Clozapine CHAMPION-ECHO (Center for Help and Assistance for Maryland Prescribers- Improving Outcomes Network Using Extension for Community Healthcare Outcomes); Randomized Educational Study to Improve Clozapine Prescribing Through a Project ECHO Model
Phase: NA
Conditions: Schizophrenia Schizoaffective
Sponsor: University of Maryland, Baltimore

Clozapine CHAMPION-ECHO Educational Study to Improve Clozapine Use 
NCT04325386 
06/09/2025 

CHAMPION PROTOCOL 
 
Contents 
INVESTIGATOR ................................................................................................................................................................... 2 
PROJECT SUMMARY ........................................................................................................................................................ 2 
SPECIFIC AIMS ................................................................................................................................................................... 3 
Aim 1: ................................................................................................................................................................................. 3 
Aim 2: ................................................................................................................................................................................. 3 
Exploratory Aims: ............................................................................................................................................................. 3 
PARTICPANTS AND RECRUITMENT AND RETENTION PLAN ................................................................................ 4 
Participants and Recruitment and Referral Sources................................................................................................... 4 
METHODS ............................................................................................................................................................................. 5 
Overview of the Study Design ........................................................................................................................................ 5 
Randomization Procedures ............................................................................................................................................ 6 
CHAMPION Intervention Condition ............................................................................................................................... 6 
Enhanced Treatment as Usual (ETAU) Condition and Justification ......................................................................... 6 
Medicaid Data and Security ............................................................................................................................................ 7 
Assessments ................................................................................................................................................................... 10 
STUDY TIMELINE ............................................................................................................................................................. 10 
STATISTICAL DESIGN AND POWER ........................................................................................................................... 13 
Primary Outcomes ......................................................................................................................................................... 13 
Specific Aim 1: ............................................................................................................................................................ 13 
Specific Aim 2: ............................................................................................................................................................ 13 
Power ............................................................................................................................................................................... 14 
Hypothesis 1: .............................................................................................................................................................. 14 
Hypothesis 2: .............................................................................................................................................................. 14 
Hypothesis 3: .............................................................................................................................................................. 14 
Hypothesis 4: .............................................................................................................................................................. 14 
Statistical Analyses Overview ...................................................................................................................................... 14 
Missing Data ............................................................................................................................................................... 15 
Multiple Comparisons ................................................................................................................................................ 15 
Analyses for Each Specific Aim and Hypothesis ....................................................................................................... 15 
Specific Aim 1: ............................................................................................................................................................ 15 
Specific Aim 2: ............................................................................................................................................................ 16 
Exploratory Analyses ..................................................................................................................................................... 16 
PROTECTION OF HUMAN SUBJECTS ........................................................................................................................ 16 

 
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CHAMPION PROTOCOL 
Human Subjects Involvement, Characteristics, and Design .................................................................................... 16 
Source of Research Materials ...................................................................................................................................... 17 
Potential Risks and Protections Against Risks .......................................................................................................... 18 
Recruitment and Informational Sheet Details ............................................................................................................ 18 
Potential Benefits of the Proposed Research to Human Subjects and Others .................................................... 19 
Benefits to Maximize Enrollment.................................................................................................................................. 19 
Importance of the Knowledge to Be Gained .............................................................................................................. 20 
Data and Safety Monitoring Plan ................................................................................................................................. 20 
Roles and Responsibilities ............................................................................................................................................ 21 
Reportable Events .......................................................................................................................................................... 21 
Clinical Trials.Gov Requirements ................................................................................................................................ 21 
Inclusion or women, minorities and children .............................................................................................................. 21 
Compensation ................................................................................................................................................................. 22 
     Consultation Center……………………………………………………………………………………………………….………………………………………19 
     References…………………………………………………………………………………………………………………………………………     ………….20-27 
 
INVESTIGATOR 
 
Principal Investigator:    Dr. Deanna L. Kelly, PharmD, BCCPP 
                                           Professor of Psychiatry 
 
 
 
University of Maryland School of Medicine 
 
 
 
Director, Treatment Research Program 
 
 
 
Maryland Psychiatric Research Center 
 
 
 
dlkelly@som.umaryland.edu 
 
 
 
410-402-6861 
 
PROJECT SUMMARY 
 
 
Schizophrenia is one of the leading causes of disability worldwide and the burden of this disease on individual 
health and society at large is substantial (1). While new pharmacological treatments are emerging, no 
treatment for schizophrenia has been found to rival the efficacy of clozapine (2-16). Yet, the number of people 
with schizophrenia who are prescribed clozapine nationally is <5%, despite its recommended use in about 30-
50% of people with treatment-resistant schizophrenia (17, 18). Arguably, clozapine is one of the most 
underutilized evidence-based treatments in psychiatry and optimization of its use could drastically improve 
patient outcomes and lower treatment costs (19-21). Many barriers contribute to clozapine underutilization; 
however, our pilot data and data from others show that lack of prescriber competence to use clozapine  and 
challenging logistics for absolute neutrophil count (ANC) monitoring are two of the greatest barriers to 

 
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CHAMPION PROTOCOL 
clozapine use (22-25). Further, pilot data shows that prescriber self-reported competence in using clozapine 
correlates with their prescription of clozapine. Therefore, without improving competence, changes in 
prescribing of clozapine are unlikely to occur.   
In the last 15 years, a unique, structured and empirically validated tele-mentoring model has emerged called 
Project ECHO (Extension for Community Healthcare Outcomes). ECHO is a “hub” and “spoke” sharing 
network led by an expert academic team (the “hub”) that uses multipoint video-conferencing to conduct virtual 
clinics with non-expert prescribers (the “spokes”) located in areas outside the academic hub site. The use of 
ECHO has been shown to significantly improve best-practice specialty care in sites that lack expertise in a 
variety of disease states (26, 27). Importantly, multiple studies have established its efficacy in improving 
prescriber competence, the “target mechanism” we hypothesize to be linked to increased clozapine prescribing 
(26, 28-30).  
In a randomized controlled design with approximately 26 biweekly sessions over 12 months, we propose to 
test the effectiveness of an ECHO-based intervention for improving the use of clozapine in people with 
treatment-resistant schizophrenia. The sessions will include: 1) active dissemination of knowledge and 
information by an expert “hub” followed by 2) clozapine case presentations and vignettes submitted by the 
“spokes”.  
This intervention, Clozapine CHAMPION-ECHO (Center for Help and Assistance for Maryland Prescribers- 
Improving Outcomes Network using Extension for Community Healthcare Outcomes, will be referred to as 
“CHAMPION” throughout the application. To minimize ANC monitoring barriers and maximize recruitment, we 
will provide Food and Drug Administration (FDA)-approved ANC point of care (POC) monitoring devices to all 
study sites, including those in the control condition (the PI and clinical team has used this previously). We will 
enroll at least 300 prescribers and additional clinical team members (up to 300) from approximately 60 
outpatient mental health clinics (OMHCs) and other treatment sites. Individual prescribers can also enroll. 
Approximately half the sites/individuals will be randomized to CHAMPION and half randomized to enhanced 
treatment as usual (ETAU).  
 
