The identification of genes associated with NF1, NF2, and some forms of schwannomatosis has opened new opportunities for testing medications that may be effective in preventing or treating complications of neurofibromatosis. As an international leader in advancing neurofibromatosis research, UAB serves as the coordinating center for the NF Clinical Trials Consortium, an innovative research initiative committed to transforming the NF therapeutic landscape.
This collaborative group of 15 primary and 10 affiliate clinical centers across the country and in Australia is dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. Established in 2006, the Consortium is funded by the Department of Defense (DoD) through the Neurofibromatosis Research Program (NFRP), one of the Congressionally Directed Medical Research Programs. Following a recent successful renewal application, the Consortium is now funded by the DoD for the next 10 years.
The Consortium partners with well-established NF Centers that pool expertise and resources to accelerate the pace of research by providing opportunities for patients to participate in clinical trials at sites around the country and in Australia. I serve as the Principal Investigator of the Consortium and lead the Operations Center based at UAB; Children’s of Alabama Division Director of Pediatric Hematology and Oncology Girish Dhall, MD, serves as Deputy Director of the Operations Center.
This month’s blog features insight from members the NF Clinical Trials Consortium Operations Center administrative team, which is based at UAB, including: Program Director Karen Cole-Plourde, BS; Clinical Research Nurse Manager Lynn Merritt, RN; and Research Compliance Manager Juliette Southworth, BS, CCRP. These dedicated professionals explain their roles and share observations about the impact of the NF Clinical Trials Consortium in accelerating the pace of NF research and providing meaningful opportunities for patients across the country and internationally to participate in clinical trials of promising new therapies.
What specific responsibilities are associated with your roles in the NF Clinical Trials Consortium?
Karen: My position as Program Director has various functions, including working closely with the executive team to carry out the work of the Consortium. The activities of the executive team include developing and maintaining the clinical trial budgets, developing grant submissions, and coordinating the activity of clinical trial sites. I also lead the day-to-day activities of the Operations Center, helping to ensure all members of our team are on the same page. We are a small unit, but by prioritizing and working together, we accomplish a great deal. Our team works together continually to coordinate and monitor all sites in the areas of regulatory approvals, finance, and data management.
Some of the day-to-day responsibilities that I supervise with the Operations Center include: providing quarterly and annual reporting updates to the DoD; working closely with the clinical trials office and individual pharmaceutical companies that provide medications to our clinical trial sites; managing Consortium finances, including grant awards from the federal government, industry, or private donations; working closely with the finance departments to establish sub-contracts for all clinical trial sites; and overseeing the budget for the Operations Center.
Lynn: As the Clinical Research Nurse Manager, my primary responsibilities include serving as the clinical liaison between the Operations Center and the clinical trial sites, monitoring sites to ensure that patient safety remains a top priority, and providing initial and ongoing training during the course of each study. As part of safety monitoring, I am responsible for ensuring adverse events are reported in a timely manner, and appropriate actions are taken. I also monitor patient data during on-site or remote monitoring visits to ensure they are accurate and supported by source documentation.
During COVID, we performed remote site monitoring visits, although we are now resuming in-person visits as allowed. Prior to a site visit, I have a video call with the site coordinator to explain our expectations for the visit. As part of the visit, I review the medical records, lab reports, procedure reports, and drug accountability. I’m responsible for ensuring that each site’s data are supported by accurate and complete source documentation.
Another important responsibility I have is reviewing and approving drug requests submitted by our clinical trial sites. This involves ensuring that each site has regulatory approvals in place before I submit drug orders to the applicable drug distributor for each study.
Juliette: My priority as the Regulatory Compliance Manager is ensuring compliance with the ICH-GCP, which stands for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP). This is an internationally agreed-upon standard that ensures ethical practices and scientific quality in designing, recording, and reporting trials that involve human subjects. The purpose of the standard is to safeguard the rights, safety, and well-being of participants recruited for clinical trials and also to ensure that clinical trial data are credible and reliable regardless of where the trial was conducted. For patients, these standards ensure confidentiality and informed consent throughout the duration of the study.
