Units

Administration

Co-Leads: Jeremy Pizzola,

Serves to coordinate the activities of the ACTC, interfacing with all of the other Units and Committees, the project teams and each of the sites. Essential components of the Administration Unit include Regulatory Affairs, Fiscal Management, Contracts, Human Resources, and Quality Assurance (QA).

Biomarkers

Co-Leads: Robert Rissman, PhD,

Includes the Biospecimen Bank in San Diego and distributed efforts on assay optimization (Harvard, Wash U and USC) for early stage trials. The key objective of the Unit is to provide the infrastructure necessary for storage, pharmacokinetics screening, and optimization of tools for preventive studies.

Biostatistics

Co-Leads: Rema Raman, PhD, Michael Donohue, PhD,

The Biostatistics Unit provides the statistical leadership and oversight for all ACTC studies. The Unit aims to advance AD and related dementias (ADRD) clinical trials research through the utilization and development of efficient clinical trial designs, a comprehensive quality assurance program, and state-of-the-art statistical methodologies and analytic approaches. These approaches allow the rapid start-up of trials, real-time monitoring of data quality, sophisticated statistical analysis, and effective sharing of archived data. The primary aims of the Unit are to provide biostatistics leadership in the design, execution and analysis of ACTC clinical trials to ensure the scientific integrity and statistical rigor of study results, and to conduct innovative statistical research in ADRD in collaboration with the larger research community.

Clinical Outcome Instruments

Co-Leads: Dorene Rentz, PhD, Ron Petersen, MD, PhD,

Establishing clinical meaningfulness on cognitive and functional measures used in AD trials is a critical FDA requirement. This entails advising applicants applying to utilize the ACTC infrastructure as to the best cognitive and functional measures that would be responsive to targeted change in clinical trials across the neurodegenerative disease continuum from preclinical, MCI and dementia trials. The Clinical Outcome Instrument Unit brings extensive experience in designing and implementing novel tools to assess cognitive function across the continuum. The Unit in addition provides oversight and guidance to quality of cognitive assessment in ACTC trials. This effort is managed by Cecily Jenkins, PhD (Alzheimer’s Therapeutic Research Institute) and includes training and certification of raters, and audio recording of all primary outcome assessments with central review and performance feedback.

Inclusion, Diversity, and Education in Alzheimer’s disease Clinical Trials (IDEA-CT)

Co-Leads: Reisa Sperling, MD, Rema Raman, PhD,

The Inclusion, Diversity and Education in Alzheimer’s disease – Clinical Trials (IDEA-CT) Committee is a standing ACTC unit, charged with developing goals, formulating a strategic plan, and serving as a source of oversight to support the ACTC’s core values of inclusion, diversity and training in ADRD clinical trials.

1. Plan and organize research training programs with the purpose of identifying and training a diverse group of staff, junior investigators and leaders interested in and committed to the design and conduct of ADRD clinical trials.
2. Develop policies and practices to improve the messaging and commitment to diversity and inclusion within the ACTC committees and the ADRD clinical research community at large, with diversity being broadly defined to emphasize inclusiveness.
3. Guide the development of a multi-institutional academic fellowship program to train the next generation of ADRD clinical trialists.

Informatics

Co-Leads: Gustavo Jimenez-Maggiora, MBA,

Develops and maintains the ACTC Informatics Platform (ACTC-IP) to support the ACTC program and its scientific aims. The ACTC-IP serves as an extensible, secure, and scalable information, collaboration, and process management infrastructure to facilitate the effective execution of program- and study-related research activities by ACTC Units, investigators, study teams, and performance sites. The ACTC-IP provides facilities to collect, store, process, analyze, visualize, audit and share scientific, operational, and administrative data using standardized data models, formats, and taxonomies. The Informatics unit is composed of two groups: Data Management and Informatics. Each group's key personnel and activities are described below:

