INTERAGENCY SERVICE AGREEMENT (ISA)

AMENDMENT

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

CPAE Registry & Biospecimen Repository

Effective upon signature by both parties, it is mutually agreed that the ISA is amended as follows:

1. Pursuant to the Uniform Terms and Conditions, Provision Twenty-Six (26), Miscellaneous, Section 26.3, the Agreement is hereby revised as follows:

1.1. The Scope of Services is revised and replaced.

1.2. The Price Sheet is revised and replaced.

ALL CHANGES ARE REFLECTED IN RED

ALL OTHER PROVISIONS SHALL REMAIN IN THEIR ENTIRETY

Contractor hereby acknowledges receipt and acceptance of above amendment and that a signed copy must be filed with the Procurement Office before the effective date

The above referenced Contract Amendment is hereby executed this _____ day of __________ 20______ at Phoenix, Arizona

(To be filled out by ADHS Procurement Office)

Contractor Signature

Contractor Signature Date

Authorized Signatory’s Name and Title

AZ Board of Regents, University of Arizona

Contractor’s Name Procurement Officer Signature

Elisha Johnson, JD Sr. Director, Clinical Trials & Contracting

8/15/2024

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

1. Background

1.1. The Arizona Biomedical Research Centre (ABRC) receives funding from the Arizona Tobacco Tax Fund in accordance with Arizona Revised Statutes §36-275 (https://www.azleg.gov/ars/36/00275.htm), and §36-773 (https://www.azleg.gov/ars/36/00773.htm), to engage with various institutions to conduct biomedical research. The University of Arizona (U of A) is conducting research regarding Childhood Postinfectious Autoimmune Encephalopathy (CPAE) disease. They have learned that CPAE produces ongoing brain injury in children due to persistent inflammation from an untreated infection, with severe developmental consequences. Children with these disorders present with acute-onset psychiatric symptoms. CPAE includes disorders such as Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS), and Sydenham chorea.

1.2. Arizona is leading the nation in CPAE research discovery and clinical services. The goal of this Agreement is to expand investigation and knowledge regarding this condition. Research over the past several decades has greatly increased medical knowledge of CPAE, and clinical leadership by the U of A CPAE Center and its partners across the country have contributed to the understanding of treatment needs and methods. However, there are still unanswered questions regarding the mechanisms that trigger these disorders, methods of prevention, and most effective treatments. There is a critical need for research to clarify the etiology, individual risk, time course, and treatment strategies that can respond to core questions regarding this condition.

1.3. A concerted two-pronged approach is expected to reduce pediatric risk related to CPAE in Arizona and will contribute substantially to efforts in the state, nationally, and globally to reduce the detrimental impact on children’s lives. This approach includes development of a CPAE patient registry previously initiated with ABRC support to provide researchers in Arizona and national colleagues with expanded accessibility of comprehensive clinical data for diagnostic assessment, evaluating varied interventions, and measuring treatment success. Secondly, it includes the establishment of a biorepository linked to the patient registry to promote basic science and translational research aimed at discovering the biological causes, diagnostic and outcome markers, and potential cures for these conditions.

1.4. This work will contribute to knowledge in the field regarding factors that cause/predict CPAE as well as treatment response and effectiveness. Over five (5) years, this will advance Arizona as a national leader in basic science and clinical relational research, providing endless research and collaborative opportunities.

1.5. CPAE encompasses PAN and PANDAS. These conditions are characterized by a sudden onset of obsessive-compulsive disorder (OCD) or severe food restriction (ARFID) along with symptoms of anxiety, emotional lability, depression, aggression, developmental regressions, school performance deterioration, tics, or somatic issues. While behavior therapy is suggested to reduce challenging behaviors and improve treatment adherence, the efficacy of such interventions for CPAE remains understudied. The primary objectives of this project are to evaluate the efficacy of behavioral treatments for families affected by CPAE and disseminate findings to professionals to improve care systems for children with CPAE.

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

2. Objective

Major Aims of the Project

2.1. AIM 1: Develop the CPAE Patient Registry

2.1.1. Objective 1.1: Enhance services to those with CPAE by maintaining the currently-established research registry and continuing to expand the study cohort.

2.1.2. Objective 1.2: Use the web-based application for data collection, surveys, and databases, Research Electronic Data Capture (REDCap), to refine data collection instruments utilized to collect and maintain the CPAE Registry.

2.1.3. Objective 1.3: Expand the use of the registry to accelerate CPAE research both internally and through collaboration with other researchers.

2.2. AIM 2: Establish a Biorepository to Promote Basic Science and Translational Research

2.2.1. Objective 2.1: Design an Arizona CPAE biorepository that will integrate with the existing repositories of national collaborators.