SPECIFIC AIMS 
 
Aim 1:  
To determine the effect of 12 months of CHAMPION exposure on: a) the clozapine prescribing 
practices of prescribers/clinical team; and b) the persistence of their patients use of prescribed 
clozapine. Hypothesis 1: Relative to the prescribers randomized to ETAU, prescribers randomized to 
CHAMPION will significantly increase the proportion of patients in their care who are prescribed clozapine as 
assessed using Maryland Medicaid prescription data. Hypothesis 2: For patients who are prescribed 
clozapine, the patients of prescribers randomized to CHAMPION will exhibit significantly greater persistence to 
clozapine treatment compared to patients of prescribers randomized to ETAU.   
 
Aim 2:  
To determine the effect of 12 months of CHAMPION exposure on prescriber knowledge and self-
reported competence of prescribing clozapine and how those mechanisms of change are associated 
with increased clozapine prescribing and persistence of clozapine use. Hypothesis 3: Relative to the 
prescribers randomized to ETAU, prescribers randomized to CHAMPION will demonstrate significantly 
increased levels of clozapine knowledge and self-reported competence. Hypothesis 4: Prescriber self-
reported competence will mediate the effect of CHAMPION on clozapine prescribing and persistence.  
 
Exploratory Aims:  

 
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CHAMPION PROTOCOL 
To determine the effect of patient race in moderating the effect of 12 months of exposure to 
CHAMPION on the clozapine prescribing practices of prescribers and objectively measured medication 
persistence of their patients prescribed clozapine. We will also examine the impact of site and 
participant characteristics as well as attendance on outcomes.  
 
In summary, if demonstrated to be efficacious, CHAMPION will have significant public impact by increasing the 
use of clozapine. This project addresses key NIMH priorities including improving access to evidence-based 
practices, focusing on disparities, and including innovative technologies. This project features a novel 
intervention, a renowned team of experts and the support of local and national organizations positioned to 
ensure its success.   
 
 
PARTICPANTS AND RECRUITMENT AND RETENTION PLAN 
 
Participants and Recruitment and Referral Sources 
 
We will complete all recruitment and enrollment prior to initiation of the intervention. We will enroll 300 
prescribers (physicians, nurse practitioners, physician assistants or other doctoral level providers approved to 
prescribe clozapine in the State of Maryland) as well as other team members at the sites (up to 300). We will 
recruit prescribers/clinical team from State of Maryland Outpatient Mental Health Centers (OMHC) and other 
clinical sites. We plan to attempt to enroll approximately 2 OMHCs by county; overall, we plan to enroll 
approximately 60 sites (approximately 5 prescribers/clinical team per site) with 30 in the CHAMPION group 
and 30 in the enhanced treatment as usual (TAU) group with N=150 prescribers per group. We may have a 
few more or less sites to reach the 300 prescriber target for the primary outcome and up to 600 total.  We will 
allow individual prescribers to enroll if they are not affiliated with an enrolled study site, however they will not 
receive the ANC Point of Care Device, laptop computer, or site stipend.  They are eligible for the individual 
compensation and education benefits if applicable. 
 
Inclusion and Exclusion Criteria 
Sites that enroll will have approximately 5 prescribers per site. Other members at the site can enroll. The 
specific inclusion/exclusion criteria for prescribers includes: 
1) Located at a site in the State of Maryland with at least 3 prescribers at the site.   
2) Prescribers/clinical team should be licensed in the State of Maryland and have prescribed 
antipsychotics previously.  
3) Between the ages of 22 and 85 years old 
4) Willing to agree to try to participate in the CHAMPION sessions 
5) Willing to participate in pre- and post-testing 
6) Individual prescribers not located at an enrolled study site may enroll with modified benefits. 
 
All sites will benefit from participating in the study, as we will provide free of charge the newly FDA Class II 
approved Point of Care (POC) monitoring device for absolute neutrophil counts (ANC). We have partnered with 
the Behavioral Health Administration (BHA) at the State of Maryland Department of Health and are working 
with the State Core Service Agencies (CSA) and the Clozapine Authorization and Monitoring Program (CAMP) 
to ensure that we are aware of all clinics in the State that prescribe clozapine and they all receive information 

 
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CHAMPION PROTOCOL 
and encouragement from the State of Maryland to participate in the proposed study. We also have access and 
relationships with the clinics due to our establishment of the Maryland Psychiatric Research Center (MPRC) 
Practice Research Network (PRN).   
The steps for recruitment are as follows: 
1) We will develop recruitment materials and flyers describing the study benefits and details to be 
submitted to IRB. We will advertise on our Facebook and Website pages for the TRP only after IRB 
approval of advertisements. We will also advertise by Twitter, send an email to the Maryland 
Psychiatric Association, Department of Psychiatry Newsletter and other outlets in the State, only with 
IRB approval, for the ads.  We will be using #CHAMPION as our hashtag symbol. 
2) BHA, the CSA and our research team will do outreach to clinics as well. We will stay in contact with the 
clinics and personnel once we get them enrolled. 
3) All clinics that agree to participate will receive the POC device; training on how to use the device; and 
access to our REDCap data collection system, which will allow them to participate in two study 
assessment queries, separated by 12 months, on their knowledge and self-reported competence of 
using clozapine.   
4) All groups will be randomly assigned to receive the CHAMPION intervention or be an enhanced 
treatment as usual (ETAU) (control site). If they are assigned to CHAMPION, then they will agree to 
participate in a one-year biweekly (26 session) tele-mentoring program (approximately 1.25 hours each 
session. They will receive AMA Category 1 PRA CME credit hours (or corresponding CEU) for each 
session they attend and take the evaluation post-test for the session. CME participants will have to 
complete an evaluation to receive the credits. This process will be automated, and the University of 
Maryland Department of Faculty Affairs is partnering with us to provide the CME credits. 
We will attempt to enroll OMHCs and clinics from all geographic regions and counties in the State of Maryland. 
Our goal is to enroll at least two OMHC clinics per county (one randomized to each condition). If we do not get 
OMHC representation from all counties, then we will open recruitment up to other clinics to apply for 
participation in the study. We will place an emphasis on underserved and rural areas of Maryland including 
those with a prominent African-American population; this is a cornerstone to our application. The State of 
Maryland is unique and well suited for studying and focusing on this minority population. We will have a formal 
application process, which will be used to select the clinics. Based on the high demand of getting the POC 
device, the demand for telemedicine for consultation and the demand to get clozapine training (based on our 
pilot data) we will recommend that the clinics and prescribers/clinical team meet the following criteria: 
In our initial outreach/recruitment efforts, we will focus on recruiting clinics from rural counties in order to 
ensure that we have adequate OMHC representation from rural counties. We will complete this initial outreach 
effort in the first nine months. Once we enroll these clinics, then we will open recruitment to clinics in non-rural 
counties.  
 
METHODS 
 
Overview of the Study Design 
 
Our study outcomes are all individual participant outcomes and randomized by sites to ensure we have enough 
Athelas devices to pass out.  We will randomize the individuals by site (N = 60 sites, approximately 3-5 
prescribers per site) randomized controlled effectiveness trial to assess if CHAMPION (150 prescribers) 
significantly increases clozapine prescribing, persistence, knowledge and self-reported competence compared 
to Enhanced Treatment as Usual (ETAU, N = 30 sites, 150 prescribers). We may have participants from more 

 
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CHAMPION PROTOCOL 
than 60 sites and more than 300 enrollments to reach the target of 300 prescribers. In addition, individual 
prescribers signing up will also be randomized to the two conditions. . 
 