1. Key personnel in the Informatics group include Phuoc Hong, BS, Stefania Bruschi, MS, MBA, Hongmei Qui, MS, Jia-shing So, BS, with a combined experience of over 60 years in clinical research informatics, software engineering, database design and management, and cloud-based infrastructure architecture and operations. The group is responsible for ACTC-IP platform and study-specific development and management activities.
2. Key personnel in the Data Management group include Olusegun Adegoke, MSc, Veasna Tan, MA, and Olga Baryshnikava, MS. The group is responsible for developing the study Data Management Plan (DMP), creating case report forms, managing data transfers, and conducting data cleaning processes. The data management group has extensive experience in managing complex data transfers, sometimes from more than 50 distinct data sources for a single trial, and brings robust standard operating procedures, risk-based methods, and an experienced team, which are essential to the successful implementation of this platform study.

Medical Safety

Co-Leads: Michael Rafii, MD, PhD,

Provides medical and regulatory supervision for all clinical trials coordinated by the ACTC. This is generally accomplished by five key activities:

1. Medical and safety monitoring;
2. Clinical site monitoring;
3. Coding and review of adverse and serious adverse events;
4. Review of protocol deviations;
5. Responding to medical questions from sites regarding study conduct.

The ultimate goal of the ACTC Medical Safety unit is to develop better methods for clinical trials safety monitoring, including risk-based monitoring, semi-automated coding of adverse events and concomitant medications and real time support for clinical trial sites. The Medical Safety Unit is comprised of 4 physicians and 20 site monitors.

MRI

Co-Leads: Clifford Jack, MD, Michael Weiner, MD,

Provides a comprehensive set of services that address all aspects of MRI needed for clinical trials. These include:

1. Designing imaging acquisition protocols tailored to any proposed study design (may include use of MRI for inclusion/exclusion, safety monitoring, and outcome assessment or any desired combination).
2. Implementing protocols on any/all vendor systems needed for any given trial,
3. Site qualification,
4. Updating protocols as needed when sites’ MR systems are upgraded/changed,
5. Ongoing monitoring and image quality control,
6. Designing or implementing image analysis methods that address needs of any proposed study.

The ACTC MR Unit is modeled on the MR Core of ADNI, with a central core lab at Mayo under Dr. Jack, with Dr. Weiner’s group providing image analysis services.

Neuropathology

Co-Leads: Bradley Hyman, MD, PhD, Matthew Frosch, MD, PhD,

Captures the critical information available from autopsy examination of clinical trial subjects, in order to: confirm pathologic diagnosis, define endophenotypes, elucidate the biological action of the treatment, including both on- and off-target effects that may underlie adverse events, unravel multifactorial contributions to the clinical state, including comorbid pathologies that may alter the response to the intervention and potentially bank tissue for future investigations. The Neuropathology Unit works collaboratively with other neuropathologists committed to understanding neurodegenerative diseases in order to fulfill this mandate.

PET

Co-Leads: Keith Johnson, MD,

Provides a comprehensive set of services that address all aspects of PET needed for clinical trials supported by ACTC. These services depend on the needs of specific projects and includes:

1. Designing protocols tailored to a proposed study design, including project-specific use of amyloid PET for inclusion/exclusion and outcome assessment, and use of Tau PET, FDG, or other tracers for outcome assessments;
2. Implementing protocols at sites identified for each project, including site qualification.

Recruitment, Engagement, and Retention Unit

Co-Leads: Rema Raman, PhD, Joshua Grill, PhD,

The ACTC Recruitment Unit serves to integrate the strategic and scientific mission of efficient and representative recruitment for all ACTC trials with the necessary operational infrastructure to achieve study accrual. The Unit is composed of three committees with the following aims:

1. Protocol Review and Implementation Committee: Ensure study designs minimize barriers to recruitment and complement and identify unique opportunities to enhance participation.
2. Inclusive Recruitment Committee: Enhance the diversity and inclusivity of all ACTC trials though an innovative Hub and Spoke approach that utilizes expert mentorship from national recruitment experts.
3. Science of Recruitment Committee: Identify opportunities to advance the knowledge and evidence base for methods to efficiently recruit and retain ACTC trial participants.