2.2.2. Objective 2.2: Collect and catalog biospecimens from pediatric patients seen at the U of A CPAE Clinic.

2.2.3. Objective 2.3: Manage an Arizona CPAE Biorepository that can provide access to researchers with specimens from children with CPAE from varied time points of the disease.

2.3. Aim 3: Explore and analyze the effectiveness of direct behavioral interventions through weekly treatment sessions with participants from the CPAE clinic.

2.4. Aim 4: Evaluate the relation of caregiver stress to treatment outcomes and acceptability of treatment procedures.

2.5. Aim 5: Provide education and training to health care providers, psychologists, and other mental health professionals in Arizona to increase awareness of effective behavioral intervention.

3. Patient Registry

The patient registry will provide a powerful tool that facilitates observing the course of disease, understanding variations in treatment and outcomes, and examining factors that influence prognosis and quality of life. Over the project period, researchers will focus on maintaining, refining, and expanding data collection and use of the CPAE patient research registry. This registry is a repository of collected medical and clinical data, securely housed within a secure web application for building and managing online surveys and databases commonly referred to as REDCap to analyze and determine the natural course of CPAE symptoms using validated tests of cognitive function, anxiety, neurologic signs, and overall disease severity. During this project period, U of A will be transitioning the existing database to REDCap so that it will become a secure, searchable entity containing data that can be accessed by teams of researchers in Arizona and from other institutions and can be linked to a biorepository of specimens from children with PANS/ PANDAS, normal controls, and

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson non-neurotypical controls. REDCap’s ease-of-use and accessibility offers a convenient method of sharing data collaboratively. U of A will aim to foster and maintain professional collaborations that expand awareness, accelerate promising research, and improve the health of patients with CPAE.

4. Biorepository

4.1. The Biorepository to Promote Basic Science and Translational Research will work in conjunction with partner institutions locally and nationally. Arizona will contribute to efforts to assemble a large dataset across institutions to fuel collaborative research. Over the course of this project, a biorepository will be established at the U of A that will collect and store samples of blood, feces, and other biological specimens. Patients currently enrolled in the research registry will be invited to participate in sample collection; for those who consent, efforts will be made to obtain specimens longitudinally, at various points in their disease progression (initial onset, flare, recovery).

4.2. Samples will be collected by the U of A Clinical and Translational Sciences Research Center (CATS), and stored and maintained by the existing University of Arizona Health Sciences Biorepository (UAHS Biorepository), allowing users to set aside samples for their own use, while making samples available to investigators both inside and outside of the university. Initially, the project will be focused on collecting samples from children seen at the U of A CPAE Clinic with a confirmed diagnosis. Over the course of the project, the possibility of expanding the scope to include a cohort of neurotypical controls will be explored. The biorepository will serve as an essential component in streamlining ongoing research of PANS and PANDAS at the CPAE Center of Excellence, while also contributing to the forward progress of other researchers.

5. Data Analysis

5.1. This project will employ a data analyst whose primary responsibility will be to abstract information from patient clinical records to ensure accurate and uniform data entry into the REDCap database. Data also will be collected in the registry from direct family input into demographic variables. Clinical variables will be abstracted from the patient clinical record. Information submitted to the UA Biological Specimen Repository will be managed with strict guidelines for sample preparation and management.

5.2. Data Collection: Data will be gathered about behavioral challenges through rating scales and caregiver reports (using the following scales: Parenting Stress Index, Caregiver Burden Inventory, Family Accommodation Scale – Parent Report, Child Behavior Checklist) at baseline and at the end of treatment to assess changes in child challenging behavior and levels of caregiver stress. Additionally, direct observation of behavior via a functional analysis will be conducted at baseline to directly evaluate the conditions under which the child engages in challenging behavior. Based on the results of the functional analysis, behavioral interventions will be individualized to each child and will include therapies based on the science of behavior analysis, including Functional Communication Training and Parent Management Training. Families will receive coaching from a qualified behavior specialist on their individualized behavioral intervention during weekly sixty (60) minute sessions. Weekly treatment sessions will continue until challenging behavior is reduced by at least eighty percent (80%) (compared to baseline), which may take between eight (8) to twenty (20) sessions. The data collected will provide insights into the effectiveness of behavioral interventions for this population.

5.3. Professional Education: To ensure that practitioners in Arizona are well-informed about the latest behavioral treatments for CPAE, we are seeking support to provide accessible education to providers

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson throughout the state to increase awareness of effective, empirically supported behavioral interventions for children with CPAE. Two (2) additional training workshops will be provided each year, with emphasis on empirically supported behavioral interventions. The workshops will be provided to local groups including the Arizona Psychological Association, Arizona Association of Behavior Analysts, and Banner Children’s Virtual Lunch Lecture series. We will reach additional frontline providers including behavior analysts, psychologists, behavioral and mental health practitioners, school counselors, and psychiatrists.