We will assess provider level outcomes (knowledge and self-reported competence) immediately before and 
after the intervention (12 months) and patient level prescribing outcomes (from administrative data) for the year 
prior to the intervention, during the year of the intervention and for the year following the intervention. This will 
allow us to estimate the baseline level of clozapine prescribing, the impact during the intervention year and the 
sustainability of any effects during the year after the intervention is no longer active.  
 
Randomization Procedures 
 
Randomization will occur at the site level for enrolled sites and individual level for prescribers not at enrolled 
sites. There are NO site outcomes, this randomization allows for the devices to be given to providers in groups 
to ensure all groups can get a device.  The randomization schedule will be created by the study statistician 
using a randomized block design (block = rural/urban/suburban). We will randomly assign each 
clinic/prescriber into one of the two study groups using a 1 (CHAMPION) to 1 (ETAU) assignment. Random 
assignment will occur after agency recruitment and prescriber baseline assessments are completed. 
 
CHAMPION Intervention Condition 
 
Sites included in the CHAMPION will receive the POC ANC device to use during the 12-month study (and for 
12 months post intervention) as well as access to clozapine consultation as described in the ETAU condition 
for 12 months during the intervention and 12 months follow-up. In addition, approximately half of the 
CHAMPION sites/individuals will receive biweekly ECHO telementoring education sessions. These 
telementoring sessions will occur simultaneously for all intervention sites and may consist of one or two 
identical sessions during the week. Each session will consist of a 15-20-minute didactic period on specific 
topics which will be followed by approximately 1 hour of site supplied case and patient consultations. All the 
prescribers and the clinicians at the sites are welcome to attend the online session even if they enroll for study 
inclusion or not. Attendance will be tracked by the study team at the beginning of each session. 
 
The session will conclude with a discussion and question and answer period. At the end of the session the 
team of clozapine experts will provide a written summary of treatment recommendations regarding the cases. 
Each CHAMPION session will have at least one clozapine expert delivering the didactic topic and at least 2 
additional clozapine experts providing mentoring for the case-based consultation session. This will allow us to 
call upon the diverse group of experts in our proposed study personnel. We will complement the sessions with 
dissemination of any relevant publications, toolkits and tips.  
 
Enhanced Treatment as Usual (ETAU) Condition and Justification 
 
Clinics randomized to ETAU will receive (1) a Point of Care (POC) device to use during the 12 months 
intervention for ANC monitoring and 12 months post intervention , and (2) access to the MPRC clozapine team 
for consultation and questions during this time period. First, we will provide an Athelas One POC monitoring 
device, which has just received FDA class II clearance, to each clinic in order to provide easy and immediate 
results for the ANC and other white blood cell count results needed for the mandatory FDA monitoring 
requirements associated with clozapine prescribing. We have installed the device and provided training on its 
use in 3 sites; these sites have performed over 220 ANC measurements using this novel technology. The 
Athelas One POC monitoring device provides ANC results using a small drop of capillary blood drawn by a 
quick fingerstick and drop placed on a slide (unlimited supply to be supplied for free); the fingerstick can be 
done in the clinic and mitigates against having to refer the patient to another site for their blood draw. The 

 
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CHAMPION PROTOCOL 
device images and automatically analyzes the cells morphologically with machine learning and pathologist 
oversight, and then generates a final count report, which is highly correlated to national reference laboratory 
values For the ease of each prescriber and healthcare team, the returned ANC values can be entered 
automatically into the FDA mandated Clozapine Risk and Mitigation Evaluation System (REMS), which is the 
required and often cumbersome system of reporting the weekly ANC values. All sites will receive a laptop that 
can receive the ANC result with a simple log-in to the website and secure password. We will have the study 
coordinator (already familiar and using Athelas One) to set up the device at all of the sites and be available for 
any troubleshooting or questions. Athelas has also pledged to be available to help with all devices. The 
devices will be available for routine use for all clozapine patients during the study. There will be no charge for 
the devices and Athelas will help with Medicaid billing to receive payment for time of use. Individual prescribers 
enrolling and not affiliated with a site will not have access to the device. Following the conclusion of the 
observation period in August of 2023 we will work with the sites to transition the Athelas devices to their own 
custody and will work with sites to make arrangements with Athelas 
       
Second, we will disseminate a centralized MPRC phone number and email contact to all 60 sites and individual 
prescribers for questions and consultative questions for clozapine starting at the CHAMPION randomization 
and continuing throughout the entire study period. At the conclusion of the entire grant funding we will post all 
ECHO sessions and make them available to the ETAU sites. 
 
Medicaid Data and Security 
 
We will be getting Medicaid Data from the Hilltop Institute www.hilltopinstitute.org  
The Hilltop Institute at the University of Maryland, Baltimore County (UMBC), is a non-partisan health research 
organization dedicated to advancing the health and wellbeing of people and communities. Hilltop conducts 
research, analysis, and evaluations on behalf of government agencies, foundations, and nonprofit 
organizations at the national, state, and local levels. Hilltop is committed to addressing complex issues through 
informed, objective, and innovative research and analysis. 
Formed in 1994 as the Center for Health Program Development and Management in a unique collaboration 
with the Maryland Medicaid program, Hilltop was instrumental in the 1997 launch of HealthChoice, Maryland’s 
Medicaid managed care program. Since its inception, Hilltop has maintained a nationally recognized 
partnership with the Maryland Department of Health to analyze state health policies and develop solutions for 
the Maryland Medicaid program.  
Hilltop developed and manages a data warehouse containing Maryland’s Medicaid claims and encounter data. 
Hilltop processes and warehouses data on service utilization by more than 1,200,000 Medicaid enrollees and 
Medicaid payments totaling over $7 billion. Hilltop currently processes and archives more than 12 million 
records each month. These records are used to generate standardized and customized reviews of Maryland’s 
Medicaid system. Among Maryland Medicaid enrollees are approximately 105,000 individuals who are also 
eligible for Medicare (Medicare-Medicaid enrollees). Since 2002, CMS has provided Hilltop with Medicare 
claims corresponding to those Medicare-Medicaid enrollees, which Hilltop refines and maintains. Hilltop is also 
expert in linking Medicare and Medicaid data to study issues that affect Medicare-Medicaid enrollees.  
The Hilltop institute maintains private and secure files and will be transferring requested data to the University 
of Maryland School of Medicine, Division of Services Research only through a secure file transfer protocol, 
Accellion. All data kept at the Division of Services Research are strictly confidential and secure.  
 