The local regulatory body is the Institutional Review Board (IRB), which is the group formally designated to review and monitor biomedical research involving human subjects. The IRB grants us approval and provides oversight to each clinical trial we conduct. They can audit our regulatory work at any time to review our compliance measures. I also serve as the liaison with the DoD regarding regulatory compliance issues. My job is to obtain study approvals from the FDA, IRB, and the DoD annually for each clinical trial we conduct. Karen, Lynn, and I travel to our affiliate clinical sites at least once every three years to ensure we are in compliance as part of our Quality Management Plan.
How does the NF Clinical Trials Consortium prioritize patient care and safety for clinical trial participants?
Karen: Good clinical practice and patient safety are paramount for the Consortium. We continuously work to ensure compliance in all areas. Lynn and Juliette are responsible for specific compliance and training measures that are designed to ensure patient safety throughout the study duration.
Lynn: I’m responsible for evaluating reports of adverse events that may occur during a clinical trial. Based on the seriousness of the event, I ensure it is reported to the appropriate regulatory authorities, which may be the IRB and the FDA. I also determine whether an adverse event meets the criteria for expedited reporting.
Juliette: As a part of regulatory compliance, we require all participating personnel on our trials to obtain HSP and GCP training certifications. We monitor sites to ensure that these standards are implemented. These trainings focus on educating clinical trial investigators and personnel about standards in patient safety, ethical research, and patient confidentiality.
In your view, what has been the impact of the NF Clinical Trials Consortium in advancing NF research, and what unique insights can you share about your work with the Consortium?
Karen: Since its inception in 2006, the Consortium has experienced tremendous growth and achieved numerous milestones that have impacted both the NF scientific community and individuals living with NF. We began in 2006 with a $2 million foundational grant providing funding for nine sites and nine investigators, and the Consortium has expanded since that time to 25 sites in the U.S. and internationally and 140+ investigators. After receiving 5-year funding awards in 2011 and 2016, the Consortium recently received a new 10-year award from the DoD for $25 million. Since 2006, the Consortium has received approximately $65 million from all entities, including federal grants, non-profit charitable gifts, and industry donations.
The Consortium has leveraged this funding to complete a total of 14 clinical trials with six trials currently in progress or development at our participating sites. These clinical trials test therapies that may be helpful in preventing or treating complications associated with all forms of NF, including plexiform neurofibromas, low-grade gliomas, malignant peripheral nerve sheath tumors (MPNSTs), and vestibular schwannomas. Since 2006, the Consortium has produced 18 peer-reviewed publications, presented multiple scientific abstracts, and participated in numerous invited talks nationally and internationally.
A unique strength of the Consortium is that the collaborative dynamic facilitates faster turnaround of scientific reviews and regulatory approvals by allowing investigators to develop mature protocols through discussions with various disease and discipline committees. This approach accelerates the pace of research so that therapies can be identified more quickly to improve the lives of those living with NF. While we have experienced tremendous growth since our inception, I believe we are only scratching the surface of what can be accomplished. For example, a future goal of the Consortium is to expand our collaborations both within the US and internationally. We are actively planning additional clinical trials for all forms of NF.
From a personal standpoint, my association with the NF community through my work with the Consortium is both rewarding and encouraging. I had the privilege of meeting patients and physicians at a recent NF conference, which gave me a renewed appreciation for and dedication to the important work the Consortium is doing to identify potentially life-changing therapies for those living with NF.
Lynn: As a nurse with a previous career in critical care and multiple therapeutic areas of clinical research, the impact of the NF Consortium in providing opportunities for patients to participate in clinical trials and connect with NF specialists is personally meaningful. To observe trial participants respond positively to many of the medications that are being tested is also exciting to witness firsthand.
Juliette: Fundamentally, the NF Consortium facilitates research that improves the quality of life for individuals with NF. Like Karen, I also had the opportunity to meet patients and families at the NF Summit in Chicago. Their stories inspire each of us to work even harder to advance the Consortium’s goals with a renewed commitment and vision for what is possible.