Multicenter Trial Management Unit Expands the Scope of Research at Yale

In the past, Yale investigators who led multicenter trials had to put together ad hoc study teams, relying on unconnected siloed services to carry out their research. At the end of these trials, these teams, which had compiled so much experience and knowledge, disbanded and their knowledge was lost. This system was inefficient and put Yale at a disadvantage when competing with other institutions for grants for multicenter studies.

To harness this capacity, and to allow Yale to lead multicenter trials more efficiently, YCCI formed a Multicenter Trial Management Unit in 2014 in collaboration with the Yale Cancer Center. “The multicenter unit is a wonderful example of Yale’s ability to leverage the resources of CTSA and NCI-funded Cancer Center Support Grant to aid our faculty in translating innovative science into the clinic,” said Charles S. Fuchs, MD, MPH, Richard Sackler and Jonathan Sackler Professor of Medicine (Medical Oncology); Director, Yale Cancer Center and Physician-in-Chief, Smilow Cancer Hospital. This unit offers full-scale clinical trial management services, allowing Yale to operate much like a sponsor of a multicenter study with all the necessary services, just as a pharmaceutical company is able to do.

Led by YCCI Associate Director Rhoda Arzoomanian, RN, MSN, the unit:

  • Assists with selection and oversight of external sites and provides site activation and training.
  • Oversees project managers for individual trials.
  • Manages central or multiple IRBs.
  • Develops management and communication plans, SOPs, and milestones.
  • Provides remote or on-site monitoring.
  • Sets up Data and Safety Monitoring Boards and helps conduct those meetings.
  • Tracks progress.

The Yale Data Coordinating Center (YDCC), part of the Yale Center for Analytical Sciences (YCAS), offers investigators comprehensive data management (including design and implementation of data management systems, data entry, quality control and security), and data monitoring. As part of the YDCC, faculty from the Schools of Medicine and Public Health offer their expertise in biostatistics, epidemiology, clinical trials, and informatics along with a highly trained technical staff skilled in systems programming, data management, data analysis, and statistical programming.

Providing centralized multicenter trial management allows YCCI to retain and leverage institutional knowledge and expertise, which is more efficient and cost-effective for investigators. 

The multicenter unit is a wonderful example of Yale’s ability to leverage the resources of CTSA and NCI-funded Cancer Center to aid our faculty in translating innovative science into the clinic.

Charles S. Fuchs, MD, MPH

The unit now manages approximately 30 investigator-initiated studies in a variety of disciplines, and is planning to add several more. In some cases, the unit works with investigators from the time of grant submission; in others, investigators turn to the unit in the middle of a project for additional help. The following projects have utilized the services of the Multicenter Trial Management Unit:

  • The Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Led by James McPartland, PhD, Director of the Yale Developmental Disabilities Clinic, this multicenter study includes Yale, Boston Children’s Hospital, Duke University, UCLA, and the University of Washington/Seattle Children’s Hospital. The goal is to develop a set of reliable and objective measures of social function and communication in children with autism. These measures can then be used to determine which children are more likely to respond to treatment and to demonstrate that treatments are influencing targeted brain systems.
  • The STRIDE Trial (Strategies to Reduce Injuries and Develop confidence in Elders), a collaboration between investigators, patients, and other stakeholders from 14 aging programs and 10 health care systems that is evaluating the effectiveness of an evidence-based intervention to reduce the risk of serious fall injuries among older adults. STRIDE involves data management services; preparation of DSMB reports and data analytic files; and statistical analysis. YDCC serves as the Data Coordinating Center.

Another service YCCI provides to multicenter trials is Quality Assurance (QA) evaluation to ensure patient safety and the appropriate use of resources; to assess the ability of the study to achieve realistic accrual targets; and to monitor timelines. The YCCI Quality 

Assurance unit is led by Alyssa Gateman, MPH, CCRP (former Director of Quality Assurance for the Dana-Farber Cancer Center). The Quality Assurance program reflects an institutional culture focused on carrying out research of the highest quality; ensuring its safe and ethical conduct; and reducing administrative burdens on faculty and staff in order to speed the translation of scientific discoveries.

YCCI’s QA efforts focus on working with Yale’s Human Research Protection Program (HRPP) to manage research, including QA reviews of all Yale studies and monitoring multicenter studies at other sites. Milestones, timelines, and other metrics are continuously tracked in OnCore and CTMS to identify issues that may require QA intervention or a targeted component review. By tracking audit trends, the QA team identifies areas for targeted retraining and introduction of new study workflow.

The QA team conducts study audits that enable YCCI to recognize trends within a team, across teams, or across the entire institution, and put in place additional training. Taken together, these steps provide continuous monitoring of enterprise-wide trends and afford Yale an agility that helps to ensure the quality and efficiency of clinical research. The goal of the program is not only to promote regulatory compliance, but also to improve patient safety and educate researchers about  best practices in clinical trials.

With these comprehensive services aimed at improving the quality of research at Yale in place, it is even more likely that the scope of research at Yale will increase as well. With the support offered, Yale investigators increasingly lead multicenter trials, with the ultimate end result of speeding the development of novel therapies that will help patients everywhere.

This article was submitted by Lisa Brophy on December 5, 2017.

Linda Coleman: Innovating Yale's Regulatory Structure to Better Support Research

Having a single IRB of record is an important component of conducting multicenter trials. YCCI is working with Yale’s Human Research Protection Program (HRPP) to ensure this capability. “The IRB is the gatekeeper for ensuring the ethical protection of human research participants in clinical trials,” said Linda Coleman, JD, Director of Yale’s HRPP, who joined Yale in April 2016. YCCI works closely with Yale’s HRPP, which is fully accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP) and provides regulatory and administrative support to the institution’s five institutional review boards.

As the director of the HRPP, Coleman brings to Yale the experience she gained in the areas of legal and regulatory compliance, strategic planning, quality improvement, and operations management while at Quorum Review and its division, Kinetiq. Quorum is an organization that provides commercial IRB and regulatory and technology consulting services to industry-sponsors, institutions, and other organizations conducting research in the United States, Canada, and other countries.

The initiatives Coleman implemented or is considering at Yale include: using external IRBs more extensively for industry-sponsored trials that meet certain Yale guidelines and studies that require the use of a single IRB; revamping the internal IRB convened meeting schedule to move studies more efficiently through the review process; adding videoconferencing capabilities so that members can participate remotely; and adding special IRB meetings to address workload demands of the various IRB panels. The HRPP also fully implemented a new electronic IRB system earlier this year to simplify the IRB submission and review process.

Changing Yale’s policies to allow use of commercial IRBs and to improve the efficiency of Yale’s internal submission and review process is part of positioning Yale as a better partner for industry participation, supporting continued growth and expansion of clinical trials.

Linda Coleman, JD, CIP, CHC, CHRC, CCEP-I