 
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CHAMPION PROTOCOL 
Data Elements will include:  
We will begin to collect data retrospectively for one year prior to the start of the CHAMPION intervention. This 
is slated to occur in approximately June of 2021 for the period of December of 2019 onward. We will collect 
data until one year after the CHAMPION ends or around June of 2023.  Thus, we will be examining Medicaid 
data for a period of December 2019 to December of 2023 approximately.  
The elements we will be collecting include collecting Maryland Medicaid recipient data for those who are over 
the age of 18. We are asking for data on those with a 295 diagnosis so we can examine antipsychotic and 
clozapine treatment. We anticipate approximately 350,000 antipsychotic prescriptions and 75,000 clozapine 
prescriptions annually. 
We will have participant ID to link records for examining adherence and persistence. Thus, we will have 
Medicaid enrollment and demographic data, inpatient and outpatient claims data, other professional fee 
services, pharmacy data and provider information. The provider linkage is needed to link the knowledge and 
competence testing to rates of prescribing.  Specifically, this includes: 
 
Date of Service 
Dates for prescription 
Drug Name 
Identification of antipsychotic name 
Drug Formulation 
Route of administration of type of 
antipsychotic 
Strength 
Dose of the Antipsychotic 
Quantity 
Number dispensed  
Participant’s Medicaid ID 
Identification number of the patient 
Claims data 
Inpatient and Outpatient services for 
295 diagnosis 
Age 
Age of patient 
Zip code 
Zip code where living 
Race 
Race  
Prescriber ID 
Prescriber identification number 
Prescriber zip code 
Zip code of where the prescriber 
resides 
Prescriber county 
County where the prescriber resides 
 
 
HMIS Data and Security 
 
        

 
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CHAMPION PROTOCOL 
In a randomized controlled design with 26 biweekly sessions over 12 months, we were funded by the 
National Institute of Mental Health (NIMH) to test the effectiveness of an ECHO-based intervention for 
improving the use of clozapine in people with treatment-resistant schizophrenia. This intervention, Clozapine 
CHAMPION-ECHO (Center for Help and Assistance for Maryland Prescribers- Improving Outcomes Network 
using Extension for Community Healthcare Outcomes, is referred to as “CHAMPION.”   We are measuring 
antipsychotic prescribing before, during and after the intervention period as the primary study outcome. 
Statewide Medicaid data from Maryland is the prime source of prescribing data for this study.  
 
We completed recruitment of study sites/prescribers/clinicians in 2021 and included approximately 278 
prescribers. The intervention concluded in August of 2022. We have an existing Data Use Agreement for the 
Medicaid data component with the Hilltop Institute and MDH and that data collection is progressing as planned.  
 
       We included clinics and hospitals from around the State of Maryland, and staff and prescribers from State 
of Maryland inpatient psychiatric facilities also participated.  Inpatient prescribing data are not contained in 
Maryland Medicaid prescription data. Therefore, we must obtain inpatient prescribing records for 
antipsychotis (not protected health information) from the state hospital facilities via the Hospital 
Management Information System (HMIS).   
 
SCOPE OF DATA: 
 
Time Period:  
We are requesting hospital prescription records of antipsychotic prescribing from HMIS and Eastern Shore 
Hospital (outside HMIS)) for the dates of January 1, 2020 to July 31, 2023. This will enable us to examine 
prescribing patterns during three time periods:  
 
Pre-intervention period: January 1, 2020-July 31, 2021 
Intervention period: August 1, 2021 – July 31, 2022 
Post-intervention period: August 1, 2022 – July 31, 2023 
  
Variables and Acquisition: 
The variables we are requesting include those in the following table and represent NO protected health 
information (PHI). HMIS personnel will code patient name, prescriber name and date of birth to client ID, NPI 
number and age, respectively. Instead of prescriber names we want to receive the prescriber NPI which will 
also enable a linkage to the Medicaid data we’ve already obtained (separate approval and data use 
agreement). NPI numbers are not considered protected health information (see 
https://npiregistry.cms.hhs.gov/search). We also do not want to receive individual patient names though if there 
are Medicaid identification number we would want that.   
 
HMIS Variable  
Eastern Shore Variable* 
Client ID and ANR# and Medicaid ID if applicable 
(do not want patient name) 
Entity name 
SS# 
Sex 
Gender (M/F) 
Admission Date 
Admiss Date 
Age (recoded from DOB) 
Age (recoded from DOB) 
Start date of Medication 
Start date and order date 
DC date of Medication 
 
End date of Medication  
Stop date 
Gen name 
 
Strength 
 
Drug form 
 
Sig 
Sig comment 

 
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CHAMPION PROTOCOL 
Admin qty 
 
Prescriber NPI (Coded from prescriber name) 
Prescriber NPI (Coded from Entity name (doc)) 
DH date (discharge date) 
DH date 
Location 
 
Inst (Institution) 
 
Diagnosis 
 
Race 
 
*Eastern Shore Hospital has different variable names 
 
Data Storage and Protection: 
No PHI will be sent. All downloaded data will be stored at the University of Maryland Division of Psychiatric 
Services Research on a virtual computer server maintained by Information Technology staff who provides 
these services for the University of Maryland School of Medicine, Department of Psychiatry. We have a 
Certificate of Confidentiality from the Federal Government that protects all research data from subpoena.  
 
Approvals: 
We have received UMB and MDH approval to collect these variables from an amendment to a fully 
approved IRB approved study for the collection of human subject data. We will send data to a team 
member with a Maryland.gov email address and no data will be shared outside the research team.  
Other Data: 
 
We will also collect deidentified prescribing data from Gladstone as they do not participate in Medicaid or 
HMIS. The same security provisions as above will apply. 
 
Assessments 
 
We will be collecting data before and after the 12- month CHAMPION.  The assessments include: 
1. Demographic, degree, NPI number and general information about practice and education (all 
participants, baseline only) 
2. Multiple Choice Questions on clozapine knowledge (all participants) 
3. Self-reported competence for clozapine use (prescribers only) 
4. Survey on intervention (all participants, endpoint only) 
 
STUDY TIMELINE 
 
Our grant proposes approximately 4 years of study. In the first year, we will recruit all the study sites, set up the 
CHAMPION sites and finalize the CHAMPION intervention.  Additionally, we will capture Medicaid data for a 
one-year period. In the second year, we will start the CHAMPION intervention, which will run for one full year. 
We will complete the administration of the intervention in the second quarter of the third year. In years 2 and 3, 
we will collect Medicaid data for the 12 months following the intervention, then initiate analyses. The schematic 
below details the approximately study timeline visually. 
Year 
 
Year 1 
Year 2 
Year 3 
Year 4 
Quarter (Q) 
Q1 Q2 
Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 
Q4 

 
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CHAMPION PROTOCOL 
Set up Medicaid 
Contract with Hilltop 
Institute 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Set up 
videoconferencing and 
iECHO  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Team Members 
trained on Project 
ECHO in New Mexico, 
ensure they have 
reviewed our materials 
and methods   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Validate the questions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initial meetings with 
BHA and OMHCs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Organization of Project 
ECHO team 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Project ECHO team 
meetings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meet with OMHCs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRB approvals 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Period of Medicaid 
Data Collection 1 (After 
IRB approval) (Aim )1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Website/Portal 
Development for 
REDCap 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meet with the 
SAMSHA/APA group  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uploading clozapine 
materials, guidelines 
into iECHO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Advertising materials, 
BHA and CSAs send 
info 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meet with all OMHCs 
and prescriber groups  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Send letters and 
emails to all 
prescribers/clinical 
team within CSA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Install POC devices 
and training 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Provide ongoing POC 
help 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECHO team available 
for phone or email 
consultation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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CHAMPION PROTOCOL 
Enrollment 300 
prescribers/clinical 
team and Pre-testing 
ECHO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECHO Lecture series 
announcement 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization by 
Statistician 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
OK to begin from 
ECHO headquarters 
and final check of all 
details 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of 
Baseline Knowledge 
and Self-Reported 
Efficacy  (Aim 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clozapine 
CHAMPION ECHO 
Intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Travel to national and 
regional meetings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis of Medicaid 
Data for primary aim 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis of Secondary 
and Exploratory aims. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Archive ECHO lectures 
for website at end of 12 
months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Period of Medicaid 
Data Collection 2 (Aim 
1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post Testing on 
Knowledge and Self-
Reported Competence 
(Aim 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meetings with 
NASHMPD  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis of Project 
ECHO Post data 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Make videotaped 
ECHOs available to all 
participants once 12- 
month Medicaid data 
completed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
National Webinar with 
NASHMPD and APA 
CSS SMI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Submit symposium 
abstract to national 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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CHAMPION PROTOCOL 
meetings, e.g. IPS, 
SIRS 
Data Repository 
Submission 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STATISTICAL DESIGN AND POWER 
 
