8 
DATA ANALYSIS 
AIM 1: 
 
Interview data will be transcribed, coded and entered into NVivo software for analysis. We will use a 
preliminary coding scheme based on the Theoretical Domains Framework (TDF) and prior work by Huijg and 
Birken consisting of a three step process including: 1) coding affirmative and negative utterances regarding 
ADT use as localized treatment into TDF domains, 2) collecting responses across respondents into themes, 
3) tallying the total number of mentions per theme, as well as conflicting beliefs within a theme (e.g., ADT is 
good vs. ADT is bad), according to the TDF domains, with particular emphasis on those included in our 
conceptual model. This qualitative work will inform Aim 2 and gather rich information for our proposed pilot 
intervention strategies. 
 
AIMS 2: 
 
Discrete choice experiments are based on Random Utility Theory which assumes participants will select 
responses with the most personal utility.80,83 Because respondents respond to a variety of choice sets, we 
will be able to estimate the relative priority of our barrier attributes and their levels. We will model urologists 
stated preferences providing quantitative information about the relative value, or utility, providers place on 
barrier attributes such as physician autonomy or clinical time, for example, using the equations below.  
There are ~250 urologists on the listserv. If 50% respond: 125 surveys with ~5 scenarios – 625 scenarios x 
5 attributes = 3125 data elements for analysis. Dr. Wiitala is an expert in multi-level and multinomial 
regression techniques and will conduct the analyses with direction from Drs. Hawley and Sriram given their 
DCE expertise. Our methods will adjust for dependency of responses within individuals as they respond to 
different choice sets and will be modeled after published DCEs according to the following example equation:  

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Utility = (Constant) +β1 (e.g., physician autonomy) + β2 (e.g., clinical time) …  
We will assess for model fit and need for random parameters among the attributes. Attribute levels will 
range from -1 for our reference level to +1 for the alternative to allow determination of relative 
importance.80 Our outcomes will be based on the beta parameter values (β1, β2, etc.) and standard errors 
that correspond to each attribute where a negative value will indicate preference for the reference group, 
statistical significance will be set at 0.05. Once we have our leading barrier attributes and corresponding TDF 
domains, we will select the most relevant candidate evidence-based behavior change technique components 
based on prior work by Michie et al.47 to guide tailoring of pilot de-implementation interventions. We also 
plan to adjust our models for facility-level ADT rates, and perform a subgroup analysis for facilities  
with high primary ADT rates to better understand barriers to tailor towards 
9 
QUALITY CONTROL AND QUALITY ASSURANCE 
AIM 1: 
 
Interviews will be audiotaped and transcribed verbatim for content. We will conduct analyses concurrently 
with ongoing interviews, if timing permits, to inform subsequent data collection and analysis. We will use a 
preliminary coding scheme based on the TDF and prior work by Huijg et al.,41 and Birken et al.,76 
consisting of a three step process including: 1) coding affirmative and negative utterances regarding ADT 
use as localized treatment into TDF domains, 2) collecting responses across respondents into themes (e.g., 
“ADT prevents cancer spread” into a ‘ADT is beneficial’ theme, “urologists should be able to treat patients as 
they wish” into a ‘Physician autonomy’ theme), 3) tallying the total number of mentions per theme, as well 
as conflicting beliefs within a theme (e.g., ADT is good vs. ADT is bad), according to the TDF domains, with 
particular emphasis on those included in our conceptual model. Study interviewers and qualitative analysts 
will both independently review and code transcripts and meet regularly to compare coding results until 
reaching agreement on code definitions and establish the reliability of the coding process (>80% simple 
agreement). During this process, study investigators and interviewers will also meet to categorize the codes 
into TDF domains, identify emerging themes, and document ongoing data interpretation in memos. Once 
data are coded, we will use QSR NVivo software to organize the data. Drs. Skolarus and the research team 
will meet regularly to discuss code summaries and memos, developing findings with a focus on informing the 
Aim 2 discrete choice tool. At the end of this aim we will have identified the highest frequency themes and 
themes with conflicting provider and patient beliefs across TDF domains for de-implementing ADT. 
 
AIMS 2 AND 3: tbd 
10 
STATISTICAL CONSIDERATIONS 
Please see above for information on qualitative analysis. 
PILOT OUTCOMES 
 
Primary Outcome Measures 
 
A. Feasibility – Site level 
 
• 
Title: Percentage of approached pilot sites with Medical Center Director approval to implement the 
intervention (Order Check (OR) or Progress Note/Patient Handout (SC))  
o 
Description: The percentage of pilot sites asked to participate that received MCD approval 
to implement the intervention (Order Check or Progress Note/Patient Handout) 
o 
Time frame: Within 1 month.  
 
• 
Title: Percentage of director-approved pilot sites with intervention implementation.  