We will incorporate this information about behavioral interventions into the existing Arizona CPAE Research Brief disseminated by email to healthcare professionals.

5.4. Regional Conferences: Presentations will be delivered in person or virtually at two (2) regional conferences a year, which provides a platform for the researchers to share their work and collaborate with other researchers in the field. Additionally, we expect to publish our presented results in scientific, peer-reviewed journals, which allows for external peer-review from outside experts.

6. Tasks

The University shall:

6.1. Objective 1 – Enroll Participants, hire research technician, and audit data.

6.1.1. Enroll consenting subjects to participate in the CPAE registry that allows for the longitudinal assessment of CPAE symptoms.

6.1.2. Hire and train a research technician to abstract medical and clinical data relating to CPAE symptoms from consented subjects.

6.1.3. Audit collected data to ensure database integrity, consistency, and regulatory compliance.

6.2. Objective 2 – Effective use REDCap to collect and analyze data.

6.2.1. Design and improve REDCap collection tools to maximize data collection efficiency and efficacy.

6.2.2. Train investigators to expand the effective use of REDCap as a survey tool and data collection instrument.

6.2.3. Extract and analyze the REDCap data to explore key research questions.

6.3. Objective 3 – Harmonize the database structure to facilitate research and analyze treatment response elements.

6.3.1. Harmonize database structure and information to facilitate joint research opportunities across CPAE sites interested in collaborative inquiry.

6.3.2. Utilize collected data to determine elements associated with response to specific treatments that impact CPAE.

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

7. Requirements

The University shall provide:

7.1. A fully functioning CPAE Patient Registry by the end of the Contract.

7.2. A fully operational CPAE Biorepository by the end of the Contract.

8. Deliverables

The University shall provide:

8.1. Quarterly Program Progress Reports on a form provided by the ABRC.

8.1.1. These reports are due not later than thirty (30) days after the end of each calendar quarter with the exception of the quarter ending December 31, which shall be due on February 28.

8.1.2. Reimbursement for expenses will not be approved until the corresponding Program Progress Report is received.

8.2. Quarterly Contractor Expenditure Report (CER)

8.2.1. These reports are due no later than thirty (30) days after the end of each calendar quarter with the exception of the quarter ending December 31, which shall be due on February 28.

8.2.2. Reimbursement for expenses in these CERs will not be approved until the corresponding Program Progress Report is received.

9. Notices, Correspondence, Reports, and Invoices

9.1. Notices, correspondence, reports, and Contractor Expenditure Reports from the University to ADHS shall be sent to: Biomedical@azdhs.gov.

John S. Garcia, Program Director Arizona Biomedical Research Centre 250 North 17th Avenue Phoenix, AZ 85007 Phone: (602) 364-0157 Email: Biomedical@azdhs.gov

9.2. Notices, Correspondence, Reports, and Payments from ADHS to the University shall be sent to Administration:

The University of Arizona Sponsored Projects & Contracting Services P. O. Box 41867 Tucson, AZ 85717-1867 mailto:Biomedical@azdhs.gov

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

Email: sponsor@arizona.edu

Program:

University of Arizona Sydney Rice, M.D, MSc University of Arizona College of Medicine Tucson – Pediatrics

(520) 626-6301 srice@peds.arizona.edu

9.3. Payments from ADHS to the University shall be sent to the “Remit To” address listed in the University’s Arizona Procurement Portal (APP) profile.

mailto:sponsor@arizona.edu mailto:srice@peds.arizona.edu

ARIZONA DEPARTMENT OF

HEALTH SERVICES

OFFICE OF PROCUREMENT

150 N 18th Ave., Ste. #530 Phoenix, Arizona 85007

AGREEMENT NO.: CTR065451 AMENDMENT NO.: 1 Procurement Officer Kaitlin Burreson

Price Sheet

Description Year One

Year Two

Year Three

Year Four

Year Five TOTAL

Personnel and Benefits*

$160,945.00 $190,713.00 $208,713.00 $214,291.00 $116,746.00 $891,408.00

Professional & Outside Services *

$61,328.00 $38,378.00 $38,378.00 $37,345.00 $37,345.00 $212,774.00

Other Expenses* $5,000.00 $11,818.00 $12,000.00 $12,000.00 $5,000.00 $45,818.00

Indirect Costs (10% rounded to the nearest dollar)

$22,727.00 $24,091.00 $25,909.00 $26,364.00 $15,909.00 $115,00.00

CONTRACT TOTAL $250,000.00 $265,000.00 $285,000.00 $290,000.00 $175,000.00 $1,265,000.00