Primary Outcomes 
 
Specific Aim 1: The primary outcome examines Maryland Medicaid (and HMIS for inpatient) prescription data, 
which will be used to assess the increase in the proportion of patients treated with clozapine for those in the 
care of prescribers/clinical team randomized to the CHAMPION relative to the ETAU condition. We will also 
examine persistence in the use of clozapine for patients who are prescribed clozapine under the care of 
prescribers/clinical team randomized to CHAMPION compared to prescribers/clinical team randomized to the 
ETAU. The specific outcome assessments using Medicaid data include: 
 
a. Proportion of clozapine prescriptions: Clozapine prescribing rates will be calculated from Medicaid 
prescription data. National Prescriber Identification (NPI) numbers will be used to identify the antipsychotic 
prescription records for each prescriber in the study. The denominator will be the number of unique individuals 
with a diagnosis of schizophrenia who had at least 1 prescription for an antipsychotic during each time period 
(12 months prior to start of study, during active study participation, and 12 months after the intervention period 
ends). For each individual in the sample, an indicator will be created that reflects whether the person had any 
prescription for clozapine during each of the time periods.  
 
b. Persistence to clozapine: Incident episodes of clozapine prescriptions will be identified by a 90 day 
look back period to identify a new episode of care. Persistence will be measured as the duration of the 
clozapine episode (in days) from the date of the first prescription record until the first gap of more than 45 days 
between prescriptions. Prescribing gaps will be calculated by first adding the days' supply to the dispensing 
date of each prescription to identify the date the prescription should be exhausted. Days that the patient is 
hospitalized will not be included in the calculation of episode duration. The first gap in prescribing of 46 days or 
more will be considered a discontinuation of the medication. An episode will only be right censored at the study 
endpoint, otherwise an episode can continue into the next time period. If a person has more than 1 episode of 
clozapine use during any time period, we will select the first episode. 
  
 
Specific Aim 2: We will measure two educational outcomes: self-reported competence of prescribers/clinical 
team in using clozapine and knowledge associated with clozapine treatment. These will both be measured 
before and after the 12-month intervention period. These outcomes have been selected, because they are 
measurable and pilot data has already established that prescribers/clinical team will rate competence and 
answer questions on clozapine knowledge. In addition, we will pilot-test all questions and review the self-
reported competence measure prior to the administration of the CHAMPION intervention.  
 
a. Competence: Our measurement of competence will be based upon self-report assessment guided by 
Bandura’s theory of self-efficacy (2, 3) and we are using a definition of competence as “the perceived self-
efficacy rating of one’s judgment to use clozapine”(2, 4). We will use a Visual Analog Scale (VAS) (0-100 mm) 
will serve as the primary outcome. Self-reported competence ratings will be evaluated for the overall use of 
clozapine and for each of the CHAMPION session topic areas.  The VAS format has been found to be superior 

 
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CHAMPION PROTOCOL 
to using a standard Likert scale for self-reported competence evaluation (2). Self-efficacy ratings of 
competence have been shown to be increased in a mental health ECHO model (6); are recommended as a 
measure for approaching measurement of practice outcomes (7); and, when using VAS to measure self-
efficacy competence, have been found to be a reliable and valid measure for this construct (8-10).   
 
b. Knowledge: We will use multiple-choice questions (MCQ) to assess knowledge. The knowledge-
based test questions will consist of 52 questions that will cover 2 questions per 26 topic areas and will conform 
to best practices and guidelines for design of the questions (11). MCQ have been used to assess knowledge 
with ECHO models (6, 12) and are known to be a reliable and valid measure for measuring knowledge (11). 
The total score will range from 0-52 correct answers.  
 
Power 
 
Hypothesis 1: Considering the intent to treat (ITT) approach to analyses, we will be able to assess 
administrative data prescription records for all prescriber participants regardless of their level of participation in 
the CHAMPION intervention sessions or other research data collections efforts. Missing data will be a concern 
only for those time periods where prescriber participants were not practicing in the Maryland public health 
system (before or after the intervention time period). We assume that we will have administrative data records 
from at least 85% of the prescribers/clinical team across all time points. We calculated the needed sample size 
using PASS version 13 (13) for independent proportions in a clustered-randomized design with the following 
specifications: alpha-level = .05, power = .80, effect size (h) = .39 (small to medium) and ICC = .01 
(prescribers/clinical team nested within site). Effect size is based on estimating an 11% improvement in the 
rate of clozapine prescribing in CHAMPION; e.g. a 4% rate of clozapine prescribing in the ETAU group and a 
15% rate in the CHAMPION condition. The required sample size is 254 based on clusters of 4-5 
prescribers/clinical team per site.  
 
Hypothesis 2: Even with a conservative estimate of the number of patients per prescriber on clozapine, a high 
ICC (.20) for patients nested within prescriber, and a small effect (d = .3), the power to detect differences in 
clozapine persistence between conditions is greater than 95%.  
 
Hypothesis 3: Although the variables for hypothesis 3 are normally distributed, the specifications are the 
same and the power calculations are identical to those noted above. Based on literature described in Approach 
section 10 above, we anticipate changes in knowledge and competence to be large (>.8).  
 
Hypothesis 4: Using the values above and the SAS macro from O’Rourke and MacKinnon (14),  the power to 
detect indirect effects (mediation) will be greater than .80 when using the bias corrected bootstrap procedure 
when paths a and b are at least 0.3 (small to medium effects anticipated).  
 
 
 
Statistical Analyses Overview   
 
All data will be screened for errors using frequency and contingency tables and univariate and bivariate plots 
before formal analysis. These informal plots and summaries will allow us to be cognizant of data distribution 
characteristics before building regression models. We anticipate that our dependent variables will either have a 
distribution that is relatively bell-shaped or can be transformed to be relatively bell-shaped. Site will be included 
in all models as a random effect. Prescriber is nested within intervention arm, by design, and will be specified 
as a random effect in all analyses that include patient level data. The intercept will be designated as random to 
account for the non-independence across time point when appropriate. SAS PROC MIXED or GLIMIX will be 
used for the analyses described below (15). 

 
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Missing Data 
 
All analyses will be conducted within an ITT framework. As described above, missing data for hypotheses 1 
and 2 will be limited due to the use of Medicaid prescription records for those outcomes. For hypotheses 3 and 
4, we will compare the baseline characteristics of the prescribers/clinical team who drop out prior to completing 
the 12-month assessment to those prescribers/clinical team who do complete the assessment. If necessary, 
we will investigate how estimates/results change over a range of several plausible assumptions regarding the 
missing mechanism together with multiple imputations to most accurately capture existent random variability.  
 