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o 
Description: The percentage of approved pilot sites with fully operationalized intervention 
within the site. Depending on randomization arm, this includes either health factor 
placement or script assignment prior to at least one patient visit.  
o 
Time frame: Within 3 months of approval.  
 
B. Feasibility – Clinic level 
 
• 
Title: Percentage of total pilot site clinics with intervention implementation.  
• 
Description: The percentage of clinics at approved pilot sites with at least 1 health factor assigned 
and/or at least 1 progress note assigned to a provider. Clinics may include Urology, Medical 
Oncology, and Radiation Oncology. 
• 
Time frame: Within 3 months of intervention implementation. 
 
Secondary Outcome Measures 
 
A. Reach 
• 
Title: 1.00 - The percentage of providers prescribing ADT for prostate cancer sent an information 
sheet who did not opt out of the study. 
• 
Description: The percentage of providers in the study prescribing ADT for prostate cancer sent an 
information sheet who remained in the study. 
• 
Time frame: Within 6 months of intervention.  
 
B. Penetration 
• 
Title: Percentage of SC intervention clinic notes assigned to providers that were signed.  
• 
Definition: Percentage of clinic notes assigned to ADT providers by the study team that were 
successfully used by providers (signed and became part of EMR). 
• 
Time frame: Within 6 months of intervention. 
 
• 
Title: Percentage of OR intervention order checks justified. 
• 
Definition: The number of low-value ADT orders with justification / the total number of low-value 
ADT orders placed. 
• 
Time frame: Within 6 months of intervention.  
 
11 
REGULATORY REQUIREMENTS 
11.1 Informed Consent  
• The AAVA IRB has granted waivers of written informed consent and 
HIPAA authorization for Aim 1 of this study. 
• VA providers and patients will be sent a study Information Sheet and 
verbal consent will be obtained by study staff and interviewers during 
recruitment calls and at the start of the interview. 
11.2 SUBJECT CONFIDENTIALITY  
• Confidentiality will be protected by restricting access to identifiable 
research data to key authorized study personnel only. In particular, data 

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will be stored on VA servers and in study folders that can only be 
accessed by specified study personnel. We will maintain an electronic list 
of potential participants so we can invite them to participate. The digital 
recordings will be stored in electronic files with filenames that indicate only 
generic roles and facility ID. A written verbatim transcript will be created 
for each participant, but all personal identifiers will be stripped from the 
transcript. Subjects will be instructed at the start of the interview to refrain 
from mentioning names of colleagues or from identifying the medical 
center. The transcripts and digital recordings will be stored in access-
limited files in a project specific folder maintained on a VA server behind 
the VA firewall. All study data will be accessible only by approved study 
staff.  
• Data for the Aim 2 DCE survey is collected anonymously. 
• The following UM study team members are also listed on the VA IRB and 
will have access to identifiers: Ted Skolarus, Sarah Hawley, Daniela 
Wittmann, Tabitha Metreger. 
• Access to personally identifiable information is required for recruitment 
purposes, to confirm diagnoses and eligibility and to verify contact 
information. Access to protected health information is required to fulfill the 
Aims of this study.  
• A Certificate of Confidentiality is not required for this study. 
11.3 Unanticipated Problems1 
• Dr. Skolarus will be responsible for reporting all adverse events that might 
arise during the course of the study to the University of Michigan and the 
Ann Arbor Veterans Affairs Health System IRB. Adverse Events during 
this study would likely consist only of breaches in confidentiality. As 
outlined above, precautions have been taken to prevent this. However, 
 
1 The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to subjects or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
• 
unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-
related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics 
of the subject population being studied; 
• 
related or possibly related to participation in the research (in the guidance document, possibly related means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the 
research); and 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or 
social harm) than was previously known or recognized. 
 
An incident, experience, or outcome that meets the three criteria above generally will warrant consideration of substantive 
changes in order to protect the safety, welfare, or rights of subjects or others.   

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should such breaches occur, Dr. Skolarus will report to the UM IRB 
according to the standard reporting schedule listed here: 
https://az.research.umich.edu/medschool/guidance/adverse-event-
reporting.  

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72. Elwyn G, Pickles T, Edwards A, et al. Supporting shared decision making using an Option 
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McVey, R. Merritt. Oxford University Press, 2010. 
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APPENDICES 
Email to Urology Chief 
Email to MCDs 
Provider Information Sheet 
Provider Recruitment and Eligibility Email 
Provider Interview Guide_providers who do NOT use LV-ADT 
Provider Interview Guide_providers who use LV-ADT 
List of VHA facilities 
 
 
Please note: the following recruitment materials will be submitted with a future 
project modification. Patient recruitment activities will not begin until IRB 
approval has been obtained for these materials: 
Patient Recruitment Letter 
Patient Information Sheet 
Patient Recruitment Phone Script 
Patient Interview Guide