In the late 1990s, the Therapeutics Development Network (TDN) Coordinating Center was located in an old brick school building a few miles northwest of Seattle Children’s Hospital. The Coordinating Center was the brainchild of Dr. Bonnie Ramsey, now director of the CCTR, and Dr. Bob Beall, then president and CEO of the Cystic Fibrosis Foundation (CFF). They had basic science research results, but they didn’t have a system by which to test their findings. They knew that because cystic fibrosis is a rare disease, multicenter trials were going to be the only way to advance new therapies for CF. Today, 30,000 people in the U.S. have CF, which is considered to be an orphan disease.
Their vision had three main goals: to create a national network of academic medical centers to evaluate potential new and existing therapies for the treatment of patients with CF, to establish a central coordinating center and to incentivize industry to conduct clinical trials for CF treatments. With collaborative funding between the CFF and the National Institutes of Health , the TDN (comprised of 7 clinical sites initially) and its Coordinating Center (TDN-CC) were born in 1998.
Fast forward to 2016. The TDN Coordinating Center is housed in the towering West 8th building in bustling South Lake Union, with more than 55 staff and faculty contributing to its success — and overseeing 82 sites at last count. It is closely intertwined with the CCTR in what has become a fruitful symbiotic relationship: the TDN-CC has expertise in running large, multicenter clinical trials, and shares its lessons learned with CCTR investigators when they undertake similar research. Conversely, CCTR offers complementary expertise to support the complex operations of the TDN-CC and provides insight on strategic and collaborative research opportunities with colleagues who have different areas of expertise.
I sat down to talk with TDN-CC co-directors Drs. Christopher Goss and Nicole Mayer Hamblett to learn more about their roles within the TDN-CC. Goss is an adult pulmonologist at University of Washington in the Division of Pulmonary and Critical Care Medicine and Associate Adult CF Clinic Director. Hamblett is co-director of the biostatistics core at Seattle Children’s Research Institute. They both have a long history with the TDN-CC.
Christopher Goss, MD, MS, FCCP
Nicole Mayer Hamblett, PhD
How did you get started with the TDN-CC?
Goss: I was an adult pulmonary critical care fellow in 1999, and as part of my training, I collaborated with Bonnie Ramsey to learn how to conduct randomized, controlled multicenter trials. At that time, I was already studying CF. Learning from Bonnie how to do large-scale clinical trials was my introduction to the TDN.
Hamblett: In 1999, I had completed my PhD in biostatistics at the University of Washington. I was hired to manage the statistical group at the TDN-CC, which consisted of myself and one other person that I hired. The group has now expanded to include data management and is 16 people strong.
What’s different now from when you started with this network some 17 years ago?
Goss: The growth has been impressive. The TDN-CC is running approximately 15-20 ongoing clinical trials right now, and the network overall has 65 clinical trials beginning this year alone. That requires tremendous coordination — we try to run these trials as efficiently as possible, to accelerate the pace of research.
Hamblett: I think one thing that sets us apart is the specialized skills we have in interventional clinical trials due to the number of years and number of trials we’ve coordinated. We are in a position to broaden our impact by sharing our expertise with other researchers here at Seattle Children’s to help them move their therapeutic research forward.
What are some of the major accomplishments of the TDN and TDN-CC, in your opinion?
Goss: Early on we incorporated quality improvement and therefore have detailed performance metrics for various measures. We’ve been doing this since 2006, which was unheard of. So weve also gathered data on the process of doing clinical trials, similar to Seattle Children’s lean initiatives. We were tracking how long it took to get contracts signed, how long it took patients to get study materials — important components in the lifecycle of a clinical trial. We also matched underperforming sites with sites that were excelling, and assigned coaches to help improve the quality or pace of the research at the lagging site.
Looking back, we’ve definitely accomplished the goal of becoming a robust network of clinical trial sites. We now have significant expertise to design studies, harnessing our statistics group. And we’ve been able to push forward highly specialized outcomes measures developed specifically for CF. By this, I’m thinking of measures such as lung clearance index, quantitative CT, sweat chloride assessment and inflammatory markers, to name a few. Now one of our challenges — a pleasant one — is how to educate and engage with our patient population to increase participation in clinical trials so that we can ensure enrollment across trials in multiple development programs.
Hamblett: We’ve created seven National Resource Centers to provide consultation to researchers on specialized topics such as diagnostic imaging and interpretive cytology. Seattle Children’s is the main microbiology resource for all the sites in the TDN, under the direction of Dr. Lucas Hoffman.
Additionally, we are now targeting the genetic defects of the disease, not just symptoms — so this is truly personalized medicine in that we are creating mutation-specific medicines. This puts us in a new position in terms of navigating the regulatory pathway, so we’ve been proactive about engaging with the Cystic Fibrosis Foundation and with regulatory bodies such as the FDA to streamline and address challenges in developmental pathways for these newer classes of medicines.
These newer therapies pinpoint and ultimately change the underlying genetic defect in a patient with CF. One patient’s genetic mutation might be the same as maybe only two other people, for example. These innovations, along with the other infrastructure the TDN offers, has accelerated research results and improved patient treatments significantly. This combination of research and clinical improvements is a large part of why life expectancy has jumped from 15-18 to 35-40 years in the past decade. It’s a very exciting time to be involved in CF research.
– E. Kuwana