 
Multiple Comparisons 
 
To control for Type I errors, we will use the sequential Bonferroni-type procedure for dependent hypothesis 
tests of Benjamini and Hochberg (16) to control the false discovery rate at 5%. The false discovery rate is the 
expected (or on average) proportion of falsely rejected hypotheses. This procedure will be applied to the family 
of tests on the multiple associated measures corresponding to each aim.  We will also control for if randomized 
to site or individual. 
 
 
Analyses for Each Specific Aim and Hypothesis 
 
Specific Aim 1: To determine the effect of 12 months of exposure to CHAMPION on the clozapine prescribing 
practices of prescriber participants and the objectively measured medication persistence of the patients 
prescribed clozapine.  
 
Specific Aim 1, Hypothesis 1: Relative to the prescribers/clinical team randomized to the ETAU condition 
(POC and consultation), prescribers/clinical team randomized to CHAMPION will significantly increase the 
proportion of patients in their care who are prescribed clozapine, as assessed using Maryland Medicaid 
prescription data. Clozapine prescribing will be measured as the proportion of patients with any clozapine  
prescriptions (See Approach 5a). We will use a mixed-effects, 2-level model generalized linear mixed model 
(SAS Proc GLIMIX, log link) with percent adherence as the dependent variable and treatment group 
(CHAMPION/ETAU), time (pre-CHAMPION year (t=1), CHAMPION year (t=2), follow-up CHAMPION year 
(t=3), and time by treatment group as the independent variables of interest. However, since the main outcome 
will be calculated at t=3, a contrast statement, within the context of the full model, will be used to compare the 
two treatment conditions at t = 3, controlling for baseline, to test the primary hypothesis with a random site 
effect to account for intra-site correlation (ICC). The test of hypothesis 1 will operationally be the test of 
whether the coefficient of the CHAMPION/ETAU condition term is significantly >0 (two-sided test) at time t = 3. 
Post hoc analyses will use the same model to test effects at t = 2.  
 
Specific Aim 1, Hypothesis 2: For patients who are prescribed clozapine, the patients of prescribers/clinical 
team randomized to CHAMPION will exhibit significantly greater persistence to clozapine treatment compared 
to patients of prescribers/clinical team randomized to the ETAU condition, as assessed using Maryland 
Medicaid prescription data.   Persistence (Approach Section 5b) will be measured as number of days of 
clozapine use. An episode will be identified as having begun during the 1 year prior to CHAMPION, during 
CHAMPION, or in the year after CHAMPION ends. A person can only have one episode in each of the time 
periods. We will use a generalized linear mixed-effects, 3-level model (SAS Proc GLIMIX, Poisson link), with a 
random site and a random prescriber effect to account for within site and within prescriber correlation (ICC). 
The longitudinal portion of the model will be treated as described for hypothesis 1. The test of hypothesis 2 will 

 
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CHAMPION PROTOCOL 
operationally be the test of whether the coefficient of the CHAMPION/ETAU condition term is significantly 
greater than zero (two-sided test) at time 3. Post hoc analyses will use the same model to test for effects at 
time 2.  
 
Specific Aim 2: To determine the effect of 12 months of exposure to the CHAMPION intervention on the 
knowledge and self-reported competence of prescribers/clinical team prescribing clozapine and how those 
mechanisms of change are associated with increased clozapine prescribing and persistence. 
 
Specific Aim 2, Hypothesis 3: Relative to the prescribers/clinical team randomized to the ETAU condition, 
prescribers/clinical team randomized to CHAMPION will demonstrate significantly increased levels of 
knowledge (correct number of MCQs) and self-reported competence (mean score on 0-100 mm VAS). 
Knowledge and competence are continuous measures that can be assumed to be normally distributed. 
Transformations will be used if necessary. They will be measured at two time points (baseline and end of the 
1-year CHAMPION. A General Linear Mixed Model (Proc MIXED) will be used to estimate the effects of the 
two groups on change in knowledge and competence with site as a random effect. The test of hypothesis 3 will 
operationally be the test of whether the coefficient of the CHAMPION/ETAU condition term is significantly 
greater than zero (two-sided test) at the post CHAMPION time point controlling for baseline. In exploratory 
analyses, we will examine individual competence scores related to outcomes as above while controlling for 
multiple comparisons. 
 
Specific Aim 2, Hypothesis 4: Prescriber self-reported competence will mediate the effect of the CHAMPION 
on clozapine prescribing and persistence. A separate model will be used for each outcome. The independent 
variable will be group assignment, the dependent variable will be rate of clozapine prescribing during the year 
following CHAMPION and the persistence of clozapine episodes, and the mediator will be the overall self-
reported competence score (0-100 mm VAS) measured at 12 months, controlling for baseline. We will use the 
product of coefficients approach to test mediation. The rationale behind this method is that mediation depends 
on the extent to which the independent variable changes the mediator (i.e., path a), and the extent to which the 
mediator affects the outcome variable (i.e., path b). The PROCESS (17) macro for SAS will be used to 
generate 95% bias corrected confidence intervals for the relative indirect effects and other parameters.  
 
Exploratory Analyses 
We will examine the role of race in moderating the effects of CHAMPION. To determine whether there was 
differential benefit of the program for the AA patients, race and interaction terms (time by race) will be added to 
the models described above. Despite our previous work, it is possible that increases in prescribing will not 
occur similarly between AA and Caucasian patients, however, we will use data collected to adapt future 
iterations of the topics related to AA if we do not see similar improvements in prescribing. Specifically, we will 
examine the two competence questions related to AA and ascertain the relationship of these specific measures 
to prescribing for AA and Caucasian patients.  We will also look at other variables by site and patient that may 
contribute to outcomes and will analyze the other clinicians and examine.  
We will also explore the satisfaction of the POC device to clozapine prescribing. 
 
PROTECTION OF HUMAN SUBJECTS 
 
Human Subjects Involvement, Characteristics, and Design 
 

 
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We anticipate including a total of 300 individual prescriber participants as our target enrollment but also can 
enroll up to 300 clinical team for the secondary analyses  at approximately 60 outpatient Mental Health Clinics 
(OMHC) in the State of Maryland for the one-year intervention versus enhanced treatment as usual (TAU) 
(control) (1:1 randomization; 30 sites and 150 individual prescribers per group).  This would include up to 600 
people enrolled in the study. Additionally, individual prescribers not located at study sites can enroll in the 
study with limited benefits. 
All research team members involved in this study are required to receive training in the protection of human 
subjects. This includes both Good Clinical Practices at University of Maryland and the Collaborative 
Institutional Training Initiative (CITI).  All work with human subjects (State of Maryland clinicians) will be 
conducted by the Principal Investigators and study team at the Maryland Psychiatric Research Center (MPRC) 
and its affiliated team.   
 
