Paul Aisen, MD
Alzheimer’s Therapeutic Research Institute, USC
Reisa Sperling, MD
Brigham and Women’s Hospital Massachusetts General Hospital
Ron Petersen, MD
Department of Neurology
Mayo Clinic, Rochester
Mayo Clinic, Rochester
Laurie Ryan, PhD
Project Scientist, National Institute on Aging (NIA)
National Institutes of Health (NIH)
National Institutes of Health (NIH)
Co-Lead:Deborah Tobias (Alzheimer’s Therapeutic Research Institute, USC)
Co-Lead: Jeremy Pizzola (Alzheimer’s Therapeutic Research Institute, USC)
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).
Lead: Robert Rissman, PhD (Alzheimer’s Therapeutic Research Institute, USC)
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.
Lead: Rema Raman, PhD (Professor, Alzheimer’s Therapeutic Research Institute, University of Southern California)
Co-Lead: Michael Donohue, PhD (Associate Professor, Alzheimer’s Therapeutic Research Institute, University of Southern California)
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.
Lead: Devon Gessert (Alzheimer’s Therapeutic Research Institute, USC)
Consists of teams with extensive experience in AD study project management, data management and site support who are responsible for the organization, operationalization, implementation and central day-to-day management of the studies. Responsibilities include initial study planning and timeline management, protocol development, data collection and cleaning, and site training and logistical support, including provision of the supplies for study procedures and collection of biospecimens.
Co-Lead: Dorene Rentz, PhD (Harvard)
Co-Lead: Ron Petersen, MD (Mayo Clinic)
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.
Lead: Gustavo Jimenez-Maggiora, MBA (Alzheimer’s Therapeutic Research Institute, USC)
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.
Lead: Michael Rafii, MD, PhD (Alzheimer’s Therapeutic Research Institute, USC)
Provides medical and regulatory supervision for all clinical trials coordinated by the ACTC.
This is generally accomplished by five key activities:
- Medical and safety monitoring;
- Clinical site monitoring;
- Coding and review of adverse and serious adverse events;
- Review of protocol deviations;
- 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.
Co-Lead: Clifford Jack, MD (Mayo Clinic, Rochester)
Co-Lead: Michael W Weiner, MD (University of California, San Franscisco)
Provides a comprehensive set of services that address all aspects of MRI needed for clinical trials. These include:
- 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).
- Implementing protocols on any/all vendor systems needed for any given trial,
- Site qualification,
- Updating protocols as needed when sites’ MR systems are upgraded/changed,
- Ongoing monitoring and image quality control,
- 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.
Co-Lead Matthew Frosch, MD PhD (Massachusetts General Hospital, Harvard University)
Co-Lead Bradley Hyman, MD PhD (Massachusetts General Hospital, Harvard University)
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.
Lead: Keith Johnson, MD (Massachusetts General Hospital, Harvard University)
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:
- 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;
- Implementing protocols at sites identified for each project, including site qualification.
Co-Lead: Joshua Grill, PhD (Associate Professor, University of California, Irvine)
Co-Lead: Rema Raman, PhD (Professor, Alzheimer’s Therapeutic Research Institute, University of Southern California)
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:
- Protocol Review and Implementation Committee: Ensure study designs minimize barriers to recruitment and complement and identify unique opportunities to enhance participation.
- 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.
- Science of Recruitment Committee: Identify opportunities to advance the knowledge and evidence base for methods to efficiently recruit and retain ACTC trial participants.
The Steering Committee is comprised of the Principal Investigator from each of the 35 member sites, the Leads from each of the working Units of ACTC, and the NIA Project Scientist and Program Official (ex-officio).
The Executive Committee is comprised of the Leadership team, the Lead/Leads from each of the ACTC Units, The Chairs of the Project Evaluation Committee, as well as 3 Site PIs nominated by the Steering Committee, and the NIA Program Officer (ex-officio).
Chair: Tom Montine, MD (Stanford University)
The ACTC BARC is an independent committee, appointed by the NIA (which determines its policies, rules, and functions). Members will be selected by NIA.
Co-Chair: Rema Raman, PhD (Alzheimer’s Therapeutic Research Institute)
Co-Chair: Reisa Sperling, MD (Brigham and Women’s, Harvard)
The Inclusion, Diversity and Education in Alzheimer’s disease – Clinical Trials (IDEA-CT) Committee is a standing ACTC committee, 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. The IDEA-CT committee, reports to the ACTC leadership, and works in partnership with the rest of the ACTC committees and workgroups to promote inclusion and diversity in all ACTC activities.
- 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.
- 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.
- Guide the development of a multi-institutional academic fellowship program to train the next generation of ADRD clinical trialists.
Chair: Jason Karlawish, MD (University of Pennsylvania)
Co-Chair: Joshua Grill, PhD (University of California, Irvine).
The Internal Ethics Committee (IEC) is a standing ACTC committee. The IEC monitors and manages the financial relationships of ACTC participants who have a role in protocol selection, development and data analyses. This includes ACTC Steering Committee members, advisors, unit leads and selected unit members, and Project Evaluation Committee (PEC) members. Relationships include industry ties and intellectual property holdings. The IEC develops policies to address these relationships and provides the ACTC investigators, staff and collaborators with ethics education and consultation.
Chair: Jeffrey Cummings, MD (Cleveland Clinic Lou Ruvo).
- To advise on trial design for studies of agents, devices, or non-pharmacologic interventions targeting neuropsychiatric symptoms (NPS) such as agitation, psychosis, depression, apathy, and sleep disorders.
- To assist in designing trials for non-AD dementia such as frontotemporal dementia and dementia with Lewy bodies where behavioral symptoms are prominent.
- To encourage companies and others with drugs with psychotropic properties to approach the ACTC for review and possible trial conduct.
Co-Chair: Adam Boxer, MD (University of California San Francisco)
Co-Chair: Brad Boeve (Mayo Clinic Rochester)
Aim: To advise on trial design for studies where population is non-AD age-related Dementia.
Chair: Laura Baker, MD (Wake Forest University)
Co-Chair: Bruno Dubois, MD, PhD (Université de Toulouse)
Aim: To provide expert guidance in the development and management of trials of non-pharmacological interventions.
Co-Chair: Christopher van Dyck, MD (Yale University)
Co-Chair: Ron Petersen, MD, (Mayo Clinic Rochester)
- To perform preliminary evaluation of proposals submitted to the ACTC for scientific merit, feasibility, and appropriateness. Refer suitable proposals to the ACTC Steering Committee for vote. Prepare feedback for proposers.
- For each proposal, review the ACTC Clinical Study Concept Proposal and the ACTC Protocol Synopsis, discuss the proposal, and provide a score.
Chair: Gad Marshall, MD (Brigham and Women’s Hospital, Harvard University).
- To develop guidelines for publication.
- To review all abstracts and manuscripts utilizing ACTC data for adherence to ACTC publication policy guidelines.
Co-Chair: Suzanne Craft, PhD (Wake Forest University)
Co-Chair: David Geldmacher, MD, (University of Alabama).
- To review and provide input on metrics used for network membership.
- To participate in review of new potential ACTC sites.
- To participate in Site Selection Process for ACTC studies.
- To review and provide input on study site budgets.
- To consider site staffing and capacity issues, and make recommendations on optimizing site performance.