Source of Research Materials 
 
Project ECHO has an application available for tracking some data for standardized data collection and 
programming. We will use iECHO, a teleECHO clinic management application that is provided by the 
University of New Mexico to streamline information about clinic participation, reference material, continuing 
medical education materials (CME), etc. iECHO is the web-based, proprietary teleECHO program 
management software and database developed and managed by the ECHO Institute. Due to its key role in 
tracking the movement, iECHO usage is mandatory for partners conducting Project ECHO activities. Non-
exclusive right and license to use iECHO in conducting Project ECHO activities is provided to each partner at no 
cost per the Project ECHO Intellectual Property Terms of Use Agreement. The software will specifically 
organize, manage, track, and report on the programmatic components of our Clozapine CHAMPION ECHO. 
iECHO is not designed to store Protected Heath Information (PHI) and PHI will never be entered into iECHO. 
The specific data collected includes program administrative data, attendance records for participants and 
facilitators, case presentation metrics, didactic presentations, and program documents. iECHO organizes data 
into 4 primary categories: organizations, contacts, programs, and resources. 
Additionally, prescriber self-reported competence and knowledge assessments will be completed and entered 
into a secured web-based database to which all prescribers/clinical team will be granted access through a 
secure link in REDCap. Prescribers/clinical team will be given access to enter the system through a secure 
remote, web-based portal. Once in the system, they will be able to access the informational sheet They will 
also complete the baseline and 12-month Multiple Choice Questions (MCQ) and the Clozapine Competence 
Visual Analog Scale (VAS) assessments. This system will be backed up by routine project-copy and 
downloaded as a structured .csv file on a monthly basis. Each account will have a secure login and password 
and a centralized person from the Education Core to be available to answer and help with all login and data 
entry queries. 
Additionally, for those participating in CHAMPION, we can administer the session evaluations needed to earn 
CME (or CEU) credits. We will include here the link for the Cloud CME assessments that may be earned at 
each of the 26 sessions (http://cloud-cme.com/). 
We will be collecting demographic and some basic information on training and employment from 
prescribers/clinical team.  We will plan to collect 1) current age, 2) current employment status, 3) current 
educational attainment and type of practitioner, 4) sex, 5) years in practice, 6) ethnicity, and other demographic 
variables related to education and practice.  We will collect contact information and will specify in the 
informational sheet that we will be sending reminders and information by email, phone or text. 

 
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CHAMPION PROTOCOL 
All forms are identified within this database by a unique participant ID number, participant initials, protocol ID 
number and acronym, together with the protocol phase and visit.  The protocol data collection schedule is kept 
in a database table and is used to monitor the progress of participants through the protocol, missing 
assessments, and other protocol deviations during the study.  Data entry screens incorporate range checks or 
lists of valid responses for each item.  Prescriber confidentiality is maintained by restricting study data access 
to specified study personnel.  Most authorized personnel will have read-only access and write/edit access will 
be restricted to data entry and data management staff assigned to the study.  An electronic audit trail records 
all changes to the database once data have been entered.  The database resides on a cloud-based server, 
and all server data are backed up several times weekly.  Access to the server from outside the MPRC is 
restricted by a firewall.  Norton Anti-Virus software, updated automatically whenever new virus data files are 
provided, is installed on the server and all computers are linked to the server.  For HMIS data no identifying 
data will be collected outside MDThink. 
Separately, as the primary aim revolves around the change in clozapine prescribing, we will partner with the 
Hilltop Institute to obtain prescriptions of clozapine from prescribers/clinical team located at OMHCs with those 
of prescribers/clinical team from enhanced TAU sites in the State of Maryland.  These datasets will be 
captured in HIPAA-compliant database and transferred securely via Accellion (UMB secure file transfer 
protocol, FTP) to the MPRC and the Division for Psychiatric Services Research at UMB, were they will be 
stored in HIPAA-compliant manner.   
 
Potential Risks and Protections Against Risks 
 
Prescriber participant risks associated with the study are minimal.   
Participation in the CHAMPION sessions:  Participation in the sessions may be tiring or boring.  The sessions 
involve a time component of about 1.25 hours and this could be challenging to busy clinicians or jeopardize 
billing time to clinicians and offices. It is possible prescribers/clinical team may feel embarrassed if they ask 
questions and show their lack of knowledge in front of other prescriber peers.  These are not mandatory. 
Study assessments:  The participant will be reminded that they can refuse to answer any question that makes 
them uncomfortable. Prescribers/clinical team may feel inadequate or embarrassed if they do not know 
answers to the questions. There is a slight risk of breach of confidentiality. All data will be coded with an ID 
number that is unique. All data will be labeled by ID only. Only the study team will have access to the link 
between the ID and participant’s name. Data containing names and personal information will never be included 
in published materials. 
Medicaid data:  There is a slight risk of breach of confidentiality.  All data will be coded with a unique ID 
number. All data will be labeled by ID only and all data will be carefully transferred and stored. Only the study 
team will have access to the link between the ID and participant’s name. Data containing names and personal 
information will never be included in published materials. 
 
Recruitment and Informational Sheet 
 
Recruitment procedures have been described in the Recruitment and Retention Plan above. 
Enrollmentwill occur electronically. The State of Maryland IRB will rely on the UMB IRB for this study. The 
informational sheet contains the risks and benefits of the study, but participants are not required to sign.  The 

 
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CHAMPION PROTOCOL 
participant is free to withdraw from the study at any time. Prescribers/clinical team will be informed in the 
informational sheet that the information they provide will be kept confidential except within the research team 
and how that confidentiality will be ensured. They will be told that their records are filed by a number, not by 
name, and that all records are kept in secure servers or locked files accessible only to research personnel.  
Protection Against Risk: Participants and their data are safeguarded from undue risk by procedures listed in 
the informational sheet which describes how we ensure confidentiality and minimize possible risks associated 
with the study. Each is described below. 
a) Informational Sheet:  This study if considered exempt will not require informed consent. We will, however, 
provide an informational sheet where participants will be advised fully of the study procedures, the amount of 
time required of them, the possible risks and benefits, the voluntary nature of their participation, their right to 
refuse participation without prejudice, their right to terminate participation at any moment without prejudice, and 
the name and telephone number of the Principal Investigator. The informational sheet will state that that we 
may share de-identified subject data with a clinical trial data repository maintained by the National Institute of 
Mental Health, using procedures outlined in NIH NOT-MH-14-015 (http://grants1.nih.gov/grants/guide/notice-
files/NOT-MH-14-015.html).  This repository will allow other researchers access to data from this clinical trial, 
with the assurance that the participant's individual name or other identifying information will not be included in 
the data shared with other researchers. 
b) Confidentiality: In the informational sheet participants will be told that the information they provide, and all 
findings will be kept strictly confidential, with access limited to the research staff, with one exception: state or 
federal regulatory personnel and legal advocacy organizations authorized by law will have access to review 
records. Data collected with identifying information will be stored in locked cabinets or in password-protected 
computer files. Participant identity will not be revealed in the presentation or publication of any results.  All staff 
working on the project will be educated about the importance of strictly respecting patient confidentiality. 
c) Research Procedures: Described above are the potential risks of the research procedures and specific 
measures to minimize each of those risks. Below are general safeguards that will be used to minimize risks. 
These include termination of participants from research participation if it is believed that such participation 
endangers their welfare. 
 
Potential Benefits of the Proposed Research to Human Subjects and Others 
 
Benefits to Maximize Enrollment 
 
Reaching our recruitment goals is paramount to our success. We have many strategies in place to reach our 
participant enrollment goals.  This summarizes the benefits that will be given to maximize the likelihood that 
busy prescribers/clinical team will participate: 
1) All participating sites will receive the POC ANC monitoring device. Athelas, the company will give each 
clinic at no charge and will help with sites for Medicaid billing so that sites can receive compensation for 
patients enrolled 
2) All participating sites and individual prescribers will receive a centralized phone number and email for 
questions and consultation advice from the clozapine team 
3) All participating sites will receive a laptop to ensure that, if randomized, they can participate in the 
telementoring CHAMPION sessions and if not randomized, has a means to complete the baseline and 
endpoint assessments and use for watching CHAMPION sessions when granted permission at the end 
of this study. 

 
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CHAMPION PROTOCOL 
4) All prescriber participants that complete the baseline and 12-month competence and knowledge 
assessments will receive compensation for their time and effort to complete these assessments. For 
other team members participating (nonprescriber) knowledge and competence is optional.   They will 
also receive compensation for time and effort.  
5) All prescribers/clinical team randomized to CHAMPION can get 1.25 PRA Category 1 CME (or 
equivalent CEU credits) for participation. These will be available online through https:/cloud-cme.com 
6) All sites randomized to the CHAMPION will receive a stipend for snacks and drinks and organizing the 
CHAMPION sessions.  
7) All sites will receive the Clozapine Handbook authored by Jonathan Meyer and Stephen Stahl. 
Thus, we feel as if we have created an exciting opportunity for sites to participate and have several enhanced 
pieces included to maximize recruitment and eliminate the logistics of getting weekly ANC blood draws. 
The prescribers/clinical team that are randomized to the CHAMPION have the benefit of improving knowledge 
and self-reported competence with clozapine through active discussion, interactions and cases. Others have 
reported the benefits of the social environment for the prescribers/clinical team. They are included together in 
one virtual room where everyone can interact. This social environment has benefits of camaraderie and 
satisfaction. Other benefits reported have been increased career satisfaction and improved staff interactions 
and communication. Lastly, the benefits include time savings on complex cases that would involve coordination 
for referral or phone calls under other circumstances.  
However, the indirect benefits to patients with serious mental illness and psychotic disorders in the State of 
Maryland are more considerable, as we believe that this study will increase prescriber self-reported 
competence and use of this superior antipsychotic medication. Patients may receive clozapine trials or be 
maintained more successfully than in the past. This could improve outcomes and may decrease 
hospitalizations and emergency room visits. It may lead to better job productivity and a host of other possible 
outcomes known to be associated with the path to remission and recovery.  Also, unnecessary treatments with 
non-evidence-based treatments and long wait times for care could all be improved.  
While financial compensation will be provided for the time and effort that participants provide and a stipend to 
the sites to organize snacks at the time of the CHAMPION, this is not considered a benefit of study 
participation. 
 
Importance of the Knowledge to Be Gained 
 
The risks that this study poses to participants are reasonable in relation to the anticipated benefits and 
potential heuristic value of the research. This study has the potential to improve clozapine prescribing, improve 
lives of many patients and decrease overall health system costs. We will learn if an ECHO intervention, 
CHAMPION, is effective for improving clozapine prescribing and we will understand if this effect can be 
mediated by prescriber self-reported competence scores. Given the importance of the information to be gained 
and the low risks, we feel this project has a high importance on knowledge to be gained.  
We believe the risks of this study are far outweighed by the potential benefits to the participants and their 
patients with schizophrenia and that this will demonstrate an effective and sustainable way to improve the 
treatment of these patients 
Data and Safety Monitoring Plan  
 

 
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This study puts forth a randomized double-blind trial where prescribers/clinical team of antipsychotic 
medications will be the enrolled population. The study is an educational intervention and no biophysiological 
intervention will be performed; being a minimal risk study.  No Data Safety Monitoring Board (DSMB) is 
required but the PI and team will monitor this study as described below.  
 
Roles and Responsibilities 
The DSMP holds the Principal Investigator (PI) responsible for overall data and safety monitoring, sharing her 
responsibility with coinvestigators.  The PI will review trial data yearly at minimum but will review any and all 
safety or confidentiality issues promptly should they arise.  We will have an ombudsmen for this study. This will 
allow prescribers/clinical team at sites to report if they feel they have issues with other participants during the 
videoconferencing calls. These complaints will be brought to the PI and committee to discuss and a plan made 
for addressing any problems within 7 days of the complaint. We will also have a full-time coordinator who will 
manage and ensure participants receive CME and stipends in a timely fashion. 
Reportable Events 
Serious adverse events, unexpected adverse events, and non-serious adverse events will be reported 
according to NIH/NIMH, University of Maryland, and Federal guidelines.  The PI and will receive all SAE 
reports within 24 hours of their occurrence (albeit unlikely).  All serious adverse events (SAEs) will be reported 
to the PI, the University of Maryland School of Medicine IRB, if required by IRB guidelines, and the appropriate 
NIMH program officer per University and Federal regulations.  If the incidence of any reported problem or event 
occurs, we will examine all as we do not anticipate adverse events or side effects as with a pharmacologic 
intervention. In the event any pattern emerges in either treatment group, the PI and coinvestigators will 
determine whether possible protocol modifications are required to minimize the further occurrence of such 
events. 
 
Clinical Trials.Gov Requirements 
The study will be registered on ClinicalTrials.gov prior to the enrollment of prescriber participants. 
Inclusion or women, minorities and children 
 
This project specifically targets clozapine prescribing.  As such, only persons who are old enough to have 
completed medical, nurse practitioner, physician assistant, or other relevant health care training and provide 
mental health care to patients in Maryland will be eligible for inclusion.  Thus, children shall be excluded from 
this study and we will target the ranges of 22 -85 years to cover the range of prescribers/clinical team in the 
State of Maryland. This study does not involve any biophysiological interventions, so there are no issues with 
including women regardless of reproductive status.  Women and minority prescribers/clinical team will be 
eligible for recruitment and inclusion.   We estimate that, based on available gender data for psychiatrists and 
nurse practitioners, approximately 40-50% of those eligible for enrollment will be women providers.  Although 
Maryland is a state diverse in ethnicity, a better indicator of minority provider estimates would be the 
nationwide data on prescribers/clinical team with our state ethnicity breakdown taken into account.  Thus, we 
estimate potential recruitment of up to 8% Hispanic, 20% Black, 18% Asian, and smaller percentages of 
American India and Hawaiian Pacific Islanders.   All efforts will be made to include women and minorities in 
this study. 

 
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Compensation 
 
All prescriber participants who enroll will receive $100 by check, cash or giftcard after the baseline and the 12-
month assessments ($200 total) at the conclusion of the CHAMPION for their time completing thee knowledge 
and competence assessments. All non-prescriber clinicians receive $25 for their participation at each 
assessment ($50 total).  Each site will receive a POC monitoring device and laptop and each site will be given 
a stipend of $1000 at the beginning when three prescribers have been enrolled at the site. This is 
approximately $40 for drinks and food for each session, or in the case of being in the ETAU group for group 
snacks as well.  Individual prescribers who enroll and are not affiliated with an enrolled site will be eligible for 
the CME/CEU credits, and will receive the $100 compensation at the beginning and end of the study ($200 
total). 
 
Consultation Service (Not part of research aims) 
As a service component to support the project, a consultation phone line and email address will allow 
participants in the study and other people outside the study to ask for advice or questions. This service is not 
part of the study aims of this research study. We maintain information on callers around the state for purposes 
of returning calls and quality improvement. All calls will be answered or sent to an expert to help answer.  For 
quality improvement purposes we will track number of calls and types of calls. This information could be used 
to improve call procedures and provide the best ways to help with specific clozapine questions. 
 
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Wahlbeck K, Cheine M, Essali A, Adams C. Evidence of clozapine's effectiveness in schizophrenia: a 
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Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation 
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